研究者データベース

白土 博樹(シラト ヒロキ)
医学研究院 連携研究センター
教授

基本情報

所属

  • 医学研究院 連携研究センター

職名

  • 教授

学位

  • 博士(医学)(北海道大学)

ホームページURL

J-Global ID

研究キーワード

  • 放射線腫瘍学   Electric chart   Radiation physics   Radiation Biology   Radiation Oncology   

研究分野

  • ライフサイエンス / 放射線科学

所属学協会

  • 米国放射線腫瘍学会   日本放射線腫瘍学会   日本頭頚部腫瘍学会   日本定位放射線治療学会   日本定位放射線学会   日本高精度外部照射研究会世話人   日本放射線治療品質管理機構理事   日本医学放射線学会   日本癌治療学会   日本癌学会   欧州放射線腫瘍学会   American Society of Therapeutic Radiology and Oncology   

研究活動情報

論文

  • Yasuka Kikuchi, Masanao Naya, Noriko Oyama-Manabe, Osamu Manabe, Hiroyuki Sugimori, Kohsuke Kudo, Fumi Kato, Tadao Aikawa, Hiroyuki Tsutsui, Nagara Tamaki, Hiroki Shirato
    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 18 2 134 - 141 2019年04月10日 [査読有り][通常論文]
     
    PURPOSE: The aim of this study was to verify coronary flow velocity reserve (CFVR) on the left main trunk (LMT) in comparison with myocardial flow reserve (MFR) by 15O-labeled water positron emission tomography (PET) (MFR-PET) in both the healthy adults and the patients with coronary artery disease (CAD), and to evaluate the feasibility of CFVR to detect CAD. METHODS: Eighteen healthy adults and 13 patients with CAD were evaluated. CFVR in LMT was estimated by 3T magnetic resonance imaging (MRI) with phase contrast technique. MFR-PET in the LMT territory including anterior descending artery and circumflex artery was calculated as the ratio of myocardial blood flow (MBF)-PET at stress to MBF-PET at rest. RESULTS: There was a significant positive relationship between CFVR and MFR-PET (R = 0.45, P < 0.0001). Inter-observer calculations of CFVR showed good correlation (R2 = 0.93, P < 0.0001). The CFVR in patients with CAD was significantly lower than that in healthy adults (1.90 ± 0.61 vs. 2.77 ± 1.03, respectively, P = 0.01), which were similar to the results of MFR-PET (2.23 ± 0.84 vs. 3.96 ± 1.04, respectively, P < 0.0001). For the detection of patients with CAD, the area under the curve was 0.78 (P = 0.01). The sensitivity was 0.77 and specificity was 0.72 when a cut-off of 2.15 was used. CONCLUSION: CFVR by 3T was validated with MFR-PET. CFVR could detect the patients with CAD. This method is a simple and reliable index without radiation or contrast material.
  • Tetsuya Inoue, Norio Katoh, Yoichi M Ito, Tomoki Kimura, Yasushi Nagata, Kengo Kuriyama, Hiroshi Onishi, Tadamasa Yoshitake, Yoshiyuki Shioyama, Yusuke Iizuka, Koji Inaba, Koji Konishi, Masaki Kokubo, Katsuyuki Karasawa, Takuyo Kozuka, Kensuke Tanaka, Jun Sakakibara-Konishi, Ichiro Kinoshita, Hiroki Shirato
    Lung Cancer 122 107 - 112 2018年08月01日 [査読有り][通常論文]
     
    Objectives: Even with advanced image guidance, biopsies occasionally fail to diagnose small lung lesions, which are highly suggestive of primary lung cancer by radiological examination. The aim of this study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) to treat small lung lesions clinically diagnosed as primary lung cancer. Materials and methods: This is a prospective, multi-institutional observation study. Strict inclusion and exclusion criteria were determined in a nation-wide consensus meeting and used to include patients who were clinically diagnosed with primary lung cancer using precise imaging modalities, for whom further surgical intervention was not feasible, who refused watchful waiting, and who were highly tolerable of SBRT with informed consent. SBRT was performed with 48 Gy in 4 fractions at the tumor isocenter. Results: From August 2009 to August 2014, 62 patients from 11 institutions were enrolled. Their median age was 80 years. The tumors ranged in size from 9 to 30 mm in diameter (median, 18 mm). The median follow-up interval was 55 months. The 3-year overall survival rate was 83.3% (95% confidence interval (CI) 71.1–90.7%) for all the patients and 94.7% (95% CI 68.1–99.2%) for the patients younger than 75 years. Local failure, regional lymph node metastases and distant metastases occurred in 4 (6.4%), 3 (4.8%) and 11 (17.7%) patients, respectively. Grades 3 and 4 toxicities were observed in 8 (12.9%) patients and 1 (1.6%) patient, respectively. No grade 5 toxicities were observed. Conclusions: SBRT is safe and effective for patients with small lung lesions clinically diagnosed as primary lung cancer that satisfied the proposed strict indication criteria as previously reported. A prospective interventional study is required to ascertain if SBRT is an alternative strategy for these patients.
  • Hirayama S, Matsuura T, Ueda H, Fujii Y, Fujii T, Takao S, Miyamoto N, Shimizu S, Fujimoto R, Umegaki K, Shirato H
    Medical physics 45 7 3404 - 3416 2018年07月 [査読有り][通常論文]
  • Onodera Y, Nam JM, Horikawa M, Shirato H, Sabe H
    Nature communications 9 1 2682  2018年07月 [査読有り][通常論文]
  • Takamasa Kayama, Shinya Sato, Kaori Sakurada, Junki Mizusawa, Ryo Nishikawa, Yoshitaka Narita, Minako Sumi, Yasuji Miyakita, Toshihiro Kumabe, Yukihiko Sonoda, Yoshiki Arakawa, Susumu Miyamoto, Takaaki Beppu, Kazuhiko Sugiyama, Hirohiko Nakamura, Motoo Nagane, Yoko Nakasu, Naoya Hashimoto, Mizuhiko Terasaki, Akira Matsumura, Eiichi Ishikawa, Toshihiko Wakabayashi, Yasuo Iwadate, Shiro Ohue, Hiroyuki Kobayashi, Manabu Kinoshita, Kenichiro Asano, Akitake Mukasa, Katsuyuki Tanaka, Akio Asai, Hideo Nakamura, Tatsuya Abe, Yoshihiro Muragaki, Koichi Iwasaki, Tomokazu Aoki, Takao Watanabe, Hikaru Sasaki, Shuichi Izumoto, Masahiro Mizoguchi, Takayuki Matsuo, Hideo Takeshima, Motohiro Hayashi, Hidefumi Jokura, Takashi Mizowaki, Eiji Shimizu, Hiroki Shirato, Masao Tago, Hiroshi Katayama, Haruhiko Fukuda, Soichiro Shibui
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology JCO2018786186  2018年06月20日 [査読有り][通常論文]
     
    Purpose Whereas whole-brain radiotherapy (WBRT) has been the standard treatment of brain metastases (BMs), stereotactic radiosurgery (SRS) is increasingly preferred to avoid cognitive dysfunction; however, it has not been clearly determined whether treatment with SRS is as effective as that with WBRT or WBRT plus SRS. We thus assessed the noninferiority of salvage SRS to WBRT in patients with BMs. Patients and Methods Patients age 20 to 79 years old with performance status scores of 0 to 2-and 3 if caused only by neurologic deficits-and with four or fewer surgically resected BMs with only one lesion > 3 cm in diameter were eligible. Patients were randomly assigned to WBRT or salvage SRS arms within 21 days of surgery. The primary end point was overall survival. A one-sided α of .05 was used. Results Between January 2006 and May 2014, 137 and 134 patients were enrolled in the WBRT and salvage SRS arms, respectively. Median overall survival was 15.6 months in both arms (hazard ratio, 1.05; 90% CI, 0.83 to 1.33; one-sided P for noninferiority = .027). Median intracranial progression-free survival of patients in the WBRT arm (10.4 months) was longer than that of patients in the salvage SRS arm (4.0 months). The proportions of patients whose Mini-Mental Status Examination and performance status scores that did not worsen at 12 months were similar in both arms; however, 16.4% of patients in the WBRT arm experienced grade 2 to 4 cognitive dysfunction after 91 days postenrollment, whereas only 7.7% of those in the SRS arm did ( P = .048). Conclusion Salvage SRS is noninferior to WBRT and can be established as a standard therapy for patients with four or fewer BMs.
  • Hiroki Shirato
    International Journal of Clinical Oncology 23 3 421 - 422 2018年06月01日 [査読有り][通常論文]
  • Masashi Mizumoto, Shigeyuki Murayama, Tetsuo Akimoto, Yusuke Demizu, Takashi Fukushima, Yuji Ishida, Yoshiko Oshiro, Haruko Numajiri, Hiroshi Fuji, Toshiyuki Okumura, Hiroki Shirato, Hideyuki Sakurai
    Cancer Medicine 7 5 1870 - 1874 2018年05月01日 [査読有り][通常論文]
     
    To evaluate preliminary results of proton radiotherapy (PRT) for pediatric patients with rhabdomyosarcoma (RMS). From 1987 to 2014, PRT was conducted as initial radiotherapy in 55 patients (35 males, 20 females, median age 5 years, range 0–19) with RMS at four institutes in Japan. Thirty-one, 18, and six patients had embryonal, alveolar, and other RMS, respectively. One, 11, 37, and six patients were in IRSG groups I, II, III, and IV, respectively, and the COG risk group was low, intermediate, and high for nine, 39, and seven patients, respectively. The irradiation dose was 36–60 GyE (median: 50.4 GyE). The median follow-up period was 24.5 months (range: 1.5–320.3). The 1- and 2-year overall survival rates were 91.9% (95% CI: 84.3–99.5%) and 84.8% (95% CI 75.2–94.3%), respectively, and these rates were 100% and 100%, 97.1% and 90.1%, and 57.1% and 42.9% for COG low-, intermediate-, and high-risk groups, respectively. There were 153 adverse events of Grade ≥3, including 141 hematologic toxicities in 48 patients (87%) and 12 radiation-induced toxicities in nine patients (16%). Proton-specific toxicity was not observed. PRT has the same treatment effect as photon radiotherapy with tolerable acute radiation-induced toxicity.
  • Sumito Yoshida, Hiroaki Shime, Yohei Takeda, Jin-Min Nam, Ken Takashima, Misako Matsumoto, Hiroki Shirato, Masanori Kasahara, Tsukasa Seya
    Cancer Science 109 4 956 - 965 2018年04月01日 [査読有り][通常論文]
     
    Radiotherapy induces anti-tumor immunity by induction of tumor antigens and damage-associated molecular patterns (DAMP). DNA, a representative DAMP in radiotherapy, activates the stimulator of interferon genes (STING) pathway which enhances the immune response. However, the immune response does not always parallel the inflammation associated with radiotherapy. This lack of correspondence may, in part, explain the radiation-resistance of tumors. Additive immunotherapy is expected to revive tumor-specific CTL facilitating radiation-resistant tumor shrinkage. Herein pre-administration of the double-stranded RNA, polyinosinic-polycytidylic acid (polyI:C), in conjunction with radiotherapy, was shown to foster tumor suppression in mice bearing radioresistant, ovalbumin-expressing Lewis lung carcinoma (LLC). Extrinsic injection of tumor antigen was not required for tumor suppression. No STING- and CTL-response was induced by radiation in the implant tumor. PolyI:C was more effective for induction of tumor growth retardation at 1 day before radiation than at post-treatment. PolyI:C targeted Toll-like receptor 3 with minimal effect on the mitochondrial antiviral-signaling protein pathway. Likewise, the STING pathway barely contributed to LLC tumor suppression. PolyI:C primed antigen-presenting dendritic cells in draining lymph nodes to induce proliferation of antigen-specific CTL. By combination therapy, CTL efficiently infiltrated into tumors with upregulation of relevant chemokine transcripts. Batf3-positive DC and CD8+ T cells were essential for therapeutic efficacy. Furthermore, polyI:C was shown to stimulate tumor-associated macrophages and release tumor necrosis factor alpha, which acted on tumor cells and increased sensitivity to radiation. Hence, polyI:C treatment prior to radiotherapy potentially induces tumor suppression by boosting CTL-dependent and macrophage-mediated anti-tumor responses. Eventually, polyI:C and radiotherapy in combination would be a promising therapeutic strategy for radiation-resistant tumors.
  • Ryo Takagi, Yuriko Komiya, Kenneth L Sutherland, Hiroki Shirato, Hiroyuki Date, Masahiro Mizuta
    Journal of Radiation Research 59 suppl_1 i32 - i39 2018年03月01日 [査読有り][通常論文]
     
    In this paper, we compare two radiation effect models: the average surviving fraction (ASF) model and the integral biologically effective dose (IBED) model for deriving the optimal irradiation scheme and show the superiority of ASF. Minimizing the effect on an organ at risk (OAR) is important in radiotherapy. The biologically effective dose (BED) model is widely used to estimate the effect on the tumor or on the OAR, for a fixed value of dose. However, this is not always appropriate because the dose is not a single value but is distributed. The IBED and ASF models are proposed under the assumption that the irradiation is distributed. Although the IBED and ASF models are essentially equivalent for deriving the optimal irradiation scheme in the case of uniform distribution, they are not equivalent in the case of non-uniform distribution. We evaluate the differences between them for two types of cancers: high α/β ratio cancer (e.g. lung) and low α/β ratio cancer (e.g. prostate), and for various distributions i.e. various dose-volume histograms. When we adopt the IBED model, the optimal number of fractions for low α/β ratio cancers is reasonable, but for high α/β ratio cancers or for some DVHs it is extremely large. However, for the ASF model, the results keep within the range used in clinical practice for both low and high α/β ratio cancers and for most DVHs. These results indicate that the ASF model is more robust for constructing the optimal irradiation regimen than the IBED model.
  • Kentaro Nishioka, Anussara Prayongrat, Kota Ono, Shunsuke Onodera, Takayuki Hashimoto, Norio Katoh, Tetsuya Inoue, Rumiko Kinoshita, Koichi Yasuda, Takashi Mori, Rikiya Onimaru, Hiroki Shirato, Shinichi Shimizu
    Journal of Radiation Research 59 suppl_1 i63 - i71 2018年03月01日 [査読有り][通常論文]
     
    © The Author(s) 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. This is a report of a single-institution prospective study evaluating the safety of a spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy (PBT) system. Data collection was performed for 56 patients with 59 treatment sites who received proton beam therapy at Hokkaido University Hospital between March 2014 and July 2015. Forty-one patients were male and 15 were female. The median age was 66 years. The primary lesion sites were prostate (n = 17), bone/soft tissue (n = 10), liver (n = 7), lung (n = 6), central nervous system (n = 5), colon (n = 2), pancreas (n = 2), kidney (n = 2) and others (n = 5). Chemotherapy was administered in 11 patients. The prescribed total dose was from 20 to 76 GyE (Radiobiological equivalent dose, RBE = 1.1), with the median dose of 65 GyE in 4 to 35 fractions. No PBT-related Common Terminology Criteria for Adverse Events Grade 4 or 5 toxicities were observed; the incidence of early PBT-related Grade 4 adverse events was 0% (95% confidence interval 0 to 6.38%). The most common Grade 3 toxicities were hematologic toxicity (12.5%) unlikely to be related to the PBT. One patient developed a left femoral neck fracture (Grade 3) at 14.5 months after PBT for chondrosarcoma of the left pelvis. The pathological findings showed no other malignancies, suggesting that it was possibly related to the PBT. In conclusion, the spot-scanning dedicated, synchrotron-based PBT system is feasible, but further studies on its long-term safety and efficacy are warranted.
  • Hiroki Shirato, Quynh-Thu Le, Keiji Kobashi, Anussara Prayongrat, Seishin Takao, Shinichi Shimizu, Amato Giaccia, Lei Xing, Kikuo Umegaki
    Journal of Radiation Research 59 suppl_1 i2 - i10 2018年03月01日 [査読有り][通常論文]
     
    Physically precise external-beam radiotherapy (EBRT) technologies may not translate to the best outcome in individual patients. On the other hand, clinical considerations alone are often insufficient to guide the selection of a specific EBRT approach in patients. We examine the ways in which to compare different EBRT approaches based on physical, biological and clinical considerations, and how they can be enhanced with the addition of biophysical models and machine-learning strategies. The process of selecting an EBRT modality is expected to improve in tandem with knowledge-based treatment planning.
  • Hiromitsu Iwata, Hitoshi Ishikawa, Masaru Takagi, Tomoaki Okimoto, Sigeyuki Murayama, Tetsuo Akimoto, Hitoshi Wada, Takeshi Arimura, Yoshitaka Sato, Masayuki Araya, Jun-Etsu Mizoe, Masahiko Gosho, Katsumasa Nakamura, Hiroki Shirato, Hideyuki Sakurai
    Cancer medicine 7 3 677 - 689 2018年03月 [査読有り][通常論文]
     
    This is the first multi-institutional retrospective survey of the long-term outcomes of proton therapy (PT) for prostate cancer in Japan. This retrospective analysis comprised prostate cancer patients treated with PT at seven centers between January 2008 and December 2011 and was approved by each Institutional Review Board. The NCCN classification was used. Biochemical relapse was based on the Phoenix definition (nadir + 2.0 ng/mL). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. There were 215, 520, and 556 patients in the low-risk, intermediate-risk, and high-risk groups, respectively. The median follow-up period of surviving patients was 69 months (range: 7-107). Among all patients, 98.8% were treated using a conventional fractionation schedule and 1.2% with a hypofractionation schedule; 58.5% and 21.5% received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The 5-year biochemical relapse-free survival (bRFS) and overall survival rates in the low-risk, intermediate-risk, and high-risk groups were 97.0%, 91.1%, and 83.1%, and 98.4%, 96.8%, and 95.2%, respectively. In the multivariate analysis, the NCCN classification was a significant prognostic factor for bRFS, but not overall survival. The incidence rates of grade 2 or more severe late gastrointestinal and genitourinary toxicities were 4.1% and 4.0%, retrospectively. This retrospective analysis of a multi-institutional survey suggested that PT is effective and well-tolerated for prostate cancer. Based on this result, a multi-institutional prospective clinical trial (UMIN000025453) on PT for prostate cancer has just been initiated in order to define its role in Japan.
  • Le QT, Shirato H
    Journal of radiation research 59 suppl_1 i1  2018年03月 [査読有り][通常論文]
  • Anussara Prayongrat, Kikuo Umegaki, Arjen van der Schaaf, Albert C Koong, Steven H Lin, Thomas Whitaker, Todd McNutt, Naruhiro Matsufuji, Edward Graves, Masahiko Mizuta, Kazuhiko Ogawa, Hiroyuki Date, Kensuke Moriwaki, Yoichi M Ito, Keiji Kobashi, Yasuhiro Dekura, Shinichi Shimizu, Hiroki Shirato
    Journal of radiation research 59 suppl_1 i72-i76 - i76 2018年03月01日 [査読有り][通常論文]
     
    Particle beam therapy (PBT), including proton and carbon ion therapy, is an emerging innovative treatment for cancer patients. Due to the high cost of and limited access to treatment, meticulous selection of patients who would benefit most from PBT, when compared with standard X-ray therapy (XRT), is necessary. Due to the cost and labor involved in randomized controlled trials, the model-based approach (MBA) is used as an alternative means of establishing scientific evidence in medicine, and it can be improved continuously. Good databases and reasonable models are crucial for the reliability of this approach. The tumor control probability and normal tissue complication probability models are good illustrations of the advantages of PBT, but pre-existing NTCP models have been derived from historical patient treatments from the XRT era. This highlights the necessity of prospectively analyzing specific treatment-related toxicities in order to develop PBT-compatible models. An international consensus has been reached at the Global Institution for Collaborative Research and Education (GI-CoRE) joint symposium, concluding that a systematically developed model is required for model accuracy and performance. Six important steps that need to be observed in these considerations include patient selection, treatment planning, beam delivery, dose verification, response assessment, and data analysis. Advanced technologies in radiotherapy and computer science can be integrated to improve the efficacy of a treatment. Model validation and appropriately defined thresholds in a cost-effectiveness centered manner, together with quality assurance in the treatment planning, have to be achieved prior to clinical implementation.
  • Kobashi K, Prayongrat A, Kimoto T, Toramatsu C, Dekura Y, Katoh N, Shimizu S, Ito YM, Shirato H
    Journal of radiation research 59 suppl_1 i50 - i57 2018年03月01日 [査読有り][通常論文]
     
    Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP ('NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the 'NTCP with uncertainty might potentially guide the use of PBT however, clinical validation and a cost-effectiveness study are needed to determine the appropriate 'NTCP threshold.
  • Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Daisuke Yoshida, Kohsuke Kudo, Hiroki Shirato
    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 17 1 21 - 27 2018年01月10日 [査読有り][通常論文]
     
    PURPOSE: To evaluate the diagnostic power of hybrid intravoxel incoherent motion (IVIM)-diffusion kurtosis imaging (DKI) model parameters in pretreatment for the prediction of future distant metastasis in head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: We retrospectively evaluated 49 HNSCC patients who underwent curative chemoradiation therapy. Diffusion-weighted image (DWI) acquired by single-shot spin-echo echo-planar imaging with 12 b-values (0-2000) was performed in all patients before any treatment. We calculated the IVIM-DKI parameters and the conventional apparent diffusion coefficient (ADC) in the ROI placed on the primary lesion. The presence of future distant metastasis was determined by histological findings or clinical follow-up. RESULTS: A univariate analysis revealed significant differences between the patients with distant metastasis and those without in slow diffusion coefficient (D) and kurtosis value (K). Highest diagnostic accuracy was obtained by the D value. In addition, a multivariate analysis revealed that the D value was an independent predictor of future distant metastasis. CONCLUSION: The D and K values obtained by this hybrid IVIM-DKI model can be one of the diagnostic tools for the prediction of future distant metastasis in HNSCC patients.
  • Noriyuki Fujima, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Akiko Tsukahara, Yukie Shimizu, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato
    EUROPEAN RADIOLOGY 27 3 956 - 965 2017年03月 [査読有り][通常論文]
     
    To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) and diffusional kurtosis imaging (DKI) parameters in nasal or sinonasal squamous cell carcinoma (SCC) patients to determine local control/failure. Twenty-eight patients were evaluated. MR acquisition used single-shot spin-echo EPI with 12 b-values. Quantitative parameters (mean value, 25th, 50th and 75th percentiles) of IVIM (perfusion fraction f, pseudo-diffusion coefficient D*, and true-diffusion coefficient D), DKI (kurtosis value K, kurtosis corrected diffusion coefficient D-k) and apparent diffusion coefficient (ADC) were calculated. Parameter values at both the pretreatment and early-treatment period, and the percentage change between these two periods were obtained. Multivariate logistic regression analysis: the percentage changes of D (mean, 25th, 50th, 75th), K (mean, 50th, 75th), Dk (mean, 25th, 50th), and ADC (mean, 25th, 50th) were predictors of local control. ROC curve analysis: the parameter with the highest accuracy = the percentage change of D value with the histogram 25th percentile (0.93 diagnostic accuracy). Multivariate Cox regression analyses: the percentage changes of D (mean, 25th, 50th), K (mean, 50th, 75th), Dk (mean, 25th, 50th) and ADC (mean, 25th, 50th) are predictors. IVIM and DKI parameters, especially the D-value's histogram 25th percentile, are useful for predicting local control. Noninvasive assessment of treatment outcome in SCC patients was achieved using IVIM/DKI. Several IVIM and DKI parameters can predict the local control. Especially, the D-value's histogram 25th percentile has high diagnostic accuracy.
  • Yi Cui, Jie Song, Erqi Pollom, Muthuraman Alagappan, Hiroki Shirato, Daniel T. Chang, Albert C. Koong, Ruijiang Li
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 96 1 102 - 109 2016年09月 [査読有り][通常論文]
     
    Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board-approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n = 90) and a validation cohort (n = 49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT F-18-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162 robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P = .002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P = .018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P = .037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P = .123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). Conclusion: Quantitative analysis identified novel F-18-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy. (C) 2016 Elsevier Inc. All rights reserved.
  • Yae Harada, Kenji Hirata, Naoki Nakayama, Shigeru Yamaguchi, Michiharu Yoshida, Shunsuke Onodera, Osamu Manabe, Tohru Shiga, Satoshi Terae, Hiroki Shirato, Nagara Tamaki
    Acta radiologica open 4 6 2058460115584112 - 2058460115584112 2015年06月 [査読有り][通常論文]
     
    A 55-year-old woman underwent radiosurgery for a left cerebral hemisphere arteriovenous malformation (AVM) and developed radiation-induced necrosis causing a massive edema in the surrounding brain tissues. Despite various therapies, the edema expanded to the ipsilateral hemisphere and induced neurological symptoms. The radiation-induced necrotic lesion was surgically removed 4 years after radiosurgery. While the preoperative FDG PET revealed severe hypometabolism in the left cerebrum, the necrotomy significantly ameliorated the brain edema, glucose metabolism (postoperative FDG PET), and symptoms. This case indicates that radiation necrosis-induced neurological deficits may be associated with brain edema and hypometabolism, which could be reversed by appropriate necrotomy.
  • Khin K Tha, Satoshi Terae, Shin Nakagawa, Takeshi Inoue, Nobuki Kitagawa, Yuki Kako, Yasuya Nakato, Kawser Akter Popy, Noriyuki Fujima, Yuri Zaitsu, Daisuke Yoshida, Yoichi M Ito, Tamaki Miyamoto, Tsukasa Koyama, Hiroki Shirato
    Psychiatry research 212 3 208 - 15 2013年06月30日 [査読有り][通常論文]
     
    Diffusion tensor imaging (DTI) is considered to be able to non-invasively quantify white matter integrity. This study aimed to use DTI to evaluate white matter integrity in non-geriatric patients with major depressive disorder (MDD) who were free of antidepressant medication. DTI was performed on 19 non-geriatric patients with MDD, free of antidepressant medication, and 19 age-matched healthy subjects. Voxel-based and histogram analyses were used to compare fractional anisotropy (FA) and mean diffusivity (MD) values between the two groups, using two-sample t tests. The abnormal DTI indices, if any, were tested for correlation with disease duration and severity, using Pearson product-moment correlation analysis. Voxel-based analysis showed clusters with FA decrease at the bilateral frontal white matter, anterior limbs of internal capsule, cerebellum, left putamen and right thalamus of the patients. Histogram analysis revealed lower peak position of FA histograms in the patients. FA values of the abnormal clusters and peak positions of FA histograms of the patients exhibited moderate correlation with disease duration and severity. These results suggest the implication of frontal-subcortical circuits and cerebellum in MDD, and the potential utility of FA in evaluation of brain parenchymal integrity.
  • Yukinori Matsuo, Hiroshi Onishi, Keiichi Nakagawa, Mitsuhiro Nakamura, Takaki Ariji, Yu Kumazaki, Munefumi Shimbo, Naoki Tohyama, Teiji Nishio, Masahiko Okumura, Hiroki Shirato, Masahiro Hiraoka
    Journal of Radiation Research 54 3 561 - 568 2013年05月 [査読有り][通常論文]
     
    Respiratory motion management (RMM) systems in external and stereotactic radiotherapies have been developed in the past two decades. Japanese medical service fee regulations introduced reimbursement for RMM from April 2012. Based on thorough discussions among the four academic societies concerned, these Guidelines have been developed to enable staff (radiation oncologists, radiological technologists, medical physicists, radiotherapy quality managers, radiation oncology nurses, and others) to apply RMM to radiation therapy for tumors subject to respiratory motion, safely and appropriately. © 2012 The Author 2012.
  • Tomohiro Sakashita, Akihiro Homma, Nobuhiko Oridate, Seigo Suzuki, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    AURIS NASUS LARYNX 40 2 211 - 215 2013年04月 [査読有り][通常論文]
     
    Objectives: Although three-weekly high-dose (100 mg/m(2)) cisplatin (three cycles) chemoradiotherapy has been considered a standard regimen for patients with advanced head and neck squamous cell carcinomas (HNSCC), this protocol is associated with significant acute and late toxicities. Therefore, weekly cisplatin at a dose of 40 mg/m(2) has been used at our institution since 2006. This retrospective study was aimed at assessing the oncologic efficacy of weekly cisplatin chemoradiotherapy for the control of nodal metastasis. Methods: We analyzed 28 patients with node-positive HNSCC treated with weekly cisplatin and concurrent radiotherapy. Computed tomography was performed 4-8 weeks after the completion of chemoradiotherapy to evaluate nodal response. If residual neck disease was apparent or suspected, we performed early salvage neck dissection (ND). In cases with a complete response (CR), we took a "wait and see" approach. When no viable tumor cells were observed in the surgical specimens obtained by ND, nodal metastasis was defined as controlled by weekly cisplatin chemoradiotherapy alone. Results: Nodal metastasis was evaluated as having a CR in 20 patients (71%). Eight patients (29%) underwent early salvage ND. Recurrent primary tumors were observed in the other four patients (14%). Salvage primary resection and associated ND were performed for these four patients. In 7 of 12 patients undergoing ND, no viable tumor cells were observed. In 23 of 28 patients, neck diseases were controlled by chemoradiotherapy alone (not including salvage by ND). In 27 of 28 patients, neck diseases were controlled by the overall treatment (including salvage by ND). The rate of nodal control by chemoradiotherapy alone and by the overall treatment was found to be 82.0% and 96.3%, respectively, using the Kaplan-Meier method. The three-year overall and disease free survival rates were 86.8% and 80.8%, respectively. Conclusion: Concomitant weekly cisplatin at a dose of 40 mg/m(2) chemoradiotherapy showed a good control rate of not only primary lesions but also neck diseases. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  • Kohsuke Kudo, Soren Christensen, Makoto Sasaki, Leif Ostergaard, Hiroki Shirato, Kuniaki Ogasawara, Max Wintermark, Steven Warach
    RADIOLOGY 267 1 201 - 211 2013年04月 [査読有り][通常論文]
     
    Purpose: To design a digital phantom data set for computed tomography (CT) perfusion and perfusion-weighted imaging on the basis of the widely accepted tracer kinetic theory in which the true values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and tracer arrival delay are known and to evaluate the accuracy and reliability of postprocessing programs using this digital phantom. Materials and Methods: A phantom data set was created by generating concentration-time curves reflecting true values for CBF (2.5-87.5 mL/100 g per minute), CBV (1.0-5.0 mL/100 g), MTT (3.4-24 seconds), and tracer delays (0-3.0 seconds). These curves were embedded in human brain images. The data were analyzed by using 13 algorithms each for CT and magnetic resonance (MR), including five commercial vendors and five academic programs. Accuracy was assessed by using the Pearson correlation coefficient (r) for true values. Delay-, MTT-, or CBV-dependent errors and correlations between time to maximum of residue function (T-max) were also evaluated. Results: In CT, CBV was generally well reproduced (r > 0.9 in 12 algorithms), but not CBF and MTT (r > 0.9 in seven and four algorithms, respectively). In MR, good correlation (r > 0.9) was observed in one-half of commercial programs, while all academic algorithms showed good correlations for all parameters. Most algorithms had delay-dependent errors, especially for commercial software, as well as CBV dependency for CBF or MTT calculation and MTT dependency for CBV calculation. Correlation was good in T-max except for one algorithm. Conclusion: The digital phantom readily evaluated the accuracy and characteristics of the CT and MR perfusion analysis software. All commercial programs had delay-induced errors and/or insufficient correlations with true values, while academic programs for MR showed good correlations with true values. (C) RSNA, 2012
  • Hidefumi Aoyama, Shunsuke Onodera, Norihito Takeichi, Rikiya Onimaru, Shunsuke Terasaka, Yutaka Sawamura, Hiroki Shirato
    International Journal of Radiation Oncology Biology Physics 85 2 329 - 334 2013年02月01日 [査読有り][通常論文]
     
    Purpose: The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known. Methods and Materials: This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months. Results: The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P<.0001) and trigeminal nerve (P<.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients. Conclusions: Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention. © 2013 Elsevier Inc. All rights reserved.
  • Koichi Yasuda, Rikiya Onimaru, Shozo Okamoto, Tohru Shiga, Norio Katoh, Kazuhiko Tsuchiya, Ryusuke Suzuki, Wataru Takeuchi, Yuji Kuge, Nagara Tamaki, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 85 1 142 - 147 2013年01月 [査読有り][通常論文]
     
    Purpose: The impact of a new type of positron emission tomography (New PET) with semiconductor detectors using F-18-labeled fluoromisonidazole (FMISO)-guided intensity modulated radiation therapy (IMRT) was compared with a state-of-the-art PET/computed tomography (PET/CT) system in nasopharyngeal cancer (NPC) patients. Methods and Materials: Twenty-four patients with non-NPC malignant tumors (control group) and 16 patients with NPC were subjected to FMISO-PET. The threshold of the tumor-to-muscle (T/M) ratio in each PET scan was calculated. The hypoxic volume within the gross tumor volume (GTVh) was determined using each PET ((NewPET)GTVh and (PET/CT)GTVh, respectively). Dose escalation IMRT plans prescribing 84 Gy to each GTVh were carried out. Results: The threshold of the T/M ratio was 1.35 for New PET and 1.23 for PET/CT. The mean volume of NewPETGTVh was significantly smaller than that of PET/CTGTVh (1.5 +/- 1.6 cc vs 4.7 +/- 4.6 cc, respectively; P = .0020). The dose escalation IMRT plans using New PET were superior in dose distribution to those using PET/CT. Dose escalation was possible in all 10 New PET-guided plans but not in 1 PET/CT-guided plan, because the threshold dose to the brainstem was exceeded. Conclusions: New PET was found to be useful for accurate dose escalation in FMISO-guided IMRT for patients with NPC. (c) 2013 Elsevier Inc.
  • Masahiro Mizuta, Seishin Takao, Hiroyuki Date, Naoki Kishimoto, Kenneth L. Sutherland, Rikiya Onimaru, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 84 3 829 - 833 2012年11月 [査読有り][通常論文]
     
    Purpose: Hypofractionated irradiation is often used in precise radiotherapy instead of conventional multifractionated irradiation. We propose a novel mathematical method for selecting a hypofractionated or multifractionated irradiation regimen based on physical dose distribution adding to biologic consideration. Methods and Materials: The linear-quadratic model was used for the radiation effects on tumor and normal tissues, especially organs at risk (OARs). On the basis of the assumption that the OAR receives a fraction of the dose intended for the tumor, the minimization problem for the damage effect on the OAR was treated under the constraint that the radiation effect on the tumor is fixed. Results: For an N-time fractionated irradiation regimen, the constraint of tumor lethality was described by an N-dimensional hypersphere. The total dose of the fractionated irradiations was considered for minimizing the damage effect on the OAR under the hypersphere condition. It was found that the advantage of hypofractionated or multifractionated irradiation therapies depends on the magnitude of the ratio of alpha/beta parameters for the OAR and tumor in the linear-quadratic model and the ratio of the dose for the OAR and tumor. Conclusions: Our mathematical method shows that multifractionated irradiation with a constant dose is better if the ratio of alpha/beta for the OAR and tumor is less than the ratio of the dose for the OAR and tumor, whereas hypofractionated irradiation is better otherwise. (C) 2012 Elsevier Inc.
  • Masahiro Mizuta, Hiroyuki Date, Seishin Takao, Naoki Kishimoto, Kenneth L. Sutherland, Rikiya Onimaru, Hiroki Shirato
    MEDICAL PHYSICS 39 11 6791 - 6795 2012年11月 [査読有り][通常論文]
     
    Purpose: The authors propose a graphical representation of the relation between the effect on the tumor and the damage effect on an organ at risk (OAR) against the irradiation dose, as an aid for choosing an appropriate fractionation regimen. Methods: The graphical relation is depicted by the radiation effect on the tumor E-1 versus that on an OAR E-0. By observing the features of the E-1 vs E-0 relation curve, i.e., convex or concave shape, one can judge whether multifractionation is better or not. This method is applied to the linear-quadratic model (with alpha and beta parameters) as an example. Further, the method is extended to the general case for nonuniform dose distribution to the OAR, which is frequently seen in clinical situations. Results: The criterion for selecting multi- or hypofractionation is based on the relation between the dose for the OAR and the alpha/beta ratio of the OAR to the tumor. It is also shown that the graphical relation enables us to estimate the final effect after multifractionated treatment by plotting a tangent line on the curve. Conclusions: The graphical representation method is of use for improving planning in radiotherapy by determining the effective fractionation scheme. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4757580]
  • Shigenari Taki, Akihiro Homma, Fumiyuki Suzuki, Nobuhiko Oridate, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Jun Furusawa, Tomohiro Sakashita, Naoya Inamura, Daisuke Yoshida, Rikiya Onimaru, Hiroki Shirato, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 17 5 441 - 446 2012年10月 [査読有り][通常論文]
     
    Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.
  • Taeko Matsuura, Kenichiro Maeda, Kenneth Sutherland, Taisuke Takayanagi, Shinichi Shimizu, Seishin Takao, Naoki Miyamoto, Hideaki Nihongi, Chie Toramatsu, Yoshihiko Nagamine, Rintaro Fujimoto, Ryusuke Suzuki, Masayori Ishikawa, Kikuo Umegaki, Hiroki Shirato
    MEDICAL PHYSICS 39 9 5584 - 5591 2012年09月 [査読有り][通常論文]
     
    Purpose: In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). Methods: A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCPr) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, alpha/beta values of 1.5, 3, and 10 Gy (RBE) were considered. Results: It was found that the marker of 1.5 mm diameter does not affect the TCPs with all alpha/beta values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCPr by less than 3%. This is especially true when multiple (two or three) markers are used for alignment of a patient. Conclusions: It is recommended that 1.5-mm markers be used to avoid the reduction of TCP as well as to spare the surrounding critical organs, as long as the markers are visible on x-ray fluoroscopy. When 2-mm markers are implanted, more than two fields should be used and the markers should not be placed close to the distal edge of any of the beams. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4745558]
  • Daisuke Abo, Yu Hasegawa, Yusuke Sakuhara, Satoshi Terae, Tadashi Shimizu, Khin Khin Tha, Eiichi Tanaka, Satoshi Hirano, Satoshi Kondo, Hiroki Shirato
    JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 19 4 431 - 437 2012年07月 [査読有り][通常論文]
     
    To describe the feasibility of a dual microcatheter-dual interlocking detachable coil (DMDI) technique for preoperative embolization of the common hepatic artery (CHA) in preparation for distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for locally advanced pancreatic body cancer. From January 2007 to December 2009, 26 patients underwent embolization of the CHA by the DMDI technique. We compared the results with those of 37 patients in whom the CHA was embolized by conventional techniques from August 1998 to February 2007. With the DMDI technique, no coil migration or other embolization-related complications occurred. The success rate was 100%. The rate of embolization-related complications was significantly lower in the DMDI embolization group (0%) than in the conventional embolization group (24.3%) (P = 0.008). The frequency of improper positioning of the embolic material necessitating its removal during DP-CAR was significantly lower in the DMDI embolization group (10%) than in the conventional embolization group (37.5%) (P = 0.044). The DMDI technique allows the development of collateral pathways, reduces the surgeon's burden in ligating the distal CHA, and prevents coil migration. For these reasons, we believe that this technique is feasible for embolization of the CHA in preparation for DP-CAR for locally advanced pancreatic body cancer.
  • Khin K Tha, Satoshi Terae, Akiko Tsukahara, Hiroyuki Soma, Ryo Morita, Ichiro Yabe, Yoichi M Ito, Hidenao Sasaki, Hiroki Shirato
    BMC neurology 12 39 - 39 2012年06月18日 [査読有り][通常論文]
     
    BACKGROUND: Hyperintense putaminal rim (HPR) is an important magnetic resonance imaging (MRI) sign for multiple system atrophy (MSA). Recent studies have suggested that it can also be observed in normal subjects at 3 T. Whether it can be observed in normal subjects at 1.5 T is not known. This study aimed to determine whether HPR could be observed in normal subjects at 1.5 T; and if so, to establish its prevalence, the MRI characteristics, and the features which distinguish from HPR in MSA patients. METHODS: Axial T2-weighted images of 130 normal subjects were evaluated for the prevalence of HPR, its age and gender distribution, laterality, maximum dimension, association with hypointensity of nearby putamen, and presence of discontinuity. To distinguish from that observed in MSA, axial T2-weighted images of 6 MSA patients with predominant parkinsonism (MSA-P) and 15 MSA patients with predominant cerebellar symptoms (MSA-C) were also evaluated. The characteristics of HPR were compared between these patients and age-matched normal subjects. The mean diffusivity (MD) values of putamen were also compared. Fisher's exact test, t-test, and one way analysis of variance were used to determine significance at corrected p < 0.05. RESULTS: HPR was observed in 38.5% of normal subjects. Age and gender predilection and laterality were not observed. In most cases, it occupied the full length or anterior half of the lateral margin of putamen, and was continuous throughout its length. Maximum transverse dimension was 2 mm. There was no association with hypointensity of nearby putamen. However, in MSA-P, HPR was located predominantly at the posterolateral aspect of putamen, and associated with putaminal atrophy. Discontinuity of HPR was more frequently observed in MSA-P. On visual analysis, the characteristics of HPR were similar between MSA-C patients and normal subjects. Patients with MSA of either type had significantly higher MD values of putamen than normal subjects. CONCLUSIONS: HPR can be observed in 38.5% of normal subjects at 1.5 T. Thin linear hyperintensity without discontinuity, occupying the full length or anterior half of the lateral margin of the putamen, is suggestive of "normal." In doubtful cases, measurement of the MD values of nearby putamen may be valuable.
  • Onodera Y, Nam JM, Hashimoto A, Norman JC, Shirato H, Hashimoto S, Sabe H
    The Journal of cell biology 197 7 983 - 996 7 2012年06月 [査読有り][通常論文]
     
    Epidermal growth factor receptor (EGFR) signaling is one of the crucial factors in breast cancer malignancy. Breast cancer cells often overexpress Arf6 and its effector, AMAP1/ASAP1/DDEF1; in these cells, EGFR signaling may activate the Arf6 pathway to induce invasion and metastasis. Active recycling of some integrins is crucial for invasion and metastasis. Here, we show that the Arf6-AMAP1 pathway links to the machinery that recycles beta 1 integrins, such as alpha 3 beta 1, to promote cell invasion upon EGFR stimulation. We found that AMAP1 had the ability to bind directly to PRKD2 and hence to make a complex with the cytoplasmic tail of the beta 1 subunit. Moreover, GTP-Rab5c also bound to AMAP1, and activation of Rab5c by EGFR signaling was necessary to promote the intracellular association of AMAP1 and PRKD2. Our results suggest a novel mechanism by which EGFR signaling promotes the invasiveness of some breast cancer cells via integrin recycling.
  • Qing Ren, Seiko Nishioka, Hiroki Shirato, Ross Berbeco
    PHYSICS IN MEDICINE AND BIOLOGY 57 9 N145 - N157 2012年05月 [査読有り][通常論文]
     
    The purpose of this study is to evaluate the performance of an adaptive gating method, which is designed to accommodate the beam-to-beam and day-today variation of the internal/external correlation, as well as the real tumor position during respiratory-gated fractionated radiotherapy. We define a two-step procedure: (1) before each treatment, target positions are detected and synchronized with an external surrogate for establishing the internal/external correlation model and determining the position of the gating window, and then (2) during the delivery of the treatment beam, the gating is triggered by an external signal based on the updated internal/external correlation and window position. This correlation is described by a linear-quadratic model including a time shift between the internal and external signals. To simulate the proposed method, data of tumor motion in the superior-inferior direction synchronized with an external surrogate during hypo-fractionated radiotherapy from five lung patients are analyzed retrospectively. Duty cycle (DC), target coverage (TC) and the average distance (AD) between the internal target position and the edge of the gating window for all false positives are calculated as evaluative criteria. Under a 5 mm gating window, the average TC is 88.9%, with a DC around 45% and a mean AD of 0.7 mm. A daily update is also simulated for comparison, and it is found that beam-to-beam updating is superior. In conclusion, the combined updating of internal/external correlation and the gating window for each beam can improve the accuracy and reliability of respiratory-gated radiotherapy.
  • Yusuke Sakuhara, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Toshiya Kamiyama, Satoshi Hirano, Daisuke Fukumori, Takeshi Kawamura, Yoichi M Ito, Khin Khin Tha, Hiroki Shirato, Satoshi Terae
    AJR. American journal of roentgenology 198 4 914 - 22 2012年04月 [査読有り][通常論文]
     
    OBJECTIVE: The purpose of this article is to evaluate the feasibility and efficacy of preoperative percutaneous transhepatic portal vein embolization with ethanol injection. MATERIALS AND METHODS: We retrospectively evaluated 143 patients who underwent percutaneous transhepatic portal vein embolization. Hypertrophy of the future liver remnant was assessed by comparing the volumetric data obtained from CT image data before and after percutaneous transhepatic portal vein embolization. The evaluation of effectiveness was based on changes in the absolute volume of the future liver remnant and the ratio of the future liver remnant to the total estimated liver volume. RESULTS: Ten of 143 patients (7.0%) underwent additional embolization because of recanalization and insufficient hypertrophy of the future liver remnant. The mean increase in the ratio of the future liver remnant was 33.6% (p < 0.0001), and the mean ratio of future liver remnant to total estimated liver volume increased from 34.9% to 45.7% (p < 0.0001). Although most of the patients complained of pain after ethanol injection, they were gradually relieved of pain in a few minutes by conservative treatment. Fever (38-39°C) was reported after 47 of 151 (31.1%) percutaneous transhepatic portal vein embolization sessions and was resolved within a few days. Transient elevation of the liver transaminases was observed after the procedures and resolved within about a week. Major complications occurred in nine of 151 (6%) percutaneous transhepatic portal vein embolization sessions, but no patients developed hepatic insufficiency or severe complications precluding successful resection. One hundred twenty patients underwent hepatic resection, and two patients developed hepatic failure after surgery. CONCLUSION: Preoperative percutaneous transhepatic portal vein embolization with ethanol is a feasible and effective procedure to obtain hypertrophy of the future liver remnant for preventing hepatic failure after hepatectomy.
  • Hidemichi Watari, Rumiko Kinoshita, Yimin Han, Lei Wang, Masayoshi Hosaka, Hiroshi Taguchi, Kazuhiko Tsuchiya, Shinya Tanaka, Hiroki Shirato, Noriaki Sakuragi
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 22 3 465 - 470 2012年03月 [査読有り][通常論文]
     
    Objective: Overexpression of clusterin (CLU), an antiapoptotic molecule, has been reported to induce resistance to radiotherapy (RT) in a variety of cancer cell types. The aim of this study was to evaluate the significance of CLU expression to predict survival of patients with advanced-stage cervical cancer who received curative intended RT. Methods: Biopsy tissue specimens of advanced-stage cervical cancer before curative intended RT were obtained from 34 patients who were treated at Hokkaido University Hospital between 1998 and 2008 and whose complete medical records were available. The expression of CLU protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed using the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Results: Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of CLU protein in cervical cancer tissues before curative intended RT was not significantly related to any clinicopathological factors analyzed, including age, clinical stage, histologic type, and response to RT. Univariate analysis on prognostic factors showed that histologic type (P = 0.001), and CLU expression (P = 0.02) were related to survival. Multivariate analysis revealed that both histologic type (P = 0.002), and CLU expression (P = 0.02) were independent prognostic factors for overall survival. Conclusion: We conclude that CLU could be a new molecular marker to predict overall survival of patients with advanced-stage cervical cancer treated with curative intended RT.
  • Norio Katoh, Koichi Yasuda, Tohru Shiga, Masakazu Hasegawa, Rikiya Onimaru, Shinichi Shimizu, Gerard Bengua, Masayori Ishikawa, Nagara Tamaki, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 82 4 E671 - E676 2012年03月 [査読有り][通常論文]
     
    Purpose: We compared two treatment planning methods for stereotactic boost for treating nasopharyngeal carcinoma (NPC): the use of conventional whole-body bismuth germanate (BGO) scintillator positron emission tomography (PETCONVWB) versus the new brain (BR) PET system using semiconductor detectors (PETNEWBR). Methods and Materials: Twelve patients with NPC were enrolled in this study. [F-18]Fluorodeoxyglucose-PET images were acquired using both the PETNEWBR and the PETCONVWB system on the same day. Computed tomography (CT) and two PET data sets were transferred to a treatment planning system, and the PETCONVWB and PETNEWBR images were coregistered with the same set of CT images. Window width and level values for all PET images were fixed at 3000 and 300, respectively. The gross tumor volume (GTV) was visually delineated on PET images by using either PETCONVWB (GTV(CONV)) images or PETNEWBR (GTV(NEW)) images. Assuming a stereotactic radiotherapy boost of 7 ports, the prescribed dose delivered to 95% of the planning target volume (PTV) was set to 2000 cGy in 4 fractions. Results: The average absolute volume (+/- standard deviation [SD]) of GTV(NEW) was 15.7 ml (+/- 9.9) ml, and that of GTV(CONV) was 34.0 (+/- 20.5) ml. The average GTV(NEW) was significantly smaller than that of GTV(CONV) (p = 0.0006). There was no statistically significant difference between the maximum dose (p = 0.0585) and the mean dose (p = 0.2748) of PTV. The radiotherapy treatment plan based on the new gross tumor volume (PLAN(NEW)) significantly reduced maximum doses to the cerebrum and cerebellum (p = 0.0418) and to brain stem (p = 0.0041). Conclusion: Results of the present study suggest that the new brain PET system using semiconductor detectors can provide more accurate tumor delineation than the conventional whole-body BGO PET system and may be an important tool for functional and molecular radiotherapy treatment planning. (C) 2012 Elsevier Inc.
  • Hiroki Shirato, Rikiya Onimaru, Masayori Ishikawa, Jun-ichi Kaneko, Tsuguhide Takeshima, Kenta Mochizuki, Shinichi Shimizu, Kikuo Umegaki
    CANCER SCIENCE 103 1 1 - 6 2012年01月 [査読有り][通常論文]
     
    Respiratory motion considerably influences dose distribution, and thus clinical outcomes in radiotherapy for lung cancer. Breath holding, breath coaching, respiratory gating with external surrogates, and mathematical predicting models all have inevitable uncertainty due to the unpredictable variations of internal tumor motion. The amplitude of the same tumor can vary with standard deviations >5 mm occurring in 23% of T12N0M0 non-small cell lung cancers. Residual motion varied 16 mm (95th percentile) for the 40% duty cycle of respiratory gating with external surrogates. The 4-D computed tomography is vulnerable to problems relating to the external surrogates. Real-time 4-D radiotherapy (4DRT), where the temporal changes in anatomy during the delivery of radiotherapy are explicitly considered in real time, is emerging as a new method to reduce these known sources of uncertainty. Fluoroscopic, real-time tumor-tracking technology using internal fiducial markers near the tumor has +/- 2 mm accuracy, and has achieved promising clinical results when used with X-ray therapy. Instantaneous irradiation based on real-time verification of internal fiducial markers is considered the minimal requisite for real-time 4DRT of lung cancers at present. Real-time tracking radiotherapy using gamma rays from positron emitters in tumors is in the preclinical research stage, but has been successful in experiments in small animals. Real-time tumor tracking via spot-scanning proton beam therapy has the capability to cure large lung cancers in motion, and is expected to be the next-generation real-time 4DRT. (Cancer Sci 2012; 103: 16)
  • Yu Hasegawa, Daisuke Abo, Yusuke Sakuhara, Fumi Kato, Tamotsu Kamishimma, Tadashi Shimizu, Yoichi M. Ito, Satoshi Terae, Hiroki Shirato
    JAPANESE JOURNAL OF RADIOLOGY 30 1 53 - 61 2012年01月 [査読有り][通常論文]
     
    To assess the usefulness of portography and contrast-enhanced computed tomography (CECT) for predicting the embolized area after the first injection of absolute ethanol (AE) in right portal vein embolization (RPVE). Portograms were retrospectively reviewed in 50 patients (30 men and 20 women, mean age 65 years) who had undergone percutaneous transhepatic RPVE with AE under temporary balloon occlusion (TBO) between February 2002 and October 2009. The enhancement pattern before embolization and the embolization pattern after the first AE injection were analyzed by portography. The angles of portal branches against the horizontal plane were measured in 48 patients using pre-treatment CECT. The enhancement pattern was not consistent with the embolization pattern in 35 patients (p < 0.001). When the anterior branch angles were divided into two groups at -5A degrees, 0A degrees, 10A degrees, and 15A degrees, the frequency of the posterior-branch-dominant embolization pattern was higher in the more negatively angled group (p = 0.002-0.041). The distribution of AE is different from that of contrast medium in percutaneous transhepatic RPVE under TBO. The pre-treatment measurement of the angles of portal branches against the horizontal plane on CECT is suggested to be useful for predicting the embolized area.
  • Yae Harada, Kenji Hirata, Hiroyuki Kobayashi, Reiko Usui, Tohru Shiga, Satoshi Terae, Hiroki Shirato, Nagara Tamaki
    CLINICAL NUCLEAR MEDICINE 37 1 110 - 111 2012年01月 [査読有り][通常論文]
     
    A 31-year-old woman presenting with tonic seizures was radiologically investigated using CT, MR imaging, and positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and C-11 methionine (MET). Initial CT, C-11 MET PET, and F-18 FDG PET suggested a low-grade tumor such as oligodendroglial tumor. However, MR imaging findings strongly suggested venous infarction. We chose observation rather than surgical intervention. Two months later, self-regression of the lesion confirmed the diagnosis of venous infarction. Therefore, to avoid unnecessary invasive operations, we should keep in mind that high C-11 MET accumulation does not always signify a tumoral lesion but is sometimes the result of vascular pathology.
  • Inoue T, Katoh N, Onimaru R, Shirato H
    Pulmonary medicine 2012 369820  2012年 [査読有り][通常論文]
  • Hiroshi Onishi, Hiroki Shirato, Yasushi Nagata, Masahiro Hiraoka, Masaharu Fujino, Kotaro Gomi, Katsuyuki Karasawa, Kazushige Hayakawa, Yuzuru Niibe, Yoshihiro Takai, Tomoki Kimura, Atsuya Takeda, Atsushi Ouchi, Masato Hareyama, Masaki Kokubo, Takuyo Kozuka, Takuro Arimoto, Ryusuke Hara, Jun Itami, Tsutomu Araki
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81 5 1352 - 1358 2011年12月 [査読有り][通常論文]
     
    Purpose: To review treatment outcomes for stereotactic body radiotherapy (SBRT) in medically operable patients with Stage I non small-cell lung cancer (NSCLC), using a Japanese multi-institutional database. Patients and Methods: Between 1995 and 2004, a total of 87 patients with Stage I NSCLC (median age, 74 years; T1N0M0, n = 65; T2N0M0, n = 22) who were medically operable but refused surgery were treated using SBRT alone in 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. Total dose was 45-72.5 Gy at the isocenter, administered in 3-10 fractions. Median calculated biological effective dose was 116 Gy (range, 100-141 Gy). Data were collected and analyzed retrospectively. Results: During follow-up (median, 55 months), cumulative local control rates for T1 and T2 tumors at 5 years after SBRT were 92% and 73%, respectively. Pulmonary complications above Grade 2 arose in 1 patient (1.1%). Five-year overall survival rates for Stage IA and IB subgroups were 72% and 62%, respectively. One patient who developed local recurrences safely underwent salvage surgery. Conclusion: Stereotactic body radiotherapy is safe and promising as a radical treatment for operable Stage NSCLC. The survival rate for SBRT is potentially comparable to that for surgery. (C) 2011 Elsevier Inc.
  • Seishin Takao, Shigeru Tadano, Hiroshi Taguchi, Koichi Yasuda, Rikiya Onimaru, Masayori Ishikawa, Gerard Bengua, Ryusuke Suzuki, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81 3 871 - 879 2011年11月 [査読有り][通常論文]
     
    Purpose: To establish a method for the accurate acquisition and analysis of the variations in tumor volume, location, and three-dimensional (3D) shape of tumors during radiotherapy in the era of image-guided radiotherapy. Methods and Materials: Finite element models of lymph nodes were developed based on computed tomography (CT) images taken before the start of treatment and every week during the treatment period. A surface geometry map with a volumetric scale was adopted and used for the analysis. Six metastatic cervical lymph nodes, 3.5 to 55.1 cm before treatment, in 6 patients with head and neck carcinomas were analyzed in this study. Three fiducial markers implanted in mouthpieces were used for the fusion of CT images. Changes in the location of the lymph nodes were measured on the basis of these fiducial markers. Results: The surface geometry maps showed convex regions in red and concave regions in blue to ensure that the characteristics of the 3D tumor geometries are simply understood visually. After the irradiation of 66 to 70 Gy in 2 Gy daily doses, the patterns of the colors had not changed significantly, and the maps before and during treatment were strongly correlated (average correlation coefficient was 0.808), suggesting that the tumors shrank uniformly, maintaining the original characteristics of the shapes in all 6 patients. The movement of the gravitational center of the lymph nodes during the treatment period was everywhere less than +/-5 mm except in 1 patient, in whom the change reached nearly 10 mm. Conclusions: The surface geometry map was useful for an accurate evaluation of the changes in volume and 3D shapes of metastatic lymph nodes. The fusion of the initial and follow-up CT images based on fiducial markers enabled an analysis of changes in the location of the targets. Metastatic cervical lymph nodes in patients were suggested to decrease in size without significant changes in the 3D shape during radiotherapy. The movements of the gravitational center of the lymph nodes were almost all less than +/-5 mm. (C) 2011 Elsevier Inc.
  • Jun Sakakibara-Konishi, Satoshi Oizumi, Ichiro Kinoshita, Naofumi Shinagawa, Junko Kikuchi, Mototsugu Kato, Tetsuya Inoue, Norio Katoh, Rikiya Onimaru, Hiroki Shirato, Hirotoshi Dosaka-Akita, Masaharu Nishimura
    LUNG CANCER 74 2 248 - 252 2011年11月 [査読有り][通常論文]
     
    Introduction: Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT). Patients and methods: Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m(2) followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5 mg/m(2) per level. Results: Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m(2) and 45 mg/m(2)), carboplatin (AUC = 2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m(2) and carboplatin, AUC = 2). At Level 2 (paclitaxel, 45 mg/m(2) and carboplatin, AUC = 2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m(2) and 40 mg/m(2), respectively. Conclusions: This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m(2) at AUC = 2, respectively. Further studies are warranted to evaluate the efficacy of this regimen. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Shinichi Shimizu, Yasuhiro Osaka, Nobuo Shinohara, Ataru Sazawa, Kentaro Nishioka, Ryusuke Suzuki, Rikiya Onimaru, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81 4 E393 - E399 2011年11月 [査読有り][通常論文]
     
    Purpose: Interportal adjustment was applied to patients with prostate cancer using three fiducial markers and two sets of fluoroscopy in a real-time tumor-tracking radiotherapy (RTRT) system. The incidence of table position adjustment required to keep intrafractional uncertainty within 2.0 mm was investigated in this study. Methods and Materials: The coordinates of the center of gravity of the three fiducial markers were measured at the start of every portal irradiation in intensity-modulated radiotherapy (IMRT) with seven ports. The table position was adjusted to the planned position if the discrepancy was larger than 2.0 mm in the anterior-posterior (AP), cranial-caudal (CC), or left-right (LR) directions. In total, we analyzed 4,541 observations in 20 patients who received 70 Gy in 30 fractions (7.6 times a day on average). Results: The incidence of table position adjustment at 10 minutes from the initial setup of each treatment was 14.2%, 12.3%, and 5.0% of the observations in the AP, CC, and LR directions, respectively. The accumulated incidence of the table position adjustment was significantly higher at 10 minutes than at 2 minutes for AP (p = 0.0033) and CC (p = 0.0110) but not LR (p = 0.4296). An adjustment greater than 5 mm was required at least once in the treatment period in 11 (55%) patients. Conclusions: Interportal adjustment of table position was required in more than 10% of portal irradiations during the 10-minute period after initial setup to maintain treatment accuracy within 2.0 mm. (C) 2011 Elsevier Inc.
  • Noriko Oyama-Manabe, Naoki Ishimori, Hiroyuki Sugimori, Marc Van Cauteren, Kohsuke Kudo, Osamu Manabe, Tomoyuki Okuaki, Tamotsu Kamishima, Yoichi M Ito, Hiroyuki Tsutsui, Khin Khin Tha, Satoshi Terae, Hiroki Shirato
    European radiology 21 11 2362 - 8 2011年11月 [査読有り][通常論文]
     
    OBJECTIVES: To investigate whether subendocardial and transmural myocardial infarction can be identified and differentiated using the peak circumferential and longitudinal strains measured by fast strain-encoded (SENC). METHODS: Nineteen patients with ischemic heart diseases underwent imaging with fast SENC and late gadolinium enhancement (LGE) MRI at 3 T. Fast SENC measurements were performed in three short-axis slices (basal, mid-ventricular and apical levels) and one long-axis view (four-chamber) to assess peak longitudinal and circumferential systolic strains. RESULTS: All patients showed myocardial infarction with an average of 7 positive LGE segments. A total of 304 segments for longitudinal strains (LS) and 114 segments for circumferential strains (CS) could be analysed. Positive LGE segments showed lower peak CS and LS compared with the no LGE segments (P < 0.0001 for both). Segments with subendocardial infarction showed reduced CS and LS compared with the no LGE segments (P < 0.0001 for both). There was a significant difference in CS between subendocardial and transmural infarct segments (P = 0.03), but no significant difference in LS between them (P = 0.64). CONCLUSIONS: Fast SENC can identify old myocardial infarction and differentiate subendocardial from transmural infarction.
  • Kamishima T, Nishida M, Horie T, Narita A, Sagawa A, Henmi M, Shirato H, Terae S
    Clinical and experimental rheumatology 29 1057  6 2011年11月 [査読有り][通常論文]
  • Takashi Yokota, Shintaro Kinugawa, Koichi Okita, Kagami Hirabayashi, Tadashi Suga, Masaaki Hattori, Yoshinao Nakagawa, Noriko Oyama-Manabe, Hiroki Shirato, Hiroyuki Tsutsui
    HYPERTENSION RESEARCH 34 9 1029 - 1034 2011年09月 [査読有り][通常論文]
     
    Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex-and activity-matched control subjects to assess the aerobic capacity. We performed (31)phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO(2); 34.1 +/- 6.2 vs. 41.4 +/- 8.4 ml kg(-1) min(-1), P < 0.05) and anaerobic threshold (AT; 18.0 +/- 2.4 vs. 23.1 +/- 3.7 ml kg(-1) min(-1), P < 0.01) adjusted by lean body mass were lower in MetS patients than control subjects. Phosphocreatine (PCr) loss during exercise was 1.5-fold greater in MetS, suggesting reduced intramuscular oxidative capacity. PCr loss was inversely correlated with peak VO(2) (r = -0.64) and AT (r = -0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO(2) (r = -0.47) and AT (r = -0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r = 0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism. Hypertension Research (2011) 34, 1029-1034; doi: 10.1038/hr.2011.78; published online 14 July 2011
  • Akihiro Homma, Naoya Inamura, Nobuhiko Oridate, Seigo Suzuki, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 41 8 980 - 986 2011年08月 [査読有り][通常論文]
     
    Objective: The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. Methods: Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. Results: Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). Conclusions: Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy.
  • Naoki Miyamoto, Masayori Ishikawa, Gerard Bengua, Kenneth Sutherland, Ryusuke Suzuki, Suguru Kimura, Shinichi Shimizu, Rikiya Onimaru, Hiroki Shirato
    PHYSICS IN MEDICINE AND BIOLOGY 56 15 4803 - 4813 2011年08月 [査読有り][通常論文]
     
    In the real-time tumor-tracking radiotherapy system, fluoroscopy is used to determine the real-time position of internal fiducial markers. The pattern recognition score (PRS) ranging from 0 to 100 is computed by a template pattern matching technique in order to determine the marker position on the fluoroscopic image. The PRS depends on the quality of the fluoroscopic image. However, the fluoroscopy parameters such as tube voltage, current and exposure duration are selected manually and empirically in the clinical situation. This may result in an unnecessary imaging dose from the fluoroscopy or loss of the marker because of too much or insufficient x-ray exposure. In this study, a novel optimization method is proposed in order to minimize the fluoroscopic dose while keeping the image quality usable for marker tracking. The PRS can be predicted in a region where the marker appears to move in the fluoroscopic image by the proposed method. The predicted PRS can be utilized to judge whether the marker can be tracked with accuracy. In this paper, experiments were performed to show the feasibility of the PRS prediction method under various conditions. The predicted PRS showed good agreement with the measured PRS. The root mean square error between the predicted PRS and the measured PRS was within 1.44. An experiment using a motion controller and an anthropomorphic chest phantom was also performed in order to imitate a clinical fluoroscopy situation. The result shows that the proposed prediction method is expected to be applicable in a real clinical situation.
  • Fumi Kato, Tamotsu Kamishima, Ken Morita, Natalia S. Muto, Syozou Okamoto, Tokuhiko Omatsu, Noriko Oyama, Satoshi Terae, Kakuko Kanegae, Katsuya Nonomura, Hiroki Shirato
    EUROPEAN JOURNAL OF RADIOLOGY 79 1 15 - 20 2011年07月 [査読有り][通常論文]
     
    Purpose: To evaluate the speed and precision of split renal volume (SRV) measurement, which is the ratio of unilateral renal volume to bilateral renal volume, using a newly developed software for computed tomographic (CT) volumetry and to investigate the usefulness of SRV for the estimation of split renal function (SRF) in kidney donors. Method: Both dynamic CT and renal scintigraphy in 28 adult potential living renal donors were the subjects of this study. We calculated SRV using the newly developed volumetric software built into a PACS viewer (n-SRV), and compared it with SRV calculated using a conventional workstation, ZIOSOFT (z-SRV). The correlation with split renal function (SRF) using 99mTc-DMSA scintigraphy was also investigated. Results: The time required for volumetry of bilateral kidneys with the newly developed software (16.7 +/- 3.9 s) was significantly shorter than that of the workstation (102.6 +/- 38.9 s, p < 0.0001). The results of n-SRV (49.7 +/- 4.0%) were highly consistent with those of z-SRV (49.9 +/- 3.6%), with a mean discrepancy of 0.12 +/- 0.84%. The SRF also agreed well with the n-SRV, with a mean discrepancy of 0.25 +/- 1.65%. The dominant side determined by SRF and n-SRV showed agreement in 26 of 28 cases (92.9%). Conclusion: The newly developed software for CT volumetry was more rapid than the conventional workstation volumetry and just as accurate, and was suggested to be useful for the estimation of SRF and thus the dominant side in kidney donors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Makoto Chuma, Hiroshi Taguchi, Yoshiya Yamamoto, Shinichi Shimizu, Mitsuru Nakanishi, Koji Ogawa, Takuya Sho, Hiromasa Horimoto, Tomoe Kobayashi, Masato Nakai, Katsumi Terashita, Yusuke Sakuhara, Daisuke Abo, Yoko Tsukuda, Seiji Tsunematsu, Shuhei Hige, Mototsugu Kato, Hiroki Shirato, Masahiro Asaka
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 26 7 1123 - 1132 2011年07月 [査読有り][通常論文]
     
    Background and Aim: To evaluate the efficacy of intra-arterial 5-fluorouracil (5-FU) and subcutaneous interferon (IFN) combined with image-guided radiation therapy (IGRT) in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: Twenty HCC patients with PVTT were treated with 5-FU and IFN combined with image-guided radiation therapy (IGRT) (IGRT group), and as controls, 20 patients with PVTT were treated with 5-FU and IFN alone (non-IGRT group). Overall survival (OS) time, response rates, time to progression (TTP) and safety were compared across groups. Results: Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) of PVTT were 5%, 55%, 40% and 0% in the IGRT group and 0%, 30%, 35% and 35%, in the non-IGRT group, respectively. CR, PR, SD, and PD of the whole tumor were 0%, 35%, 45% and 20% in the IGRT group and 0%, 30%, 35% and 35%, in the non-IGRT group, respectively. Overall median survival was significantly longer in the IGRT group (12.0 months 95% confidence interval [CI], 9.3-17.6 months) than in the non-IGRT group (9.1 months [95% Cl, 5.5-11.1 months]) (P = 0.041). TTP was significantly longer in the IGRT group (6.9 months [95% CI, 5.6-10.2 months]) than in the non-IGRT group (4.0 months [95% Cl, 3.3-6.4 months]) (P = 0.034). Conclusions: The response rates, median OS time and TTP in patients with advanced HCC with PVTT who received this novel combination therapy of intra-arterial 5-FU and subcutaneous IFN with TORT are encouraging, and this combination therapy warrants further investigation.
  • Satoshi Kano, Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Jun Furusawa, Tomohiro Sakashita, Daisuke Yoshida, Rikiya Onimaru, Hiroki Shirato, Satoshi Fukuda
    ORAL ONCOLOGY 47 7 665 - 670 2011年07月 [査読有り][通常論文]
     
    The treatment of base of tongue (BOT) cancer is highly controversial with differing options according to individual institutions, or the primary surgical or radiation therapy bias. We aimed to determine patient outcomes and discuss technical aspects following treatment with concurrent radiation therapy and targeted cisplatin chemotherapy (RADPLAT). We utilized RADPLAT for the definitive treatment of patients with BOT cancers. The 5-year local control and overall survival rate was 92.3% and 90.9% for all patients, respectively, and all surviving patients achieved normal swallowing without a feeding-tube and normal speech without tracheostoma after treatment. Our study found that RADPLAT gave excellent survival rates and organ functions for patients with BOT cancers. We consider that BOT cancer is a good indication for RADPLAT and that the angiographic technique and patient selection are keys to success. (C) 2011 Elsevier Ltd. All rights reserved.
  • Kentaro Kobayashi, Khin Khin Tha, Satoshi Terae, Yuki Iijima, Kenichi Katabami, Yosuke Minami, Shinji Uegaki, Satoshi Gando, Hiroki Shirato
    JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 35 4 498 - 500 2011年07月 [査読有り][通常論文]
     
    We report a case of heat stroke in which detection of brain injury was improved by high b-value diffusion-weighted imaging (DWI). High b-value DWI revealed moderate to marked hyperintensity at/around bilateral dentate nuclei and part of thalami. Apparent diffusion coefficient maps revealed apparent diffusion coefficient decrease of the dentate lesions. Routine DWI showed only mild hyperintensity of part of dentate lesions. High b-value DWI could be valuable for improved detection of heat stroke-induced brain injury.
  • Tamotsu Kamishima, Kazuhide Tanimura, Masato Shimizu, Megumi Matsuhashi, Jun Fukae, Yujiro Kon, Hiromi Hagiwara, Akihiro Narita, Yuko Aoki, Naoki Kosaka, Tatsuya Atsumi, Hiroki Shirato, Satoshi Terae
    SKELETAL RADIOLOGY 40 6 745 - 755 2011年06月 [査読有り][通常論文]
     
    To compare quantitative magnetic resonance imaging (MRI) and power Doppler ultrasonography (PDUS) with conventional measures of disease activity in rheumatoid arthritis (RA) patients treated with the anti-interleukin 6 (anti-IL 6) receptor antibody tocilizumab in terms of responsiveness at a few months to disease activity and ability to predict structural damage at 1 year. A cohort of patients with RA (n = 29) was evaluated clinically including disease activity score 28 (DAS28) and by semiquantitative (SQ-) and quantitative (Q-) PDUS (bilateral metacarpophalangeal joints) and MRI (one hand and wrist) at initiation of treatment with anti-IL 6 receptor antibody agents and after 2 and 5 months. Conventional radiography for both hands and wrists was performed at baseline and at 12 months. Responsiveness was assessed by standardized response means (SRM). Areas under the curve (AUC) for measures at baseline, 2 and 5 months were correlated with structural damage at 1 year. Among the laboratory and clinical parameters, DAS28-ESR was the most responsive with a large effect size of SRM. Structural damage progressions for radiography and MR erosion were correlated with AUC of MR bone erosion and Q-PDUS, respectively. In the evaluation of disease activity in RA patients in the first few months after starting anti-IL 6 receptor antibody tocilizumab treatment, the semiquantitative MR bone erosion score of the hand and quantitative value for power Doppler signal in the finger joint were both responsive and predictive of structural damage progression at 1 year.
  • Natalia Sayuri Muto, Tamotsu Kamishima, Ardene A. Harris, Fumi Kato, Yuya Onodera, Satoshi Terae, Hiroki Shirato
    EUROPEAN JOURNAL OF RADIOLOGY 78 1 151 - 156 2011年04月 [査読有り][通常論文]
     
    Purpose: To evaluate the relationship between renal cortical volume, measured by an automatic contouring software, with body mass index (BMI), age and renal function. Materials and methods: The study was performed in accordance to the institutional guidelines at our hospital. Sixty-four patients (34 men, 30 women), aged 19 to 79 years had their CT scans for diagnosis or follow-up of hepatocellular carcinoma retrospectively examined by a computer workstation using a software that automatically contours the renal cortex and the renal parenchyma. Body mass index and estimated glomerular filtration rate (eGFR) were calculated based on data collected. Statistical analysis was done using the Student t-test, multiple regression analysis, and intraclass correlation coefficient (ICC). Results: The ICC for total renal and renal cortical volumes were 0.98 and 0.99, respectively. Renal volume measurements yielded a mean cortical volume of 105.8 cm(3) +/- 28.4 SD, mean total volume of 153 cm(3) +/- 39 SD and mean medullary volume of 47.8 cm(3) +/- 19.5 SD. The correlation between body weight/height/BMI and both total renal and cortical volumes presented r = 0.6, 0.6 and 0.4, respectively, p < 0.05, while the correlation between renal cortex and age was r = -0.3, p < 0.05. eGFR showed correlation with renal cortical volume r = 0.6, p < 0.05. Conclusion: This study demonstrated that renal cortical volume had a moderate positive relationship with BMI, moderate negative relationship with age, and a strong positive relationship with the renal function, and provided a new method to routinely produce volumetric assessment of the kidney. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Yuya Onodera, Noriko Nishoka, Koichi Yasuda, Noriyuki Fujima, Mylin Torres, Tamotsu Kamishima, Noriko Ooyama, Rikiya Onimaru, Satoshi Terae, Satoshi Ooizumi, Masaharu Nishimura, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 79 5 1408 - 1413 2011年04月 [査読有り][通常論文]
     
    Purpose: For lung cancer patients with poor pulmonary function because of emphysema or fibrosis, it is important to predict the amplitude of internal tumor motion to minimize the irradiation of the functioning lung tissue before undergoing stereotactic body radiotherapy. Methods and Materials: Two board-certified diagnostic radiologists independently assessed the degree of pulmonary emphysema and fibrosis on computed tomography scans in 71 patients with peripheral lung tumors before real-time tumor-tracking radiotherapy. The relationships between the computed tomography findings of the lung parenchyma and the motion of the fiducial marker near the lung tumor were investigated. Of the 71 patients, 30 had normal pulmonary function, and 29 had obstructive pulmonary dysfunction (forced expiratory volume in 1 s/forced vital capacity ratio of < 70%), 6 patients had constrictive dysfunction (percentage of vital capacity < 80%), and 16 had mixed dysfunction. Results: The upper region was associated with smaller tumor motion, as expected (p = .0004), and the presence of fibrosis (p = .088) and pleural tumor contact (p = .086) were weakly associated with tumor motion. The presence of fibrotic changes in the lung tissue was associated with smaller tumor motion in the upper region (p <.05) but not in the lower region. The findings of emphysema and pulmonary function tests were not associated with tumor motion. Conclusion: Tumors in the upper lung region with fibrotic changes have smaller motion than those in the upper region of the lungs without fibrotic changes. The tumor motion in the lower lung region was not significantly different between patients with and without lung fibrosis. Emphysema was not associated with the amplitude of tumor motion. (C) 2011 Elsevier Inc.
  • Shunsuke Onodera, Hidefumi Aoyama, Norio Katoh, Hiroshi Taguchi, Kouichi Yasuda, Daisuke Yoshida, Ken Surtherland, Ryusuke Suzuki, Masayori Ishikawa, Bengua Gerard, Shunsuke Terasaka, Hiroki Shirato
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 41 4 462 - 468 2011年04月 [査読有り][通常論文]
     
    Objective: To investigate the outcome of linac-based fractionated stereotactic radiotherapy over the last 10 years for intracranial skull base benign meningiomas in patients who were inoperable, who had residual tumors with some components of high mitotic index after surgery and who experienced relapse of the tumor. Methods: Twenty-seven patients with intracranial skull base benign meningiomas treated with fractionated stereotactic radiotherapy were retrospectively reviewed. Twenty-seven cases were diagnosed as benign meningiomas on pathological (17 cases) or radiological (10 cases) examination. The median follow-up time was 90 months after initial treatment and 63 months after fractionated stereotactic radiotherapy. The median biological equivalent dose calculated using an alpha/beta ratio of 2.0 Gy was 82.0 Gy (range, 60-106 Gy). Results: The 5-year overall survival was 95.7 (95% confidence interval: 87.3-100)% after initial treatment and 96.2 (88.8-100)% after fractionated stereotactic radiotherapy. The 5-year overall survival and local control rate of patients who received fractionated stereotactic radiotherapy alone were both 100%. The 5-year progression-free survival and local control rate after fractionated stereotactic radiotherapy were all 100% with a tumor volume of <9.1 cc and 68.2 (37.2-99.2) and 75.8 (45.2-100)% for the tumors 9.1 cc, respectively. The difference was significant in progression-free survival (P=0.022) and local control rate (P=0.044). The local control rate was significantly worse in patients who received fractionated stereotactic radiotherapy for relapsed tumors (P=0.01). No late radiation damage was observed in the follow-up period. Conclusions: The long-term outcome suggests that fractionated stereotactic radiotherapy is a safe and effective treatment for intracranial skull base benign meningioma, especially for those who have tumors <9.1 cc or would receive fractionated stereotactic radiotherapy with or without surgery as the initial treatment.
  • Eric W. Pepin, Huanmei Wu, Hiroki Shirato
    MEDICAL PHYSICS 38 4 1912 - 1918 2011年04月 [査読有り][通常論文]
     
    Purpose: To analyze and evaluate the necessity and use of dynamic gating techniques for compensation of baseline shift during respiratory-gated radiation therapy of lung tumors. Methods: Motion tracking data from 30 lung tumors over 592 treatment fractions were analyzed for baseline shift. The finite state model (FSM) was used to identify the end-of-exhale (EOE) breathing phase throughout each treatment fraction. Using duty cycle as an evaluation metric, several methods of end-of-exhale dynamic gating were compared: An a posteriori ideal gating window, a predictive trend-line-based gating window, and a predictive weighted point-based gating window. These methods were evaluated for each of several gating window types: Superior/inferior (SI) gating, anterior/posterior beam, lateral beam, and 3D gating. Results: In the absence of dynamic gating techniques, SI gating gave a 39.6% duty cycle. The ideal SI gating window yielded a 41.5% duty cycle. The weight-based method of dynamic SI gating yielded a duty cycle of 36.2%. The trend-line-based method yielded a duty cycle of 34.0%. Conclusions: Dynamic gating was not broadly beneficial due to a breakdown of the FSM's ability to identify the EOE phase. When the EOE phase was well defined, dynamic gating showed an improvement over static-window gating. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3556588]
  • Kohsuke Kudo, Makoto Sasaki, Leif Ostergaard, Soren Christensen, Ikuko Uwano, Masako Suzuki, Kuniaki Ogasawara, Hiroki Shirato, Akira Ogawa
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 31 3 908 - 912 2011年03月 [査読有り][通常論文]
     
    The time-to-maximum of the tissue residue function (T-max) perfusion index has proven very predictive of infarct growth in large clinical trials, yet its dependency on simple tracer delays remains unknown. Here, we determine the dependency of computed tomography (CT) perfusion (CTP) T-max estimates on tracer delay using a range of deconvolution techniques and digital phantoms. Digital phantom data sets simulating the tracer delay were created from CTP data of six healthy individuals, in which time frames of the left cerebral hemisphere were shifted forward and backward by up to +/- 5 seconds. These phantoms were postprocessed with three common singular value decomposition (SVD) deconvolution algorithms-standard SVD (sSVD), block-circulant SVD (bSVD), and delay-corrected SVD (dSVD)-with an arterial input function (AIF) obtained from the right middle cerebral artery (MCA). The T-max values of the left hemisphere were compared among different tracer delays and algorithms by a region of interest-based analysis. The T-max values by sSVD were positively correlated with 'positive shifts' but unchanged with 'negative shifts,' those by bSVD had an excellent positive linear correlation with both positive and negative shifts, and those by dSVD were relatively constant, although slightly increased with the positive shifts. The T-max is a parameter highly dependent on tracer delays and deconvolution algorithm. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 908-912; doi:10.1038/jcbfm.2010.169; published online 22 September 2010
  • Takahiro Yamada, Gen Nishimura, Keiichiro Nishida, Hideaki Sawai, Tokuhiko Omatsu, Taichi Kimura, Hiroshi Nishihara, Rina Shono, Shigeki Shimada, Mamoru Morikawa, Masato Mizushima, Takashi Yamada, Kazutoshi Cho, Shinya Tanaka, Hiroki Shirato, Hisanori Minakami
    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 37 2 151 - 155 2011年02月 [査読有り][通常論文]
     
    We present a case of short-rib polydactyly syndrome (SRPs) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRP encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). As accurate prenatal diagnosis of SRP is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of 'short-rib dysplasia group' on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as short-rib dysplasia group led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias.
  • Satoshi Yamaguchi, Masayori Ishikawa, Gerard Bengua, Kenneth Sutherland, Teiji Nishio, Satoshi Tanabe, Naoki Miyamoto, Ryusuke Suzuki, Hiroki Shirato
    PHYSICS IN MEDICINE AND BIOLOGY 56 4 965 - 977 2011年02月 [査読有り][通常論文]
     
    A feasibility study of a novel PET-based molecular image guided radiation therapy (m-IGRT) system was conducted by comparing PET-based digitally reconstructed planar image (PDRI) registration with radiographic registration. We selected a pair of opposing parallel-plane PET systems for the practical implementation of this system. Planar images along the in-plane and cross-plane directions were reconstructed from the parallel-plane PET data. The in-plane and cross-plane FWHM of the profile of 2 mm diameter sources was approximately 1.8 and 8.1 mm, respectively. Therefore, only the reconstructed in-plane image from the parallel-plane PET data was used in the PDRI registration. In the image registration, five different sizes of (18)F cylindrical sources (diameter: 8, 12, 16, 24, 32 mm) were used to determine setup errors. The data acquisition times were 1, 3 and 5 min. Image registration was performed by five observers to determine the setup errors from PDRI registration and radiographic registration. The majority of the mean registration errors obtained from the PDRI registration were not significantly different from those obtained from the radiographic registration. Acquisition time did not appear to result in significant differences in the mean registration error. The mean registration error for the PDRI registration was found to be 0.93 +/- 0.33 mm. This is not statistically different from the radiographic registration which had a mean registration error of 0.92 +/- 0.27 mm. Our results suggest that m-IGRT image registration using PET-based reconstructed planar images along the in-plane direction is feasible for clinical use if PDRI registration is performed at two orthogonal gantry angles.
  • Noriko Oyama, Daisuke Goto, Yoichi M Ito, Naoki Ishimori, Rie Mimura, Tomoo Furumoto, Fumi Kato, Hiroyuki Tsutsui, Nagara Tamaki, Satoshi Terae, Hiroki Shirato
    Japanese journal of radiology 29 2 104 - 9 2011年02月 [査読有り][通常論文]
     
    PURPOSE: The aim of this study was to assess a method for measuring epicardial fat volume (EFV) by means of a single-slice area measurement. We investigated the relation between a single-slice fat area measurement and total EFV. METHODS AND METHODS: A series of 72 consecutive patients (ages 65 ± 11 years; 36 men) who had undergone cardiac computed tomography (CT) on a 64-slice multidetector scanner with prospective electrocardiographic triggering were retrospectively reviewed. Pixels in the pericardium with a density range from -230 to -30 Hounsfield units were considered fat, giving the per-slice epicardial fat area (EFA). The EFV was estimated by the summation of EFAs multiplied by the slice thickness. We investigated the relation between total EFV and each EFA. RESULTS: EFAs measured at several anatomical landmarks-right pulmonary artery, origins of the left main coronary artery, right coronary artery, coronary sinus-all correlated with the EFV (r = 0.77-0.92). The EFA at the LMCA level was highly reproducible and showed an excellent correlation with the EFV (r = 0.92). CONCLUSION: The EFA is significantly correlated with the EFV. The EFA is a simple, quick method for representing the time-consuming EFV, which has been used as a predictive indicator of cardiovascular diseases.
  • Sutherland K, Ishikawa M, Bengua G, Ito YM, Miyamoto Y, Shirato H
    Journal of applied clinical medical physics / American College of Medical Physics 12 3492  3 2011年02月 [査読有り][通常論文]
  • Tamotsu Kamishima, Kazuhide Tanimura, Yuko Aoki, Naoki Kosaka, Masato Shimizu, Megumi Matsuhashi, Jun Fukae, Yujiro Kon, Satoshi Terae, Hiroki Shirato
    SKELETAL RADIOLOGY 40 1 65 - 74 2011年01月 [査読有り][通常論文]
     
    To determine an optimal threshold in a simplified 3D-based volumetry of abnormal signals in rheumatoid wrists utilizing contrast and non-contrast MR data, and investigate the feasibility and reliability of this method. MR images of bilateral hands of 15 active rheumatoid patients were assessed before and 5 months after the initiation of tocilizumab infusion protocol. The volumes of abnormal signals were measured on STIR and post-contrast fat-suppressed T1-weighted images. Three-dimensional volume rendering of the images was used for segmentation of the wrist by an MR technologist and a radiologist. Volumetric data were obtained with variable thresholding (1, 1.25, 1.5, 1.75, and 2 times the muscle signal), and were compared to clinical data and semiquantitative MR scoring (RAMRIS) of the wrist. Intra- and interobserver variability and time needed for volumetry measurements were assessed. The volumetric data correlated favorably with clinical parameters almost throughout the pre-determined thresholds. Interval differences in volumetric data correlated favorably with those of RAMRIS when the threshold was set at more than 1.5 times the muscle signal. The repeatability index was lower than the average of the interval differences in volumetric data when the threshold was set at 1.5-1.75 for STIR data. Intra- and interobserver variability for volumetry was 0.79-0.84. The time required for volumetry was shorter than that for RAMRIS. These results suggest that a simplified MR volumetric data acquisition may provide gross estimates of disease activity when the threshold is set properly. Such estimation can be achieved quickly by non-imaging specialists and without contrast administration.
  • Rikiya Onimaru, Masakazu Hasegawa, Kouichi Yasuda, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda, Hiroki Shirato
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 41 1 103 - 109 2011年01月 [査読有り][通常論文]
     
    We retrospectively investigated treatment outcomes in patients with glottic T1 carcinoma treated with 65 Gy in 26 fractions four times a week and discuss the importance of the overall treatment time. Two hundred one patients with glottic T1 carcinoma were evaluated. Sixty-five Gray in 26 fractions were delivered for 200 patients, whereas 1 patient received 62.5 Gy in 25 fractions. We delivered radiotherapy once daily four times a week in this period, for a weekly dose of 10 Gy. Weekdays except Wednesday were treatment days. The overall survival rate was 96.8 +/- 1.3% (standard error) at 3 years and 90.8 +/- 2.2% at 5 years. The local control rate was 91.9 +/- 2.0% at 3 years and 89.8 +/- 2.3% at 5 years. In patients with an overall treatment time equal to or longer than 47 days, the local control rate was 82.6 +/- 6.0% at both 3 and 5 years. In the patients with overall treatment time equal to or less than 46 days, the local control rate was 94.6 +/- 1.9% at 3 years and 91.8 +/- 2.4% at 5 years. There was a significant difference between these two groups (P = 0.0349). A severe late radiation reaction occurred in one patient. He experienced severe laryngeal edema that required tracheotomy at 6 months after the completion of radiotherapy. The tracheotomy was closed at 14 months after completion of radiotherapy. Overall treatment time seems to be an important factor for a good local control rate for glottic T1N0 carcinoma even when treated with slight hypofractionation.
  • Takeshi Nishioka, Motoaki Yasuda, Tsuguhide Takeshima, Hisashi Haga, Yusuke Miyai, Ken-ichiro Shibata, Rie Yamazaki, Hiroki Shirato, Masahiro Teduka, Hiroyuki Date
    CELL STRUCTURE AND FUNCTION 36 1 13 - 20 2011年 [査読有り][通常論文]
     
    Purpose: Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. Materials and Methods: A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. Results: cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p < 0.01, Student's t-test). Conclusions: This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.
  • Ishizaka K, Oyama N, Mito S, Sugimori H, Nakanishi M, Okuaki T, Shirato H, Terae S
    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 10 1 41 - 48 1 2011年 [査読有り][通常論文]
  • Fumi Kato, Tokuhiko Omatsu, Wakana Matsumura, Masato Takahashi, Mitsuchika Hosoda, Hiromasa Takahashi, Kanako Kubota, Noriko Oyama-Manabe, Satoshi Terae, Hiroki Shirato
    MAGNETIC RESONANCE IN MEDICAL SCIENCES 10 2 129 - 132 2011年 [査読有り][通常論文]
     
    We report magnetic resonance (MR) imaging findings of ductal carcinoma in situ (DCIS) within a fibroadenoma in a 42-year-old woman. Dynamic MR imaging revealed the mass to have 2 components with different kinetics. A nodular area within the mass showed faster initial enhancement followed by earlier washout and was histologically proven to be DCIS. Dynamic MR imaging reflected differences in vascularity between the fibroadenoma and DCIS, and parameter color maps generated from the dynamic data clearly demonstrated the extent of the DCIS.
  • Tamotsu Kamishima, Yuichiro Fujieda, Tatsuya Atsumi, Rie Mimura, Takao Koike, Satoshi Terae, Hiroki Shirato
    AMERICAN JOURNAL OF ROENTGENOLOGY 195 4 W287 - W292 2010年10月 [査読有り][通常論文]
     
    OBJECTIVE. The purpose of this article is to examine the feasibility of whole-body joint MRI for detecting systemic joint synovitis and for analyzing the relationship between the hands and systemic joint involvement in patients with unclassified arthritis who later develop early rheumatoid arthritis (RA). MATERIALS AND METHODS. The study included 17 patients (five men and 12 women; median age, 65 years [range, 38-77 years]; median symptom duration, 3 months [range, 1-6 months]). MRI of the systemic joints was performed for patients with unclassified arthritis without radiographic evidence of RA and who were diagnosed as having RA according to 1987 revised classification criteria within 2 years. RESULTS. The chosen 4-point scale for image quality was moderate to excellent. MRI findings of systemic joints were in accordance with joint swelling and tenderness (chi-square test, p < 0.0001). Sixty percent (45/75) of hand joints and 67% (12/18) of systemic joints other than hands showed MR synovitis without swelling. With regard to the correlation of MRI findings between hands and joints other than hands, there was a statistically significant positive correlation in the joint count (r = 0.5514 and p = 0.0218) and semiquantitative value of hand synovitis (r = 0.5382 and p = 0.0258). CONCLUSION. Whole-body joint MRI in early RA is feasible in terms of image quality and agreement with the results of clinical examination. MRI may be more sensitive for depicting synovitis-positive joints than clinical examination. Estimation of the systemic burden of synovitis detected by MRI may be possible via MRI of the hands.
  • Gerben R. Borst, Masayori Ishikawa, Jasper Nijkamp, Michael Hauptmann, Hirk Shirato, Gerard Bengua, Rikiya Onimaru, A. de Josien Bois, Joos V. Lebesque, Jan-Jakob Sonke
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 77 5 1596 - 1603 2010年08月 [査読有り][通常論文]
     
    Purpose: To evaluate the linear quadratic (LQ) model for hypofractionated radiotherapy within the context of predicting radiation pneumonitis (RP) and to investigate the effect if a linear (L) model in the high region (LQL model) is used. Methods and Materials: The radiation doses used for 128 patients treated with hypofractionated radiotherapy were converted to the equivalent doses given in fractions of 2 Gy for a range of alpha/beta ratios (1 Gy to infinity) according to the LQ(L) model. For the LQL model, different cut-off values between the LQ model and the linear component were used. The Lyman model parameters were fitted to the events of RP grade 2 or higher to derive the normal tissue complication probability (NTCP). The lung dose was calculated as the mean lung dose and the percentage of lung volume (V) receiving doses higher than a threshold dose of xGy (V(x)). Results: The best NTCP fit was found if the mean lung dose, or V(x), was calculated with an alpha/beta ratio of 3 Gy. The NTCP fit of other alpha/beta ratios and the LQL model were worse but within the 95% confidence interval of the NTCP fit of the LQ model with an alpha/beta ratio of 3 Gy. The V(50) NTCP fit was better than the NTCP fit of lower threshold doses. Conclusions: For high fraction doses, the LQ model with an alpha/beta ratio of 3 Gy was the best method for converting the physical lung dose to predict RP. (C) 2010 Elsevier Inc.
  • Tetsuya Inoue, Norio Katoh, Hidefumi Aoyama, Rikiya Onimaru, Hiroshi Taguchi, Shunsuke Onodera, Satoshi Yamaguchi, Hiroki Shirato
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 40 8 788 - 794 2010年08月 [査読有り][通常論文]
     
    Several recent studies have shown that oligometastatic disease has curative potential, although it was previously considered to signal a patient's last stage of life. Stereotactic body radiotherapy has been available for extra-cranial metastases in addition to stereotactic cranial radiotherapy for brain metastases. The aim of the present study was to retrospectively evaluate the clinical outcomes of stereotactic radiotherapy for patients with oligometastatic lesions. Between 1999 and 2008, 41 patients with five or fewer detectable metastases were treated with stereotactic radiotherapy at our institution. The treated oligometastatic lesions were in the brain, lung and adrenal glands. With a median follow-up period of 20 months, the 3-year overall survival, progression-free survival, local control and distant control rates were 39%, 20%, 80% and 35%, respectively, and the respective 5-year rates were 28%, 20%, 80% and 35%. The median survival time was 24 months. According to interval to recurrence, the 3- and 5-year overall survival rates were 19% and 10%, respectively, for patients with < 12 months (n = 18), compared with 53% and 40% for those with >= 12 months (n = 23) (P = 0.006). Precise stereotactic radiotherapy was effective in controlling oligometastatic lesions for patients with a median survival time of 24 months. Interval to recurrence may impact the overall survival rate and should be included in the stratification criteria in a prospective randomized trial to investigate the benefits of stereotactic radiotherapy for patients with oligometastases.
  • Michalis Aristophanous, Joerg Rottmann, Sang-June Park, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco
    PHYSICS IN MEDICINE AND BIOLOGY 55 15 4321 - 4333 2010年08月 [査読有り][通常論文]
     
    The purpose of this study is to investigate the effect that image-guided adaptation of the gating window during treatment could have on the residual tumor motion, by simulating different gated radiotherapy techniques. There are three separate components of this simulation: (1) the 'Hokkaido Data', which are previously measured 3D data of lung tumor motion tracks and the corresponding 1D respiratory signals obtained during the entire ungated radiotherapy treatments of eight patients, (2) the respiratory gating protocol at our institution and the imaging performed under that protocol and (3) the actual simulation in which the Hokkaido Data are used to select tumor position information that could have been collected based on the imaging performed under our gating protocol. We simulated treatments with a fixed gating window and a gating window that is updated during treatment. The patient data were divided into different fractions, each with continuous acquisitions longer than 2 min. In accordance to the imaging performed under our gating protocol, we assume that we have tumor position information for the first 15 s of treatment, obtained from kV fluoroscopy, and for the rest of the fractions the tumor position is only available during the beam-on time from MV imaging. The gating window was set according to the information obtained from the first 15 s such that the residual motion was less than 3 mm. For the fixed gating window technique the gate remained the same for the entire treatment, while for the adaptive technique the range of the tumor motion during beam-on time was measured and used to adapt the gating window to keep the residual motion below 3 mm. The algorithm used to adapt the gating window is described. The residual tumor motion inside the gating window was reduced on average by 24% for the patients with regular breathing patterns and the difference was statistically significant (p-value = 0.01). The magnitude of the residual tumor motion depended on the regularity of the breathing pattern suggesting that image-guided adaptive gating should be combined with breath coaching. The adaptive gating window technique was able to track the exhale position of the breathing cycle quite successfully. Out of a total of 53 fractions the duty cycle was greater than 20% for 42 fractions for the fixed gating window technique and for 39 fractions for the adaptive gating window technique. The results of this study suggest that real-time updating of the gating window can result in reliably low residual tumor motion and therefore can facilitate safe margin reduction.
  • Ardene Harris, Tamotsu Kamishima, Hong Yi Hao, Fumi Kato, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato
    EUROPEAN JOURNAL OF RADIOLOGY 75 1 E97 - E101 2010年07月 [査読有り][通常論文]
     
    Objective: The present research was conducted to establish the normal splenic volume in adults using a novel and fast technique. The relationship between splenic volume and age, gender, and anthropometric parameters was also examined. Materials and methods: The splenic volume was measured in 230 consecutive patients who underwent computed tomography (CT) scans for various indications. Patients with conditions that have known effect on the spleen size were not included in this study. A new technique using volumetric software to automatically contour the spleen in each CT slice and quickly calculate splenic volume was employed. Inter- and intra-observer variability were also examined. Results: The average splenic volume of all the subjects was 127.4 +/- 62.9 cm(3), ranging from 22 to 417 cm(3). The splenic volume (S) correlated with age (A) (r = -0.33, p < 0.0001), body weight (W) (r = 0.35, p < 0.0001), body mass index (r = 0.24, p < 0.0001) and body surface area (BSA) (r = 0.31, p < 0.0001). The age-adjusted splenic volume index correlated with gender (p = 0.0089). The formulae S = W[6.47A((-0,31))] and S = BSA[278A((-0,36))] were derived and can be used to estimate the splenic volume. Inter- and intra-observer variability were 6.4 +/- 9.8% and 2.8 +/- 3.5% respectively. Conclusion: Of the anthropometric parameters, the splenic volume was most closely linked to body weight. The automatically contouring software as well as formulae can be used to obtain the volume of the spleen in regular practice. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Takeshi Nishioka, Masaharu Fujino, Akihiro Homma, Tetsuro Yamashita, Akira Sato, Keiichi Ohmori, Kenichi Obinata, Hiroki Shirato, Kenichi Notani, Masamichi Nishio
    YONSEI MEDICAL JOURNAL 51 4 557 - 561 2010年07月 [査読有り][通常論文]
     
    Purpose: Deciding on treatment carcinoma of the tongue when the tumor has a thickness of 1.5 cm or more is difficult. Surgery often requires wide resection and re-construction, leading to considerable functional impairment. A cesium implant is an attractive option, but according to the Manchester System, a two plane implant is needed. Materials and Methods: According to the textbook, a tumor is sandwiched between the needles, which are implanted at the edge of the tumor. This may cause an unnecessarily high dose to the outer surface of the tongue, which sometimes leads to a persistent ulcer. To avoid this complication, we invented a modified implantation method, and applied the method to five consecutive patients. Results: With a minimum follow-up of 2 years, all primary tumors in 5 consecutive patients have been controlled. No complications occurred in soft tissue of the tongue or in the mandible. Conclusion: Our modified Manchester System was feasible and effective for tumors that has a thickness of 1.5 cm or more.
  • Gerard Bengua, Masayori Ishikawa, Kenneth Sutherland, Kenji Horita, Rie Yamazaki, Katsuhisa Fujita, Rikiya Onimaru, Noriwo Katoh, Tetsuya Inoue, Shunsuke Onodera, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 77 2 630 - 636 2010年06月 [査読有り][通常論文]
     
    Purpose: To evaluate the effectiveness of the stereotactic body frame (SBF), with or without a diaphragm press or a breathing cycle monitoring device (Abches), in controlling the range of lung tumor motion, by tracking the real-time position of fiducial markers. Methods and Materials: The trajectories of gold markers in the lung were tracked with the real-time tumor-tracking radiotherapy system. The SBF was used for patient immobilization and the diaphragm press and Abches were used to actively control breathing and for self-controlled respiration, respectively. Tracking was performed in five setups, with and without immobilization and respiration control. The results were evaluated using the effective range, which was defined as the range that includes 95% of all the recorded marker positions in each setup. Results: The SBF, with or without a diaphragm press or Abches, did not yield effective ranges of marker motion which were significantly different from setups that did not use these materials. The differences in the effective marker ranges in the upper lobes for all the patient setups were less than 1mm. Larger effective ranges were obtained for the markers in the middle or lower lobes. Conclusion: The effectiveness of controlling respiratory-induced organ motion by using the SBF+diaphragm press or SBF + Abches patient setups were highly dependent on the individual patient reaction to the use of these materials and the location of the markers. They may be considered for lung tumors in the lower lobes, but are not necessary for tumors in the upper lobes. (C) 2010 Elsevier Inc.
  • Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, Hiroki Shirato, Takeshi Nishioka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 396 3 651 - 655 2010年06月 [査読有り][通常論文]
     
    Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin beta 1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin beta 1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin beta 1-dependent phenotype, and integrin beta 1 might be a potentially effective therapeutic target in combination with radiotherapy. (C) 2010 Elsevier Inc. All rights reserved.
  • Eric W. Pepin, Huanmei Wu, George A. Sandison, Mark Langer, Hiroki Shirato
    PHYSICS IN MEDICINE AND BIOLOGY 55 12 3325 - 3337 2010年06月 [査読有り][通常論文]
     
    The treatment of lung cancer with radiation therapy is hindered by respiratory motion. Real-time adjustments to compensate for this motion are hampered by mechanical system latencies and imaging-rate restrictions. To better understand tumour motion behaviour for adaptive image-guided radiation therapy of lung cancer, the volume of a tumour's motion space was investigated. Motion data were collected by tracking an implanted fiducial using fluoroscopy at 30 Hz during treatment sessions. A total of 637 treatment fractions from 31 tumours were used in this study. For each fraction, data points collected from three consecutive breathing cycles were used to identify instantaneous tumour location. A convex hull was created over these data points, defining the tumour motion envelope. The study sought a correlation between the tumour location in the lung and the convex hull's volume and shape. It was found that tumours located in the upper apex had smaller motion envelopes (<50 mm(3)), whereas tumours located near the chest wall or diaphragm had larger envelopes (>70 mm(3)). Tumours attached to fixed anatomical structures had small motion spaces. Three general shapes described the tumour motion envelopes: 50% of motion envelopes enclosed largely 1D oscillation, 38% enclosed an ellipsoid path, 6% enclosed an arced path and 6% were of hybrid shape. This location-space correlation suggests it may be useful in developing a predictive model, but more work needs to be done to verify it.
  • Tamotsu Kamishima, Akira Sagawa, Kazuhide Tanimura, Masato Shimizu, Megumi Matsuhashi, Masahide Shinohara, Hiromi Hagiwara, Mihoko Henmi, Akihiro Narita, Satoshi Terae, Hiroki Shirato
    SKELETAL RADIOLOGY 39 5 457 - 465 2010年05月 [査読有り][通常論文]
     
    To determine the timing for follow-up study of power Doppler ultrasonography (PDUS) by evaluating the response of finger joint synovitis in patients with rheumatoid arthritis (RA) to treatment including infliximab, an antitumor necrosis factor alpha agent. Bilateral second/third metacarpo-phalangeal (MCP) joints and second proximal inter-phalangeal (PIP) joints (total of six joints) in 21 patients (18 women and three men; median age 53 years) with chronic active RA were assessed by PDUS before and after 2 weeks, 6 weeks, 14 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks of infliximab infusion. Pulse Doppler settings were standardized for each patient and optimized for the detection of synovial blood flow by adjustment of color gain, pulse repetition, and flow optimization. Power Doppler signal was graded for each joint [joint grade for power Doppler (JGPD) signals], and the sum of the grades of six joints was defined as the PDUS index [joint index for power Doppler signals (JIPD)] at each visit. PDUS and clinical parameters [28-joint disease activity score (DAS28), health assessment questionnaire, and C-reactive protein (CRP) level] were independently assessed and compared with baseline values. The American College of Rheumatology (ACR) core set responders and non-responders at week 54 were compared for clinical parameters and PDUS index at each visit. Fourteen patients completed the planned treatment for 1 year, while six patients dropped out for various reasons and one died suddenly. PDUS was performed a total of 146 times on 467 joints. DAS28 was assessed 127 times. Both DAS28 and JIPD had decreased at the follow-up. Comparative analysis between DAS28 and PDUS was available 125 times. The transverse correlation between the PDUS index and DAS28 was not significant throughout the follow-up period. When responders and non-responders were discriminated at week 54, a logistic regression model for the binary endpoint of responder vs non-responder, with PDUS index as explanatory variable at time point 0, and follow-up revealed statistical significance from week 38 and on. PDUS reflected infliximab's effect on pannus vascular signals; this effect was observed as early as 2 weeks after treatment had begun. Also, the responders to treatment at 54 weeks tended to have fewer JIPD than non-responders in the follow-up period. PDUS may be performed at week 38 or later to foresee the response to the treatment at week 54.
  • Noriko Oyama, Daisuke Goto, Tsukasa Sasaki, Hiroyuki Tsutsui, Nagara Tamaki, Satoshi Terae, Hiroki Shirato
    JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY 4 3 218 - 220 2010年05月 [査読有り][通常論文]
     
    Electrocardiographic-gated 64-slice multidetector computed tomography (MDCT) was performed on a 30-year-old man who presented with a complete endocardial cushion defect (ECD) and severe pulmonary hypertension diagnosed when he was 3 years old. Multiplanar reconstruction image showed the common atrium without an atrial septum, a large ventricular septum defect, and a small right ventricle due to a complete atrioventricular canal defect. Three-dimensional CT volume-rending imaging showed a patent ductus arteriosus, dilation of the ascending aorta, and an anomalous-origin right coronary artery. This patient also had heterotaxy syndrome with polysplenia and azygos continuation. MDCT proved to be a good noninvasive imaging method for the evaluation of ECD associated with cardiac as well as extracardiac abnormalities. (C) 2010 Society of Cardiovascular Computed Tomography. All rights reserved.
  • Rie Mimura, Tamotsu Kamishima, Kanako C. Kubota, Fumihito Nakano, Ichiro Yabe, Hidenao Sasaki, Satoru Maruyama, Nobuo Shinohara, Ardene A. Harris, Hironori Haga, Hiroki Shirato, Satoshi Terae
    Japanese Journal of Radiology 28 4 309 - 313 2010年05月 [査読有り][通常論文]
     
    A 62-year-old man was referred to us after unsuccessful treatment of bilateral weakness in his upper and lower extremities with paresthesia in both lower extremities. Computed tomography (CT) revealed soft tissue masses in the left kidney along the capsule and paraaortic region that were of relatively low attenuation with accompanying granular calcifications. Pathological diagnosis of the biopsy specimen was extramedullary plasmacytoma accompanied by extramedullary hematopoiesis and amyloid deposition. Although the CT findings correlated well with the pathological results, the case was extremely atypical for extramedullary plasmacytoma in respect to location and the accompaniment with extramedullary hematopoiesis. © 2010 Japan Radiological Society.
  • Tsuguhide Takeshima, Kenji Chamoto, Daiko Wakita, Takayuki Ohkuri, Yuji Togashi, Hiroki Shirato, Hidemitsu Kitamura, Takashi Nishimura
    CANCER RESEARCH 70 7 2697 - 2706 2010年04月 [査読有り][通常論文]
     
    Radiation therapy is one of the primary treatment modalities for cancer along with chemotherapy and surgical therapy. The main mechanism of the tumor reduction after irradiation has been considered to be damage to the tumor DNA. However, we found that tumor-specific CTL, which were induced in the draining lymph nodes (DLN) and tumor tissue of tumor-bearing mice, play a crucial role in the inhibition of tumor growth by radiation. Indeed, the therapeutic effect of irradiation was almost completely abolished in tumor-bearing mice by depleting CD8(+) T cells through anti-CD8 monoclonal antibody administration. In mice whose DLN were surgically ablated or genetically defective (Aly/Aly mice), the generation of tetramer(+) tumor-specific CTL at the tumor site was greatly reduced in parallel with the attenuation of the radiation-induced therapeutic effect against the tumor. This indicates that DLN are essential for the activation and accumulation of radiation-induced CTL, which are essential for inhibition of the tumor. A combined therapy of local radiation with Th1 cell therapy augmented the generation of tumor-specific CTL at the tumor site and induced a complete regression of the tumor, although radiation therapy alone did not exhibit such a pronounced therapeutic effect. Thus, we conclude that the combination treatment of local radiation therapy and Th1 cell therapy is a rational strategy to augment antitumor activity mediated by tumor-specific CTL. Cancer Res; 70(7); 2697-706. (C) 2010 AACR.
  • Berbeco RI, Nishioka S, Shirato H
    Journal of applied clinical medical physics / American College of Medical Physics 11 3203  2 2010年04月 [査読有り][通常論文]
  • Kinya Ishizaka, Kohsuke Kudo, Noriyuki Fujima, Yuri Zaitsu, Rie Yazu, Khin Khin Tha, Satoshi Terae, E. Mark Haacke, Makoto Sasaki, Hiroki Shirato
    JOURNAL OF MAGNETIC RESONANCE IMAGING 31 1 32 - 38 2010年01月 [査読有り][通常論文]
     
    Purpose: To evaluate the visualization of the spinal veins using susceptibility-weighted imaging (SWI). Materials and Methods: A 1.5-T magnet equipped with a spine matrix coil was used. Axial SWI scans of 20 healthy volunteers were obtained with a three-dimensional fast low-angle shot (3D-FLASH) sequence. Maximum intensity projection (MIP) of the phase images were reconstructed and five MIP images (at the levels of T11, T11/12, T12, T12/L1, and L1) were selected for the evaluation. The anterior median vein (AMV), posterior median vein (PMV), anterior radiculomedullary vein (ARV), posterior radiculomedullary vein (PRV), and sulcal vein (SV) were evaluated using a 4-grade scale (0, none; 1, weak; 2, moderate: and 3, prominent). Results: The AMV was detected in all the subjects (100%). The detection rates of the other veins were lower: PMV, 65%: right ARV. 45%: left ARV, 15%; right PRV. 10%; left PRV, 30%; and SV, 0%. The average scores for AMV, PMV, right ARV. left ARV, right PRV, left PRV, and SV were 0.98, 0.24, 0.20, 0.08, 0.08, 0.14, and 0, respectively. Conclusion: SWI of the spine is feasible. The extrinsic spinal veins can be visualized by SWI without using contrast materials.
  • Kohsuke Kudo, Makoto Sasaki, Kei Yamada, Suketaka Momoshima, Hidetsuna Utsunomiya, Hiroki Shirato, Kuniaki Ogasawara
    RADIOLOGY 254 1 200 - 209 2010年01月 [査読有り][通常論文]
     
    Purpose: To examine the variability in the qualitative and quantitative results of computed tomographic (CT) perfusion imaging generated from identical source data of stroke patients by using commercially available software programs provided by various CT manufacturers. Materials and Methods: Institutional review board approval and informed consent were obtained. CT perfusion imaging data of 10 stroke patients were postprocessed by using five commercial software packages, each of which had a different algorithm: singular-value decomposition (SVD), maximum slope (MS), inverse filter (IF), box modulation transfer function (bMTF), and by using custom-made original software with standard (sSVD) and block-circulant (bSVD) SVD methods. Areas showing abnormalities in cerebral blood flow (CBF), mean transit time (MTT), and cerebral blood volume (CBV) were compared with each other and with the final infarct areas. Differences among the ratios of quantitative values in the final infarct areas and those in the unaffected side were also examined. Results: The areas with CBF or MTT abnormalities and the ratios of these values significantly varied among software, while those of CBV were stable. The areas with CBF or MTT abnormalities analyzed by using SVD or bMTF corresponded to those obtained with delay-sensitive sSVD, but overestimated the final infarct area. The values obtained from software by using MS or IF corresponded well with those obtained from the delay-insensitive bSVD and the final infarct area. Given the similarities between CBF and MTT, all software were separated in two groups (ie, sSVD and bSVD). The ratios of CBF or MTTs correlated well within both groups, but not across them. Conclusion: CT perfusion imaging maps were significantly different among commercial software even when using identical source data, presumably because of differences in tracer-delay sensitivity. (C) RSNA, 2010
  • Hee Chul Park, Shinichi Shimizu, Akio Yonesaka, Kazuhiko Tsuchiya, Yasuhiko Ebina, Hiroshi Taguchi, Norio Katoh, Rumiko Kinoshita, Masayori Ishikawa, Noriaki Sakuragi, Hiroki Shirato
    YONSEI MEDICAL JOURNAL 51 1 93 - 99 2010年01月 [査読有り][通常論文]
     
    Purpose: The purpose of this study is to evaluate the clinical results of treatment with a high dose of 3-dimensional conformal boost (3DCB) using a real-time tracking radiation therapy (RTRT) system in cervical cancer patients. Materials and Methods: Between January 2001 and December 2004, 10 patients with cervical cancer were treated with a high dose 3DCB using RTRT system. Nine patients received whole pelvis radiation therapy (RT) with a median dose of 50 Gy (range, 40-50 Gy) before the 3DCB. The median dose of the 3DCB was 30 Gy (range, 25-30 Gy). Eight patients received the 3DCB twice a week with a daily fraction of 5 Gy. The determined endpoints were tumor response, overall survival, local failure free survival, and distant metastasis free survival. The duration of survival was calculated from the time of the start of radiotherapy. Results: All patients were alive at the time of analysis and the median follow-up was 17.6 months (range, 4.9-27.3 months). Complete response was achieved in nine patients and one patient had a partial response. The 1- and 2-year local failure free survival was 78.8% and 54%, respectively. The 1- and 2-year distant metastasis free survival was 90% and 72%, respectively. Late toxicity of a grade 2 rectal hemorrhage was seen in one patient. A subcutaneous abscess was encountered in one patient. Conclusion: the use of the high dose 3DCB in the treatment of cervical cancer is safe and feasible where intracavitary brachytherapy (ICBT) is unable to be performed. The escalation of the 3DCB dose is currently under evaluation.
  • Jun Nakayama, Kazuo Miyasaka, Tokuhiko Omatsu, Yunya Onodera, Satoshi Terae, Yoshihiro Matsuno, Yasushi Cho, Yasuhiro Hida, Kichizo Kaga, Hiroki Shirato
    JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 34 1 1 - 8 2010年01月 [査読有り][通常論文]
     
    Objective: To evaluate diffusion-weighted magnetic resonance (DW-MR) imaging for detection of metastases in lymph nodes by using quantitative analysis. Methods: Seventy patients with non-small cell lung cancer were examined with DW and short inversion time inversion recovery (STIR) turbo-spin-echo MR imaging. Apparent diffusion coefficient of each lung cancer and lymph node was calculated from DW-MR images. Difference of the apparent diffusion coefficient in a lung cancer and a lymph node was calculated (D1). From STIR turbo-spin-echo MR images, ratios of signal intensity in a lymph node to that in a 0.9% saline phantom was calculated (lymph node-saline ratio [LSR1]). For quantitative analysis, the threshold value for a positive test was determined on a per node basis and tested for ability to enable a correct diagnosis on a per patient basis. Results of quantitative analyses of DW- and STIR-MR images were compared on a per patient basis with McNemar testing. Results: Mean D I in the lymph node group with metastases was lower than that in the group without metastases (P < 0.001). When an D I of 0.24 x 10(-3) mm(2)/S was used as the positive test threshold, sensitivity, specificity, and accuracy were 69.2%, 100%, and 94.0%, respectively, on a per patient basis. There was no significant difference (P > 0.05) between quantitative analyses of DW-MR images and STIR-MR images. Conclusions: Quantitative analysis of DW-MR images enables differentiation of lymph nodes with metastasis from those without.
  • Yuri Zaitsu, Satoshi Terae, Kohsuke Kudo, Khin Khin Tha, Mineji Hayakawa, Noriyuki Fujima, Daisuke Yoshida, Akiko Tsukahara, Hiroki Shirato
    Journal of computer assisted tomography 34 1 107 - 12 2010年01月 [査読有り][通常論文]
     
    Cerebral fat embolism (CFE) causes microinfarcts, vasogenic edema, and petechiae in the brain. Conventional magnetic resonance imaging has been reported to effectively visualize microinfarcts and vasogenic edema in CFE, but not petechiae. We report 3 cases of CFE in which susceptibility-weighted imaging distinctly demonstrated multiple minute hypointense foci in the brain, which were interpreted as petechiae, susceptibility-weighted imaging is a useful adjunct to conventional magnetic resonance imaging for the evaluation of CFE.
  • Kenneth Sutherland, Satoshi Miyajima, Hiroyuki Date, Hiroki Shirato, Masayori Ishikawa, Masao Murakami, Mitsuru Yamagiwa, Paul Bolton, Toshiki Tajima
    Radiological Physics and Technology 3 1 16 - 22 2010年01月 [査読有り][通常論文]
     
    The results of Monte Carlo calculated dose distributions of proton treatment of ocular melanoma are presented. An efficient spot scanning method utilizing active energy modulation, which also minimizes the number of target spots was developed. We simulated various parameter values for the particle energy spread and the pencil beam diameter in order to determine values suitable for medical treatment. We found that a 2.5-mm-diameter proton beam with a 5% Gaussian energy spread was suitable for treatment of ocular melanoma while preserving vision for the typical case that we simulated. The energy spectra and the required proton current were also calculated and are reported. The results are intended to serve as a guideline for a new class of low-cost, compact accelerators. © 2009 Japanese Society of Radiological Technology and Japan Society of Medical Physics.
  • Kentaro Nishioka, Daisuke Abo, Hidefumi Aoyama, Yasushi Furuta, Rikiya Onimaru, Shunsuke Onodera, Yutaka Sawamura, Masayori Ishikawa, Satoshi Fukuda, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 5 1415 - 1419 2009年12月 [査読有り][通常論文]
     
    Purpose: Although the effectiveness of stereotactic radiosurgery for nonacoustic schwannomas is currently being assessed, there have been few studies on the efficacy of stereotactic radiotherapy (SRT) for these tumors. We investigated the long-term outcome of SRT for nonacoustic intracranial nerve schwannomas. Methods and Materials: Seventeen patients were treated between July 1994 and December 2006. Of these patients, 7 had schwannomas located in the jugular foramen, 5 in the trigeminal nerve, 4 in the facial nerve, and I in the oculomotor nerve. Radiotherapy was used as an initial treatment without surgery in 10 patients (59 %) and after initial subtotal resection in the remaining patients. The tumor volume ranged from 0.3 to 31.3 mL (mean, 8.2 mL). The treatment dose was 40 to 54 Gy in 20 to 26 fractions. The median follow-up period was 59.5 months (range, 7.4-122.6 months). Local control was defined as stable or decreased tumor size on follow-up magnetic resonance imaging. Results: Tumor size was decreased in 3 patients, stable in 13, and increased in I after SRT. Regarding neurologic symptoms, 8 patients (47 %) had improvement and 9 patients were unchanged. One patient had an increase in tumor size and received microsurgical resection at 32 months after irradiation. No patient had worsening of pre-existing neurologic symptoms or development of new cranial nerve deficits at the last follow-up. Conclusions: SRT is an effective alternative to surgical resection for patients with nonacoustic intracranial nerve schwannomas with respect to not only long-term local tumor control but also neuro-functional preservation. (C) 2009 Elsevier Inc.
  • Tetsuya Inoue, Shinichi Shimizu, Rikiya Onimaru, Atsuya Takeda, Hiroshi Onishi, Yasushi Nagata, Tomoki Kimura, Katsuyuki Karasawa, Takuro Arimoto, Masato Hareyama, Elki Kikuchi, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 3 683 - 687 2009年11月 [査読有り][通常論文]
     
    Purpose: Image-guided biopsy occasionally fails to diagnose small lung lesions, which are highly suggestive of primary lung cancer. The aim of the present study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) for small lung lesions that were clinically diagnosed as primary lung cancer without pathologic confirmation. Methods and Materials: A total of 115 patients were treated with SBRT in 12 institutions. Tumor size ranged from 5 to 45 mm in diameter, with a median of 20 mm. Results: The 3-year and 5-year overall survival rates for patients with a tumor size <= 20 mm in diameter (it = 58) were both 89.8%, compared with 60.7% and 53.1% for patients with tumors >20 mm (n = 57) (p < 0.0005), respectively. Local progression occurred in 2 patients (3.4%) with a tumor size <= 20 mm and in 3 patients (5.3%) with tumors >20 mm. Among the patients with a tumor size <= 20 mm, Grade 2 pulmonary complications were observed in 2 (3.4%), but no Grade 3 to 5 toxicity was observed. In patients with a tumor size >20 mm, Grades 2, 3, and 5 toxicity were observed in 5 patients (8.8%), 3 patients (5.3%), and 1 patient (1.8%), respectively. Conclusion: In patients with a tumor <= 20 mm in diameter, SBRT was reasonably safe in this retrospective study. The clinical implications of the high local control rate depend on the accuracy of clinical/radiologic diagnosis for small lung lesions and are to be carefully evaluated in a prospective study. (C) 2009 Elsevier Inc.
  • Tadashi Shimizu, Yusuke Sakuhara, Daisuke Abo, Yu Hasegawa, Yoshihisa Kodama, Hideho Endo, Hiroki Shirato, Kazuo Miyasaka
    JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 16 6 816 - 823 2009年11月 [査読有り][通常論文]
     
    To assess the mid-term results of MR-guided percutaneous cryoablation for small hepatocellular carcinoma (HCC). Using an argon-based cryoablation system, MR-guided percutaneous cryoablation was performed. The number of tumors was three or fewer. The maximum diameter of tumors was less than 5 cm when solitary and no more than 3 cm when multiple. The Kaplan-Meier method was used to calculate the survival of patients. Among 15 patients, 16 tumors were treated. The maximum tumor diameter ranged from 1.2 to 4.5 cm, with a mean of 2.5 +/- A 0.8 cm (mean +/- A standard deviation). The volume of iceballs measured on MR-images was greater than that of the tumors in all cases. The follow-up period ranged from 10 to 52 months, with a mean of 36.6 +/- A 12.1 months. One-year and 3-year overall survival were 93.8 and 79.3%, respectively. The complete ablation rate was 80.8% at 3 years. Immediate complications were pneumothorax, hemothorax, and pleural effusion. An ablation zone was not absorbed and content exuded from a scar of the probe tract 4 months after cryoablation in one patient. MR-guided percutaneous cryoablation appears to be a feasible modality and potentially good option for the treatment of small HCC.
  • Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Shigenari Taki, Takeshi Asano, Daisuke Yoshida, Rikiya Onimaru, Takeshi Nishioka, Hiroki Shirato, Satoshi Fukuda
    CANCER 115 20 4705 - 4714 2009年10月 [査読有り][通常論文]
     
    BACKGROUND: The current study aimed to evaluate the efficacy of superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with advanced cancer of the nasal cavity and paranasal sinuses. METHODS: Between October 1999 and December 2006, 47 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional external-beam radiotherapy (65-70 grays), RESULTS: There were 7 patients (14.9%) diagnosed with T3, 22 (46.8%) with T4a, and 18 (38.3%) with T4b disease. During the median follow-up period of 4.6 years, the 5-year local progression-free survival rate was 78.4% for all patients (n=47), 69.0% for patients with T4b disease (n=18), and 83.2% for patients with <T4b disease (n=29). The 5-year overall survival rate was 69.3% for all patients, 61.1% for patients with T4b disease, and 71.1% for patients with < T4b disease. RADPLAT was feasible in 45 patients (95.7%). No patient died as a result of treatment toxicity or had a cerebrovascular accident. Osteonecrosis (n=7), brain necrosis (n=2), and ocular/visual problems (n=16) were observed as late adverse reactions. CONCLUSIONS: Although a single institution experience, the results of the current study suggest that RADPLAT can cure the majority of patients with advanced cancer of the nasal cavity and paranasal sinuses, as well as preserve organs. Late adverse reactions should be monitored in future studies. Cancer 2009;115:4705-14. (C) 2009 American Cancer Society.
  • Yasushi Nagata, Masahiro Hiraoka, Takashi Mizowaki, Yuichiro Narita, Yukinori Matsuo, Yoshiki Norihisa, Hiroshi Onishi, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 2 343 - 347 2009年10月 [査読有り][通常論文]
     
    Purpose: To recognize the current status of stereotactic body radiotherapy (SBRT) in Japan, using a nationwide survey conducted by the Japan 3-D Conformal External Beam Radiotherapy Group. Methods and Materials: The questionnaire was sent by mail to 117 institutions. Ninety-four institutions (80%) responded by the end of November 2005. Fifty-three institutions indicated that they have already started SBRT, and 38 institutions had been reimbursed by insurance. Results: A total of 1111 patients with histologically confirmed lung cancer were treated. Among these patients, 637 had TIN0M0 and 272 had T2N0M0 lung cancer. Metastatic lung cancer was found in 702 and histologically unconfirmed lung tumor in 291 patients. Primary liver cancer was found in 207 and metastatic liver cancer in 76 patients. The most frequent schedule used for primary lung cancer was 48Gy in 4 fractions at 22 institutions (52%), followed by 50Gy in 5 fractions at I I institutions (26%) and 60Gy in 8 fractions at 4 institutions (10%). The tendency was the same for metastatic lung cancer. The average number of personnel involved in SBRT was 1.8 radiation oncologists, including 1.1 certified radiation oncologists, 2.8 technologists, 0.7 nurses, and 0.6 certified quality assurance personnel and 0.3 physicists. The most frequent amount of time for treatment planning was 61-120min, for quality assurance was 50-60min, and for treatment was 30min. There were 14 (0.6% of all cases) reported Grade 5 complications: 11 cases of radiation pneumonitis, 2 cases of hemoptysis, and 1 case of radiation esophagitis. Conclusion: The current status of SBRT in Japan was surveyed. (C) 2009 Elsevier Inc.
  • Shinichi Shimizu, Masao Hosokawa, Kazuo Itoh, Masahiro Fujita, Hiroaki Takahashi, Hiroki Shirato
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 14 5 421 - 425 2009年10月 [査読有り][通常論文]
     
    We aimed to determine the appropriateness of adding 18F-fluorodeoxyglucose (FDG)-positronemission tomography (PET) to computed tomography (CT) and other pre-existing diagnostic imaging modalities for detecting subclinical lymph node metastasis of esophageal cancer, by comparing images from these modalities with the results of histopathological analysis. Twenty patients who received radical surgery for squamous cell carcinoma of the esophagus were examined by PET-CT, and endoscopic ultrasound (EUS) examination before surgery. Based on these diagnostic modalities, the clinical target volume (CTV) was set as the gross tumor volume (GTV) plus a 1-cm margin. Histopathological diagnosis was performed in all patients immediately after resection. Fifty-three (3.0%) of 1764 nodes in the 20 patients were histopathologically positive for cancer cells. The CTV was not adequate to cover these histopathologically detected positive lymph nodes in 8 of 20 patients on CT, 5 of 20 on CT+EUS, 7 of 20 on PET-CT, and 5 of 20 on PET-CT+EUS. The detection rate of subclinical lymph node metastasis did not improve with the use of PET-CT, for either the cervical and supraclavicular, mediastinal, or abdominal regions. It is not recommended to use FDG-PET or PET-CT alone as a diagnostic tool to determine CTV if pathologically involved lymphatic regions are to be included in the CTV in the treatment protocol. The accuracy of PET-CT must be further improved in order to better detect positive nodes and improve the definition of the CTV.
  • Tamotsu Kamishima, Akiko Hasegawa, Kanako C. Kubota, Naomi Oizumi, Norimasa Iwasaki, Akio Minami, Satoru Sasaki, Yuhei Yamamoto, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato
    JAPANESE JOURNAL OF RADIOLOGY 27 8 328 - 332 2009年10月 [査読有り][通常論文]
     
    Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report two cases of intravenous pyogenic granuloma localized in the finger, giving details of the magnetic resonance imaging (MRI) findings. These two cases had similar locations in fingers and identical MRI findings. The differential diagnoses of this rare entity are also discussed.
  • Noriko Oyama, Tomonori Ooka, Tsukasa Sasaki, Suguru Kubota, Yuya Onodera, Yoshiro Matsui, Satoshi Terae, Hiroki Shirato
    Journal of Cardiovascular Computed Tomography 3 5 346 - 347 2009年09月 [査読有り][通常論文]
     
    We diagnosed unroofed coronary sinus preoperatively by the 3D volume rendering and endocardial views with 64-slice MDCT, and those clearly showed the defect of the roof of the coronary sinus and the relationship with the surrounding structure. MDCT is a good non-invasive tool for the evaluation of unroofed coronary sinus, and the reconstructed endocardial view is useful for preoperative surgical planning. © 2009 Society of Cardiovascular Computed Tomography.
  • Takeshi Nishioka, Seiko Nishioka, Masaki Kawahara, Shigeru Tanaka, Hiroki Shirato, Ken Nishi, Tadao Hiromura
    JAPANESE JOURNAL OF RADIOLOGY 27 7 285 - 289 2009年08月 [査読有り][通常論文]
     
    Purpose. Four-dimensional (4D) radiotherapy, in particular respiration gating for the treatment of lung tumors, is gaining popularity. Its utility for other sites, however, has not been investigated fully. The purpose of this study was to see whether 4D therapy is feasible for liver tumors. Material and methods. Six patients (five with hepatomas and one with metastatic liver tumor) had a fiducial, gold marker 1.5 mm in diameter implanted in the vicinity of their liver tumors. The inner and external (i.e., upper abdominal wall) respiratory movements were simultaneously recorded using a real-time tumor-tracking radiotherapy system and respiration monitor equipment applied to the mid to upper abdomen. Results. The fluctuations from the baseline position of liver tumors were small; the mean absolute value was 3.92 +/- 1.94 mm. The mean right-left, anteroposterior, and craniocaudal total movements were 4.19 +/- 2.46, 7.23 +/- 2.96, and 15.98 +/- 6.02 mm, respectively. The phase shift was negligible. Conclusion. Liver tumors may be suitable for respiration-gated radiotherapy, and they may become curable with 4D radiotherapy.
  • Keishiro Suzuki, Takeshi Nishioka, Akihiro Homma, Kazuhiko Tsuchiya, Motoaki Yasuda, Hidefumi Aoyama, Rikiya Onimaru, Nagara Tamaki, Hiroki Shirato
    JAPANESE JOURNAL OF RADIOLOGY 27 6 237 - 242 2009年07月 [査読有り][通常論文]
     
    Purpose. The aim of this study was to determine if the standardized uptake value (SUV) of fluorodeoxyglucose positron emission tomography (FDG-PET) for head and neck cancer can predict the outcome of radiotherapy and if the SUV is correlated with histological grade, mitosis, and apoptosis. Materials and methods. The study included 45 head and neck cancer patients who underwent FDG-PET scanning before radiotherapy. The maximum SUV (SUVmax) of their primary lesions were measured. Biopsy was performed in all patients to determine the histological diagnosis. Altogether, 14 biopsy specimens were available for mitotic and apoptotic cell counts. Results. The mean SUVmax of T3 tumors was significantly higher than that of T1 (P = 0.01) and T2 (P = 0.011) tumors. The mean SUVmax of stage II disease was significantly lower than that of stage III (P = 0.028) and stage IV (P = 0.007) disease. There was a tendency toward a better locoregional control rate and disease-free survival for the lower SUV group using a cutoff value of 5.5. For 41 patients with squamous cell carcinoma or undifferentiated carcinoma, SUVmax did not reflect the histological grade. There was no correlation between the SUVmax and the mitotic/apoptotic status. Conclusion. SUVmax may correlate with the T classification and stage, but there was no predictive value for outcome of radiation therapy. Neither histological grading nor mitotic/apoptotic status is correlated with SUVmax.
  • Gerben R. Borst, Masayori Ishikawa, Jasper Nijkamp, Michael Hauptmann, Hiroki Shirato, Rikiya Onimaru, Michel M. van den Heuvel, Jose Belderbos, Joos V. Lebesque, Jan-Jakob Sonke
    RADIOTHERAPY AND ONCOLOGY 91 3 307 - 313 2009年06月 [査読有り][通常論文]
     
    Purpose: We evaluated the relationship between the mean lung dose (MLD) and the incidence of radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT), and compared this with conventional fractionated radiation therapy (CFRT). Materials and methods: For both SBRT (n=128) and CFRT (n=142) patients, RP grade >= 2 was scored. Toxicity models predicting the probability of RP as a function of the MLD were fitted Using Maximum log likelihood analysis. The MLD was NTD (Normalized Total Dose) corrected using an alpha/beta ratio of 3 Gy. Results: SBRT patients were treated with 6-12 Gy per fraction with a median MLD of 6.4 Gy (range: 1.5-6.5 Gy). CFRT patients were treated with 2 Gy or 2.25 Gy per fraction, the median MLD was 13.2 Gy (range: 3.0-23.0 Gy). The crude incidence rates of RP were 10.9% and 17.6% for the SBRT and CFRT patients, respectively. A significant close-response relationship for RP was found after SBRT, which was not significantly different from the dose-response relationship for CFRT (p = 0.18). Conclusion: We derived a significant dose-response relationship between the risk of RP and the MLD for SBRT from the clinical data. This relation was not significantly different from the dose-response relation for CFRT, although statistical analysis was hampered by the low number of patients in the high dose range. D 2009 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 91 (2009) 307-313
  • Tamotsu Kamishima, Toru Harabayashi, Syuhei Ishikawa, Kanako C. Kubota, Katsuya Nonomura, Tokuhiko Omatsu, Yuya Onodera, Hiroki Shirato, Satoshi Terae
    Japanese Journal of Radiology 27 5 225 - 228 2009年06月 [査読有り][通常論文]
     
    Echinococcosis is a parasitic infection of humans caused by the larval stage of the tapeworm Echinococcus. Primary alveolar echinococcosis of the adrenal gland is rare. We report a case of alveolar hydatid disease of the adrenal gland that presented as a multiloculated cystic mass without calcification. The lesion was purely cystic in nature, suggesting that it was at an early stage of development. © 2009 Japan Radiological Society.
  • Kenji Chamoto, Tsuguhide Takeshima, Daiko Wakita, Takayuki Ohkuri, Shigeru Ashino, Tokuhiko Omatsu, Hiroki Shirato, Hidemitsu Kitamura, Yuji Togashi, Takashi Nishimura
    CANCER SCIENCE 100 5 934 - 939 2009年05月 [査読有り][通常論文]
     
    Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG + OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG + OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG + OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG + OVA-liposome allowed the augmented induction of OVA-tetramer(+) LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (Cancer Sci 2009; 100: 934-939).
  • Tamotsu Kamishima, Kazuhide Tanimura, Mihoko Henmi, Akihiro Narita, Fumihiko Sakamoto, Satoshi Terae, Hiroki Shirato
    SKELETAL RADIOLOGY 38 5 467 - 472 2009年05月 [査読有り][通常論文]
     
    The objective of this study was to assess interobserver uncertainties in power Doppler (PD) examination of the fingers of patients with rheumatoid arthritis (RA), by separating the source of the discrepancy into (1) acquisition of the images and (2) criteria for assessment of the images. Twenty patients who had been diagnosed with RA were enrolled in this study. Ultrasound examinations were performed by one inexperienced and two experienced sonographers. Interobserver variation was measured using a conventional semiquantitative image grading scale. Interobserver variation of the quantitative PD (QPD) index (the summation of the colored pixels in a region of interest) was also assessed. The agreement was higher between the two experienced sonographers (kappa value of 0.8) than between experienced and inexperienced sonographers (kappa value, 0.6-0.7) in the semiquantitative image grading scale. Results suggest that the difference in the assessment on the image grading scale was due more to the difference in the acquisition of the images than to variations in the grading criteria between sonographers. An excellent relationship was noted between the image grading scale and the QPD index for Doppler signal with a Spearman's coefficient of rank correlation of 0.83 (P < 0.0001). Interobserver discrepancies in the image grading and QPD index methods were due more to the difference in the acquisition of the image than to the grading criteria used. The QPD index seems to be as reliable as the image grading scale with reasonable interobserver agreement between experienced sonographers.
  • Fumi Kato, Yukihiko Sato, Noriaki Yuasa, Daisuke Abo, Yusuke Sakuhara, Noriko Oyama, Rikiya Onimaru, Hidefumi Aoyama, Hiroki Shirato, Satoshi Terae
    JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 20 5 587 - 592 2009年05月 [査読有り][通常論文]
     
    PURPOSE: To evaluate the feasibility of shortening the bed rest time from 4 hours to 2 hours after transfemoral noncardiac angiography with a 4-F sheath (outer diameter, 1.93 mm), a 5-17 sheath (outer diameter, 2.27 mm), and a 4-F catheter. MATERIALS AND METHODS: Patients were randomized into two groups, receiving either 2 or 4 hours of bed rest after hemostasis by manual compression of the puncture site. The authors evaluated the frequency of bleeding complications. An interim analysis was performed wherein 40 patients were assigned to each group. After the analysis, a single-arm 2-hour bed rest trial was conducted in an additional 115 procedures. RESULTS: In the interim analysis, three of the 40 patients in the 4-hour group and none of the 40 patients in the 2-hour group developed minor bleeding within 2 hours after manual compression (P =.24). After 2 hours of bed rest, no bleeding complication was observed in either group. In the single-arm 2-hour bed rest trial, minor bleeding developed in one of the 115 procedures (0.8%). Through the study, minor bleeding occurred in four of the 195 total procedures (2%), and no major complications developed. The occurrence of a bleeding complication was significantly higher in patients with platelet counts of less than 100 x 109/L than in the other patients (4/67 vs 0/128, P =.01). CONCLUSIONS: Two hours of bed rest is feasible for patients undergoing transfemoral noncardiac angiography by using a 4-5-F sheath and/or a 4-F catheter, especially those with a normal platelet count.
  • Noriyuki Miyamoto, Kazuhide Hiramatsu, Kazuhiko Tsuchiya, Yukihiko Sato, Satoshi Terae, Hiroki Shirato
    Japanese Journal of Radiology 27 4 185 - 193 2009年05月 [査読有り][通常論文]
     
    Purpose: The purpose of this study was to assess the usefulness of contrast harmonic sonography with a newly developed sonographic contrast agent as a means of guidance for percutaneous radiofrequency (RF) ablation of hepatocellular carcinoma (HCC). Materials and methods: A total of 52 consecutive HCC lesions in 42 patients with HCC who underwent percutaneous RF ablation were included in this study. Altogether, 40 lesions in 35 patients were untreated HCC, and 12 lesions in 7 patients were local tumor progression of an HCC that had already been treated by other methods. We investigated tumors by Kupffer-phase imaging and vascular-phase imaging after reinjection. We performed RF ablation guided by Sonazoid-enhanced sonography using Kupffer-phase imaging and vascular-phase imaging after reinjection. Results: Conventional sonography identified 30 (57%) of 52 HCCs, whereas Sonazoid-enhanced sonography detected 50 (96%) of 52 HCCs (P < 0.01, McNemar's χ2 test). Complete ablation was achieved at a single session in 48 of 50 tumors. Conclusion: Sonazoid-enhanced sonography is a useful technique for guiding RF ablation of HCCs, even when treating local progression of a previously treated HCC. © 2009 Japan Radiological Society.
  • Ataru Sazawa, Nobuo Shinohara, Toru Harabayashi, Takashige Abe, Hiroki Shirato, Katsuya Nonomura
    INTERNATIONAL JOURNAL OF UROLOGY 16 4 410 - 412 2009年04月 [査読有り][通常論文]
     
    Patients with an adrenal tumor usually undergo laparoscopic adrenalectomy. However, an alternative treatment approach might be needed in some patients with adrenal metastasis from malignancy or with severe complications. Real-time tracking radiotherapy (RTRT) with a gold marker is considered one of the feasible treatment options because this system can reduce the adverse effects of organ movement such as that in the adrenal gland or kidney. A 64-year-old patient with hormone refractory prostate cancer presented with clinically isolated adrenal metastasis. The patient underwent RTRT treatment with an implanted gold marker in the right adrenal metastasis. There were no adverse events. Although disease progression with elevated prostate-specific antigen occurred 8 months later, there was no further growth of the right adrenal metastasis before he died. From our experience, RTRT with an implanted gold marker might be feasible for the treatment of isolated adrenal metastasis from malignancies including prostate cancer.
  • Tohru Shiga, Yuichi Morimoto, Naoki Kubo, Norio Katoh, Chietsugu Katoh, Wataru Takeuchi, Reiko Usui, Kenji Hirata, Shinichi Kojima, Kikuo Umegaki, Hiroki Shirato, Nagara Tamaki
    JOURNAL OF NUCLEAR MEDICINE 50 1 148 - 155 2009年01月 [査読有り][通常論文]
     
    An autoradiography method revealed intratumoral inhomogeneity in various solid tumors. It is becoming increasingly important to estimate intratumoral inhomogeneity. However, with low spatial resolution and high scatter noise, it is difficult to detect intratumoral inhomogeneity in clinical settings. We developed a new PET system with CdTe semiconductor detectors to provide images with high spatial resolution and low scatter noise. Both phantom images and patients' images were analyzed to evaluate intratumoral inhomogeneity. Methods: This study was performed with a cold spot phantom that had 6-mm-diameter cold sphenoid defects, a dual-cylinder phantom with an adjusted concentration of 1:2, and an "H"-shaped hot phantom. These were surrounded with water. Phantom images and (18)F-FDG PET images of patients with nasopharyngeal cancer were compared with conventional bismuth germanate PET images. Profile curves for the phantoms were measured as peak-to-valley ratios to define contrast. Intratumoral inhomogeneity and tumor edge sharpness were evaluated on the images of the patients. Results: The contrast obtained with the semiconductor PET scanner (1.53) was 28% higher than that obtained with the conventional scanner (1.20) for the 6-mm-diameter cold sphenoid phantom. The contrast obtained with the semiconductor PET scanner (1.43) was 27% higher than that obtained with the conventional scanner (1.13) for the dual-cylinder phantom. Similarly, the 2-mm cold region between 1-mm hot rods was identified only by the new PET scanner and not by the conventional scanner. The new PET scanner identified intratumoral inhomogeneity in more detail than the conventional scanner in 6 of 10 patients. The tumor edge was sharper on the images obtained with the new PET scanner than on those obtained with the conventional scanner. Conclusion: These phantom and clinical studies suggested that this new PET scanner has the potential for better identification of intratumoral inhomogeneity, probably because of its high spatial resolution and low scatter noise.
  • Takeshi Nishioka, Yusuke Miyai, Hisashi Haga, Kazushige Kawabata, Hiroki Shirato, Akihiro Homma, Kenichiro Shibata, Motoaki Yasuda
    CELL STRUCTURE AND FUNCTION 34 1 17 - 22 2009年 [査読有り][通常論文]
     
    Purpose: To find a new molecule that affects p53-dependent radiosensitivity.Methods and Materials: A mouse sarcoma cell line, QRsP(p53+/+), was used. From this cell line, we established a radiosensitive clone and a radioresistant one. Colony assay, p53 gene transfer, a luciferase assay for p53 and p21, animal transplantation experiment, and DNA array analyses were performed.Results: Microarray showed marked reduction of a transcription factor, ATF5, both in vitro and in vivo for the radiosensitive clone. Interestingly, flow cytometric analysis demonstrated marked apoptosis for the radiosensitive clone by p53 cloned adenovirus infection. Luciferase reporter assay revealed that ATF5 suppressed the transactivational activity of p53 and p63. By ATF5 gene transfer, the radiosensitive clone regained resistance to both ionizing-radiation and Ad-p53 infection-induced cell death. Surprisingly, time-lapse cell migration observation revealed greater cell motility for ATF5-transfected radiosensitive clone.Conclusions: It seems likely that ATF5 is a potent repressor of p53 and elevated expression of ATF5 in a tumor may relate to enhanced malignant phenotypes, such as radioresistance or greater cell motility.
  • Kaori Tsutsumi, Masumi Tsuda, Natsuka Yazawa, Hirotaka Nakamura, Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Rie Yamazaki, Hiroki Shirato, Hideaki Kawaguchi, Takeshi Nishioka, Yusuke Ohba
    CELL STRUCTURE AND FUNCTION 34 2 89 - 96 2009年 [査読有り][通常論文]
     
    Radiotherapy is an important noninvasive treatment for many types of cancer. However, it has been reported that the proliferative, invasive, and metastatic capacities of tumor cells can be increased in the repopulated tumors that survive radiotherapy. We have previously established a radiation-surviving cell model for the human non-small cell lung cancer cell line H1299 by harvesting relic cells 14 days after irradiation (IR cells). Here, we report that cell invasion, cell migration, and cell adhesion are enhanced in these surviving cancer cells. The mRNA expression levels of matrix metalloproteinases (MMPs), including mmp1, mmp2, and mmp9, were upregulated in IR cells compared with parental cells. A gelatin zymogram, wound healing assay, and invasion assay showed increased MMP activity, cell motility, and invasiveness in IR cells, respectively. Moreover, IR cells adhered more tightly to collagen-coated dishes than parental cells. Consistently, paxillin, phosphorylated FAK, integrin beta 1, and vinculin were strongly localized at focal adhesions in IR cells, as visualized by immunofluorescence. In this report, we identify molecules responsible for the malignant properties of tumor cells that survive irradiation. These molecules may be important therapeutic targets for the control of repopulated tumors after radiotherapy.
  • Keishiro Suzuki, Yukinori Hirasawa, Yuji Yaegashi, Hideki Miyamoto, Hiroki Shirato
    JOURNAL OF TELEMEDICINE AND TELECARE 15 8 414 - 418 2009年 [査読有り][通常論文]
     
    We developed a web-based, remote radiation treatment planning system which allowed staff at an affiliated hospital to obtain support from a fully staffed central institution. Network security was based on a firewall and a virtual private network (VPN). Client computers were installed at a cancer centre, at a university hospital and at a staff home. We remotely operated the treatment planning computer using the Remote Desktop function built in to the Windows operating system. Except for the initial setup of the VPN router, no special knowledge was needed to operate the remote radiation treatment planning system. There was a time lag that seemed to depend on the volume of data traffic on the Internet, but it did not affect smooth operation. The initial cost and running cost of the system were reasonable.
  • Huanmei Wu, Qingya Zhao, Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang
    PHYSICS IN MEDICINE AND BIOLOGY 53 24 7137 - 7150 2008年12月 [査読有り][通常論文]
     
    Precise localization of mobile tumor positions in real time is critical to the success of gated radiotherapy. Tumor positions are usually derived from either internal or external surrogates. Fluoroscopic gating based on internal surrogates, such as implanted fiducial markers, is accurate however requiring a large amount of imaging dose. Gating based on external surrogates, such as patient abdominal surface motion, is non-invasive however less accurate due to the uncertainty in the correlation between tumor location and external surrogates. To address these complications, we propose to investigate an approach based on hybrid gating with dynamic internal/external correlation updates. In this approach, the external signal is acquired at high frequency (such as 30 Hz) while the internal signal is sparsely acquired (such as 0.5 Hz or less). The internal signal is used to validate and update the internal/external correlation during treatment. Tumor positions are derived from the external signal based on the newly updated correlation. Two dynamic correlation updating algorithms are introduced. One is based on the motion amplitude and the other is based on the motion phase. Nine patients with synchronized internal/external motion signals are simulated retrospectively to evaluate the effectiveness of hybrid gating. The influences of different clinical conditions on hybrid gating, such as the size of gating windows, the optimal timing for internal signal acquisition and the acquisition frequency are investigated. The results demonstrate that dynamically updating the internal/external correlation in or around the gating window will reduce false positive with relatively diminished treatment efficiency. This improvement will benefit patients with mobile tumors, especially greater for early stage lung cancers, for which the tumors are less attached or freely floating in the lung.
  • Yasushi Furuta, Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Keishiro Suzuki, Takeshi Nishioka, Hiroki Shirato, Satoshi Fukuda
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 13 6 521 - 527 2008年12月 [査読有り][通常論文]
     
    Surgical complication rates of total laryngectomy vary according to the preoperative treatments performed and patient factors. Wound complications after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were analyzed. Eighty-six patients who had undergone total laryngectomy for laryngeal cancer at Hokkaido University Hospital, Japan, between 1990 and 2006 were divided into three groups according to preoperative treatments received: group I (n = 35) without radiotherapy (RT) or CCRT, group II (n = 17) RT alone, and group III (n = 34) low-dose CCRT. Salvage total laryngectomy was performed as a consequence of residual or recurrent disease after completion of the treatments. Wound complications such as pharyngocutaneous fistulas, bleeding, infections, and skin necrosis were retrospectively analyzed in each group. A considerable (not statistically significant) difference in the incidence of major wound complications was observed between groups I and III (11.4% vs 29.4%, P = 0.078), but not between groups II and III. In stage III/IV patients, a significant increase in the incidence of wound complications was observed in group III compared to group I. Pharyngocutaneous fistulas were the most common complication, occurring in 8/34 (23.5%) of the group III patients. Additional pharyngeal reconstruction surgery was performed in 5 of the 8 (62.5%) group III patients with pha ryngocutaneous fistulas, while no such patients (0/3) in group I required reconstruction surgery. There was an increased risk of wound complications in patients undergoing salvage laryngectomy following CCRT. Patients who developed pharyngocutaneous fistulas after CCRT tended to require surgical reintervention for repair. These findings should be taken into account before the initiation of CCRT and salvage surgery.
  • Yuuta Kamoshima, Yutaka Sawamura, Jun Ikeda, Hiroki Shirato, Hidefumi Aoyama
    JOURNAL OF NEURO-ONCOLOGY 90 2 205 - 211 2008年11月 [査読有り][通常論文]
     
    Central nervous system (CNS) germinoma is a curable tumor and its recurrence rate after initial therapy may be approximately 10% or higher. This study elucidates the time-course of recurrence and results of salvage therapy. Twenty-five patients with recurrent germinoma treated at Hokkaido University Hospital were retrospectively reviewed. The median age at initial treatment was 12 years (range: 8-37). All patients had been tumor-free for at least 6 months after the initial treatment. The median follow-up period was 134 months (range: 44-338). The median age at first recurrence was 18 years and the median time to the first recurrence was 50 months. Among the patients, 9 (36%) had the first recurrence at 60 months or later. The latest recurrence in a patient occurred 230 months after the initial treatment. The results of salvage therapy were estimated in all 25 patients. Seventeen patients (68%) were salvaged and were tumor-free at the final observation. The remaining 8 patients died of disease. At first recurrence, 11 patients were treated using radiation therapy with or without surgery and 7 out of the 11 patients died due to the recurrent tumor. On the other hand, 13 patients who received salvage chemotherapy and radiotherapy were tumor-free at the last follow-up. In conclusion, late recurrence is not a rare event in patients with CNS germinoma. To identify a true cure rate of this disease, a 10-year or longer observation period may be required. As a salvage therapy, platinum-based chemotherapy followed by wide-field low-dose radiation therapy appears to be effective.
  • Daisuke Abo, Satoshi Terae, Yuichiro Fukasawa, Hideyuki Seki, Yu Hasegawa, Yusuke Sakuhara, Tadashi Shimizu, Hiroki Shirato
    JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 32 6 890 - 892 2008年11月 [査読有り][通常論文]
     
    A splenic mass was found in an asymptomatic 76-year-old woman who had been treated with steroids for autoimmune hepatitis. The lesion was found to be hyperechoic on ultrasound examination, hypovascular on angiography, low attenuating on postcontrast computed tomography, isointense to splenic parenchyma on precontrast T1- and T2-weightcd images, and showed inhomogeneous enhancement on gadolinium-enhanced T1-weighted images. Splenic peliosis should be considered when diagnosing tumorlike conditions of the spleen because of its potential to cause splenic rupture.
  • Yusuke Sakuhara, Yoshihisa Kodama, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Tokuhiko Omatsu, Tamotsu Kamishika, Yuya Onodera, Satoshi Terae, Hiroki Shirato
    ABDOMINAL IMAGING 33 5 563 - 570 2008年09月 [査読有り][通常論文]
     
    Background: To evaluate the vascular supply of regions of the pancreas on computed tomography (CT) during arteriography with selective catheterization. Methods: Thirteen patients were included. In each patient we performed conventional arteriography followed by CT during arteriography of each of the arteries: the superior mesenteric artery (SMA), gastroduodenal artery (GDA), and splenic artery (SPA). The regions of the pancreas that were most enhanced on CT during arteriography were considered to be the areas receiving the greatest infusion of blood from the selected artery. Results: In all 13 patients, the uncinate process, the superior head, and the tail of the pancreas were predominantly supplied by the SMA, GDA, and SPA, respectively. The inferior head of the pancreas was predominantly supplied by the SMA in five patients, the GDA in nine patients, and both the SMA and GDA in one patient. The body of the pancreas was predominantly supplied by the SMA, GDA, and SPA in seven, two, and ten patients, respectively. Conclusions: The uncinate process predominantly infused by the SMA, the superior head by the GDA, and the tail by the SPA. The patterns of the vascular supply of the inferior head and the body vary from patient to patient.
  • Hiroaki Motegi, Satoshi Kuroda, Nobuaki Ishii, Hidefumi Aoyama, Satoshi Terae, Hiroki Shirato, Yoshinobu Iwasaki
    NEUROLOGIA MEDICO-CHIRURGICA 48 9 397 - 400 2008年09月 [査読有り][通常論文]
     
    A 47-year-old male underwent stereotactic radiosurgery (25 Gy) for a cerebral arteriovenous malformation located in the right caudate nucleus, using a linear accelerator. Complete obliteration of nidus was confirmed 20 months after radiosurgery. However, a hypointense mass on T-2-weighted magnetic resonance imaging developed in the area adjacent to the nidus after approximately 80 months. The mass gradually increased in size and induced severe perifocal edema over 2 years. The mass was successfully excised. Histological examination revealed that the mass consisted of dilated sinusoid vessels attached to the hematoma capsule, and the hematoma included clots in various stages of organization encapsulated by dense collagenous tissue. The histological diagnosis was cavernoma. De novo formation of cavernoma is well known to occur after radiation surgery for intracranial tumor, especially in pediatric patients, but is rare in adults. Based on the radiological and histological findings in the present case, the radiation-induced cavernoma underwent repeated bleedings resulting in chronic encapsulated expanding hematoma.
  • Koichi Yasuda, Hiroshi Taguchi, Yutaka Sawamura, Jun Ikeda, Hidefumi Aoyama, Kenji Fujieda, Nobuaki Ishii, Masaaki Kashiwamura, Yoshinobu Iwasaki, Hiroki Shirato
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 38 7 486 - 492 2008年07月 [査読有り][通常論文]
     
    Objective: The current study was conducted to evaluate the effects of low-dose craniospinal irradiation (CSI) combined with chemotherapy on non-metastatic embryonal tumors in the central nervous system (CNS), including medulloblastoma and supra-tentorial primitive neuroectodermal tumors (ST-PNET). Methods: All patients were treated according to the following protocol. After surgery, the patients <= 5 years old received 18 Gy and the patients > 5 years old received 24 Gy CSI. The dose to the primary tumor bed was 39.6-54 Gy. Chemotherapy consisted of ifosfamide, cisplatin and etoposide (ICE chemotherapy). Results: Sixteen patients aged 0.5-20.4 (median 6.1) years were enrolled and followed for 11-165 (median 112) months. Both 5-year actuarial overall survival (OAS) and progression-free survival (PFS) were 81% (95% confidence interval (CI): 62-100%) for the 16 patients. Both 5-year OAS and PFS were 82% (CI: 59-100%) for the patients with medulloblastoma and 80% (CI: 45-100%) for the patients with ST-PNET. Both 5-year OAS and PFS were 75% for the eight patients <= 5 years old and 88% for the eight patients > 5 years old. Both 5-year OAS and PFS were 100% for six average-risk patients (3 years or older, total resection and posterior fossa) and 70% for 10 poor-risk patients (others). The median total intellectual quotient at the last follow-up was 85 (ranging from 48 to 103) in 12 patients who were followed for 3-145 (median 49) months. Eight patients received hormone replacement therapy. Conclusion: Low-dose CSI and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the CNS.
  • Norio Katoh, Rikiya Onimaru, Yusuke Sakuhara, Daisuke Abo, Shinichi Shimizu, Hiroshi Taguchi, Yoshiaki Watanabe, Nobuo Shinohara, Masayori Ishikawa, Hiroki Shirato
    RADIOTHERAPY AND ONCOLOGY 87 3 418 - 424 2008年06月 [査読有り][通常論文]
     
    Purpose: To investigate the three-dimensional movement of internal fiducial markers near the adrenal tumors using a real-time tumor-tracking radiotherapy (RTRT) system and to examine the feasibility of high-dose hypofractionated radiotherapy for the adrenal tumors. Materials and methods: The subjects considered in this study were 10 markers of the 9 patients treated with RTRT. A total of 72 days in the prone position and 61 treatment days in the supine position for nine of the 10 markers were analyzed. All but one patient were prescribed 48 Gy in eight fractions at the isocenter. Results: The average absolute amplitude of the marker movement in the prone position was 6.1 +/- 4.4 mm (range 2.3-14.4), 11.1 +/- 7.1 mm (3.5-25.2), and 7.0 +/- 3.5 mm (3.9-12.5) in the left-right (LR), craniocaudal (CC), and anterior-posterior (AP) directions, respectively. The average absolute amplitude in the supine position was 3.4 +/- 2.9 mm (0.6-9.1), 9.9 +/- 9.8 mm (1.1-27.1), and 5.4 +/- 5.2 mm (1.7-26.6) in the LR, CC, and AP directions, respectively. Of the eight markers, which were examined in both the prone and supine positions, there was no significant difference in the average absolute amplitude between the two positions. No symptomatic adverse effects were observed within the median follow-up period of 16 months (range 5-21 months). The actuarial freedom-from-local-progression rate was 100% at 12 months. Conclusions: Three-dimensional motion of a fiducial marker near the adrenal tumors was detected. Hypofractionated RTRT for adrenal tumors was feasible for patients with metastatic tumors. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
  • Shogo Endo, Kazutoshi Hida, Shunsuke Yano, Masaki Ito, Shigeru Yamaguchi, Daina Kashiwazaki, Rumiko Kinoshita, Hiroki Shirato, Yoshinobu Iwasaki
    NEUROLOGICAL SURGERY 36 4 345 - 349 2008年04月 [査読有り][通常論文]
     
    Objectives Intramedurally spinal cord metastasis (ISCM) tends to be seen in the end period of the malignant tumor, so it is important to choose a therapeutic method regarding the QOL (quality of life) of the patient. In this study, we reported three cases of ISCM treated by radiation therapy alone, and demonstrated the utility of this therapeutic procedure. Patients and Methods From 2005 to 2006, 3 cases of ISCM underwent radiotherapy in our institution. The mean age of the patients was 64.0 years old, and all patients were men, having lung carcinoma as their primary lesions. The lesions were located at the cervical cord in one case and the conus medullaris in the other two cases. They were treated by radiotherapy at the department of radiology in our institute. Results The tumor size and intramedullary high signal area on MR images after the radiotherapy were reduced in all patients. During the clinical course, neurological symptoms were improved in two patients, and progression of the symptoms was stopped in one patient. All of the patients obtained a better ADL due to the radiotherapy. Conclusions Radiotherapy has an advantage over surgical treatment in that it involves less invasion. The treatment brought improvements of clinical symptoms and radiological findings in the patients with ISCM. So, radiotherapy could be used as one of the major treatments for patients with ISCM who desire a better QOL after treatment.
  • Rumiko Kinoshita, Shinichi Shimizu, Hiroshi Taguchi, Norio Katoh, Masaharu Fujino, Rikiya Onimaru, Hidefumi Aoyama, Fumi Katoh, Tokuhiko Omatsu, Masayori Ishikawa, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 3 931 - 934 2008年03月 [査読有り][通常論文]
     
    Purpose: To evaluate the three-dimensional intrafraction motion of the breast during tangential breast irradiation using a real-time tracking radiotherapy (RT) system with a high-sampling frequency. Methods and Materials: A total of 17 patients with breast cancer who had received breast conservation RT were included in this study. A 2.0-mm gold marker was placed on the skin near the nipple of the breast for RT. A fluoroscopic real-time tumor-tracking RT system was used to monitor the marker. The range of motion of each patient was calculated in three directions. Results: The mean standard deviation of the range of respiratory motion was 1.0 +/- 0.6 mm (median, 0.9; 95% confidence interval [CI] of the marker position, 0.4-2.6), 1.3 +/- 0.5 mm (median, 1.1; 95 % CI, 0.5-2.5), and 2.6 +/- 1.4 (median, 2.3; 95 % CI, 1.0-6.9) for the right-left, craniocaudal, and anteroposterior direction, respectively. No correlation was found between the range of motion and the body mass index or respiratory function. The mean +/- standard deviation of the absolute value of the baseline shift in the right-left, craniocaudal, and anteroposterior direction was 0.2 +/- 0.2 mm (range, 0.0-0.8 mm), 0.3 +/- 0.2 mm (range, 0.0-0.7 mm), and 0.8 +/- 0.7 mm (range, 0.1-1.8 mm), respectively. Conclusion: Both the range of motion and the baseline shift were within a few millimeters in each direction. As long as the conventional wedge-pair technique and the proper immobilization are used, the intrafraction three-dimensional change in the breast surface did not much influence the dose distribution. (C) 2008 Elsevier Inc.
  • Mikado Imura, Koichi Yamazaki, Kanako C. Kubota, Tomoo Itoh, Rikiya Onimaru, Yasushi Cho, Yasuhiro Hida, Kichizo Kaga, Yuya Onodera, Shigeaki Ogura, Hirotoshi Dosaka-Akita, Hiroki Shirato, Masaharu Nishimura
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 2 382 - 384 2008年02月 [査読有り][通常論文]
     
    Purpose: Internal fiducial gold markers, safely inserted with bronchoscopy, have been used in real-time tumor-tracking radiotherapy for lung cancer. We investigated the histopathologic findings at several points after the insertion of the gold markers. Methods and Materials: Sixteen gold markers were inserted for preoperative marking in 7 patients who subsequently underwent partial resection of tumors by video-assisted thoracoscopic surgery within 7 days. Results: Fibrotic changes and hyperplasia of type 2 pneumocytes around the markers were seen 5 or 7 days after insertion, and fibrin exudation without fibrosis was detected 1 or 2 days after insertion. Conclusions: Because fibroblastic changes start approximately 5 days after gold marker insertion, real-time tumor-tracking radiotherapy should be started >5 days after gold marker insertion. (C) 2008 Elsevier Inc.
  • Rikiya Onimaru, Masaharu Fujino, Koichi Yamazaki, Yuya Onodera, Hiroshi Taguchi, Norio Katoh, Fumihiro Hommura, Satoshi Oizumi, Masaharu Nishimura, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 2 374 - 381 2008年02月 [査読有り][通常論文]
     
    Purpose: To investigate the clinical outcomes of patients with pathologically proven, peripherally located, Stage I non-small-cell lung cancer who had undergone stereotactic body radiotherapy using real-time tumor tracking radiotherapy during the developmental period. Methods and Materials: A total of 41 patients (25 with Stage T1 and 16 with Stage T2) were admitted to the study between February 2000 and June 2005. A 5-mm planning target volume margin was added to the clinical target volume determined with computed tomography at the end of the expiratory phase. The gating window ranged from 2 to 3 rum. The dose fractionation schedule was 40 or 48 Gy in four fractions within 1 week. The dose was prescribed at the center of the planning target volume, giving more than an 80% dose at the planning target volume periphery. Results: For 28 patients treated with 48 Gy in four fractions, the overall actuarial survival rate at 3 years was 82% for those with Stage IA and 32% for those with Stage IB. For patients treated with 40 Gy in four fractions within 1 week, the overall actuarial survival rate at 3 years was 50% for those with Stage IA and 0% for those with Stage IB. A significant difference was found in local control between those with Stage IB who received 40 Gy vs. 48 Gy (p = 0.0015) but not in those with Stage IA (p = 0.5811). No serious radiation morbidity was observed with either dose schedule. Conclusion: The results of our study have shown that 48 Gy in four fractions within 1 week is a safe and effective treatment for peripherally located, Stage IA non-small-cell lung cancer. A steep dose-response curve between 40 and 48 Gy using a daily dose of 12 Gy delivered within 1 week was identified for Stage IB non-small-cell lung cancer in stereotactic body radiotherapy using real-time tumor tracking radiotherapy. (C) 2008 Elsevier Inc.
  • Yusuke Sakuhara, Fumi Kato, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Satoshi Terae, Hiroki Shirato
    JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 19 2 267 - 271 2008年02月 [査読有り][通常論文]
     
    Kidney enlargement in autosomal-dominant polycystic kidney disease (ADPKD) may cause symptoms by compressing the alimentary tract, lungs, and heart. The clinical symptoms may be progressive, may markedly decrease quality of life, and may even be life-threatening. Although treatment of this disease is often difficult, transcatheter arterial embolization (TAE) with metallic coils has been reported as a renal contraction therapy that is less invasive than surgery. The present report describes a case of ADPKD successfully treated by TAE with absolute ethanol after a previous TAE procedure with metallic coils failed to contract the affected kidneys because of recanalization.
  • Seiko Nishioka, Takeshi Nishioka, Masaki Kawahara, Shigeru Tanaka, Tadao Hiromura, Kazuo Tomita, Hiroki Shirato
    RADIOTHERAPY AND ONCOLOGY 86 1 69 - 76 2008年01月 [査読有り][通常論文]
     
    Purpose: For optimal respiratory-gated radiotherapy, exhale fluctuation was assessed by monitoring internal fiducials in a synchronized internal/external marker detection system. Methods: Synchronized internal/external position data were collected during the entire course of treatments for 12 lung patients with 24 fiducials. Baseline was determined in the exhale phase during pre-treatment observation time, and a gating level of external waves was set in each treatment session in a simulation of respiratory-gated radiotherapy. Patients were treated under a real-time tumor-tracking (RTRT) system with an external (abdominal) respiratory motion detector. In the simulation, external gating windows were defined as those below the 30% amplitude level (i.e., imaginary beams would be triggered when part of the respiratory wave falls into this window). Exhale fluctuation (EF) was defined as the phenomenon in which the lowest point of the external wave crossed downward past the predetermined baseline. Gating efficiency (GE) was defined as the ratio between the amount of gate-ON time and the total treatment time. Results: EF occurred in 18.4% of total measurements. EF varied depending on the patient, fiducial sites, and treatment session. The mean incidence of EF for each patient varied from 2.9% to 37.5% (18.4 +/- 9.9). The EF magnitude was 0.2-12.2 mm in the left-right direction, 0.7-12.7 mm in the cranio-caudal direction, and 0.4-9.7 mm in the anterior-posterior direction. Total fiducial movement was 0.5-28.7 mm. GE was 36.1-69.2% (55.4 +/- 11.0). EF magnitude correlated with total fiducial movement. Conclusion: This study showed that EF is not a rare phenomenon and needs to be taken into consideration for individualized precise 4D radiotherapy. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Huanmei Wu, George Sandison, Li Zhao, Qingya Zhao, Hiroki Shirato, Steve Jiang
    AUSTRALASIAN PHYSICAL & ENGINEERING SCIENCES IN MEDICINE 30 4 341 - 344 2007年12月 [査読有り][通常論文]
     
    Characterizing respiratory-induced tumour motion is an important step in the effective image-guided radiation treatment of moving tumours, especially for tumours in the lung and lower abdomen. This study characterized turnout motion based on a piecewise linear model representing tumour motion at defined stages of the breathing cycle. Lung tumour locations were categorized based on broncho-pulmonary segments. Association rules between tumour motion characteristics and their locations in the lung were discovered and parameterized through statistical analysis. Results show there is a correlation between tumour motion characteristics and turnout location in the lungs. Generally, tumours with small motion (amplitude < 10mm) are observed most frequently in the apex region of lung or when attached to a fixed structure, Such as the chest wall or aorta. Tumours with relatively large motion (amplitude > 20mm) are located close to the diaphragm or mid-level periphery of the lungs close to the chest wall.
  • Hiroshi Yokouchi, Kenji Chamoto, Daiko Wakita, Koichi Yamazaki, Hiroki Shirato, Tsuguhide Takeshima, Hirotoshi Dosaka-Akita, Masaharu Nishimura, Zhang Yue, Hidemitsu Kitamura, Takashi Nishimura
    CLINICAL & EXPERIMENTAL METASTASIS 24 7 533 - 540 2007年11月 [査読有り][通常論文]
     
    Mice bearing established Lewis lung carcinoma (LLC) expressing model tumor antigen, ovalbumin (OVA) (LLC-OVA) marginally responded to local radiotherapy, but none of the mice was cured. In contrast, treatment of the tumor-bearing mice with intratumoral injection of tumor-specific T helper type 1 (Th1) cells and tumor antigen (OVA) after radiotherapy dramatically prolonged the survival days and induced complete cure of the mice at high frequency (80%). Radiation therapy combined with Th1 cells or OVA alone showed no significant therapeutic activity against LLC-OVA. Such a strong therapeutic activity was not induced by intratumoral injection of Th1 cells plus OVA. Compared with other treatment, radiation therapy combined with Th1 cells and OVA was superior to induce the generation of OVA/H-2(b) tetramer (+) tumor-specific cytotoxic T lymphocyte (CTL) with a strong cytotoxicity against LLC-OVA in draining lymph node (DLN). Moreover, the combined therapy is demonstrated to inhibit the growth of tumor mass, which grew at contralateral side. These results indicated that radiotherapy combined with Th1 cell/vaccine therapy induced a systemic antitumor immunity. These findings suggested that combination therapy with radiotherapy and Th1 cell/vaccine therapy may become a practical strategy for cancer treatment.
  • Yusuke Sakuhara, Tadashi Shimizu, Daisuke Abo, Yu Hasegawa, Fumi Kato, Yoshihisa Kodama, Hiroki Shirato
    CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 30 6 1201 - 1205 2007年11月 [査読有り][通常論文]
     
    Purpose During radiofrequency ablation (RFA), there is a risk that the multitined expandable electrode will come into contact with one of the surgical staples used to treat local recurrence after surgical operations. Our objective was to evaluate whether a surgical staple would influence the RFA of egg white using a multitined expandable electrode. Methods Multitined expandable electrodes, LeVeen needles (expandable diameter 3.0 cm), were sunk into an egg white bath with (a) no surgical staple, (b) a surgical staple touching one of the tines, or (c) a surgical staple touching two of the tines simultaneously. By connecting the LeVeen needle and copper plate at the bottom of the bath, RFA was then performed on the egg whites as a substitute for human tissue. Ten egg white baths were ablated under each of conditions (a), (b), and (c), for a total of 30 sets of coagulated egg white. Results There was no significant difference in the time from the power-on to the roll-off (i.e., the completion and shutting off of the electric circuit) or in the maximum diameter of the thermal lesion between conditions (a) and (b) or (a) and (c). However, the minimum diameter of the thermal lesion was significantly smaller in (c) compared with (a) (p < 0.01). Conclusions Surgical staples have the capacity to interfere with the electromagnetic field and decrease the minimum diameter of the thermal lesion in the event that a staple touches two of the tines of a multitined expandable electrode during RFA. Although the difference might be small enough to be neglected under many clinical circumstances, we recommend that, if possible, the tines not be expanded near metallic material.
  • Qing Ren, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco
    PHYSICS IN MEDICINE AND BIOLOGY 52 22 6651 - 6661 2007年11月 [査読有り][通常論文]
     
    One potential application of image-guided radiotherapy is to track the target motion in real time, then deliver adaptive treatment to a dynamic target by dMLC tracking or respiratory gating. However, the existence of a finite time delay (or a system latency) between the image acquisition and the response of the treatment system to a change in tumour position implies that some kind of predictive ability should be included in the real-time dynamic target treatment. If diagnostic x-ray imaging is used for the tracking, the dose given over a whole image-guided radiotherapy course can be significant. Therefore, the x-ray beam used for motion tracking should be triggered at a relatively slow pulse frequency, and an interpolation between predictions can be used to provide a fast tracking rate. This study evaluates the performance of an autoregressive- moving average (ARMA) model based prediction algorithm for reducing tumour localization error due to system latency and slow imaging rate. For this study, we use 3D motion data from ten lung tumour cases where the peak-to-peak motion is greater than 8 mm. Some strongly irregular traces with variation in amplitude and phase were included. To evaluate the prediction accuracy, the standard deviations between predicted and actual motion position are computed for three system latencies (0.1, 0.2 and 0.4 s) at several imaging rates (1.25-10 Hz), and compared against the situation of no prediction. The simulation results indicate that the implementation of the prediction algorithm in real-time target tracking can improve the localization precision for all latencies and imaging rates evaluated. From a common initial setting of model parameters, the predictor can quickly provide an accurate prediction of the position after collecting 20 initial data points. In this retrospective analysis, we calculate the standard deviation of the predicted position from the twentieth position data to the end of the session at 0.1 s interval. For both regular and irregular lung tumour motions, with prediction the range of average errors is 0.4-2.5mm in the SI direction from shorter to longer latency, corresponding to a range of 0.8-4.3 mm without prediction; for the AP direction a range of 0.3-1.6 mm is obtained with prediction, corresponding to a range of 0.6-3.0 mm without prediction. For 0.2 s and 0.4 s system latency, with prediction the localization based on a relatively slowimaging rate (2.5 Hz) can achieve a better or similar precision compared with no prediction but on a fast imaging rate (10 Hz). This means that precise localization can be realized at a slow imaging rate. This is important for the application of kV x-ray imaging systems and EPID-based systems in image-guided radiotherapy. In conclusion, the adaptive predictor can successfully predict irregular respiratory motion, and the adaptive prediction of respiration motion can effectively improve the delivery precision of real-time motion compensation radiotherapy.
  • Hiroshi Taguchi, Yusuke Sakuhara, Shuhei Hige, Kei Kitamura, Yasuhiro Osaka, Daisuke Abo, Daichi Uchida, Akihiro Sawada, Toshiya Kamiyama, Tadashi Shimizu, Hiroki Shirato, Kazuo Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 69 2 376 - 380 2007年10月 [査読有り][通常論文]
     
    Purpose: To assess the clinical outcome of intercepting radiotherapy, in which radiotherapy is delivered only when a tumor in motion enters a target area, using a real-time tumor-tracking radiotherapy (RTRT) system for patients with hepatocellular carcinoma who were untreatable with other modalities because the tumors were adjacent to crucial organs or located too deep beneath the skin surface. Methods and Materials: Eighteen tumors, with a mean diameter of 36 mm, were studied in 15 patients. All tumors were treated on a hypofractionated schedule with a tight margin for setup and organ motion using a 2.0-mm fiducial marker in the liver and the RTRT system. The most commonly used dose of radiotherapy was 48 Gy in 8 fractions. Sixteen lesions were treated with a BED10 of 60 Gy or more (median, 76.8 Gy). Results: With a mean follow-up period of 20 months (range, 3-57 months), the overall survival rate was 39% at 2 years after RTRT. The 2-year local control rate was 83% for initial RTRT but was 92% after allowance for reirradiation using RTRT, with a Grade 3 transient gastric ulcer in 1 patient and Grade 3 transient increases of aspartate amino transaminase in 2 patients. Conclusions: Intercepting radiotherapy using RTRT provided effective focal high doses to liver tumors. Because the fiducial markers for RTRT need not be implanted into the tumor itself, RTRT can be applied to hepatocellular carcinoma in patients who are not candidates for other surgical or nonsurgical treatments. (c) 2007 Elsevier Inc.
  • Toshiya Kamiyama, Kazuaki Nakanishi, Hideki Yokoo, Munenori Tahara, Takahito Nakagawa, Hirofumi Kamachi, Hiroshi Taguchi, Hiroki Shirato, Michiaki Matsushita, Satoru Todo
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 12 5 363 - 368 2007年10月 [査読有り][通常論文]
     
    Background The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the main trunk or the first branch is very poor. Methods. Radiotherapy (RT) to PVTT was followed by hepatectomy within 2 weeks. The dose used was 30-36 Gy, in 10-12 fractions, for 15-20 days. The efficacy of preoperative RT to PVTT in the main trunk or first branch was evaluated by comparing results in patients who underwent hepatectomy (group R; n = 15) with preoperative RT and those without preoperative RT (group N; n = 28). Results. The 1-, 3-, and 5-year survival rates in group R were 86.2%, 43.5%, and 34.8%, respectively, while these values in group N were 39.0 %, 13.1 %, and 13.1 %, respectively. The survival curve of group R was significantly better than that of group N (P = 0.0359). In group R, five (83.3 %) of six patients whose tumor thrombus was completely necrosed (based on pathological examination) and whose follow-up period was over 2 years survived for more than 2 years. Female sex (P = 0.0066), multiple tumors (P = 0.0369), and absence of preoperative RT (P = 0.0359) were ranked as significant factors for a poor prognosis by univariate analysis. Multivariate analysis revealed absence of preoperative RT and female sex to be significant factors for a poor prognosis. Conclusion. Preoperative RT to PVTT in the main trunk or first branch improved the prognosis of patients with HCC with PVTT, and could be a promising new modality in the treatment of these patients.
  • Takeshi Nishioka, Motoaki Yasuda, Kaori Tsutsumi, Hisashi Haga, Hiroki Shirato
    Radiation Medicine - Medical Imaging and Radiation Oncology 25 8 430 - 431 2007年10月 [査読有り][通常論文]
  • Dan Ionascu, Steve B. Jiang, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco
    MEDICAL PHYSICS 34 10 3893 - 3903 2007年10月 [査読有り][通常論文]
     
    In gated radiation therapy procedures, the lung tumor position is used directly (by implanted radiopaque markers) or indirectly (by external surrogate methods) to decrease the volume of irradiated healthy tissue. Due to a risk of pneumothorax, many clinics do not implant fiducials, and the gated treatment is primarily based on a respiratory induced external signal. The external surrogate method relies upon the assumption that the internal tumor motion is well correlated with the external respiratory induced motion, and that this correlation is constant in time. Using a set of data that contains synchronous internal and external motion traces, we have developed a dynamic data analysis technique to study the internal-external correlation, and to quantitatively estimate its underlying time behavior. The work presented here quantifies the time dependent behavior of the correlation between external respiratory signals and lung implanted fiducial motion. The corresponding amplitude mismatch is also reported for the, lung patients studied. The information obtained can be used to improve the accuracy of tumor tracking. For the ten patients in this study, the SI internal-external motion is well correlated, with small time shifts and corresponding amplitude mismatches. Although the AP internal -external motion reveals larger time shifts than along the SI direction, the corresponding amplitude mismatches are below 5 mm. (C) 2007 American Association of Physicists in Medicine.
  • Martin J. Murphy, James Balter, Stephen Balter, Jose A. BenComo, Indra J. Das, Steve B. Jiang, C.-M. Ma, Gustavo H. Olivera, Raymond F. Rodebaugh, Kenneth J. Ruchala, Hiroki Shirato, Fang-Fang Yin
    MEDICAL PHYSICS 34 10 4041 - 4063 2007年10月 [査読有り][通常論文]
     
    Radiographic image guidance has emerged as the new paradigm for patient positioning, target localization, and external beam alignment in radiotherapy. Although widely varied in modality and method, all radiographic guidance techniques have one thing in common-they can give a significant radiation dose to the patient. As with all medical uses of ionizing radiation, the general view is that this exposure should be carefully managed. The philosophy for dose management adopted by the diagnostic imaging community is summarized by the acronym ALARA, i.e., as low as reasonably achievable. But unlike the general situation with diagnostic imaging and image-guided surgery, image-guided radiotherapy (IGRT) adds the imaging dose to an already high level of therapeutic radiation. There is furthermore an interplay between increased imaging and improved therapeutic dose conformity that suggests the possibility of optimizing rather than simply minimizing the imaging dose. For this reason, the management of imaging dose during radiotherapy is a different problem than its management during routine diagnostic or image-guided surgical procedures. The imaging dose received as part of a radiotherapy treatment has long been regarded as negligible and thus has been quantified in a fairly loose manner. On the other hand, radiation oncologists examine the therapy dose distribution in minute detail. The introduction of more intensive imaging procedures for IGRT now obligates the clinician to evaluate therapeutic and imaging doses in a more balanced manner. This task group is charged with addressing the issue of radiation dose delivered via image guidance techniques during radiotherapy. The group has developed this charge into three objectives: (1) Compile an overview of image-guidance techniques and their associated radiation dose levels, to provide the clinician using a particular set of image guidance techniques with enough data to estimate the total diagnostic dose for a specific treatment scenario, (2) identify ways to reduce the total imaging dose without sacrificing essential imaging information, and (3) recommend optimization strategies to trade off imaging dose with improvements in therapeutic dose delivery. The end goal is to enable the design of image guidance regimens that are as effective and efficient as possible. (C) 2007 American Association of Physicists in Medicine.
  • Huanmei Wu, Gregory C. Sharp, Qingya Zhao, Hiroki Shirato, Steve B. Jiang
    PHYSICS IN MEDICINE AND BIOLOGY 52 16 4761 - 4774 2007年08月 [査読有り][通常論文]
     
    Tumors, especially in the thorax and abdomen, are subject to respiratory motion, and understanding the structure of respiratory motion is a key component to the management and control of disease in these sites. We have applied statistical analysis and correlation discovery methods to analyze and mine tumor respiratory motion based on a finite state model of tumor motion. Aggregates ( such as minimum, maximum, average and mean), histograms, percentages, linear regression and multi-round statistical analysis have been explored. The results have been represented in various formats, including tables, graphs and text description. Different graphs, for example scatter plots, clustered column figures, 100% stacked column figures and box-whisker plots, have been applied to highlight different aspects of the results. The internal tumor motion from 42 lung tumors, 30 of which have motion larger than 5 mm, has been analyzed. Results for both inter-patient and intra-patient motion characteristics, such as duration and travel distance patterns, are reported. New knowledge of patient-specific tumor motion characteristics have been discovered, such as expected correlations between properties. The discovered tumor motion characteristics will be utilized in different aspects of image-guided radiation treatment, including treatment planning, online tumor motion prediction and real-time radiation dose delivery.
  • Hidefumi Aoyama, Masao Tago, Norio Kato, Tatsuya Toyoda, Masahiro Kenjyo, Saeko Hirota, Hiroki Shioura, Taisuke Inomata, Etsuo Kunieda, Kazushige Hayakawa, Keiichi Nakagawa, Gen Kobashi, Hiroki Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 68 5 1388 - 1395 2007年08月 [査読有り][通常論文]
     
    Purpose: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS). Methods and Materials: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental State Examination (MMSE). Of the 132 enrolled patients, MMSE scores were available for 110. Results: In the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and Karnofsky performance status. Of the 92 patients who underwent the follow-up MMSE, 39 had a baseline MMSE score of <= 27 (17 in the WBRT+SRS group and 22 in the SRS-alone group). Improvements of <= 3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (p = 0.85) were observed. Of the 82 patients with a baseline MMSE score of >= 27 or whose baseline MMSE score was >= 26 but had improved to = 27 after the initial brain treatment, the 12-,24-, and 36-month actuarial free rate of the 3-point drop in the MMSE was 76.1%, 68.5 %, and 14.7 % in the WBRT+SRS group and 59.3 %, 51.9 %, and 51.9 % in the SRS-alone group, respectively. The average duration until deterioration was 16.5 months in the WBRT+SRS group and 7.6 months in the SRS-alone group (p = 0.05). Conclusion: The results of the present study have revealed that, for most brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effects of WBRT on neurocognitive function might not be negligible. (C) 2007 Elsevier Inc.
  • Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, Niibe Y, Karasawa K, Hayakawa K, Takai Y, Kimura T, Takeda A, Ouchi A, Hareyama M, Kokubo M, Hara R, Itami J, Yamada K, Araki T
    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2 S94 - 100 7 Suppl 3 2007年07月 [査読有り][通常論文]
  • Yvette Seppenwoolde, Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Ben Heijmen
    MEDICAL PHYSICS 34 7 2774 - 2784 2007年07月 [査読有り][通常論文]
     
    The Synchrony (TM) Respiratory Tracking System (RTS) is a treatment option of the CyberKnife robotic treatment device to irradiate extra-cranial tumors that move due to respiration. Advantages of RTS are that patients can breath normally and that there is no loss of linac duty cycle such as with gated therapy. Tracking is based on a measured correspondence model (linear or polynomial) between internal tumor motion and external (chest/abdominal) marker motion. The radiation beam follows the tumor movement via the continuously measured external marker motion. To establish the correspondence model at the start of treatment, the 3D internal tumor position is determined at 15 discrete time points by automatic detection of implanted gold fiducials in two orthogonal x-ray images; simultaneously, the positions of the external markers are measured. During the treatment, the relationship between internal and external marker positions is continuously accounted for and is regularly checked and updated. Here we use computer simulations based on continuously and simultaneously recorded internal and external marker positions to investigate the effectiveness of tumor tracking by the RTS. The Cyberknife does not allow continuous acquisition of x-ray images to follow the moving internal markers (typical imaging frequency is once per minute). Therefore, for the simulations, we have used data for eight lung cancer patients treated with respiratory gating. All of these patients had simultaneous and continuous recordings of both internal tumor motion and external abdominal motion. The available continuous relationship between internal and external markers for these patients allowed investigation of the consequences of the lower acquisition frequency of the RTS. With the use of the RTS, simulated treatment errors due to breathing motion were reduced largely and consistently over treatment time for all studied patients. A considerable part of the maximum reduction in treatment error could already be reached with a simple linear model. In case of hysteresis, a polynomial model added some extra reduction. More frequent updating of the correspondence model resulted in slightly smaller errors only for the few recordings with a time trend that was fast, relative to the current x-ray update frequency. In general, the simulations suggest that the applied combined use of internal and external markers allow the robot to accurately follow tumor motion even in the case of irregularities in breathing patterns. (C) 2007 American Association of Physicists in Medicine.
  • Kenichi Obinata, Keiichi Ohmori, Hiroki Shirato, Motoyasu Nakamura
    Radiation Medicine - Medical Imaging and Radiation Oncology 25 4 181 - 186 2007年05月 [査読有り][通常論文]
     
    Radiotherapy of head and neck cancer has become more successful with the advances in treatment modalities and use of a multidisciplinary approach. Higher quality treatment and a team approach to radiotherapy have thus been required for head and neck cancer. This study presents the clinical experience of high-dose-rate (HDR) brachytherapy for head and neck cancer treated by a customized intraoral mold technique. Two patients are reported for whom we created dental prostheses as the radiation carriers for HDR brachytherapy of their head and neck cancers. HDR brachytherapy with the dental prostheses reported here was feasible and effective for eradicating the head and neck cancer. It has been demonstrated that HDR brachytherapy using a customized intraoral technique can be a treatment option for patients who are not candidates for surgery or external irradiation. It is strongly suggested that specialized dentists are needed who are familiar with not only the anatomy and function of the head and neck region but also radiotherapy. Dental radiologists should take responsibility for constructing irradiation prostheses. If they do, they have the potential to improve the quality of life of patients who undergo radiotherapy for head and neck cancer. © 2007 Japan Radiological Society.
  • Hiroki Shirato, Shinichi Shimizu, Kei Kitamura, Rikiya Onimaru
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 12 1 8 - 16 2007年02月 [査読有り][通常論文]
     
    External radiotherapy using imaging technology for patient setup is often called image-guided radiotherapy (IGRT). The most important problem to solve in IGRT is organ motion. Four-dimensional radiotherapy (4DRT), in which the accuracy of localization is improved - not only in space but also in time - in comparison to 3DRT, is required in IGRT. Real-time tumor-tracking radiotherapy (RTRT) has been shown to be feasible for performing 4DRT with the aid of a fiducial marker near the tumor. Lung, liver, prostate, spinal/paraspinal, gynecological, head and neck, esophagus, and pancreas tumors are now ready for dose escalation studies using RTRT.
  • Takeshi Nishioka, Akihiro Homma, Yasushi Furuta, Hidefumi Aoyama, Fumiyuki Suzuki, Keiichi Ohmori, Takeshi Asano, Daisuke Yoshida, Hiroki Shirato, Satoshi Fukuda
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 36 12 822 - 826 2006年12月 [査読有り][通常論文]
     
    Objective: This study sought to evaluate the efficacy and safety of a novel treatment regimen, intra-arterial cisplatin infusion plus external/high-dose-rate radiotherapy. Methods: Superselective intra-arterial infusion of cisplatin (100-120 mg) was performed concomitantly with external radiotherapy in four patients with locally advanced carcinoma of the tongue. A high-dose-rate brachytherapy boost was performed after combination therapy in all patients. Brachytherapy was performed after external radiotherapy, and the treatment schedule was twice daily, with a fraction of 600 cGy up to a total of 30-48 Gy. Results: All patients completed the therapy as scheduled. There were no vascular or neurological complications. Grade III acute radiation mucositis developed in all patients but this did not necessitate a treatment break. With a mean follow-up period of 35 months, loco-regional control was obtained for all patients. Conclusions: The combination of weekly administration of intra-arterial cisplatin plus external/high-dose-rate radiotherapy seems effective for advanced carcinoma of the tongue.
  • Akihiro Homma, Yasushi Furuta, Nobuhiko Oridate, Fumiyuki Suzuki, Eisaku Higuchi, Takeshi Nishioka, Hiroki Shirato, Tatsumi Nagahashi, Katsunori Yagi, Satoshi Fukuda
    International Journal of Clinical Oncology 11 6 441 - 448 2006年12月 [査読有り][通常論文]
     
    Background. Chemoradiotherapy (CRT) is becoming more widely used for head and neck cancer. However, there are conflicting theories regarding the best management options for patients with advanced nodal disease. Methods. From 1990 to 1999, we treated 96 patients with N1-N2 neck disease by concomitant CRT for organ preservation, using weekly carboplatin or a low daily dose of cisplatin, followed by a "watch-and-see" policy for the neck. In the present study, we retrospectively analyzed the treatment outcome in 63 of these patients who received definitive CRT for primary and neck diseases and were monitored for neck disease for more than 2 years. Results. In 12 of the 22 (55%) N1 patients, CRT successfully controlled the neck disease. CRT was successful in 18 of the 41 (44%) patients with N2 disease. In 6 (60%) of 10 patients with residual or recurrent N1 disease, salvage surgery was successful. Of the 23 patients with residual or recurrent N2 disease, salvage surgery was successful in 8 patients (35%). The group of patients who showed a clinical complete response (CCR) to CRT had an overall survival rate of 62.4% (33 patients), whereas for those with a less than complete response (< CCR), the figure was 13.3% (30 patients P < 0.001). Among the < CCR-neck group, patients who underwent neck dissection (ND) as well (n = 20) did not have a significantly better overall survival than those who did not undergo ND (n = 10 P = 0.069). Conclusion. We propose a treatment plan for neck disease that involves observing the neck closely following CRT. ND should be planned only when there is evidence that neck disease exists. © 2006 The Japan Society of Clinical Oncology.
  • Teiji Nishio, Etsuo Kunieda, Hiroki Shirato, Satoshi Ishikura, Hiroshi Onishi, Kunihiko Tateoka, Masahiro Hiraoka, Yuichirou Narita, Masataka Ikeda, Tomonori Goka
    PHYSICS IN MEDICINE AND BIOLOGY 51 21 5409 - 5417 2006年11月 [査読有り][通常論文]
     
    A multicentre phase II trial of stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer was initiated in Japan as the Japan Clinical Oncology Group trial (JCOG0403). Before starting the trial, a decision was made to evaluate the treatment machine and treatment planning in participating institutions to minimize the variations of the prescription dose between the institutions. We visited the 16 participating institutions and examined the absolute dose at the centre of a simulated spherical tumour of 3.0 cm diameter in the lung using the radiation treatment planning systems in each institution. A lung phantom for stereotactic body radiotherapy (SBRT) was developed and used for the treatment planning and film dosimetry. In the JCOG radiotherapy study group, the no model-based calculation algorithm or the model-based calculation algorithm with a dose kernel unscaled for heterogeneities were selected for use in the initial SBRT trials started in 2004, and the model-based calculation algorithm with a dose kernel scaled for heterogeneities was selected for the coming trial. The findings of this study suggest that the clinical results of lung SBRT trials should be carefully evaluated in comparison with the actual dose given to patients.
  • Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang
    MEDICAL PHYSICS 33 11 4149 - 4156 2006年11月 [査読有り][通常論文]
     
    It has been noted that some lung tumors exhibit large periodic motion due to respiration. To limit the amount of dose to healthy lung tissues, many clinics have begun gating radiotherapy treatment using externally placed surrogates. It has been observed by several institutions that the end-of-exhale (EOE) tumor position is more reproducible than other phases of the breathing cycle, so the gating window is often set there. From a treatment planning perspective, end-of-inhale (EOI) phase might be preferred for gating because the expanded lungs will further decrease the healthy tissue within the treatment field. We simulate gated treatment at the EOI phase, using a set of recently measured internal/external anatomy patient data. This paper attempts to answer three questions: (1) How much is the tumor residual motion when we use an external surrogate gating window at EOI? (2) How could we reduce the residual motion in the EOI gating window? (3) Is there a preference for amplitude- versus phase-based gating at EOI? We found that under free breathing conditions the residual motion of the tumors is much larger for EOI phase than for EOE phase. The mean values of residual motion at EOI were found to be 2.2 and 2.7 mm for amplitude- and phase-based gating, respectively, and, at EOE, 1.0 and 1.2 mm for amplitude- and phase-based gating, respectively. However, we note that the residual motion in the EOI gating window is correlated well with the reproducibility of the external surface position in the EOI phase. Using the results of a published breath-coaching study, we deduce that the residual motion of a lung tumor at EOI would approach that at EOE, with the same duty cycle (30%), under breath-coaching conditions. Additionally, we found that under these same conditions, phase-based gating approaches the same residual motion as amplitude-based gating, going from a 28% difference to 11%, for the patient with the largest difference between the two gating modalities. We conclude that it is feasible to achieve the same reproducibility of tumor location at EOT as at EOE if breath coaching is implemented, enabling us to reap the benefits of the dosimetric advantage of EOI gating. (c) 2006 American Association of Physicists in Medicine.
  • H Aoyama, H Shirato, M Tago, K Nakagawa, T Toyoda, K Hatano, M Kenjyo, N Oya, S Hirota, H Shioura, E Kunieda, T Inomata, K Hayakawa, N Katoh, G Kobashi
    JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 295 21 2483 - 2491 2006年06月 [査読有り][通常論文]
     
    Context In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. Objective To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. Design, Setting, and Patients Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. Interventions Patients were randomly assigned to receive WBRT plus SRS ( 65 patients) or SRS alone ( 67 patients). Main Outcome Measures The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. Results The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P=. 42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group ( P <. 001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone ( n = 29) ( P <. 001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone ( P=. 64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. Conclusions Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.
  • N Katoh, H Shirato, H Aoyama, R Onimaru, K Suzuki, K Hida, K Miyasaka, Y Iwasaki
    JOURNAL OF NEURO-ONCOLOGY 78 1 63 - 69 2006年05月 [査読有り][通常論文]
     
    Purpose: To retrospectively analyze the outcome of post-operative radiotherapy for spinal cord glioma with the emphasis on the hypofractionated radiotherapy boost for dose escalation as a treatment option for high-grade spinal cord astrocytic tumors. Materials & methods: Forty-one patients with spinal cord glioma received post-operative radiotherapy between 1979 and 2003. The median age was 34 years (range, 10-66 years). Median follow-up was 49 months (range, 5-291 months). There were 12 low-grade astrocytic tumors, 11 high-grade astrocytic tumors, 16 low-grade ependymal tumors and 2 high-grade ependymal tumors. Among 11 patients with high-grade astrocytic tumors, 5 with anaplastic astrocytoma and 1 with glioblastoma received hypofractionated radiotherapy boost for dose escalation. The median total dose of the conventional radiotherapy was 45.5 Gy in 19 fractions (range, 30.0-60.0 Gy). The median normalized total dose (using daily dose of 2.0 Gy and an alpha/beta ratio of 2.0) of the hypofractionated radiotherapy boost was 131 Gy(2) (range, 85-249). Results: The Kaplan-Meier survival rates at 10 years from the date of the first surgery were 64% for the entire group, 47% for the astrocytic tumors and 84% for the ependymal tumors, respectively (P=0.009). Among 11 patients with high-grade astrocytic tumors, the actuarial survival rate at 10 years was 35%. The actuarial survival rates at 10 years were 67% for those who received hypofractionated radiotherapy boost for dose escalation, and 20% for those who did not (P=0.47). Discussion: The results for ependymal tumors and low-grade astrocytic tumors were comparable to those reported in the literature. Hypofractionated radiotherapy boost for dose escalation may help to prolong the survival of patients with high-grade astrocytic tumors.
  • M Oita, K Ohmori, K Obinata, R Kinoshita, R Onimaru, K Tsuchiya, K Suzuki, T Nishioka, H Ohsaka, K Fujita, T Shimamura, H Shirato, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 64 5 1581 - 1588 2006年04月 [査読有り][通常論文]
     
    Purpose: To reduce setup error and intrafractional movement in head-and-neck treatment, a real-time tumor tracking radiotherapy (RTRT) system was used with the aid of gold markers implanted in a mouthpiece. Methods and Materials: Three 2-mm gold markers were implanted into a mouthpiece that had been custom made for each patient before the treatment planning process. Setup errors in the conventional immobilization system using the shell (manual setup) and in the RTRT system (RTRT setup) were compared. Eight patients with pharyngeal tumors were enrolled. Results: The systematic setup errors were 1.8, 1.6, and 1.1 nun in the manual setup and 0.2, 0.3, and 0.3 mm in the RTRT setup in right-left, craniocaudal, and AP directions, respectively. Statistically significant differences were observed with respect to the variances in setup error (p < 0.001). The systematic and random intrafractional errors were maintained within the ranges of 0.2-0.6 mm and 1.0-2.0 mm, respectively. The rotational systematic and random intrafractional errors were estimated to be 2.2-3.2 degrees and 1.5-1.6 degrees, respectively. Conclusions: The setup error and planning target volume margin can be significantly reduced using an RTRT system with a mouthpiece and three gold markers. (c) 2006 Elsevier Inc.
  • M Abdel-Wahab, B Etuk, J Palermo, H Shirato, J Kresl, O Yapicier, G Walker, BW Scheithauer, E Shaw, C Lee, W Curran, T Thomas, A Markoe
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 64 4 1060 - 1071 2006年03月 [査読有り][通常論文]
     
    Purpose: To determine the impact of postoperative radiation therapy (POXRT) on outcome in spinal cord gliomas. Patients and Methods: Data from 242 patients were collected retrospectively from six institutions using a standardized data sheet. Pathology specimens, when available, were centrally reviewed. Results: A total of 183 patients were analyzed: 82 received surgery alone as initial treatment, whereas 101 had surgery and POXRT. Demographic, diagnostic, and treatment factors were analyzed for impact on progression-free (PFS) and overall survival (OS). PFS in ependymoma patients was 74%, 60%, and 35% at 5, 10, 15 years, respectively, and was significantly influenced by treatment type, race, age, tumor grade, and type of surgery on univariate analysis, with age being the only significant factor on multivariate analysis (MVA) (p = 0.01). OS of ependymoma patients was 91%, 84%, and 75% at 5, 10, and 15 years, respectively, and was significantly influenced by both complete resection (p = 0.04) and age (p = 0.03) on MVA. In astrocytomas, PFS was 42%, 29%, and 15% at 5, 10, and 15 years, and was significantly influenced by POXRT in low- and intermediate-grade tumors on MVA (p = 0.02). OS at 5, 10, and 15 years was 59%, 53%, and 32%, respectively, and was significantly influenced by grade on MVA (p < 0.01). Conclusion: Postoperative radiation therapy reduced disease progression in low- and moderate-grade astrocytomas. In ependymomas, complete resection significantly influenced OS. (C) 2006 Elsevier Inc.
  • H Shirato, K Suzuki, GC Sharp, K Fujita, R Onimaru, M Fujino, N Kato, Y Osaka, R Kinoshita, H Taguchi, S Onodera, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 64 4 1229 - 1236 2006年03月 [査読有り][通常論文]
     
    Background: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. Methods and Materials: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. Results: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. Conclusion: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology. (C) 2006 Elsevier Inc.
  • Fujino M, Shirato H, Onishi H, Kawamura H, Takayama K, Koto M, Onimaru R, Nagata Y, Hiraoka M
    Cancer journal (Sudbury, Mass.) 12 41 - 46 1 2006年01月 [査読有り][通常論文]
  • M Imura, K Yamazaki, H Shirato, R Onimaru, M Fujino, S Shimizu, T Harada, S Ogura, H Dosaka-Akita, K Miyasaka, M Nishimura
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 63 5 1442 - 1447 2005年12月 [査読有り][通常論文]
     
    Purpose: Internal 1.5-mm fiducial markers were used in real-time tumor-tracking radiotherapy (RT) for lung cancer. The fixation rate of the markers using the bronchial insertion technique, reliability of the setup using markers around the target volume, dislocation of the markers after real-time tumor-tracking RT, and long-term toxicity of marker insertion were investigated. Methods and Materials: Between July 2000 and April 2004, 154 gold markers were inserted into 57 patients with peripheral lung cancer. The distances between the implanted markers in 198 measurements in 71 setups in 11 patients were measured using two sets of orthogonal diagnostic X-ray images of the real-time tumor-tracking RT system. The distance between the markers and the chest wall was also measured in a transaxial CT image on 186 occasions in 48 patients during treatment planning and during follow-up. The median treatment time was 6 days (range, 4-14 days). Results: In 115 (75%) of the 154 inserted markers, the gold marker was detected throughout the treatment period. In 122 markers detected at CT planning, 115 (94%) were detected until the end of treatment. The variation in the distances between the implanted markers was within +/- 2 mm in 95% and 1 mm in 80% during treatment. The variation in the distances between the implanted markers was > 2 mm in at least one direction in 9% of the setups for which reexamination with a CT scan was indicated. The fixation rate in the left upper lobe was lower than in the other lobes. A statistically significant relationship was found between a shorter distance between the markers and the chest wall and the fixation rate, suggesting that the markers in the smaller bronchial lumens fixed better than those in the larger lumens. A learning curve among the endoscopists was suggested in the fixation rate. The distance between the markers and the chest wall changed significantly within a median of 44 days (range, 16-181 days) after treatment. Conclusion: The fixation of markers into the bronchial tree was useful for the setup for peripheral lung cancer and had an accuracy of 2 mm during the 1-2-week treatment period. The relationship between the markers and tumor can change significantly after 2 weeks, suggesting that adaptive four-dimensional RT is required. (c) 2005 Elsevier Inc.
  • R Onimaru, H Shirato, M Fujino, K Suzuki, K Yamazaki, M Nishimura, H Dosaka-Akita, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 63 1 164 - 169 2005年09月 [査読有り][通常論文]
     
    Purpose: The effects of tumor location and pulmonary function on the motion of fiducial markers near lung tumors were evaluated to deduce simple guidelines for determining the internal margin in radiotherapy without fiducial markers. Methods and Materials: Pooled data collected by a real-time tumor-tracking radiotherapy system on 42 markers in 39 patients were analyzed. The pulmonary functions of all patients were assessed before radiotherapy. Using chest X-ray film, the position of the marker was expressed relative to the geometry of the unilateral lung. Posterior location meant the area of the posterior half of the lung in a lateral chest X-ray film, and caudal location meant the caudal half of the chest X-ray film; these categories were determined by measuring the distance between the marker and anatomic landmarks, including the apex, costophrenic angle, midline of spinal canal, lateral, anterior, and posterior boundary of the lung. Results: Before the radiotherapy, 18 patients had obstructive respiratory dysfunction (ratio of forced expiratory volume in 1 s to forced vital capacity [FEV1.0/FVC] < 70), 5 patients had constrictive dysfunction (percent vital capacity [%VC] < 80), and 3 had mixed dysfunction. Means of FEV1.0/FVC and %VC were 97.0% and 66.5%, respectively. Median tumor movements in the x (left-right), y (anteroposterior), and z (craniocaudal) directions were 1.1 mm, 2.3 mm, and 5.4 mm, respectively. There was no significant correlation between respiratory function and magnitude of marker movement in any direction. Median marker movement in the z direction was 2.6 mm for the cranial location and 11.8 mm for the caudal location, respectively (p < 0.001). Median movement in the z direction was 11.8 mm for posterior location and 3.4 mm for anterior location, respectively (p < 0.01). Conclusions: Simple measurement of the relative location on plain chest X-ray film was related, but respiratory function test was not related, to the craniocaudal amplitude of the motion of the fiducial marker near lung tumors. (c) 2005 Elsevier Inc.
  • Shirato H, Aoyama H, Suzuki K, Miyasaka K
    Nihon rinsho. Japanese journal of clinical medicine 63 Suppl 9 419 - 424 2005年09月 [査読有り][通常論文]
  • RI Berbeco, S Nishioka, H Shirato, GTY Chen, SB Jiang
    PHYSICS IN MEDICINE AND BIOLOGY 50 16 3655 - 3667 2005年08月 [査読有り][通常論文]
     
    Due to respiration, many tumours in the thorax and abdomen may move as much as 3 cm peak-to-peak during radiation treatment. To mitigate motion-induced irradiation of normal lung tissue, clinics have employed external markers to gate the treatment beam. This technique assumes that the correlation between the external surface and the internal tumour position remains constant inter-fractionally and intra-fractionally. In this work, a study has been performed to assess the validity of this correlation assumption for external surface based gated radiotherapy, by measuring the residual tumour motion within a gating window. Eight lung patients with implanted fiducial markers were studied at the NTT Hospital in Sapporo, Japan. Synchronized internal marker positions and external abdominal surface positions were measured during the entire course of treatment. Stereoscopic imaging was used to find the internal markers in four dimensions. The data were used retrospectively to assess conventional external surrogate respiratory-gated treatment. Both amplitude- and phase- based gating methods were investigated. For each method, three gating windows were investigated, each giving 40%, 30% and 20% duty cycle, respectively. The residual motion of the internal marker within these six gating windows was calculated. The beam-to-beam variation and day-to-day variation in the residual motion were calculated for both gating modalities. We found that the residual motion (95th percentile) was between 0.7 and 5.8 mm, 0.8 and 6.0 mm, and 0.9 and 6.2 mm for 20%, 30% and 40% duty cycle windows, respectively. Five of the eight patients showed less residual motion with amplitude-based gating than with phase-based gating. Large fluctuations (> 300%) were seen in the residual motion between some beams. Overall, the mean beam-to-beam variation was 37% and 42% from the previous treatment beam for amplitude- and phase-based gating, respectively. The day-to-day variation was 29% and 34% from the previous day for amplitude- and phase-based gating, respectively. Although gating reduced the total tumour motion, the residual motion behaved unpredictably. Residual motion during treatment could exceed that which might have been considered in the treatment plan. Treatment margins that account for motion should be individualized and daily imaging should be performed to ensure that the residual motion is not exceeding the planned motion on a given day.
  • H Aoyama, H Shirato, N Katoh, K Kudo, T Asano, S Kuroda, T Ishikawa, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 62 4 1232 - 1238 2005年07月 [査読有り][通常論文]
     
    Purpose: To investigate the discrepancy between the arteriovenous malformations seen on magnetic resonance angiography (MRA) and on stereotactic digital subtracted angiography (DSA). Methods and Materials: The target volume on stereotactic DSA (V-DSA) and the target volume on MRA (V,(MRA) rA) were separately delineated in 28 intracranial arteriovenous malformations. The coordinates of the center and the outer edges of V-DSA and V-MRA,A were calculated and used for the analyses. Results: The standard deviations (mean value) of the displacement of centers of V-MRA from V-DSA were 2.67 mm (-1.82 mm) in the left-right direction, 3.23 mm (-0.08 mm) in the anterior-posterior direction, and 2.16 mm (0.91 mm) in the craniocaudal direction. V-MRA covered less than 80% of V-DSA, in any dimensions in 9 cases (32%), although no significant difference was seen in the target volume between each method, with a mean value of 11.9 cc for V-DSA and 12.3 cc for V-MRA (p = 0.948). Conclusion: The shift of centers between each modality is not negligible. Considering no significant difference between V-DSA and V-MRA, but inadequate coverage of the V-DSA by V (MRA), it is reasonable to consider that the target on MRA might include the feeding artery and draining vein and possibly miss a portion of the nidus. (c) 2005 Elsevier Inc.
  • Hashimoto T, Shirato H, Kato M, Yamazaki K, Kurauchi N, Morikawa T, Shimizu S, Ahn YC, Akine Y, Miyasaka K
    International journal of radiation oncology, biology, physics 61 1559 - 1564 5 2005年04月 [査読有り][通常論文]
  • Shirato H
    Gan to kagaku ryoho. Cancer & chemotherapy 32 448 - 452 4 2005年04月 [査読有り][通常論文]
  • Uchida D, Shirato H, Onimaru R, Endou H, Aoyama H, Tsuchiya K, Nishioka T, Homma A, Furuta Y, Fukuda S, Miyasaka K
    Cancer journal (Sudbury, Mass.) 11 152 - 156 2 2005年03月 [査読有り][通常論文]
  • A Homma, Y Furuta, F Suzuki, N Oridate, H Hatakeyama, T Nagahashi, S Ushikoshi, T Asano, T Nishioka, H Shirato, S Fukuda
    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK 27 1 65 - 71 2005年01月 [査読有り][通常論文]
     
    Purpose. The purpose of this study was to evaluate the efficacy of rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for previously untreated patients with advanced head and neck cancer. Methods. Forty-three patients for whom surgery was contraindicated or who rejected radical surgery were given superselective intra-arterial infusions of cisplatin (100-120 mg/m(2)/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and conventional extra-beam radiotherapy (65 Gy/26 f/6.5 weeks). Results. Thirty-nine patients had stage IV disease, and the remaining four had stage III disease. During the median follow-up period of 21 months, the 3-year locoregional progression-free rates of all patients (n = 43) and patients with unresectable disease (n = 24) were 68.9% and 56.4%, respectively. In addition, the 3-year overall survival of all patients and patients with unresectable disease was 54.0% and 39.6%, respectively. Thirty-five patients (81.4%) experienced nonhematologic grade III to Iv toxicity, including mucositis (n = 16), nausea/vomiting (n = 8), and neurologic signs (n = 2). No patient died as a result of treatment toxicity. There are 29 surviving patients without evidence of disease, all of whom are able to have oral intakes without feeding-tube support. Conclusions. We confirmed the efficacy of superselectives arterial infusion and concomitant radiotherapy, which can concentrate the attack of supradosa cisplatin on locoregional disease. Even patients with unresectable disease can be cured. Further studies are needed to establish the indications, long-term outcome, and possible side effects of this treatment. (C) 2004 Wiley Periodicals, Inc.
  • GC Sharp, SB Jiang, S Shimizu, H Shirato
    PHYSICS IN MEDICINE AND BIOLOGY 49 23 5347 - 5356 2004年12月 [査読有り][通常論文]
     
    In motion-compensated radiation therapy, radio-opaque markers can be implanted in or near a tumour and tracked in real-time using fluoroscopic imaging. Tracking these implanted markers gives highly accurate position information, except when tracking fails due to poor or ambiguous imaging conditions. This study investigates methods for automatic detection of tracking errors, and assesses the frequency and impact of tracking errors on treatments using the prototype real-time tumour tracking system. We investigated four indicators for automatic detection of tracking errors. and found that the, distance between corresponding rays was most effective. We also found that tracking errors cause a loss of gating efficiency of between 7.6 and 10.2%. The incidence of treatment beam delivery during tracking errors was estimated at between 0.8% and 1.25%.
  • HM Wu, GC Sharp, B Salzberg, D Kaeli, H Shirato, SB Jiang
    PHYSICS IN MEDICINE AND BIOLOGY 49 23 5357 - 5372 2004年12月 [査読有り][通常論文]
     
    Effective image guided radiation treatment of a moving tumour requires adequate information on respiratory motion characteristics. For margin expansion, beam tracking and respiratory gating. the rumour motion must be quantified for pretreatment planning and monitored on-line. We propose a finite state model for respiratory motion analysis that captures our natural understanding, of breathing stages. In this model. a regular breathing cycle is represented by three line segments, exhale, end-of-exhale and inhale. while abnormal breathing is represented by an irregular breathing state. In addition. we describe an on-line implementation of this model in one dimension. We found this model can accurately characterize a wide variety of patient breathing patterns. This model was used to describe the respiratory motion for 23 patients with peak-to-peak motion greater than 7 mm. The average root mean square error over all patients was less than I mm and no patient has an error worse than 1.5 mm. Our model provides a convenient toot to quantify respiratory motion characteristics, such as patterns of frequency changes and amplitude changes. and can be applied to internal or external motion. including internal tumour position, abdominal surface, diaphragm. spirometry and other surrogates.
  • T Nishioka, K Tsuchiya, S Nishioka, T Kitahara, K Ohmori, A Homma, H Aoyma, M Shindoh, H Shirato
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 60 3 847 - 852 2004年11月 [査読有り][通常論文]
     
    Purpose: To evaluate the safety and efficacy of a modified version of cyclophosphamide, doxorubicin, vincristine, prednisone (pirarubicin, cyclophosphamide, vincristine, and prednisone [THP-COP]) plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. Methods and Materials: Between December 1993 and December 1999, 41 patients with early-stage non-Hodgkin's lymphoma with intermediate-grade histologic features were enrolled in our study. The mean patient age was 51 years. Of the 41 patients, 27 had Stage I and 14 Stage 11 disease. The primary site was Waldeyer's ring, a neck node, or an extranodal site in 14, 11, and 16 patients, respectively. The immunophenotype was B cell in 29 and T cell in 12 patients. All patients were in the low-risk category according to the International Prognostic Index. Chemotherapy consisted of 40 mg/m(2) i.v. pirarubicin (THP-Adriamycin), 750 mg/m(2) i.V. cyclophosphamide, and 1.0 mg/m(2) i.V. vincristine, on Day 1 and 40 mg/m(2) p.o. prednisone on Days 1-5. The combination chemotherapy was given twice at a 14-day interval. Radiotherapy was given to involved areas at a fraction size of 2.0-2.5 Gy up to a total of 40 Gy within 4-5 weeks. The mean follow-up period was 63 months. Results: The 5-year overall survival rate was 89%. The 5-year cause-specific survival and progression-free survival rate was 90% and 81%, respectively. The 5-year progression-free survival rate for patients with Waldeyer's ring primaries was 93%. Patients with tumor <5 cm in size had greater 5-year progression-free survival than those with tumor >5 cm in size (85% vs. 33%, p < 0.05, log-rank test). Grade 4 neutropenia was seen in 12% of patients; however, 93% of patients (38 of 41) received chemotherapy as scheduled with the support of granulocyte colony-stimulating factor. Conclusion: Biweekly THP-COP plus radiotherapy is feasible and effective for Stage I-II low-risk non-Hodgkin's lymphoma. (C) 2004 Elsevier Inc.
  • TC Chang, H Shirato, H Aoyama, S Ushikoshi, N Kato, S Kuroda, T Ishikawa, K Houkin, Y Iwasaki, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 60 3 861 - 870 2004年11月 [査読有り][通常論文]
     
    Purpose: To investigate the appropriateness of the treatment policy of stereotactic irradiation using both hypofractionated stereotactic radiotherapy (HSRT) and stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) located in an eloquent region or for large AVMs and using SRS alone for the other AVMs. Methods and Materials: Included in this study were 75 AVMs in 72 patients, with a mean follow-up of 52 months. Of the 75 AVMs, 33 were located in eloquent regions or were >2.5 cm in maximal diameter and were given 25-35 Gy (mean, 32.4 Gy) in four daily fractions at a single isocenter if the patient agreed to prolonged wearing of the stereotactic frame for 5 days. The other 42 AVMs were treated with SRS at a dose of 15-25 Gy (mean, 24.1 Gy) at the isocenter. The 75 AVMs were classified according to the Spetzler-Martin grading system; 21, 23, 28, 2, and 1 AVM were Grade I, II, III, IV, V, and VI, respectively. Results: The overall actuarial rate of obliteration was 43% (95% confidence interval [CI], 30-56%) at 3 years, 72% (95% CI, 58-86%) at 5 years, and 78% (95% CI, 63-93%) at 6 years. The actuarial obliteration rate at 5 years was 79% for the 42 AVMs <2.0 cm and 66% for the 33 AVMs >2 cm. The 5- and 6-year actuarial obliteration rate was 61% (95% Cl, 39-83%) and 71% (95% CI, 47-95%), respectively, after HSRT and 81% (95% CI, 66-96%) and 81% (95% CI, 66-96%), respectively, after SRS; the difference was not statistically significant. Radiation-induced necrosis was observed in 4 subjects in the SRS group and 1 subject in the HSRT group. Cyst formation occurred in 3 patients in the SRS group and no patient in the HSRT group. A permanent symptomatic complication was observed in 3 cases (4.2%), and 1 of the 3 was fatal. All 3 patients were in the SRS group. The annual intracranial hemorrhage rate was 5.5-5.6% for all patients. Conclusion: Our treatment policy using SRS and HSRT was as effective as the policy involving SRS alone. The HSRT schedule was suggested to have a lower frequency of radiation necrosis and cyst formation than the high-dose SRS schedule. The benefit of HSRT compared with lower dose SRS has not yet been determined. (C) 2004 Elsevier Inc.
  • R Yamamoto, A Yonesaka, S Nishioka, H Watari, T Hashimoto, D Uchida, H Taguchi, T Nishioka, B Miyasaka, N Sakuragi, H Shirato
    RADIOTHERAPY AND ONCOLOGY 73 2 219 - 222 2004年11月 [査読有り][通常論文]
     
    The feasibility and accuracy of high dose three-dimensional conformal boost (3DCB) using three internal fiducial markers and a two-orthogonal X-ray set-up of the real-time tumor-tracking system on patients with gynecological malignacy were investigated in 10 patients. The standard deviation of the distribution of systematic deviations (Sigma) was reduced from 3.8, 4.6, and 4.9 mm in the manual setup to 2.3. 2.3 and 2.7 mm, in the set-up using the internal markers. The average standard deviation of the distribution of random deviations (sigma) was reduced from 3.7. 5.0, and 4.5 mm in the manual set-up to 3.3, 3.0, and 4.2 mm in the marker set-up. The appropriate PTV margin was estimated to be 10.2, 12.8, and 12.9 mm in the manual set-up and 6.9, 6.7, and 8.3 mm in the gold marker set-up, respectively, using the formula 2Sigma+0.7sigma. Set-up of the patients with three markers and two fluoroscopy is useful to reduce PTV margin and perform 3DCB. (C) 2004 Published by Elsevier Ireland Ltd.
  • H Onishi, T Araki, H Shirato, Y Nagata, M Hiraoka, K Gomi, T Yamashita, Y Niibe, K Karasawa, K Hayakawa, Y Takai, T Kimura, Y Hirokawa, A Takeda, A Ouchi, M Hareyama, M Kokubo, R Hara, J Itami, K Yamada
    CANCER 101 7 1623 - 1631 2004年10月 [査読有り][通常論文]
     
    BACKGROUND. Stereotactic irradiation (STI) has been actively performed using various methods to achieve better local control of Stage I nonsmall cell lung carcinoma (NSCLC) in Japan. The authors retrospectively evaluated results from a Japanese multiinstitutional study. METHODS. Patients with Stage I NSCLC (n = 245; median age, 76 years; T1N0M0, n = 155; T2N0M0, n = 90) were treated with hypofractionated high-dose STI in 13 institutions. Stereotactic three-dimensional treatment was performed using non-coplanar dynamic arcs or multiple static ports. A total dose of 18-75 gray (Gy) at the isocenter was administered in 1-22 fractions. The median calculated biologic effective dose (BED) was 108 Gy (range, 57-180 Gy). RESULTS. During follow-up (median, 24 months; range, 7-78 months), pulmonary complications of National Cancer Institute-Common Toxicity Criteria Grade > 2 were observed in only 6 patients (2.4%). Local progression occurred in 33 patients (14.5%), and the local recurrence rate was 8.1% for BED greater than or equal to 100 Gy compared with 26.4% for < 100 Gy (P < 0.05). The 3-year overall survival rate of medically operable patients was 88.4% for BED greater than or equal to 100 Gy compared with 69.4% for < 100 Gy (P < 0.05). CONCLUSIONS. Hypofractionated high-dose STI with BED < 150 Gy was feasible and beneficial for curative treatment of patients with Stage I NSCLC. For all treatment methods and schedules, local control and survival rates were better with BED greater than or equal to 100 Gy compared with < 100 Gy. Survival rates in selected patients (medically operable, BED greater than or equal to 100 Gy) were excellent, and were potentially comparable to those of surgery. (C) 2004 American Cancer Society.
  • H Shirato, M Oita, K Fujita, S Shimizu, R Onimaru, S Uegaki, Y Watanabe, N Kato, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 60 2 607 - 612 2004年10月 [査読有り][通常論文]
     
    Purpose: To test the accuracy of a system for correcting for the rotational error of the clinical target volume (CTV) without having to reposition the patient using three fiducial markers and two orthogonal fluoroscopic images. We call this system "three-dimensional conformal setup" (3D-CSU). Methods and Materials: Three 2.0-mm gold markers are inserted into or adjacent to the CTV. On the treatment couch, the actual positions of the three markers are calculated based on two orthogonal fluoroscopies crossing at the isocenter of the linear accelerator. Discrepancy of the actual coordinates of gravity center of three markers from its planned coordinates is calculated. Translational setup error is corrected by adjustment of the treatment couch. The rotation angles (alpha, beta, gamma) of the coordinates of the actual CTV relative to the planned CTV are calculated around the lateral (x), craniocaudal (y), and anteroposterior (z) axes of the planned CTV. The angles of the gantry head, collimator, and treatment couch of the linear accelerator are adjusted according to the rotation of the actual coordinates of the tumor in relation to the planned coordinates. We have measured the accuracy of 3D-CSU using a static cubic phantom. Results: The gravity center of the phantom was corrected within 0.9 +/- 0.3 mm (mean +/- SD), 0.4 +/- 0.2 mm, and 0.6 +/- 0.2 mm for the rotation of the phantom from 0-30 degrees around the x, y, and z axes, respectively, every 5 degrees. Dose distribution was shown to be consistent with the planned dose distribution every 10 degrees of the rotation from 0-30 degrees. The mean rotational error after 3D-CSU was -0.4 +/- 0.4 (mean +/- SD), -0.2 +/- 0.4, and 0.0 +/- 0.5 degrees around the x, y, and z axis, respectively, for the rotation from 0-90 degrees. Conclusions: Phantom studies showed that 3D-CSU is useful for performing rotational correction of the target volume without correcting the position of the patient on the treatment couch. The 3D-CSU will be clinically useful for tumors in structures such as paraspinal diseases and prostate cancers not subject to large internal organ motion. (C) 2004 Elsevier Inc.
  • H Shirato, H Aoyama, J Ikeda, K Fujieda, N Kato, N Ishi, K Miyasaka, Y Iwasaki, Y Sawamura
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 60 1 214 - 217 2004年09月 [査読有り][通常論文]
     
    Purpose: We previously published a report stating that germinomas with elevated serum beta human chorionic gonadotropin (HCG-beta) had a poor relapse rate, but these findings have not been supported by a multi-institutional trial. The margin for initial gross tumor volume (GTV) before surgery and chemotherapy of the same materials was investigated by retrospective review. Methods and Material: The 27 patients reported on in the previous paper were analyzed. The two-dimensional margin from the initial GTV to 90% of the prescribed dose of 24 Gy was 2.0 cm for a solitary lesion in the protocol. This margin was measured retrospectively without knowledge of the serum HCG-beta level. The whole ventricle field was used for patients with multifocal disease and whole central nervous system field was used for disseminated disease, respectively. Results: Six relapses were seen in 18 patients with solitary tumors, and were treated with the minimum margin of 1.5 cm or less to the initial GTV. Five of the 6 had initially elevated serum HCG-beta at the median of 7.4 mIU/mL, ranging from 0.7-233 mIU/mL. No relapses were seen in the 9 patients who were treated with whole ventricle or whole central nervous system field. Conclusions: An inadequate margin and elevated serum HCG-beta were equally determined to be candidates that caused the poor local control. The whole ventricle is recommended as the smallest target volume for germinoma with or without elevated HCG-beta after induction chemotherapy. (C) 2004 Elsevier Inc.
  • H Shirato, M Oita, K Fujita, Y Watanabe, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 60 1 335 - 341 2004年09月 [査読有り][通常論文]
     
    Purpose: Synchronization of the techniques in real-time tumor-tracking radiotherapy (RTRT) and intensity-modulated RT (IMRT) is expected to be useful for the treatment of tumors in motion. Our goal was to estimate the feasibility of the synchronization from the viewpoint of excessive dose resulting from the use of fluoroscopy. Methods and Materials: Using an ionization chamber for diagnostic X-rays, we measured the air kerma rate, surface dose with backscatter, and dose distribution in depth in a solid phantom from a fluoroscopic RTRT system. A nominal 50-120 kilovoltage peak (kVp) of X-ray energy and a nominal 1-4 ms of pulse width were used in the measurements. Results: The mean +/- SD air kerma rate from one fluoroscope was 238.8 +/- 0.54 mGy/h for a nominal pulse width of 2.0 ms and nominal 100 kVp of X-ray energy at the isocenter of the linear accelerator. The air kerma rate increased steeply with the increase in the X-ray beam energy. The surface dose was 28-980 mGy/h. The absorbed dose at a 5.0-cm depth in the phantom was 37-58% of the peak dose. The estimated skin surface dose from one fluoroscope in RTRT was 29-1182 mGy/h and was strongly dependent on the kilovoltage peak and pulse width of the fluoroscope and slightly dependent on the distance between the skin and isocenter. Conclusion: The skin surface dose and absorbed depth dose resulting from fluoroscopy during RTRT can be significant if RTRT is synchronized with IMRT using a multileaf collimator. Precise estimation of the absorbed dose from fluoroscopy during RT and approaches to reduce the amount of exposure are mandatory. (C) 2004 Elsevier Inc.
  • Homma A, Shirato H, Furuta Y, Nishioka T, Oridate N, Tsuchiya K, Nagahashi T, Aoyama H, Inuyama Y, Fukuda S
    Cancer journal (Sudbury, Mass.) 10 326 - 332 5 2004年09月 [査読有り][通常論文]
  • YC Ahn, S Shimizuz, H Shirato, T Hashimoto, Y Osaka, XQ Zhang, T Abe, M Hosokawa, K Miyasaka
    YONSEI MEDICAL JOURNAL 45 4 584 - 590 2004年08月 [査読有り][通常論文]
     
    Herein is reported our experience of radiation therapy using a real-time tumor-tracking and gated radiotherapy (RTRT) system for inoperable pancreatic cancer. Three unresectable pancreatic cancer patients were treated with intraoperative electron beam radiation therapy, at the time of open biopsy, and postoperative external beam radiation therapy using an RTRT system with a 2.0 mm diameter gold ball implanted into the pancreas. The total BED's(alpha/beta=10) was intended to be equivalent to that of delivering 60 Gy by 2.0 Gy/fraction, while the actual dose schedules were individualized. The movement of the pancreas was analyzed based on the 3-dimensional marker positions during the RTRT. The side effects and tumor responses were evaluated. During the RTRT course, the average movement of markers in the x (left to right), y (cranial to caudal) and z (dorsal to ventral) directions were 3.0 mm (1.7- 5.2 mm), 5.2 mm (3.5 - 6.8 mm) and 3.5 mm (2.7 - 5.1 mm), respectively. During and after the course of postoperative radiation therapy, no acute side effects of RTOG grade 11 or higher were detected. The objective tumor responses, as evaluated by CT scans 3 months after the treatment, were 2 partial responses and no response in one patient. Using the RTRT technique the margin of treatment planning and the possible errors in target localization were reduced, and the 3-dimensional movement of the internal marker implanted in the pancreas was able to be analyzed.
  • H Aoyama, K Kamada, H Shirato, F Takeuchi, S Kuriki, Y Iwasaki, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 58 4 1177 - 1183 2004年03月 [査読有り][通常論文]
     
    Purpose: To minimize the risk of neurologic deficit after stereotactic irradiation, functional brain information was integrated into treatment planning. Methods and Materials: Twenty-one magnetoencephalography and six magnetic resonance axonographic images were made in 20 patients to evaluate the sensorimotor cortex (n = 15 patients, including the corticospinal tract in 6), visual cortex (n = 4), and Wernicke's area (n = 2). One radiation oncologist was asked to formulate a treatment plan first without the functional images and then to modify the plan after seeing them. The pre- and postmodification values were compared for the volume of the functional area receiving greater than or equal to15 Gy and the volume of the planning target volume receiving greater than or equal to80% of the prescribed dose. Results: Of the 21 plans, 15 (71%) were modified after seeing the functional images. After modification, the volume receiving greater than or equal to15 Gy was significantly reduced compared with the values before modification in those 15 sets of plans (p = 0.03). No statistically significant difference was found in the volume of the planning target volume receiving greater than or equal to80% of the prescribed dose (p = 0.99). During follow-up, radiation-induced necrosis at the corticospinal tract caused a minor motor deficit in 1 patient for whom magnetic resonance axonography was not available in the treatment planning. No radiation-induced functional deficit was observed in the other patients. Conclusion: Integration of magnetoencephalography and magnetic resonance axonography in treatment planning has the potential to reduce the risk of radiation-induced functional dysfunction without deterioration of the dose distribution in the target volume. (C) 2004 Elsevier Inc.
  • GC Sharp, SB Jiang, S Shimizu, H Shirato
    PHYSICS IN MEDICINE AND BIOLOGY 49 3 425 - 440 2004年02月 [査読有り][通常論文]
     
    Image guidance in radiotherapy and extracranial radiosurgery offers the potential for precise radiation dose delivery to a moving tumour. Recent work has demonstrated how to locate and track the position of a tumour in real-time using diagnostic x-ray imaging to find implanted radio-opaque markers. However, the delivery of a treatment plan through gating or beam tracking requires adequate consideration of treatment system latencies, including image acquisition, image processing, communication delays, control system processing, inductance within the motor, mechanical damping, etc. Furthermore, the imaging dose given over long radiosurgery procedures or multiple radiotherapy fractions may not be insignificant, which means that we must reduce the sampling rate of the imaging system. This study evaluates various predictive models for reducing tumour localization errors when a real-time tumour-tracking system targets a moving tumour at a slow imaging rate and with large system latencies. We consider 14 lung tumour cases where the peak-to-peak motion is greater than 8 mm, and compare the localization error using linear prediction, neural network prediction and Kalman filtering, against a system which uses no prediction. To evaluate prediction accuracy for use in beam tracking, we compute the root mean squared error between predicted and actual 3D motion. We found that by using prediction, root mean squared error is improved for all latencies and all imaging rates evaluated. To evaluate prediction accuracy for use in gated treatment, we present a new metric that compares a gating control signal based on predicted motion against the best possible gating control signal. We found that using prediction improves gated treatment accuracy for systems that have latencies of 200 ms or greater, and for systems that have imaging rates of 10 Hz or slower.
  • H Shirato, Y Seppenwoolde, K Kitamura, R Onimura, S Shimizu
    SEMINARS IN RADIATION ONCOLOGY 14 1 10 - 18 2004年01月 [査読有り][通常論文]
  • RI Berbeco, SB Jiang, GC Sharp, GTY Chen, H Mostafavi, H Shirato
    PHYSICS IN MEDICINE AND BIOLOGY 49 2 243 - 255 2004年01月 [査読有り][通常論文]
     
    The design of an integrated radiotherapy imaging system (IRIS), consisting of gantry mounted diagnostic (kV) x-ray tubes and fast read-out flat-panel amorphous-silicon detectors, has been studied. The system is meant to be capable of three main functions: radiographs for three-dimensional (3D) patient set-up, cone-beam CT and real-time tumour/marker tracking. The goal of the current study is to determine whether one source/panel pair is sufficient for real-time tumour/marker tracking and, if two are needed, the optimal position of each relative to other components and the isocentre. A single gantry-mounted source/imager pair is certainly capable of the first two of the three functions listed above and may also be useful for the third, if combined with prior knowledge of the target's trajectory. This would be necessary because only motion in two dimensions is visible with a single imager/source system. However, with previously collected information about the trajectory, the third coordinate may be derived from the other two with sufficient accuracy to facilitate tracking. This deduction of the third coordinate can only be made if the 3D tumour/marker trajectory is consistent from fraction to fraction. The feasibility of tumour tracking with one source/imager pair has been theoretically examined here using measured lung marker trajectory data for seven patients from multiple treatment fractions. The patients' selection criteria include minimum mean amplitudes of the tumour motions greater than 1 cm peak-to-peak. The marker trajectory for each patient was modelled using the first fraction data. Then for the rest of the data, marker positions were derived from the imager projections at various gantry angles and compared with the measured tumour positions. Our results show that, due to the three dimensionality and irregular trajectory characteristics of tumour motion, on a fraction-to-fraction basis, a 'monoscopic' system (single source/imager) is inadequate for consistent real-time tumour tracking, even with prior knowledge. We found that, among the seven patients studied with peak-to-peak marker motion greater than 1 cm, five cases have mean localization errors greater than 2 mm and two have mean errors greater than 3 mm. Because of this uncertainty associated with a monoscopic system, two source/imager pairs are necessary for robust 3D target localization. Dual orthogonal x-ray source/imager pairs mounted on the linac gantry are chosen for the IRIS. We further studied the placement of the x-ray sources/panel based on the geometric specifications of the Varian 21EX Clinac. The best configuration minimizes the localization error while maintaining a large field of view and avoiding collisions with the floor/ceiling or couch.
  • XQ Zhang, H Shirato, H Aoyama, S Ushikoshi, T Nishioka, DZ Zhang, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 57 5 1392 - 1399 2003年12月 [査読有り][通常論文]
     
    Purpose: A three-dimensional (3D) reconstruction method of arteriovenous malformation (AVM) nidus from digital subtraction angiography (DSA) in combination with CT and/or MRI was developed, and its usefulness was evaluated in this study. Methods and Materials: The contour of the AVM nidus wits delineated on two orthogonal projected DSA images. First, the volume and center of the AVM nidus were calculated in a classic DSA plan using three maximal lengths of the nidus in three perpendicular directions, assuming that the nidus had a prolate ellipsoid shape. Second, in the 3D-DSA plan, the contours of the AVM nidus on the two orthogonal projected DSA images were segmented to be compatible with the slice thickness of the CT image. Assuming that each segment of the nidus has an ellipsoid pillar shape, the volume and center of each segment were calculated. The volume and 3D shape of the nidus were calculated by 3D reconstruction in the 3D-DSA plan. Third, in the CT-DSA plan, the contour based on the segmented DSA was superimposed on the corresponding transaxial CT image slice by slice. The cylindrical shape of the nidus in the transaxial image was modified using the enhanced CT images in the CT-DSA plan. These three planning methods were compared using dose-volume statistics from real patients' data. Eighteen patients with intracranial AVMs in different brain locations who had been treated by radiosurgery were the subjects of this study. To examine the visibility (validity) of the nidus on the CT image, the "nidus" was delineated on an enhanced CT image without DSA superposition in the CT plan and compared with the CT-DSA plan. Results: The, variance in the distance between coordinates determined by the CT plan and those determined by the classic DSA plan was significantly larger than the variance in the CT-DSA plan (p < 0.0001 for lateral, AP, and craniocaudal directions). The difference in the variance was not reduced by the addition of MRI (p < 0.0001 for each direction). The mean volume +/- SD of the nidus calculated was 5.9 +/- 8.0 cm(3) in the classic DSA plan, 4.0 +/- 5.6 cm(3) in the 3D-DSA plan, and 3.6 +/- 5.2 cm(3) in the CT-DSA plan. The 3D-DSA plan significantly reduced the mean nidus volume 31.8% +/- 12.7% from the classic DSA plan (p = 0.0054). The CT-DSA plan further significantly reduced the volume 9.8% +/- 8.8% from the 3D-DSA plan (p = 0.0021). The mean overlapping volume of the nidus between the CT plan and CT-DSA plan was 2.6 +/- 4.3cm(3) (range 0.17-18.9), corresponding to 63.7% +/- 19.2% (range 11.4-85.3%) of the volume in the CT-DSA plan. Conclusion: The superposition of the segmented DSA information on CT was shown to be an important tool to determine the precise shape of the nidus and is suggested to be useful to reduce partial occlusion of the AVM or radiation complications in radiosurgery. (C) 2003 Elsevier Inc.
  • Y Sawamura, H Shirato, T Sakamoto, H Aoyama, K Suzuki, R Onimaru, T Isu, S Fukuda, K Miyasaka
    JOURNAL OF NEUROSURGERY 99 4 685 - 692 2003年10月 [査読有り][通常論文]
     
    Object. The goal of this study was to investigate outcomes in patients with vestibular schwannoma (VS) who were treated with fractionated stereotactic radiotherapy (SRT). Methods. One hundred one patients with VS were treated with fractionated SRT at a radiation level of 40 to 50 Gy administered in 20 to 25 fractions over a 5- to 6-week period. The median tumor size in these patients was 19 rum (range 3-40 mm), and 27 tumors were larger than 25 mm. Patients were consistently followed up using magnetic resonance imaging every 6 months for 5 years in principle. The median follow-up period was 45 months. The actuarial 5-year rate of tumor control (no growth > 2 mm and no requirement for salvage surgery) was 91.4% (95% confidence interval 85.2-97.6%). Three patients with progressive tumors underwent salvage tumor resection. The actuarial 5-year rate of useful hearing preservation (Gardner Robertson Class I or 11) was 71%. The observed complications of fractionated SRT included transient facial nerve palsy (4% of patients), trigeminal neuropathy (14% of patients), and balance disturbance (17% of patients). No new permanent facial weakness occurred after fractionated SRT. Eleven patients (11%) who had progressive communicating hydrocephalus (cerebrospinal fluid malabsorption) and no evidence of tumor growth after fractionated SRT required a shunt. The symptoms of this type of hydrocephalus were similar to those of normal-pressure hydrocephalus and occurred 4 to 20 months (median 12 months) after fractionated SRT. The mean size (+/- standard deviation) of tumors causing symptomatic hydrocephalus (25.5 +/- 7.8 mm) was significantly larger than that of other tumors (18.2 +/- 8.7 mm) (p = 0.011). Only four of the 72 patients with tumors smaller than 25 mm in maximum diameter received a shunt. Conclusions. Fractionated SRT resulted in an excellent tumor control rate, even for relatively large tumors, and produced a high rate of hearing preservation that was comparable to the best results of single-fraction radiosurgery. The progression of communicating hydrocephalus should be monitored closely, particularly in patients harboring a large VS.
  • Y Hosokawa, H Shirato, T Nishioka, K Tsuchiya, TC Chang, K Kagei, K Ohomori, K Obinata, M Kaneko, K Miyasaka, M Nakamura
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 57 1 71 - 78 2003年09月 [査読有り][通常論文]
     
    Purpose: To investigate the importance of total treatment time on the outcome of external beam radiotherapy (EBRT) followed by internal brachytherapy for the treatment of oral tongue carcinoma. Methods and Materials: Ninety-four patients with T1-T2N0 squamous cell carcinoma of the oral tongue were treated using 35-40 Gy EBRT followed by 35-40 Gy interstitial Cs-137 brachytherapy between 1985 and 1995. The interval between the end of EBRT and the start of interstitial treatment varied for numerous unavoidable reasons, with a mean of 25.3 days and standard deviation of 3.5 days. The median follow-up period was 59.1 months (range 6-146). Results: The actuarial survival rate of all cases was 78.4% at 5 years. The 5-year local control rate for those with T1 and T2 was 92.8% and 62.7%, respectively (p < 0.05). The local control rate of the primary tumor in patients with a total treatment time >43 days was statistically lower than that of patients with a total treatment time less than or equal to43 days in all patients (p < 0.05) and in the subgroup of Stage T2 patients (p < 0.05). Multivariate analysis revealed that the local control rates in all cases were significantly related to the T stage (T2 or not), total treatment time (>43 days or not), and location of disease (posterior or not). Regression analysis for 5-year local control as a function of treatment duration showed a 2% loss of local control per day of treatment extension >30 days (r 0.94, p < 0.01). Conclusion: The total treatment time was associated with the local control rate in the RT of oral tongue carcinoma. The loss in local control was estimated to be 2.0% per additional day in our series for oral tongue carcinoma. (C) 2003 Elsevier Inc.
  • HI Aoyama, H Shirato, R Onimaru, K Kagei, J Ikeda, N Ishii, Y Sawamura, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 56 3 793 - 800 2003年07月 [査読有り][通常論文]
     
    Purpose: To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) using nortinvasive fixation of the skull on solitary or oligo brain metastatic patients as an alternative to stereotactic radiosurgery (SRS) using invasive fixation. Patients and Methods: The subjects were 87 patients who had 4 or fewer brain metastases (50 solitary, 37 oligometastases). Treatment was conducted on 159 metastases by using a linac-based stereotactic system. The median isocentric dose was 35 Gy in 4 fractions. Whole-brain irradiation was not applied as an initial treatment. For the salvage treatment of metachronous brain metastases, repeat HSRT or whole-brain irradiation was applied. Results: The actuarial I-year local tumor control rate was 81%. Treatment-related complications were observed in 4 patients in the early period (<3 months) and in 2 patients in the late period. The median survival period was 8.7 months. Metachronous brain metastases occurred in 30 patients, and none of the 18 patients who were eligible for salvage HSRT refused to receive it again. Conclusions: Hypofractionated stereotactic radiotherapy achieved tumor control and survival equivalent to those of SRS reported in the literature. The results suggested that HSRT could be an alternative for solitary or oligo brain metastatic patients with less toxicity and less invasiveness compared to SRS. (C) 2003 Elsevier Inc.
  • K Hida, H Shirato, T Isu, T Seki, R Onimaru, H Aoyama, S Ushikoshi, K Miyasaka, Y Iwasaki
    JOURNAL OF NEUROSURGERY 99 1 34 - 38 2003年07月 [査読有り][通常論文]
     
    Object. Radiosurgical treatment of spinal arteriovenous malformations (AVMs) is becoming a practical therapeutic option as methodology improves, but no comparative study has yet been published on focal fractionated radiotherapy. The authors report their experience with conventional and hypofractionated radiotherapy for spinal AVM. Methods. Candidates for this study were patients who experienced symptoms due to an intramedullary AVM but were ineligible for embolization or surgery. Of 21 patients with spinal AVMs, 10 cases in a 10-year period met this criterion. Angiography and contrast-enhanced computerized tomography scanning were used for treatment planning in all cases. Fractionated radiotherapy was performed using a linear accelerator, extracranial immobilization system, and frequent orthogonal linacographic verification. The starting radiation dose was 32 Gy in two, 36 Gy in three, and 40 Gy in two patients, in a regimen involving 1.8 to 2-Gy daily fractions; this was recently changed to a hypofractionation schedule of 30 Gy (in eight sessions) in one and 20 Gy (in four sessions) in two patients. Results. The follow-up period ranged from 26 to 124 months (median of 49 months). There were no hemorrhages nor any adverse reactions attributable to irradiation. Of the seven patients who consented to undergo follow-up angiography, the nidus size decreased in five, but complete obliteration did not occur in any patient. Conclusions. Because no patient experienced adverse effects, the maximum tolerable radiation dose for the spinal cord associated with an AVM could not be identified, although it presumably is higher than those administered. The lack of rebleeding in patients in whom complete angiographic occlusion was absent suggests that the natural history of spinal AVMs may be less aggressive than previously reported.
  • H Aoyama, K Kamada, H Shirato, F Takeuchi, S Kuriki, Y Iwasaki, K Miyasaka
    RADIOTHERAPY AND ONCOLOGY 68 1 27 - 32 2003年07月 [査読有り][通常論文]
     
    Corticospinal tract (CST) information using anisotropic diffusion-weighted imaging and magnetoencephalography were integrated into radiosurgical planning for two patients with deeply seated arteriovenous malformation. The volume of CST receiving > 10 Gy, > 15 Gy, and maximum dose of CST could be reduced when plans were created with the aid of CST information compared with plans without the information. The results indicate that the use of CST information might reduce the risk of post-radiosurgical motor disturbance resulting from radiation necrosis. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
  • Kitamura K, Shirato H, Shinohara N, Harabayashi T, Onimaru R, Fujita K, Shimizu S, Nonomura K, Koyanagi T, Miyasaka K
    Cancer journal (Sudbury, Mass.) 9 268 - 276 4 2003年07月 [査読有り][通常論文]
  • R Onimaru, H Shirato, S Shimizu, K Kitamura, B Xu, S Fukumoto, TC Chang, K Fujita, M Oita, K Miyasaka, M Nishimura, H Dosaka-Akita
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 56 1 126 - 135 2003年05月 [査読有り][通常論文]
     
    Purpose: To determine the organ at risk and the maximum tolerated dose (MTD) of radiation that could be delivered to lung cancer using small-volume, image-guided radiotherapy (IGRT) using hypofractionated, coplanar, and noncoplanar multiple fields. Methods and Materials: Patients with measurable lung cancer (except small-cell lung cancer) 6 cm or less in diameter for whom surgery was not indicated were eligible for this study. Internal target volume was determined using averaged CT under normal breathing, and for patients with large respiratory motion, using two additional CT scans with breath-holding at the expiratory and inspiratory phases in the same table position. Patients were localized at the isocenter after three-dimensional treatment planning. Their setup was corrected by comparing two linacographies that were orthogonal at the isocenter with corresponding digitally reconstructed images. Megavoltage X-rays using noncoplanar multiple static ports or arcs were used to cover the parenchymal tumor mass. Prophylactic nodal irradiation was not performed. The radiation dose was started at 60 Gy in 8 fractions over 2 weeks (60 Gy/8 Fr/2 weeks) for peripheral lesions 3.0 cm or less, and at 48 Gy/8 Fr/2 weeks at the isocenter for central lesions or tumors more than 3.0 cm at their greatest dimension. Results: Fifty-seven lesions in 45 patients were treated. Tumor size ranged from 0.6 to 6.0 cm, with a median of 2.6 cm. Using the starting dose, 1 patient with a central lesion died of a radiation-induced ulcer in the esophagus after receiving 48 Gy/8 Fr at isocenter. Although the contour of esophagus received 80% or less of the prescribed dose in the planning, recontouring of esophagus in retrospective review revealed that 1 cc of esophagus might have received 42.5 Gy, with the maximum dose of 50.5 Gy. One patient with a peripheral lesion experienced Grade 2 pain at the internal chest wall or visceral pleura after receiving 54 Gy/8 Fr. No adverse respiratory reaction was noted in the symptoms or respiratory function tests. The 3-year local control rate was 80.4% +/- 7.1% (a standard error) with a median follow-up period of 17 months for survivors. Because of the Grade 5 toxicity, we have halted this Phase I/II study and are planning to rearrange the protocol setting accordingly. The 3-year local control rate was 69.6 +/- 10.6% for patients who received 48 Gy and 100% for patients who received 60 Gy (p = 0.0442). Conclusion: Small-volume IGRT using 60 Gy in eight fractions is highly effective for the local control of lung tumors, but MTD has not been determined in this study. The organs at risk are extrapleural organs such as the esophagus and internal chest wall/visceral pleura rather than the pulmonary parenchyma in the present protocol setting. Consideration of the uncertainty in the contouring of normal structures is critically important, as is uncertainty in setup of patients and internal organ in the high-dose hypofractionated IGRT. (C) 2003 Elsevier Inc.
  • K Kitamura, H Shirato, Y Seppenwoolde, T Shimizu, Y Kodama, H Endo, R Onimaru, M Oda, K Fujita, S Shimizu, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 56 1 221 - 228 2003年05月 [査読有り][通常論文]
     
    Purpose: To investigate the three-dimensional (3D) intrafractional motion of liver tumors during real-time tumor-tracking radiotherapy (RTRT). Methods and Materials: The data of 20 patients with liver tumors were analyzed. Before treatment, a 2-mm gold marker was implanted near the tumor. The RTRT system used fluoroscopy image processor units to determine the 3D position of the implanted marker. A linear accelerator was triggered to irradiate the tumor only when the marker was located within a permitted region. The automatically recorded tumor-motion data were analyzed to determine the amplitude of the tumor motion, curve shape of the tumor motion, treatment efficiency, frequency of movement, and hysteresis. Each of the following clinical factors was evaluated to determine its contribution to the amplitude of movement: tumor position, existence of cirrhosis, surgical history, tumor volume, and distance between the isocenter and the marker. Results: The average amplitude of tumor motion in the 20 patients was 4 +/- 4 mm (range 1-12), 9 +/- 5 mm (range 2-19), and 5 +/- 3 mm (range 2-12) in the left-right, craniocaudal, and anterior-posterior (AP) direction, respectively. The tumor motion of the right lobe was significantly larger than that of the left lobe in the left-right and AP directions (p = 0.01). The tumor motion of the patients with liver cirrhosis was significantly larger than that of the patients without liver cirrhosis in the left-right and AP directions (p < 0.004). The tumor motion of the patients who had received partial hepatectomy was significantly smaller than that of the patients who had no history of any operation on the liver in the left-right and AP directions (p < 0.03). Thus, three of the five clinical factors examined (i.e., tumor position in the liver, cirrhosis, and history of surgery on the liver) significantly affected the tumor motion of the liver in the transaxial direction during stereotactic irradiation. Frequency analysis revealed that for 9 (45%) of the 20 tumors, the cardiac beat caused measurable motion. The 3D trajectory of the tumor showed hysteresis for 4 (20%) of the 20 tumors. The average treatment efficiency of RTRT was 40%. Conclusion: Tumor location, cirrhosis, and history of surgery on the liver all had an impact on the intrafractional tumor motion of the liver in the transaxial direction. This finding should be helpful in determining the smallest possible margin in individual cases of radiotherapy for liver malignancy. (C) 2003 Elsevier Inc.
  • H Shirato, T Harad, T Harabayashi, K Hida, H Endo, K Kitamura, R Onimaru, K Yamazaki, N Kurauchi, T Shimizu, N Shinohara, M Matsushita, H Dosaka-Akita, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 56 1 240 - 247 2003年05月 [査読有り][通常論文]
     
    Purpose: To examine the feasibility and reliability of insertion of internal fiducial markers into various organs for precise setup and real-time tumor tracking in radiotherapy (RT). Methods and Materials: Equipment and techniques for the insertion of 2.0-mm-diameter gold markers into or near the tumor were developed for spinal/paraspinal lesions, prostate tumors, and liver and lung tumors. Three markers were used to adjust the center of the mass of the target volume to the planned position in spinal/paraspinal lesions and prostate tumors (the three-marker method). The feasibility of the marker insertion and the stability of the position of markers were tested using stopping rules in the clinical protocol (i.e., the procedure was abandoned if 2 of 3 or 3 of 6 patients experienced marker dropping or migration). After the evaluation of the feasibility, the stability of the marker positions was monitored in those patients who entered the dose-escalation study. Results: Each of the following was shown to be feasible: bronchoscopic insertion for the peripheral lung; image-guided transcutaneous insertion for the liver; cystoscopic and image-guided percutaneous insertion for the prostate; and surgical implantation for spinal/paraspinal lesions. Transcutaneous insertion of markers for spinal/paraspinal lesions and bronchoscopic insertion for central lung lesions were abandoned. Overall, marker implantation was successful and was used for real-time tumor tracking in RT in 90 (90%) of 100 lesions. No serious complications related to the marker insertion were noted for any of the 100 lesions. Using three markers surgically implanted into the vertebral bone, the mean standard deviation in distance among the three markers was within 0.2 +/- 0.6 mm (range -1.4 to 0.8) through the treatment period of 30 days. The distance between the three markers gradually decreased during RT in five of six prostate cancers, consistent with a mean rate of volume regression of 9.3% (range 0.015-13%) in 10 days. Conclusion: Internal 2.0-mm-diameter gold markers can be safely inserted into various organs for real-time tumor tracking in RT using the prescribed equipment and techniques. The three-marker method has been shown to be a useful technique for precise setup for spinal/paraspinal lesions and prostate tumors. (C) 2003 Elsevier Inc.
  • T Neicu, H Shirato, Y Seppenwoolde, SB Jiang
    PHYSICS IN MEDICINE AND BIOLOGY 48 5 587 - 598 2003年03月 [査読有り][通常論文]
     
    Synchronized moving aperture radiation therapy (SMART) is a new technique for treating mobile tumours under development at Massachusetts General Hospital (MGH). The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumour motion induced by respiration. SMART is based on the concept of the average tumour trajectory (ATT) exhibited by a tumour during respiration. During the treatment simulation stage, tumour motion is measured and the ATT is derived. Then, the original IMRT MLC leaf sequence is modified using the ATT to compensate for tumour motion. During treatment, the tumour motion is monitored. The treatment starts when leaf motion and tumour motion are synchronized at a specific breathing phase. The treatment will halt when the tumour drifts away from the ATT and will resume when the synchronization between tumour motion and radiation beam is re-established. In this paper, we present a method to derive the ATT from measured tumour trajectory data. We also investigate the validity of the ATT concept for lung tumours during normal breathing. The lung tumour trajectory data were acquired during actual radiotherapy sessions using a real-time tumour-tracking system. SMART treatment is simulated by assuming that the radiation beam follows the derived ATT and the tumour follows the measured trajectory. In simulation, the treatment starts at exhale phase. The duty cycle of SMART delivery was calculated for various treatment times and gating thresholds, as well as for various exhale phases where the treatment begins. The simulation results show that in the case of free breathing, for 4 out of 11 lung datasets with tumour motion greater than I cm from peak to peak, the error in tumour tracking can be controlled to within a couple of millimetres while maintaining a reasonable delivery efficiency. That is to say, without any breath coaching/control, the ATT is a valid concept for some lung tumours. However, to make SMART an efficient technique in general, it is found that breath coaching techniques are required.
  • K Obinata, K Ohmori, K Tuchiya, T Nishioka, H Shirato, M Nakamura
    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS 95 2 246 - 250 2003年02月 [査読有り][通常論文]
     
    Objective. We sought to describe a simple method to construct a spacer and to evaluate with the use of computed tomography the spacer's effectiveness in preventing osteoradionecrosis of the mandible. Study design. Fifty-three patients with oral tongue cancers who were treated by means of interstitial brachytherapy were included in this study. Patients underwent a computed tomography examination immediately after the implantation of radioactive sources, with the spacers in place. Distances between the radioactive sources and the lingual surfaces of the mandible were measured on transverse computed tomographs and were evaluated in terms of the development of osteoradionecrosis in the mandible. Results. Statistically significant differences in the frequency of osteoradionecrosis were observed between patients who had received spacers equal to or thicker than 5 mm and those who had received spacers less than 5 mm thick. Conclusion. A spacer should have a minimum thickness of 5 mm on its lingual flange to prevent the development of osteoradionecrosis of the mandible.
  • A Takahashi, M Yanase, N Masumori, H Sasamura, T Oda, T Tanaka, N Itoh, T Tsukamoto, A Oouchi, M Hareyama, H Shirato, K Takatsuka, N Miyao
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 33 2 73 - 77 2003年02月 [査読有り][通常論文]
     
    Purpose: We report the treatment results and complications of external beam radiation monotherapy for localized or locally advanced prostate cancer patients. Methods: Fifty-four patients with T1b-3aN0(pN(0))M-0 prostate cancer were treated with external beam radiation monotherapy between 1989 and 2001 at four institutes. Results: During the 4-122 month follow-up period (median: 25 months), 11 (20%) patients experienced biochemical failure, including one with simultaneous local recurrence. The 2-year actuarial biochemical control rate was 85%. Univariate analysis showed that the clinical T classification (P = 0.01), Gleason score (P = 0.006), pretreatment PSA (P = 0.02) and PSA nadir value (P = 0.01) were associated with a higher probability of biochemical failure. Multivariate analysis using the Cox proportional hazards model demonstrated that only the PSA nadir value was a strong predictor of PSA recurrence (P < 0.01). Adverse events were mild and tolerable. No severe urinary or bowel complications were observed. Conclusions: External beam radiation monotherapy is effective for clinically organ-confined prostate cancer with a low incidence of severe complications in a mean follow-up period of 2 years.
  • Y Shibamoto, N Hayabuchi, J Hiratsuka, S Tokumaru, H Shirato, M Sougawa, N Oya, Y Uematsu, M Hiraoka
    CANCER 97 1 128 - 133 2003年01月 [査読有り][通常論文]
     
    BACKGROUND. Neurotoxicity after whole-brain irradiation remains a major problem in the treatment of primary central nervous system lymphoma (PCNSL). To clarify whether whole-brain radiation is necessary for PCNSL, the authors retrospectively analyzed the outcome of patients treated with partial-brain irradiation. METHODS. A nationwide survey was performed regarding the treatment of PCNSL. Among 62 institutions surveyed, 7 were identified in which whole-brain irradiation was not necessarily employed. Questionnaires were sent to these institutions and 43 patients who had been treated using partial-brain fields since 1985 were collected. Thirty-two patients had solitary lesions and 11 had multiple lesions. Patterns of recurrence could be identified in 38 patients. RESULTS. The cumulative in-field and out-field recurrence rates at 5 years were 57% and 49%, respectively. Of 14 out-field recurrences, 2 occurred at the safety margin of the previous radiation field. The out-field recurrence rate was 45% in patients with a single lesion and 67% in those with multiple tumors (P = 0.79). The out-field recurrence rate was 22% for patients treated with safety margins of greater than or equal to 4 cm and 83% for those treated with safety margins of < 4 cm (P = 0.0079). The median survival time and the 5-year survival rate were 28.5 months and 20%, respectively, in the former group of patients and 15 months and 11%, respectively, in the latter group (P = 0.057). CONCLUSIONS. Focal radiotherapy with safety margins of < 4 cm appears to be associated with a very high rate of out-field recurrence, but the use of a radiation field with generous safety margins (greater than or equal to 4 cm) appears to be worth further investigation.
  • Gao M, Shirato H, Miyasaka K, Koyama T
    Advances in experimental medicine and biology 530 527 - 533 2003年 [査読有り][通常論文]
  • R Onimaru, H Shirato, H Aoyama, K Kitakura, T Seki, K Hida, K Fujita, K Kagei, T Nishioka, T Kunieda, Y Iwasaki, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 54 3 939 - 947 2002年11月 [査読有り][通常論文]
     
    Purpose: The efficacy of a prototypic fluoroscopic real-time tracking radiation therapy (RTRT) system using three gold markers (2 mm, in diameter) for estimating translational error, rotational setup error, and the dose to normal structures was tested in 5 patients with spinal schwannoma and a phantom. Methods and Materials: Translational error was calculated by comparing the actual position of the marker closest to the tumor to its planned position, and the rotational setup error was calculated using the three markers around the target. Theoretically, the actual coordinates can be adjusted to the planning coordinates by sequential rotation of gamma degrees around the z axis, beta degrees around the gamma axis, and alpha degrees around the x axis, in this order. We measured the accuracy of the rotational calculation using a phantom. Five patients with spinal schwannoma located at a minimum of 1-5 mm from the spinal cord were treated with RTRT. Three markers were inserted percutaneously into the paravertebral deep muscle in 3 patients and surgically into two consecutive vertebral bones in two other patients. Results: In the phantom study, the discrepancies between the actual and calculated rotational error were -0.1 +/- 0.5degrees. The random error of rotation was 5.9, 4.6, and 3.1degrees for alpha, beta, and gamma, respectively. The systematic error was 7.1, 6.6, and 3.0degrees for alpha, beta, and gamma, respectively. The mean rotational setup error (0.2 +/- 2.2, -1.3 +/- 2.9, and -1.3 +/- 1.7degrees for alpha, beta, and Psi, respectively) in 2 patients for whom surgical marker implantation was used was significantly smaller than that in 3 patients for whom percutaneous insertion was used (6.0 +/- 8.2, 2.7 +/- 5.9, and -2.1 +/- 4.6degrees for alpha, beta, and gamma). Random translational setup error was significantly reduced by the RTRT setup (p < 0.0001). Systematic setup error was significantly reduced by the RTRT setup only in patients who received surgical implantation of the marker (p < 0.0001). The maximum dose to the, spinal cord was estimated to be 40.6-50.3 Gy after consideration of the rotational setup error, vs. a planned maximum dose of 22.4-51.6 Gy. Conclusion: The RTRT system employing three internal fiducial markers is useful to reduce translational setup error and to estimate the dose to the normal structures in consideration of the rotational setup error. Surgical implantation of the marker to the vertebral bone was shown to be sufficiently rigid for the calculation of the rotational setup error. Fractionated radiotherapy for spinal schwannoma using the RTRT system may well be an alternative or supplement to surgical treatment. (C) 2002 Elsevier Science Inc.
  • T Nishihori, H Shirato, H Aoyama, R Onimaru, T Komae, N Ishii, J Ikeda, K Miyasaka, Y Sawamura, Y Iwasaki
    JOURNAL OF NEURO-ONCOLOGY 60 2 177 - 183 2002年11月 [査読有り][通常論文]
     
    Purpose: Although a gross total removal of astrocytic tumors offers a favorable prognosis, it is often difficult to achieve in the eloquent area of the brain. This study was conducted to investigate the possible gain of three-dimensional conformal radiotherapy (3DCRT) for astrocytic tumors located in the eloquent area in children and young adults. Materials and methods: Twenty patients with astrocytic tumors received the radiotherapy. The median age was 17 years, ranging from 4 to 30 years. Fourteen low-grade tumors (seven pilocytic and seven diffuse), and six high-grade tumors (five anaplastic, one malignant pilocytic) were included. Tumors were located at the thalamus/hypothalamus in 12 cases, optic tract in one case, and the deep cerebral/cerebellar hemisphere in seven cases. A specific fixation device was used for 3DCRT. Forty-six Gy for low-grade tumors and 54 Gy for high-grade astrocytomas with 1.8-2.0 Gy per fraction were in principle employed as the standard regimen. Nominal radiotherapy fields ranged from 2.0 x 2.0 to15.0 x 11.0 cm(2). The median follow-up period was 42 months, ranging from 3 to 108 months. Results: The actuarial survival rate at 5 years was 68% +/- 13% for all patients. The actuarial survival rate for low-grade glioma was 79% +/- 14% at 5 years and 50% +/- 20% at 3 years for high-grade glioma. The actual progression-free survival rate was 83% +/- 11% at 5 years for low-grade glioma and 50% +/- 20% for high-grade glioma. A complete response was obtained in three (21%) of 14 patients with low-grade astrocytic tumors. Two patients with low-grade tumors and four of six with high-grade tumors died due to tumor progression with infield relapse but not marginal relapse. Twelve survivors with low-grade tumors showed no signs of relapse and no neurological, hormonal, or cognitive deterioration after radiotherapy and were able to attend their school or continue with a full-time job. Conclusions: 3DCRT is safe and effective for low-grade astrocytic tumors located in the eloquent area in children and young adults.
  • S Fukumoto, H Shirato, S Shimzu, S Ogura, R Onimaru, K Kitamura, K Yamazaki, K Miyasaka, M Nishimura, H Dosaka-Akita
    CANCER 95 7 1546 - 1553 2002年10月 [査読有り][通常論文]
     
    BACKGROUND. Occasionally, medically compromised and/or elderly patients with nonsmall cell lung carcinomas (NSCLCs) cannot be treated surgically. We investigated small-volume hypofractionated image-guided radiotherapy (IGRT) without the need for breath control in patients with inoperable Stage I NSCLCs. METHODS. Between September 1996 and September 1999, 22 patients with Stage 1 NSCLCs, including 19 males and 3 females, were treated with IGRT. Among these patients, there were 13 Stage IA and 9 Stage IB tumors. The tumors ranged in size from 14.2 to 58.5 mm, with a median size of 26.7 mm. Of the 22 patients, 19 were unfit for surgical treatment due to poor pulmonary function, complications, and/or advanced age and 3 refused surgery. Computed tomographic scans (CT) of the primary tumor were taken during three respiratory phases and they were analyzed to determine the planning target volume, which included only the primary tumor with allowances for respiratory movement. The radiation doses administered at the edge of the moving tumor during normal breathing were 80% of the prescribed dose, either 48 or 60 Gy given in eight fractions over 2 weeks. Clinical evaluation, chest CT scan, and pulmonary function tests were performed before irradiation and at regular intervals for the post-IGRT follow-up. The median follow-up period was 24 months (range, 2-44 months; mean, 21.8 months) (at least 24 months for survivors). RESULTS. Of 17 tumors assessed at the initial follow-up 2-6 months after treatment (5 complete responses, 11 partial responses, and 1 progressive disease), 16 (94%) were controlled locally. One local recurrence was observed during the follow-up. The lung carcinoma-specific survival rate at 1 year was 94% and the 1-year actuarial recurrence-free survival rate was 71%. The lung carcinoma-specific survival rate at 2 years was 73% and the 2-year actuarial recurrence-free survival rate was 67%. The treatment was well tolerated and no major side effects were observed. Localized radiation pneumonitis was observed in all patients who were examined by CT scan, but the patients were asymptomatic. Parameters of pulmonary function, including vital capacity, total lung capacity, and diffusion capacity for carbon monoxide, decreased very little or not at all, indicating that IGRT rarely deteriorated pulmonary functions. CONCLUSIONS. Small-volume hypofractionated IGRT without breath control is a feasible and beneficial method for the curative treatment of patients with Stage I NSCLCs. It has the potential of a high local tumor control rate and low morbidity.
  • T Harada, H Shirato, S Ogura, S Oizumi, K Yamazaki, S Shimizu, R Onimaru, K Miyasaka, M Nishimura, H Dosaka-Akita
    CANCER 95 8 1720 - 1727 2002年10月 [査読有り][通常論文]
     
    BACKGROUND. The authors developed fluoroscopic real-time tumor-tracking radiation therapy (RTRT) by insertion of a gold marker using bronchofiberscopy to reduce uncertainties in organ motion and set-up error in external radiotherapy for moving tumors. The purpose of the current study was to evaluate RTRT's feasibility in lung carcinoma treatment. METHODS. The three-dimensional position of a 1.0-2.0 mm gold marker in or near the tumor was detected by two sets of fluoroscopies every 0.03 seconds. The treatment beam was gated to irradiate the tumor only when the position of the marker coincided with its planned position using the RTRT system. Bronchofiberscopic equipment for insertion of the marker into the lung tumor was developed and used for 20 lung tumors in 18 patients. Patients were given high dose hypofractionated focal irradiation (35-48 Gy in 4-8 fractions in 4-10 days) with a planning target volume margin of 5 mm for the tumor. RESULTS. The markers were successfully inserted and maintained at the inserted position during and after the radiotherapy it) 14 (88%) of 16 peripheral-type lung tumors and in none of four central-type lung tumors, indicating that this method of RTRT was not feasible for central-type lung tumors. Tracking of the marker was successfully performed in I of 2 tumors with a 1.0 mm marker and in all of 12 tumors with a 1.5-2.0 mm marker. On the whole, 13 (65%) of the 20 tumors were successfully treated with RTRT. Local tumor control was achieved and maintained for all 12 patients (13 tumors), who were treated with RTRT, with a median followup of 9 months (range, 5-15). Localized radiation pneumonitis was found radiographically at the lung volume that was irradiated with about 20 Gy, without symptoms in all but one patient. CONCLUSIONS. The insertion of a gold marker into or near peripheral-type lung tumors using bronchofiberscopy is a feasible and safe technique. Excellent initial response and low incidence of clinical complications suggest that the high dose hypofractionated focal irradiation using the RTRT system can be a good local treatment for peripheral-type lung tumors. (C) 2002 American Cancer Society.
  • K Kitamura, H Shirato, Y Seppenwoolde, R Onimaru, M Oda, K Fujita, S Shimizu, N Shinohara, T Harabayashi, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 53 5 1117 - 1123 2002年08月 [査読有り][通常論文]
     
    Purpose: To quantify three-dimensional (3D) movement of the prostate gland with the patient in the supine and prone positions and to analyze the movement frequency for each treatment position. Methods and Materials: The real-time tumor-tracking radiotherapy (RTRT) system was developed to identify the 3D position of a 2-mm gold marker implanted in the prostate 30 times/s using two sets of fluoroscopic images. The linear accelerator was triggered to irradiate the tumor only when the gold marker was located within the region of the planned coordinates relative to the isocenter. Ten patients with prostate cancer treated with RTRT were the subjects of this study. The coordinates of the gold marker were recorded every 0.033 s during RTRT in the supine treatment position for 2 min. The patient was then moved to the prone position, and the marker was tracked for 2 min to acquire data regarding movement in this position. Measurements were taken 5 times for each patient (once a week); a total of 50 sets for the 10 patients was analyzed. The raw data from the RTRT system were filtered to reduce system noise, and the amplitude of movement was then calculated. The discrete Fourier transform of the unfiltered data was performed for the frequency analysis of prostate movement. Results: No apparent difference in movement was found among individuals. The amplitude of 3D movement was 0.1-2.7 mm in the supine and 0.4-24 mm in the prone positions. The amplitude in the supine position was statistically smaller in all directions than that in the prone position (p < 0.0001). The amplitude in the craniocaudal and AP directions was larger than in the left-right direction in the prone position (p < 0.0001). No characteristic movement frequency was detected in the supine position. The respiratory frequency was detected for all patients regarding movement in the craniocaudal and AP directions in the prone position. The results of the frequency analysis suggest that prostate movement is affected by the respiratory cycle and is influenced by bowel movement in the prone position. Conclusion: The results of this study have confirmed that internal organ motion is less frequent in the supine position than in the prone position in the treatment of prostate cancer. RTRT would be useful in reducing uncertainty due to the effects of the respiratory cycle, especially in the prone position. (C) 2002 Elsevier Science Inc.
  • Y Seppenwoolde, H Shirato, K Kitamura, S Shimizu, M van Herk, JV Lebesque, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 53 4 822 - 834 2002年07月 [査読有り][通常論文]
     
    Purpose: In this work, three-dimensional (3D) motion of lung tumors during radiotherapy in real time was investigated. Understanding the behavior of tumor motion in lung tissue to model tumor movement is necessary for accurate (gated or breath-hold) radiotherapy or CT scanning. Methods: Twenty patients were included in this study. Before treatment, a 2-mm gold marker was implanted in or near the tumor. A real-time tumor tracking system using two fluoroscopy image processor units was installed in the treatment room. The 3D position of the implanted gold marker was determined by using real-time pattern recognition and a calibrated projection geometry. The linear accelerator was triggered to irradiate the tumor only when the gold marker was located within a certain volume. The system provided the coordinates of the gold marker during beam-on and beam-off time in all directions simultaneously, at a sample rate of 30 images per second. The recorded tumor motion was analyzed in terms of the amplitude and curvature of the tumor motion in three directions, the differences in breathing level during treatment, hysteresis (the difference between the inhalation and exhalation trajectory of the tumor), and the amplitude of tumor motion induced by cardiac motion. Results: The average amplitude of the tumor motion was greatest (12 +/- 2 mm [SD]) in the cranial-caudal direction for tumors situated in the lower lobes and not attached to rigid structures such as the chest wall or vertebrae. For the lateral and anterior-posterior directions, tumor motion was small both for upper- and lower-lobe tumors (2 +/- 1 mm). The time-averaged tumor position was closer to the exhale position, because the tumor spent more time in the exhalation than in the inhalation phase. The tumor motion was modeled as a sinusoidal movement with varying asymmetry. The tumor position in the exhale phase was more stable than the tumor position in the inhale phase during individual treatment fields. However, in many patients, shifts in the exhale tumor position were observed intra- and inter-fractionally. These shifts are the result of patient relaxation, gravity (posterior direction), setup errors, and/or patient movement. The 3D trajectory of the tumor showed hysteresis for 10 of the 21 tumors, which ranged from 1 to 5 mm. The extent of hysteresis and the amplitude of the tumor motion remained fairly constant during the entire treatment. Changes in shape of the trajectory of the tumor were observed between subsequent treatment days for only one patient. Fourier analysis revealed that for 7 of the 21 tumors, a measurable motion in the range 1-4 mm was caused by the cardiac beat. These tumors were located near the heart or attached to the aortic arch. The motion due to the heartbeat was greatest in the lateral direction. Tumor motion due to hysteresis and heartbeat can lower treatment efficiency in real-time tumor tracking-gated treatments or lead to a geographic miss in conventional or active breathing controlled treatments. Conclusion: The real-time tumor tracking system measured the tumor position in all three directions simultaneously, at a sampling rate that enabled detection of tumor motion due to heartbeat as well as hysteresis. Tumor motion and hysteresis could be modeled with an asymmetric function with varying asymmetry. Tumor motion due to breathing was greatest in the cranial-caudal direction for lower-lobe unfixed tumors. (C) 2002 Elsevier Science Inc.
  • T Nishioka, T Shiga, H Shirato, E Tsukamoto, K Tsuchiya, T Kato, K Ohmori, A Yamazaki, H Aoyama, S Hashimoto, TC Chang, K Miyasaka
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 53 4 1051 - 1057 2002年07月 [査読有り][通常論文]
     
    Purpose: Accurate diagnosis of tumor extent is important in three-dimensional conformal radiotherapy. This study reports the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET) and magnetic resonance imaging/computed tomography (MRI/CT) for better targets delineation in radiotherapy planning of head-and-neck cancers. Methods and Materials: The subjects consisted of 12 patients with oropharyngeal carcinoma and 9 patients with nasopharyngeal carcinoma (NPC) who were treated with radical radiotherapy between July 1999 and February 2001. Image fusion between (18)FDG-PET and MRI/CT was performed using an automatic multimodality image registration algorithm, which used the brain as an internal reference for registration. Gross tumor volume (GTV) was determined based on clinical examination and (18)FDG uptake on the fusion images. Clinical target volume (CTV) was determined following the usual pattern of lymph node spread for each disease entity along with the clinical presentation of each patient. Results: Except for 3 cases with superficial tumors, all the other primary tumors were detected by (18)FDG-PET. The GTV volumes for primary tumors were not changed by image fusion in 19 cases (89%), increased by 49% in one NPC, and decreased by 45% in another NPC. Normal tissue sparing was more easily performed based on clearer GTV and CTV determination on the fusion images. In particular, parotid sparing became possible in 15 patients (71%) whose upper neck areas near the parotid glands were tumor-free by (18)FDG-PET. Within a mean follow-up period of 18 months, no recurrence occurred in the areas defined as CTV, which was treated prophylactically, except for 1 patient who experienced nodal recurrence in the CTV and simultaneous primary site recurrence. Conclusion: This preliminary study showed that image fusion between (18)FDG-PET and MRI/CT was useful in GTV and CTV determination in conformal RT, thus sparing normal tissues. (C) 2002 Elsevier Science Inc.
  • H Shirato, H Aoyama, K Hida, Y Sawamura, K Miyasaka, Y Iwasaki
    NEUROLOGICAL SURGERY 30 6 579 - 591 2002年06月 [査読有り][通常論文]
  • M Hareyama, K Sakata, H Shirato, T Nishioka, M Nishio, K Suzuki, A Saitoh, A Oouchi, S Fukuda, T Himi
    CANCER 94 8 2217 - 2223 2002年04月 [査読有り][通常論文]
     
    BACKGROUND. A prospective, randomized study was performed to determine the efficacy of neoadjuvant chemotherapy over radiotherapy alone in patients with locally advanced nasopharyngeal carcinoma. METHODS. From January 1991 to December 1998, 80 patients were enrolled in this study. Patients with locoregional carcinoma of the nasopharynx were randomized to receive two courses of chemotherapy, consisting of cisplatin and 5-fluorouracil (CDDP-5FU), that were administered before radiation therapy (CT arm) or radiotherapy alone. The patients who received neoadjuvant chemotherapy were treated with radiation therapy, which was scheduled to commence 2 weeks after the second course chemotherapy. RESULTS. With a median follow-up of 49 months, a trend toward improved overall survival or disease free survival favoring the CT arm was observed (5-year overall survival rate, 60% vs. 48%; 5-year disease free survival rate, 55% vs. 43%.), although this difference was not significant. There were no differences in locoregional failure free survival between the two arms. However, metastasis free survival favored the CT arm, although this difference was not significant. The results also demonstrated that most patients in the CT arm who experienced recurrent disease developed locoregional recurrences before distant metastases, suggesting that improvements in locoregional control may lead to improved disease free survival. CONCLUSIONS. The use of CDDP-5FU chemotherapy prior to radiotherapy in patients with nasopharyngeal carcinoma did not result in a significant improvement in disease free survival or overall survival. However, there was a positive tendency in favor of the CT arm for distant metastasis free survival, although there was no improvement in the locoregional recurrence free survival rate. (C) 2002 American Cancer Society.
  • K Kagei, M Hosokawa, H Shirato, T Kusumi, Y Shimizu, A Watanabe, M Ueda
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 32 4 120 - 127 2002年04月 [査読有り][通常論文]
     
    Background: The optimum management of esophageal cancers with synchronous second primary cancer (SPC) has not been determined. The aim of this study was to evaluate the efficacy of intense screening and treatment for esophageal cancers with synchronous SPC. Methods: Between 1981 and 1997, 1479 patients with esophageal cancers were screened for synchronous SPC during the process of initial staging. Radical treatment was recommended for esophageal cancer and synchronous SPC in cases for whom both cancers were curable. Treatment results for esophageal cancer patients with or without synchronous SPC were compared. Results: Among 1479 patients, 155 (10.5%) were found to have 166 synchronous SPC. Primary sites included the stomach in 65, the head and neck in 44, the colon/rectum in 27, the lung in 14 and other sites in 16 patients. Clinical stages of synchronous SPC were stage I in 41%, stage 11 in 20%, stage III in 25% and stage IV in 14%. The 5-year overall survival rates by clinical stages of esophageal cancers (stage 0, 1, 11, 111, IV) in patients with synchronous SPC were 51% (95% Cl, 23-78%),43% (95% Cl, 18-68%),11% (95% Cl, 0-22%),14% (95% Cl, 0-28%) and 12% (95% Cl, 1-22%), respectively. The 5-year overall survival rate for patients with or without synchronous SPC were 20% (95% Cl, 13-28%) and 32% (95% Cl, 29-35%), respectively. No significant difference was observed between both groups (p = 0.2562). Conclusions: Intense screening and treatment may be justifiable in the light of the high detection rate of curable SPC and the reasonable survival of patients with synchronous SPC. However, a prospective study including cost-benefit analysis is needed to provide the evidence to justify the intense screening and treatment.
  • K Kitamura, H Shirato, S Shimizu, N Shinohara, T Harabayashi, T Shimizu, Y Kodama, H Endo, R Onimaru, S Nishioka, H Aoyama, K Tsuchiya, K Miyasaka
    RADIOTHERAPY AND ONCOLOGY 62 3 275 - 281 2002年03月 [査読有り][通常論文]
     
    Background and purpose: We have developed a linear accelerator synchronized with a fluoroscopic real-time tumor-tracking system to reduce errors due to setup and organ motion. In the real-time tumor-tracking radiation therapy (RTRT) system, the accuracy of tumor tracking depends on the registration of the marker's coordinates. The registration accuracy and possible migration of the internal fiducial gold marker implanted into prostate and liver was investigated. Materials and methods: Internal fiducial gold markers were implanted in 14 patients with prostate cancer and four patients with liver tumors. computed tomography (CT) was carried out as a part of treatment planning in the IS patients. A total of 72 follow-up CT scans were taken. We calculated the relative relationship between the coordinates of the center of mass (CM) of the organs and those of the marker. The discrepancy in the CM coordinates during a follow-up CT compared to those recorded during the planning CT was used to study possible marker migration. Results: The standard deviation (SD) of interobserver variations in the CM coordinates was within 2.0 and 0.4 mm for the organ and the marker, respectively, in seven observers. Assuming that organs do not shrink, grow, or rotate, the maximum SD of migration error in each direction was estimated to be less than 2.5 and 2.0 mm for liver and prostate, respectively. There was no correlation between the marker position and the time after implantation. Conclusion: The degree of possible migration of the internal fiducial marker was within the limits of accuracy of the CT measurement. Most of the marker movement can be attributed to the measurement uncertainty, which also influences registration in actual treatment planning. Thus, even with the gold marker and RTRT system, a planning target volume margin should be used to account for registration uncertainty. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
  • H Aoyama, H Shirato, J Ikeda, K Fujieda, K Miyasaka, Y Sawamura
    JOURNAL OF CLINICAL ONCOLOGY 20 3 857 - 865 2002年02月 [査読有り][通常論文]
     
    Purpose : To investigate the efficacy of chemotherapy followed by low-dose involved-field radiotherapy for the treatment of intracranial germ cell tumors (GCTs). Patients and Methods: Thirty-three patients with GCTs, including 16 pure germinomas, 11 human chorionic gonadotropin-beta (HCG-beta)-secreting germinomas, three mixed GCTs composed of immature teratomas plus germinomas (IMT/G), and three highly malignant mixed GCTs, were treated. Etoposide and cisplatin (EP) were used for the treatment of solitary pure germinomos, and ifosfamide, cisplatin, and etoposide (ICE) were used for the treatment of other GCTs. The dose schedule was 24 Gy for germinomas and 40 to 54 Gy for other GCTs. An involved-field set-up was used except for highly malignant GCTs, in which craniospinal irradiation was used. The median follow-up was 58 months (range, 18 to 102 months). Results: Disease-related, overall, and relapse-free survival rates at S years were 100%, 93%, and 69% for all patients, 100%, 100%, and 86% for patients with pure germinomas, and 100%, 75%, and 44% for patients with HCG-beta-secreting germinomas, respectively. All six patients with nongerminomatous GCTs were alive at the last follow-up. All eight relapses (one pure germinoma, five HCG-beta-secreting germinomas, and two IMT/G), except one in a course of salvage treatment, were salvaged and free of disease at the lost follow-up. No decline was observed in the full-scale, verbal, or performance intelligence quotient at 12 to 51 months after the treatment in 11 patients. Conclusion: Our results support an excellent prognosis after EP and ICE regimens followed by radiotherapy. Dose and volume can be reduced to 24 Gy in 12 fractions and involve a field set-up after EP chemotherapy for the treatment of pure germinomas. (C) 2002 by American Society of Clinical Oncology.
  • Shirato H, Onimaru R, Kitamura K, Watanabe Y, Furuya T, Fujita K, Nangumo J, Oda M, Oita M
    Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics 21 17 - 27 1 2001年 [査読有り][通常論文]
  • Prof.
    白土 博樹
    [査読有り][通常論文]

書籍

  • Image-Guided RADIATION TEHRAPY
    PMPH-USA 2011年
  • 肺癌の臨床「疫学」「病理・分子生物学」「発見・診断」「治療」「診断・治療」
    株式会社篠原出版新社 2008年
  • エビデンス放射線治療
    中外医学社 2007年

その他活動・業績

  • Hiroyuki Kameda, Kohsuke Kudo, Tsuyoshi Matsuda, Taisuke Harada, Yuji Iwadate, Ikuko Uwano, Fumio Yamashita, Kunihiro Yoshioka, Makoto Sasaki, Hiroki Shirato Journal of magnetic resonance imaging : JMRI 48 (1) 94 -101 2018年07月 [査読無し][通常論文]
     
    BACKGROUND: Respiration-induced phase shift affects B0 /B1+ mapping repeatability in parallel transmission (pTx) calibration for 7T brain MRI, but is improved by breath-holding (BH). However, BH cannot be applied during long scans. PURPOSE: To examine whether interleaved acquisition during calibration scanning could improve pTx repeatability and image homogeneity. STUDY TYPE: Prospective. SUBJECTS: Nine healthy subjects. FIELD STRENGTH/SEQUENCE: 7T MRI with a two-channel RF transmission system was used. ASSESSMENT: Calibration scanning for B0 /B1+ mapping was performed under sequential acquisition/free-breathing (Seq-FB), Seq-BH, and interleaved acquisition/FB (Int-FB) conditions. The B0 map was calculated with two echo times, and the B1+ map was obtained using the Bloch-Siegert method. Actual flip-angle imaging (AFI) and gradient echo (GRE) imaging were performed using pTx and quadrature-Tx (qTx). All scans were acquired in five sessions. Repeatability was evaluated using intersession standard deviation (SD) or coefficient of variance (CV), and in-plane homogeneity was evaluated using in-plane CV. STATISTICAL TESTS: A paired t-test with Bonferroni correction for multiple comparisons was used. RESULTS: The intersession CV/SDs for the B0 /B1+ maps were significantly smaller in Int-FB than in Seq-FB (Bonferroni-corrected P < 0.05 for all). The intersession CVs for the AFI and GRE images were also significantly smaller in Int-FB, Seq-BH, and qTx than in Seq-FB (Bonferroni-corrected P < 0.05 for all). The in-plane CVs for the AFI and GRE images in Seq-FB, Int-FB, and Seq-BH were significantly smaller than in qTx (Bonferroni-corrected P < 0.01 for all). DATA CONCLUSION: Using interleaved acquisition during calibration scans of pTx for 7T brain MRI improved the repeatability of B0 /B1+ mapping, AFI, and GRE images, without BH. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.
  • Kinya Ishizaka, Kohsuke Kudo, Kuniaki Harada, Toru Shirai, Taro Fujiwara, Suzuko Aoike, Sayaka Takamori, Hiroki Shirato Journal of magnetic resonance imaging : JMRI 47 (1) 123 -130 2018年01月 [査読無し][通常論文]
     
    PURPOSE: To evaluate the homogeneity of the radiofrequency magnetic field (B1+ ) and signal intensity using different arm positions during 3T thoracolumbar spinal imaging. MATERIALS AND METHODS: Twenty volunteers were scanned with a four-channel radiofrequency (RF) transmit coil at 3T, with arms on the bed (conventional), arms elevated by 100 mm (arm lift), or with the arms-up position (elevated arm). Axial B1+ maps and sagittal T1 -weighted image (T1 WI)-performed RF shimming were obtained for each arm position. The mean and standard deviation (SD) of the flip angle (FA) at the center of the vertebra on each B1+ map, and contrast noise ratios (CNRs) between the spinal cord and cerebrospinal fluid of sagittal T1 WI, were calculated and compared among the different arm positions. RESULTS: Mean FA values (degrees) for the arm lift and elevated arm positions were significantly larger than for the conventional position (P < 0.001 for both) at the twelfth thoracic vertebra (Th12). FA SD values for the arm lift and elevated arm position were significantly smaller than for the conventional position (P < 0.001 for both) at Th12. CNR for the arm lift and elevated arm position were significantly higher than for the conventional position (P = 0.007 and 0.002, respectively). The mean and SD of the FA and the CNR did not differ significantly for the arm lift and elevated arm positions (P = 0.591, 0.958, and 0.927, respectively). CONCLUSION: Inhomogeneities of B1+ and signal intensities were improved by simply changing the arm position in 3T thoracolumbar spinal imaging. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:123-130.
  • Khin Khin Tha, Ulrich Katscher, Shigeru Yamaguchi, Christian Stehning, Shunsuke Terasaka, Noriyuki Fujima, Kohsuke Kudo, Ken Kazumata, Toru Yamamoto, Marc Van Cauteren, Hiroki Shirato European radiology 28 (1) 348 -355 2018年01月 [査読無し][通常論文]
     
    OBJECTIVES: This study noninvasively examined the electrical conductivity (σ) characteristics of diffuse gliomas using MRI and tested its validity. METHODS: MRI including a 3D steady-state free precession (3D SSFP) sequence was performed on 30 glioma patients. The σ maps were reconstructed from the phase images of the 3D SSFP sequence. The σ histogram metrics were extracted and compared among the contrast-enhanced (CET) and noncontrast-enhanced tumour components (NCET) and normal brain parenchyma (NP). Difference in tumour σ histogram metrics among tumour grades and correlation of σ metrics with tumour grades were tested. Validity of σ measurement using this technique was tested by correlating the mean tumour σ values measured using MRI with those measured ex vivo using a dielectric probe. RESULTS: Several σ histogram metrics of CET and NCET of diffuse gliomas were significantly higher than NP (Bonferroni-corrected p ≤ .045). The maximum σ of NCET showed a moderate positive correlation with tumour grade (r = .571, Bonferroni-corrected p = .018). The mean tumour σ measured using MRI showed a moderate positive correlation with the σ measured ex vivo (r = .518, p = .040). CONCLUSIONS: Tissue σ can be evaluated using MRI, incorporation of which may better characterise diffuse gliomas. KEY POINTS: • This study tested the validity of noninvasive electrical conductivity measurements by MRI. • This study also evaluated the electrical conductivity characteristics of diffuse glioma. • Gliomas have higher electrical conductivity values than the normal brain parenchyma. • Noninvasive electrical conductivity measurement can be helpful for better characterisation of glioma.
  • Satoshi Yabusaki, Noriko Oyama-Manabe, Osamu Manabe, Kenji Hirata, Fumi Kato, Noriyuki Miyamoto, Yoshihiro Matsuno, Kohsuke Kudo, Nagara Tamaki, Hiroki Shirato EJNMMI research 7 (1) 20 -20 2017年12月 [査読無し][通常論文]
     
    BACKGROUND: We aimed to assess the positivity, distribution, quantitative degree of vessel inflammation, and clinical characteristics of IgG4-related aortitis/periarteritis and periarteritis (IgG4-aortitis), and to examine the difference in these characteristics between cases with and without IgG4-aortitis, using fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) co-registered with contrast-enhanced CT (CECT). We retrospectively evaluated 37 patients with IgG4-related disease (IgG4-RD) who underwent both FDG-PET/CT and CECT. The arterial SUVmax and its value normalized to the background venous blood pool (BP)-the target-to-background ratio (TBR) in the entire aorta and the major first branches-were measured. Active vascular inflammation was considered in cases with a higher FDG uptake than BP and a thickened arterial wall (>2 mm). RESULTS: Fifteen (41%) patients exhibited IgG4-aortitis. Most patients (80%) showed multiple region involvement. The entire aorta, including the major first branches, were involved, typically showing a thickened wall and high FDG uptakes. The most common site was the iliac arteries (35%), followed by the infrarenal abdominal aorta (33%), thoracic aorta (8%), first branches of the thoracic aorta (8%), suprarenal abdominal aorta (6%), and the first branches of the abdominal aorta (5%). The IgG4-aortitis-positive vessel regions were thickened, with an average maximal wall thickness of 6.3 ± 2.9 mm. The SUVmax and TBR values were significantly higher in the IgG4-aortitis-positive regions (median 3.7 [1.6-5.5] and 2.1 [1.4-3.7], respectively) than in the IgG4-aortitis-negative regions (median 2.1 [1.2-3.7] and 1.3 [0.9-2.3], respectively; p < 0.0001). The IgG4-aortitis-positive group patients were older (69.5 ± 6.0 vs. 63.3 ± 12.6 years, respectively) and had a higher male predominance (80 vs. 55%, respectively) than the negative group, although the differences were not significant (p = 0.17 and p = 0.06, respectively). CONCLUSIONS: We investigated the image characteristics of IgG4-aortitis. The entire aorta and major branches can be involved with more than 2-fold higher FDG uptake than the venous background pool, and with wall thickening. The most common involved site is the iliac arteries, followed by the infrarenal abdominal aorta.
  • Keita Sakamoto, Keita Sakamoto, Noriko Oyama-Manabe, Osamu Manabe, Tadao Aikawa, Yasuka Kikuchi, Yasuka Kikuchi, Harue Sasai-Masuko, Masanao Naya, Kohsuke Kudo, Fumi Kato, Nagara Tamaki, Hiroki Shirato Japanese Journal of Radiology 1 -10 2017年11月09日 [査読無し][通常論文]
     
    © 2017 Japan Radiological Society Purpose: To evaluate heterogeneity of myocardial contraction in relation to extensive late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction, using fast strain-encoded magnetic resonance imaging. Materials and methods: Twenty-two HCM patients and 24 age-matched control subjects were included in this retrospective study. The regional and global peak values of longitudinal and circumferential strain (LS regional , LS global , CS regional , CS global ), and their regional heterogeneities were evaluated using coefficients of variation (LS CoV , CS CoV ) in relation to LGE. Receiver operating characteristic curve analysis was performed to identify patients with a total left ventricular myocardial LGE ≥ 15%. Results: LS global in HCM patients was significantly decreased compared to that in controls (− 14.4 ± 2.4% vs − 17.2 ± 2.0%; p = 0.0004), while CS global was not (p = 1.0). Negative LGE segments demonstrated decreased LS regional in HCM patients compared to in controls (p < 0.0001), while CS regional was not decreased. CS CoV demonstrated the largest area under the curve (AUC) (0.91), with high sensitivity (83%) and specificity (94%) for detection of HCM patients with extensive LGE, while the AUC of LS CoV was low (0.49). Conclusion: The heterogeneity in CS regional has a high diagnostic value for detection of HCM patients with extensive LGE.
  • Jia Wu, Xiaoli Sun, Jeff Wang, Yi Cui, Fumi Kato, Hiroki Shirato, Debra M. Ikeda, Ruijiang Li JOURNAL OF MAGNETIC RESONANCE IMAGING 46 (4) 1017 -1027 2017年10月 [査読無し][通常論文]
     
    Purpose: To determine whether dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) characteristics of the breast tumor and background parenchyma can distinguish molecular subtypes (ie, luminal A/B or basal) of breast cancer. Materials and Methods: In all, 84 patients from one institution and 126 patients from The Cancer Genome Atlas (TCGA) were used for discovery and external validation, respectively. Thirty-five quantitative image features were extracted from DCE-MRI (1.5 or 3T) including morphology, texture, and volumetric features, which capture both tumor and background parenchymal enhancement (BPE) characteristics. Multiple testing was corrected using the Benjamini-Hochberg method to control the false-discovery rate (FDR). Sparse logistic regression models were built using the discovery cohort to distinguish each of the three studied molecular subtypes versus the rest, and the models were evaluated in the validation cohort. Results: On univariate analysis in discovery and validation cohorts, two features characterizing tumor and two characterizing BPE were statistically significant in separating luminal A versus nonluminal A cancers; two features characterizing tumor were statistically significant for separating luminal B; one feature characterizing tumor and one characterizing BPE reached statistical significance for distinguishing basal (Wilcoxon P < 0.05, FDR < 0.25). In discovery and validation cohorts, multivariate logistic regression models achieved an area under the receiver operator characteristic curve (AUC) of 0.71 and 0.73 for luminal A cancer, 0.67 and 0.69 for luminal B cancer, and 0.66 and 0.79 for basal cancer, respectively. Conclusion: DCE-MRI characteristics of breast cancer and BPE may potentially be used to distinguish among molecular subtypes of breast cancer.
  • Noriyuki Kadoya, Kumiko Karasawa, Iori Sumida, Hidetaka Arimura, Yasumasa Kakinohana, Shigeto Kabuki, Hajime Monzen, Teiji Nishio, Hiroki Shirato, Syogo Yamada JOURNAL OF RADIATION RESEARCH 58 (5) 669 -674 2017年09月 [査読無し][通常論文]
     
    The promotion plan for the Platform of Human Resource Development for Cancer (Ganpro) was initiated by the Ministry of Education, Culture, Sports, Science and Technology of Japan in 2007, establishing a curriculum for medical physicists. In this study, we surveyed the educational outcomes of the medical physicist program over the past 10 years since the initiation of Ganpro. The Japan Society of Medical Physics mailing list was used to announce this survey. The questionnaire was created by members of the Japanese Board for Medical Physicist Qualification, and was intended for the collection of information regarding the characteristics and career paths of medical physics students. Students who participated in the medical physics program from 2007 to 2016 were enrolled. Thirty-one universities (17 accredited and 14 non-accredited) were represented in the survey. In total, 491, 105 and 6 students were enrolled in the Master's, Doctorate and Residency programs, respectively. Most students held a Bachelor's degree in radiological technology (Master's program, 87%; Doctorate program, 72%). A large number of students with a Master's degree worked as radiological technologists (67%), whereas only 9% (n = 32) worked as medical physicists. In contrast, 53% (n = 28) of the students with a Doctorate degree worked as medical physicists. In total, 602 students (from 31 universities) completed the survey. Overall, although the number of the graduates who worked as medical physicists was small, this number increased annually. It thus seems that medical institutions in Japan are recognizing the necessity of licensed medical physicists in the radiotherapy community.
  • Yi Cui, Shangjie Ren, Khin Khin Tha, Jia Wu, Hiroki Shirato, Ruijiang Li EUROPEAN RADIOLOGY 27 (9) 3583 -3592 2017年09月 [査読無し][通常論文]
     
    To develop and validate a volume-based, quantitative imaging marker by integrating multi-parametric MR images for predicting glioblastoma survival, and to investigate its relationship and synergy with molecular characteristics. We retrospectively analysed 108 patients with primary glioblastoma. The discovery cohort consisted of 62 patients from the cancer genome atlas (TCGA). Another 46 patients comprising 30 from TCGA and 16 internally were used for independent validation. Based on integrated analyses of T1-weighted contrast-enhanced (T1-c) and diffusion-weighted MR images, we identified an intratumoral subregion with both high T1-c and low ADC, and accordingly defined a high-risk volume (HRV). We evaluated its prognostic value and biological significance with genomic data. On both discovery and validation cohorts, HRV predicted overall survival (OS) (concordance index: 0.642 and 0.653, P < 0.001 and P = 0.038, respectively). HRV stratified patients within the proneural molecular subtype (log-rank P = 0.040, hazard ratio = 2.787). We observed different OS among patients depending on their MGMT methylation status and HRV (log-rank P = 0.011). Patients with unmethylated MGMT and high HRV had significantly shorter survival (median survival: 9.3 vs. 18.4 months, log-rank P = 0.002). Volume of the high-risk intratumoral subregion identified on multi-parametric MRI predicts glioblastoma survival, and may provide complementary value to genomic information. aEuro cent High-risk volume (HRV) defined on multi-parametric MRI predicted GBM survival. aEuro cent The proneural molecular subtype tended to harbour smaller HRV than other subtypes. aEuro cent Patients with unmethylated MGMT and high HRV had significantly shorter survival. aEuro cent HRV complements genomic information in predicting GBM survival.
  • Yukiko Nishikawa, Koichi Yasuda, Shozo Okamoto, Yoichi M. Ito, Rikiya Onimaru, Tohru Shiga, Kazuhiko Tsuchiya, Shiro Watanabe, Wataru Takeuchi, Yuji Kuge, Hao Peng, Nagara Tamaki, Hiroki Shirato RADIATION ONCOLOGY 12 2017年09月 [査読無し][通常論文]
     
    Background: Hypoxic cancer cells are thought to be radioresistant and could impact local recurrence after radiotherapy (RT). One of the major hypoxic imaging modalities is [F-18] fluoromisonidazole positron emission tomography (FMISO-PET). High FMISO uptake before RT could indicate radioresistant sites and might be associated with future local recurrence. The predictive value of FMISO-PET for intra-tumoral recurrence regions was evaluated using high-resolution semiconductor detectors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). Methods: Nine patients with local recurrence and 12 patients without local recurrence for more than 3 years were included in this study. These patients received homogeneous and standard doses of radiation to the primary tumor irrespective of FMISO uptake. The FMISO-PET image before RT was examined via a voxel-based analysis, which focused on the relationship between the degree of FMISO uptake and recurrence region. Results: In the pretreatment FMISO-PET images, the tumor-to-muscle ratio (TMR) of FMISO in the voxels of the tumor recurrence region was significantly higher than that of the non-recurrence region (p < 0.0001). In the recurrent patient group, a TMR value of 1.37 (95% CI: 1.36-1.39) corresponded to a recurrence rate of 30%, the odds ratio was 5.18 (4.87-5.51), and the area under the curve (AUC) of the receiver operating characteristic curve was 0.613. In all 21 patients, a TMR value of 2.42 (2.36-2.49) corresponded to an estimated recurrence rate of 30%, and the AUC was only 0.591. Conclusions: The uptake of FMISO in the recurrent region was significantly higher than that in the non-recurrent region. However, the predictive value of FMISO-PET before IMRT is not sufficient for up-front dose escalation for the intra-tumoral high-uptake region of FMISO. Because of the higher mean TMR of the recurrence region, a new hypoxic imaging method is needed to improve the sensitivity and specificity for hypoxia.
  • Ping-Hsiu Wu, Yasuhito Onodera, Yuki Ichikawa, Erinn B. Rankin, Amato J. Giaccia, Yuko Watanabe, Wei Qian, Takayuki Hashimoto, Hiroki Shirato, Jin-Min Nam International Journal of Nanomedicine 12 5069 -5085 2017年07月14日 [査読無し][通常論文]
     
    Gold nanoparticles (AuNPs) have recently attracted attention as clinical agents for enhancing the effect of radiotherapy in various cancers. Although radiotherapy is a standard treatment for cancers, invasive recurrence and metastasis are significant clinical problems. Several studies have suggested that radiation promotes the invasion of cancer cells by activating molecular mechanisms involving integrin and fibronectin (FN). In this study, polyethylene-glycolylated AuNPs (P-AuNPs) were conjugated with Arg-Gly-Asp (RGD) peptides (RGD/P-AuNPs) to target cancer cells expressing RGD-binding integrins such as α5-and αv-integrins. RGD/P-AuNPs were internalized more efficiently and colocalized with integrins in the late endosomes and lysosomes of MDA-MB-231 cells. A combination of RGD/P-AuNPs and radiation reduced cancer cell viability and increased DNA damage compared to radiation alone in MDA-MB-231 cells. Moreover, the invasive activity of breast cancer cell lines after radiation treatment was significantly inhibited in the presence of RGD/P-AuNPs. Microarray analyses revealed that the expression of FN in irradiated cells was suppressed by combined use of RGD/P-AuNPs. Reduction of FN and downstream signaling may be involved in suppressing radiation-induced invasive activity by RGD/P-AuNPs. Our study suggests that RGD/P-AuNPs can target integrin-overexpressing cancer cells to improve radiation therapy by suppressing invasive activity in addition to sensitization. Thus, these findings provide a possible clinical strategy for using AuNPs to treat invasive breast cancer following radiotherapy.
  • Yusuke Fujii, Taeko Matsuura, Seishin Takao, Yuka Matsuzaki, Takaaki Fujii, Naoki Miyamoto, Kikuo Umegaki, Kentaro Nishioka, Shinichi Shimizu, Hiroki Shirato JOURNAL OF RADIATION RESEARCH 58 (4) 591 -597 2017年07月 [査読無し][通常論文]
     
    For proton spot scanning, use of a real-time-image gating technique incorporating an implanted marker and dual fluoroscopy facilitates mitigation of the dose distribution deterioration caused by interplay effects. This study explored the advantages of using a real-time-image gating technique, with a focus on prostate cancer. Two patient-positioning methods using fiducial markers were compared: (i) patient positioning only before beam delivery, and (ii) patient positioning both before and during beam delivery using a real-time-gating technique. For each scenario, dose distributions were simulated using the CT images of nine prostate cancer patients. Treatment plans were generated using a single-field proton beam with 3-mm and 6-mm lateral margins. During beam delivery, the prostate was assumed to move by 5 mm in four directions that were perpendicular to the beam direction at one of three separate timings (i.e. after the completion of the first, second and third quartiles of the total delivery of spot irradiation). Using a 3-mm margin and second quartile motion timing, the averaged values for Delta D-99, Delta D-95, Delta D-5 and D5-95 were 5.1%, 3.3%, 3.6% and 9.0%, respectively, for Scenario (i) and 2.1%, 1.5%, 0.5% and 4.1%, respectively, for Scenario (ii). The margin expansion from 3 mm to 6 mm reduced the size of Delta D-99, Delta D-95, Delta D-5 and D5-95 only with Scenario (i). These results indicate that patient positioning during beam delivery is an effective way to obtain better target coverage and uniformity while reducing the target margin when the prostate moves during irradiation.
  • Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Taisuke Harada, Yukie Shimizu, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato ONCOTARGET 8 (20) 33631 -33643 2017年05月 [査読無し][通常論文]
     
    We assessed parameters of advanced diffusion weighted imaging (DWI) models for the prediction of the tumor growth rate in 55 head and neck squamous cell carcinoma (HNSCC) patients. The DWI acquisition used single-shot spin-echo echo-planar imaging with 12 b-values (0-2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, tri-exponential, stretched exponential and diffusion kurtosis imaging models. We directly measured the tumor growth rate from two sets of different-date imaging data. We divided the patients into a discovery group (n = 40) and validation group (n = 15) based on their MR acquisition dates. In the discovery group, we performed univariate and multivariate regression analyses to establish the multiple regression equation for the prediction of the tumor growth rate using diffusion parameters. The equation obtained with the discovery group was applied to the validation group for the confirmation of the equation's accuracy. After the univariate and multivariate regression analyses in the discovery-group patients, the estimated tumor growth rate equation was established by using the significant parameters of intermediate diffusion coefficient D-2 and slow diffusion coefficient D-3 obtained by the tri-exponential model. The discovery group's correlation coefficient between the estimated and directly measured tumor growth rates was 0.74. In the validation group, the correlation coefficient (r = 0.66) and intra-class correlation coefficient (0.65) between the estimated and directly measured tumor growth rates were respectively good. In conclusion, advanced DWI model parameters can be a predictor for determining HNSCC patients' tumor growth rate.
  • Noriyuki Fujima, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Kohsuke Kudo, Hiroki Shirato EUROPEAN JOURNAL OF RADIOLOGY 90 14 -19 2017年05月 [査読無し][通常論文]
     
    Purpose: To evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy. Materials and methods: We retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0-1000). We calculated 10 DWI parameters using a monoexponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up. Results: Among the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (D-s) obtained by the SDM. The multivariate analysis revealed that the D-s and diffusion heterogeneity (alpha) obtained by the SEM were predictors for the presence of residual tumour. Conclusion: DWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour. (C) 2017 Elsevier B.V. All rights reserved.
  • Masaya Tamura, Hideyuki Sakurai, Masashi Mizumoto, Satoshi Kamizawa, Shigeyuki Murayama, Haruo Yamashita, Seishin Takao, Ryusuke Suzuki, Hiroki Shirato, Yoichi M. Ito JOURNAL OF RADIATION RESEARCH 58 (3) 363 -371 2017年05月 [査読無し][通常論文]
     
    To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means +/- standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 +/- 0.52% (n = 7, P = 0.0021), (ii) 23.3 +/- 17.2% (n = 8, P = 0.0065), (iii) 16.6 +/- 19.9% (n = 8, P = 0.0497) and (iv) 50.0 +/- 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques.
  • Jeff Wang, Fumi Kato, Hiroko Yamashita, Motoi Baba, Yi Cui, Ruijiang Li, Noriko Oyama-Manabe, Hiroki Shirato JOURNAL OF DIGITAL IMAGING 30 (2) 215 -227 2017年04月 [査読無し][通常論文]
     
    Breast cancer is the most common invasive cancer among women and its incidence is increasing. Risk assessment is valuable and recent methods are incorporating novel biomarkers such as mammographic density. Artificial neural networks (ANN) are adaptive algorithms capable of performing pattern-to-pattern learning and are well suited for medical applications. They are potentially useful for calibrating full-field digital mammography (FFDM) for quantitative analysis. This study uses ANN modeling to estimate volumetric breast density (VBD) from FFDM on Japanese women with and without breast cancer. ANN calibration of VBD was performed using phantom data for one FFDM system. Mammograms of 46 Japanese women diagnosed with invasive carcinoma and 53 with negative findings were analyzed using ANN models learned. ANN-estimated VBD was validated against phantom data, compared intra-patient, with qualitative composition scoring, with MRI VBD, and inter-patient with classical risk factors of breast cancer as well as cancer status. Phantom validations reached an R (2) of 0.993. Intra-patient validations ranged from R (2) of 0.789 with VBD to 0.908 with breast volume. ANN VBD agreed well with BI-RADS scoring and MRI VBD with R (2) ranging from 0.665 with VBD to 0.852 with breast volume. VBD was significantly higher in women with cancer. Associations with age, BMI, menopause, and cancer status previously reported were also confirmed. ANN modeling appears to produce reasonable measures of mammographic density validated with phantoms, with existing measures of breast density, and with classical biomarkers of breast cancer. FFDM VBD is significantly higher in Japanese women with cancer.
  • Masashi Mizumoto, Shigeyuki Murayama, Tetsuo Akimoto, Yusuke Demizu, Takashi Fukushima, Yuji Ishida, Yoshiko Oshiro, Haruko Numajiri, Hiroshi Fuji, Toshiyuki Okumura, Hiroki Shirato, Hideyuki Sakurai Cancer Science 108 (3) 444 -447 2017年03月01日 [査読無し][通常論文]
     
    Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0–19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow-up period was 8.1 years (5.0–31.2 years). The 5-, 10- and 20-year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10- and 20-year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow-up is needed to confirm the benefits of PBT for pediatric tumors.
  • Kentaro Nishioka, Shinichi Shimizu, Nobuo Shinohara, Yoichi M. Ito, Takashige Abe, Satoru Maruyama, Norio Katoh, Rumiko Kinoshita, Takayuki Hashimoto, Naoki Miyamoto, Rikiya Onimaru, Hiroki Shirato RADIATION ONCOLOGY 12 2017年03月 [査読無し][通常論文]
     
    Background: Current adaptive and dose escalating radiotherapy for muscle invasive bladder cancer requires knowledge of both inter-fractional and intra-fractional motion of the bladder wall involved. The purpose of this study is to characterize inter-and intra-fractional movement of the partial bladder wall using implanted fiducial markers and a real-time tumor-tracking radiotherapy system. Methods: Two hundred fifty one sessions with 29 patients were analysed. After maximal transurethral bladder tumor resection and 40 Gy of whole bladder irradiation, up to six gold markers were implanted transurethrally into the bladder wall around the tumor bed and used for positional registration. We compared the systematic and random uncertainty of positions between cranial vs. caudal, left vs. right, and anterior vs. posterior tumor groups. The variance in intrafractional movement and the percentage of sessions where 3 mm and 5 mm or more of intrafractional wall movement occurring at 2, 4, 6, 8, 10, and at more than 10 min until the end of a session were determined. Results: The cranial and anterior tumor group showed larger interfractional uncertainties in the position than the opposite side tumor group in the CC and AP directions respectively, but these differences did not reach significance. Among the intrafractional uncertainty of position, the cranial and anterior tumor group showed significantly larger systematic uncertainty of position than the groups on the opposite side in the CC direction. The variance of intrafractional movement increased over time; the percentage of sessions where intrafractional wall movement was larger than 3 mm within 2 min of the start of a radiation session or larger than 5 mm within 10 min was less than 5%, but this percentage was increasing further during the session, especially in the cranial and anterior tumor group. Conclusions: More attention for intrafractional uncertainty of position is required in the treatment of cranial and anterior bladder tumors especially in the CC direction. The optimal internal margins in each direction should be chosen or a precise intrafractional target localization system is required depending on the tumor location and treatment delivery time in the setting of partial bladder radiotherapy.
  • Rikiya Onimaru, Hiroshi Onishi, Taro Shibata, Masahiro Hiraoka, Satoshi Ishikura, Katsuyuki Karasawa, Yukinori Matsuo, Masaki Kokubo, Yoshiyuki Shioyama, Haruo Matsushita, Yoshinori Ito, Hiroki Shirato Radiotherapy and Oncology 122 (2) 281 -285 2017年02月 [査読無し][通常論文]
     
    © 2016 Elsevier Ireland Ltd Purpose A dose escalation study to determine the recommended dose (RD) with stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinomas (NSCLC) was conducted. The results of the group with PTV ⩾ 100 cc are reported in this paper. Materials and methods The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was Grade 3 or higher radiation pneumonitis (RP), and Grade 2 or higher RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D 95 of the PTV. Results Thirteen patients were accrued. More patients should have been enrolled but we decided not to prolong the study period. No patients experienced Grade 3 RP. Two patients experienced Grade 2 RP at 50 Gy in 4 fractions. The predicted MTD was 50.2 Gy. The posterior probability of the Grade 2 RP frequency over 40% was 5.3% for the dose level of 50 Gy. The RD was determined to be 50 Gy. Conclusions The RD was determined to be 50 Gy in 4 fractions in this population.
  • Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Yukie Shimizu, Atsushi Yoshida, Taisuke Harada, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato MAGNETIC RESONANCE IMAGING 36 16 -23 2017年02月 [査読無し][通常論文]
     
    Purpose: We assessed advanced fitting models of diffusion weighted imaging (DWI) in head/neck squamous cell carcinoma (HNSCC) patients to determine the best goodness of fit and correlations among diffusion parameters. We compared these results with those of dynamic contrast-enhanced (DCE) perfusion parameters. Materials and methods: We retrospectively evaluated 32 HNSCC patients (12 sinonasal, 20 pharynx/oral cavity). The DWI acquisition used single-shot spin-echo echo-planar imaging (EPI) with 12 b-values (0 - 2000). We calculated 14 DWI parameters using mono-exponential, bi-exponential, and tri-exponential models, stretched exponential model (SEM) and diffusion kurtosis imaging (DKI) models. We compared each model's goodness of fit using the residual sum of squares (RSS), Akaike Information Criterion (AIC) and Bayesian information criterion (BIC) value. We determined the correlation between each pair of DWI parameters and between each DWI parameter and DCE perfusion parameter. Results: The tri-exponential fit's RSS, AIC and BIC values were significantly smaller than those for bi-exponential fit. The RSS, AIC and BIC values of the SEM fit and DKI fit were significantly smaller than mono-exponential model. Significant correlations were observed in 30 pairs (sinonasal cavity) and 31 (sinonasal cavity group) among 91 DWI parameter combinations. Significant correlations were also observed in nine pairs (both sinonasal cavity and pharynx/oral cavity group) among 64 DWI/DCE perfusion parameter pairs, in particular, high positive correlations between the tri-exponential model's intermediate diffusion fraction (f(2)) and the volume of the extracellular extravascular space per unit volume of tissue (v(e)) were observed in both patient groups. Conclusion: We identified several correlations between DWI parameters by advanced fitting models and correlations between DWI and DCE parameters. These will help determine HNSCC patients' detailed tissue structures. (C) 2016 Elsevier Inc. All rights reserved.
  • Takahiro Kanehira, Taeko Matsuura, Taeko Matsuura, Taeko Matsuura, Seishin Takao, Yuka Matsuzaki, Yusuke Fujii, Takaaki Fujii, Yoichi M. Ito, Naoki Miyamoto, Tetsuya Inoue, Norio Katoh, Shinichi Shimizu, Shinichi Shimizu, Kikuo Umegaki, Kikuo Umegaki, Hiroki Shirato, Hiroki Shirato International Journal of Radiation Oncology Biology Physics 97 (1) 173 -181 2017年01月 [査読無し][通常論文]
     
    © 2016 Elsevier Inc. Purpose To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW). Methods and Materials A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of ±1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in the time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99  > 95% and D5 to D95  < 5%, V20 for the normal lung, and treatment times were evaluated. Results Gating windows ≤ ±2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs ≥ ±3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs ≥ ±4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the ±1-mm GW, but less than 226 seconds (292 seconds) for the ±2-mm GW. The maximum increased considerably at ±1-mm GW. Conclusion Real-time-image gated proton beam therapy with a GW of ±2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time.
  • Taisuke Harada, Kohsuke Kudo, Ikuko Uwano, Fumio Yamashita, Hiroyuki Kameda, Tsuyoshi Matsuda, Makoto Sasaki, Hiroki Shirato MAGNETIC RESONANCE IN MEDICAL SCIENCES 16 (1) 23 -31 2017年 [査読無し][通常論文]
     
    Purpose: The B0 and B1+ maps required for calculation of the radiofrequency (RF) pulse of parallel transmission (pTx) are obtained in calibration scans; however, they may be affected by respiratory motion. We aimed to compare the reproducibility of B0 and B1+ maps and gradient echo (GRE) images of the brain scanned with pTx at 7T between free-breathing (FB) and breath-holding (BH) conditions during the calibration scan. Methods: Nine healthy volunteers were scanned by 7T MRI using a two-channel quadrature head coil. In the pTx calibration scans performed with FB and BH, the B0 map was obtained from two different TE images and the B1+ map was calculated by the Bloch-Siegert method. A GRE image (gradient-recalled acquisition in steady state) was also obtained with RF shimming and RF design of pTx with spoke method, as well as quadrature transmission (qTx). All the scans were repeated over five sessions. The reproducibility of the B0 and B1+ maps and GRE image was evaluated with region-of-interest measurements using inter-session standard deviation (SD) and coefficient of variation (CV) values. Intensity homogeneity of GRE images was also assessed with in-plane CV. Results: Inter-session SDs of B0 and B1+ maps were significantly smaller in BH (P < 0.01). Inter-session CVs of GRE images were significantly smaller in qTx than BH and FB (P < 0.01, both); however, the CVs of BH were significantly smaller (P < 0.01). In-plane CVs of FB and BH with RF shimming were not significantly different with qTx; however, CVs of FB and BH with RF design were significantly smaller than those of qTx (P < 0.05 and P < 0.01, respectively). Conclusion: BH could improve the reproducibility of B0 and B1+ maps in pTx calibration scans and GRE images. These results might facilitate the development of pTx in human brain at 7T.
  • Norio Katoh, Itaru Soda, Hiroyasu Tamamura, Shotaro Takahashi, Yusuke Uchinami, Hiromichi Ishiyama, Kiyotaka Ota, Tetsuya Inoue, Rikiya Onimaru, Keiko Shibuya, Kazushige Hayakawa, Hiroki Shirato RADIATION ONCOLOGY 12 2017年01月 [査読無し][通常論文]
     
    Purpose: To investigate the clinical outcomes of stage I and IIA non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using a real-time tumor-tracking radiotherapy (RTRT) system. Materials and methods: Patterns-of-care in SBRT using RTRT for histologically proven, peripherally located, stage I and IIA NSCLC was retrospectively investigated in four institutions by an identical clinical report format. Patterns-of-outcomes was also investigated in the same manner. Results: From September 2000 to April 2012, 283 patients with 286 tumors were identified. The median age was 78 years (52-90) and the maximum tumor diameters were 9 to 65 mm with a median of 24 mm. The calculated biologically effective dose (10) at the isocenter using the linear-quadratic model was from 66 Gy to 126 Gy with a median of 106 Gy. With a median follow-up period of 28 months (range 0-127), the overall survival rate for the entire group, for stage IA, and for stage IB + IIA was 75%, 79%, and 65% at 2 years, and 64%, 70%, and 50% at 3 years, respectively. In the multivariate analysis, the favorable predictive factor was female for overall survival. There were no differences between the clinical outcomes at the four institutions. Grade 2, 3, 4, and 5 radiation pneumonitis was experienced by 29 (10.2%), 9 (3.2%), 0, and 0 patients. The subgroup analyses revealed that compared to margins from gross tumor volume (GTV) to planning target volume (PTV) >= 10 mm, margins < 10 mm did not worsen the overall survival and local control rates, while reducing the risk of radiation pneumonitis. Conclusions: This multi-institutional retrospective study showed that the results were consistent with the recent patterns-of-care and patterns-of-outcome analysis of SBRT. A prospective study will be required to evaluate SBRT using a RTRT system with margins from GTV to PTV < 10mm.
  • Hisashi Narita, Khin K Tha, Naoki Hashimoto, Hiroyuki Hamaguchi, Shin Nakagawa, Hiroki Shirato, Ichiro Kusumi Progress in neuro-psychopharmacology & biological psychiatry 71 169 -75 2016年11月03日 [査読無し][通常論文]
     
    INTRODUCTION: Diffusion kurtosis imaging can provide a better understanding of microstructural white matter (WM) changes where crossing fibers exist, compared with conventional diffusion tensor imaging. Here, we aimed to examine the differences of mean kurtosis (MK) and fractional anisotropy (FA) values between patients with schizophrenia and control subjects using voxel-based analysis (VBA). Additionally, we examined the correlation between these values and severity of clinical symptoms in patients with schizophrenia. METHODS: MK and FA values were acquired with a 3.0T scanner from 31 patients with schizophrenia and 31 age-, handedness-, and sex-matched healthy controls. VBA was used to compare the MK and FA maps of the patients with schizophrenia and healthy controls. We also performed a correlation analysis between the MK and FA values of the regions with significant differences and the positive and negative syndrome scale scores in patients with schizophrenia. RESULTS: Compared to FA values, voxels with MK decrease were more widespread across bilateral cerebral the WM of patients with schizophrenia. The MK values of left superior longitudinal fasciculus were significantly negatively correlated with the severity of positive symptoms (r=-0.451, P=0.011). There was no significant correlation between MK and FA values and other clinical variables. CONCLUSION: The diffusion kurtosis indices are suitable for evaluating altered WM structures in the human brain as they may detect white matter alterations of crossing fibers alterations of WM in schizophrenia and assess the clinical state of patients.
  • Shozo Okamoto, Tohru Shiga, Koichi Yasuda, Shiro Watanabe, Kenji Hirata, Ken-ichi Nishijima, Keiichi Magota, Katsuhiko Kasai, Rikiya Onimaru, Kazuhiko Tuchiya, Yuji Kuge, Hiroki Shirato, Nagara Tamaki EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 43 (12) 2147 -2154 2016年11月 [査読無し][通常論文]
     
    The purpose of this study was to prospectively investigate reoxygenation in the early phase of fractionated radiotherapy and serial changes of tumoricidal effects associated with intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer (HNC) using F-18 fluoromisonidazole (FMISO) PET and F-18 fluorodeoxyglucose (FDG) PET. Patients with untreated HNC underwent FMISO-PET and FDG-PET studies prospectively. A PET evaluation was conducted before each IMRT (Pre-IMRT), during IMRT (at 30 Gy/15 fr) (Inter-IMRT), and after completion of IMRT (70 Gy/35 fr) (Post-IMRT). FMISO-PET images were scanned by a PET/CT scanner at 4 h after the FMISO injection. We quantitatively analyzed the FMISO-PET images of the primary lesion using the maximum standardized uptake (SUVmax) and tumor-to-muscle ratio (TMR). The hypoxic volume (HV) was calculated as an index of tumor hypoxia, and was defined as the volume when the TMR was aeyen 1.25. Each FDG-PET scan was started 1 h after injection. The SUVmax and metabolic tumor volume (MTV) values obtained by FDG-PET were analyzed. Twenty patients finished the complete PET study protocol. At Pre-IMRT, 19 patients had tumor hypoxia in the primary tumor. In ten patients, the tumor hypoxia disappeared at Inter-IMRT. Another seven patients showed the disappearance of tumor hypoxia at Post-IMRT. Two patients showed tumor hypoxia at Post-IMRT. The FMISO-PET results showed that the reduction rates of both SUVmax and TMR from Pre-IMRT to Inter-IMRT were significantly higher than the corresponding reductions from Inter-IMRT to Post-IMRT (SUVmax: 27 % vs. 10 %, p = 0.025; TMR: 26 % vs. 12 %, p = 0.048). The reduction rate of SUVmax in FDG-PET from Pre-IMRT to Inter-IMRT was similar to that from Inter-IMRT to Post-IMRT (47 % vs. 48 %, p = 0.778). The reduction rate of the HV in FMISO-PET from Pre-IMRT to Inter-IMRT tended to be larger than that from Inter-IMRT to Post-IMRT (63 % vs. 40 %, p = 0.490). Conversely, the reduction rate of the MTV in FDG-PET from Pre-IMRT to Inter-IMRT was lower than that from Inter-IMRT to Post-IMRT (47 % vs. 74 %, p = 0.003). Both the intensity and the volume of tumor hypoxia rapidly decreased in the early phase of radiotherapy, indicating reoxygenation of the tumor hypoxia. In contrast, the FDG uptake declined gradually with the course of radiotherapy, indicating that the tumoricidal effect continues over the entire course of radiation treatment.
  • Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Kenji Hirata, Tohru Shiga, Kohsuke Kudo, Hiroki Shirato PLOS ONE 11 (11) 2016年11月 [査読無し][通常論文]
     
    Objective To determine the relationship between tumor glucose metabolism and tumor blood flow (TBF) in head and neck squamous cell carcinoma (HNSCC). Methods We retrospectively analyzed 57 HNSCC patients. Tumor glucose metabolism was assessed by maximum and mean standardized uptake values (SUVmax and SUVmean) obtained by 18 F-fluorodeoxyglucose positron-emission tomography. TBF values were obtained by arterial spin labeling with 3-tesla MRI. The correlations between both SUVs and TBF were assessed in the total series and among patients divided by T-stage (T1-T3 and T4 groups) and tumor location (pharynx/oral cavity and sinonasal cavity groups). Pearson's correlation coefficients were calculated for significant correlations. Results Significant correlations were detected: a negative correlation in the advanced T-stage group (TBF and SUV max: r, -0.61, SUVmean: r, -0.62), a positive correlation in the non-advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, 0.70, SUVmean: r, 0.73), a negative correlation in the advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, -0.62, SUVmean: r, -0.65), and a negative correlation in the advanced Tstage sinonasal cavity group (TBF and SUVmax: r, -0.61, SUVmean: r, -0.65). Conclusion Significant correlations between glucose uptake and TBF in HNSCC were revealed by the division of T-stage and tumor location.
  • Kenichiro Maeda, Hironobu Yasui, Tohru Yamamori, Taeko Matsuura, Seishin Takao, Motofumi Suzuki, Akira Matsuda, Osamu Inanami, Hiroki Shirato PLOS ONE 11 (11) 2016年11月 [査読無し][通常論文]
     
    The effect of 1-(3-C-ethyny1-beta-D-ribo-pentofuranosyl)cytosine (ECyd) on proton-induced cell death was evaluated in human lung carcinoma cell line A549 and Chinese hamster fibroblast cell line V79 to enhance relative biological effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams. Treatment with ECyd significantly enhanced the proton -induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd decelerated the rate of DNA double-strand break (DSB) repair at the center, but not the distal region of SOBP, suggesting that the ECyd-induced enhancement of proton-induced cell death is partially associated with the inhibition of DSB repair. This study demonstrated that ECyd enhances proton-induced cell killing at all positions of SOBP, except for the distal region and minimizes the site-dependent differences in RBE within SOBP. Thus, ECyd is a unique radiosensitizer for proton therapy that may be useful because it levels the biological dose within SOBP, which improves tumor control and reduces the risk of adverse effects at the distal edge of SOBP.
  • Takayoshi Suzuki, Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Daisuke Yoshida, Noriyuki Fujima, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Fumiyuki Suzuki, Satoshi Fukuda EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 273 (10) 3331 -3336 2016年10月 [査読無し][通常論文]
     
    We sought to evaluate the efficacy and feasibility of superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (hereafter RADPLAT) for head and neck squamous cell cancer (hereafter HNSCC) patients with retropharyngeal lymph node (hereafter RPLN) metastasis. A retrospective case series review was conducted at University medical center in Japan. Ten HNSCC patients with RPLN metastasis treated by RADPLAT were analyzed. The ascending pharyngeal artery was targeted for the treatment of RPLN metastasis in 9 patients. The median total dose of cisplatin was 26.6 mg/m(2) (mean 31.5 mg/m(2), range 11.7-87.9 mg/m(2)). In the remaining patient, the RPLN was supplied by the ascending palatine artery. As grade 3 and 4 adverse effects, leukopenia was observed in three, mucositis in four and nausea in one patient. No neurological complications were observed in any patients. Metastatic RPLNs were evaluated as a complete response in all patients. There was no recurrence of RPLN metastasis in any patients. Four patients remain alive without any evidence of disease and six patients died of disease. The 5-year overall survival rate was 50 %. We have shown that superselective intra-arterial cisplatin infusion for RPLNs was a feasible and effective approach for HNSCC patients with RPLN metastasis.
  • Jihun Kwon, Kenneth Sutherland, Takayuki Hashimoto, Hiroki Shirato, Hiroyuki Date NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS 384 113 -120 2016年10月 [査読無し][通常論文]
     
    Gold nanoparticles (GNPs) have been recognized as a promising candidate for a radiation sensitizer. A proton beam incident on a GNP can produce secondary electrons, resulting in an enhancement of the dose around the GNP. However, little is known about the spatial distribution of dose enhancement around the GNP, especially in the direction along the incident proton. The purpose of this study is to determine the spatial distribution of dose enhancement by taking the incident direction into account. Two steps of calculation were conducted using the Geant4 Monte Carlo simulation toolkit. First, the energy spectra of 100 and 195 MeV protons colliding with a GNP were calculated at the Bragg peak and three other depths around the peak in liquid water. Second, the GNP was bombarded by protons with the obtained energy spectra. Radial dose distributions were computed along the incident beam direction. The spatial distributions of the dose enhancement factor (DEF) and subtracted dose (D-aub) were then evaluated. The spatial DEF distributions showed hot spots in the distal radial region from the proton beam axis. The spatial Daub distribution isotropically spread out around the GNP. Low energy protons caused higher and wider dose enhancement. The macroscopic dose enhancement in clinical applications was also evaluated. The results suggest that the consideration of the spatial distribution of GNPs in treatment planning will maximize the potential of GNPs. (C) 2016 Elsevier B.V. All rights reserved.
  • Noriyuki Fujima, Toshiya Osanai, Yukie Shimizu, Atsushi Yoshida, Taisuke Harada, Naoki Nakayama, Kohsuke Kudo, Kiyohiro Houkin, Hiroki Shirato JOURNAL OF MAGNETIC RESONANCE IMAGING 44 (4) 834 -845 2016年10月 [査読無し][通常論文]
     
    PurposeTo evaluate the utility of a vessel-selective four-dimensional (4D) magnetic resonance angiography (MRA) technique for the evaluation of intracranial arteriovenous malformations (AVMs). Materials and MethodsTwelve AVM patients were evaluated retrospectively. Time-of-flight (TOF) MRA, nonvessel-selective 4D-MRA (NS-4D-MRA), and vessel-selective 4D-MRA (VS-4D-MRA) were performed using a 3T MR unit in all patients, and used to identify feeding arteries and draining veins and measure nidus size. The diagnostic accuracy of the three techniques was compared using digital subtraction angiography (DSA). If a multifeeder was observed, the percentage of blood flow of each feeding artery to the entire nidus was evaluated and compared to the DSA findings using the error value, defined as the degree of overestimation of the blood flow. All imaging findings were assessed by two neuroradiologists. ResultsIn both raters, the detectability of feeding arteries by VS-4D-MRA (12 and 11 patients) was significantly higher than those of TOF-MRA (7 and 6 patients) and NS-4D-MRA (8 and 7 patients) (P < 0.016). The detectability of drainer veins by TOF-MRA (10 and 10 patients) was significantly higher than that of VS-4D-MRA (7 and 6 patients). In the percentage of the blood flow of each feed artery to the entire nidus, the DSA findings (error value; 27.15.7) indicated overestimations of the blood flow compared to the VS-4D-MRA (error value; 7.1 +/- 3.9) (P < 0.001). ConclusionVS-4D-MRA was shown to be a useful technique for the evaluation of intracranial AVMs, especially for detecting feed arteries and estimating details of the nidus structure. J. MAGN. RESON. IMAGING 2016;44:834-845.
  • Kimitoshi Kubo, Hiroshi Kawakami, Hiroshi Kawakami, Masaki Kuwatani, Mutsumi Nishida, Kazumichi Kawakubo, Shuhei Kawahata, Yoko Taya, Yoshimasa Kubota, Yoshimasa Kubota, Toraji Amano, Hiroki Shirato, Naoya Sakamoto BMC Gastroenterology 16 2016年09月20日 [査読無し][通常論文]
     
    © 2016 The Author(s). Unfortunately, after publication of this article [1], it was noticed that the title was captured incorrectly during the production process. The words, "a prospective cohort study" were erroneously added twice. The corrected title can be seen above.
  • Takaaki Yoshimura, Takaaki Yoshimura, Rumiko Kinoshita, Shunsuke Onodera, Chie Toramatsu, Ryusuke Suzuki, Yoichi M. Ito, Seishin Takao, Taeko Matsuura, Taeko Matsuura, Taeko Matsuura, Yuka Matsuzaki, Kikuo Umegaki, Kikuo Umegaki, Hiroki Shirato, Hiroki Shirato, Shinichi Shimizu, Shinichi Shimizu Physica Medica 32 (9) 1095 -1102 2016年09月 [査読無し][通常論文]
     
    © 2016 Associazione Italiana di Fisica Medica Purpose This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade ⩾3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). Methods and materials The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45 Gy(RBE) in 1.8 Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. Results The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP = 0.04 ± 0.01 and 0.19 ± 0.03, p = 0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI = 0.97 ± 0.01 and 0.96 ± 0.02, p = 0.3177, and HI = 1.24 ± 0.11 and 1.27 ± 0.05, p = 0.8473, respectively). Conclusion The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT.
  • Hiroyuki Hamaguchi, Khin Khin Tha, Hiroyuki Sugimori, Mitsuhiro Nakanishi, Shin Nakagawa, Taro Fujiwara, Hirokazu Yoshida, Sayaka Takamori, Hiroki Shirato The neuroradiology journal 29 (4) 254 -9 2016年08月 [査読無し][通常論文]
     
    The effect of respiratory gating on the major diffusion-imaging metrics and that of cardiac gating on mean kurtosis (MK) are not known. For evaluation of whether the major diffusion-imaging metrics-MK, fractional anisotropy (FA), and mean diffusivity (MD) of the brain-varied between gated and non-gated acquisitions, respiratory-gated, cardiac-gated, and non-gated diffusion-imaging of the brain were performed in 10 healthy volunteers. MK, FA, and MD maps were constructed for all acquisitions, and the histograms were constructed. The normalized peak height and location of the histograms were compared among the acquisitions by use of Friedman and post hoc Wilcoxon tests. The effect of the repetition time (TR) on the diffusion-imaging metrics was also tested, and we corrected for its variation among acquisitions, if necessary. The results showed a shift in the peak location of the MK and MD histograms to the right with an increase in TR (p ≤ 0.01). The corrected peak location of the MK histograms, the normalized peak height of the FA histograms, the normalized peak height and the corrected peak location of the MD histograms varied significantly between the gated and non-gated acquisitions (p < 0.05). These results imply an influence of respiration and cardiac pulsation on the major diffusion-imaging metrics. The gating conditions must be kept identical if reproducible results are to be achieved.
  • Akihiro Homma, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Rinnosuke Kuramoto, Yuji Nakamaru, Rikiya Onimaru, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda PLOS ONE 11 (8) 2016年08月 [査読無し][通常論文]
     
    Objective Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7-42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports. Methods We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan. Results At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303). Conclusions The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT.
  • Yuzuru Niibe, Tetsuo Nishimura, Tetsuya Inoue, Katsuyuki Karasawa, Yoshiyuki Shioyama, Keiichi Jingu, Hiroki Shirato BMC CANCER 16 2016年08月 [査読無し][通常論文]
     
    Background: To investigate the prognostic value of oligo-recurrence in patients with brain-only oligometastases of non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Methods: Patients treated with SRS or SRT for brain-only NSCLC oligometastases in 6 high-volume institutions in Japan between 1996 and 2008 were reviewed. Eligible patients met 1), 2), and 4) or 1), 3), and 4) of the following: 1) NSCLC with 1 to 4 brain metastases on magnetic resonance imaging (MRI) treated with SRS or SRT; 2) control of the primary lesions (thorax) at the time of SRS or SRT for brain metastases (patients meeting this criterion formed the oligo-recurrence group); 3) with SRS or SRT for brain metastases, concomitant treatment for active primary lesions (thorax) with curative surgery or curative stereotactic body radiotherapy (SBRT), or curative chemoradiotherapy (sync-oligometastases group); and 4) Karnofsky performance status (KPS) >= 70. Results: The median overall survival (OS) of all 61 patients was 26 months (95 % CI: 17.5-34.5 months). The 2-year and 5-year overall survival rates were 60.7 and 15.7 %, respectively. Stratified by oligostatus, the sync-oligometastases group achieved a median OS of 18 months (95 % CI: 14.8-21.1 months) and a 5-year OS of 0 %, while the oligorecurrence group achieved a median OS of 41 months (95 % CI: 27.8-54.2 months) and a 5-year OS of 18.6 %. On multivariate analysis, oligo-recurrence was the only significant independent factor related to a favorable prognosis (hazard ratio: 0.253 (95 % CI: 0.082-0.043) (p = 0.025). Conclusions: The presence of oligo-recurrence can predict a favorable prognosis of brain-only oligometastases in patients with NSCLC treated with SRS or SRT.
  • Takeshi Soyama, Yusuke Sakuhara, Kohsuke Kudo, Daisuke Abo, Jeff Wang, Yoichi M. Ito, Yu Hasegawa, Hiroki Shirato JOURNAL OF MEDICAL ULTRASONICS 43 (3) 327 -335 2016年07月 [査読無し][通常論文]
     
    This preliminary study compared ultrasonography-computed tomography (US-CT) fusion imaging and conventional ultrasonography (US) for accuracy and time required for target identification using a combination of real phantoms and sets of digitally modified computed tomography (CT) images (digital/real hybrid phantoms). In this randomized prospective study, 27 spheres visible on B-mode US were placed at depths of 3.5, 8.5, and 13.5 cm (nine spheres each). All 27 spheres were digitally erased from the CT images, and a radiopaque sphere was digitally placed at each of the 27 locations to create 27 different sets of CT images. Twenty clinicians were instructed to identify the sphere target using US alone and fusion imaging. The accuracy of target identification of the two methods was compared using McNemar's test. The mean time required for target identification and error distances were compared using paired t tests. At all three depths, target identification was more accurate and the mean time required for target identification was significantly less with US-CT fusion imaging than with US alone, and the mean error distances were also shorter with US-CT fusion imaging. US-CT fusion imaging was superior to US alone in terms of accurate and rapid identification of target lesions.
  • Masashi Mizumoto, Shigeyuki Murayama, Tetsuo Akimoto, Yusuke Demizu, Takashi Fukushima, Yuji Ishida, Yoshiko Oshiro, Haruko Numajiri, Hiroshi Fuji, Toshiyuki Okumura, Hiroki Shirato, Hideyuki Sakurai Cancer Medicine 5 (7) 1519 -1525 2016年07月 [査読無し][通常論文]
     
    © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Recent progress in the treatment for pediatric malignancies using a combination of surgery, chemotherapy, and radiotherapy has improved survival. However, late toxicities of radiotherapy are a concern in long-term survivors. A recent study suggested reduced secondary cancer and other late toxicities after proton beam therapy (PBT) due to dosimetric advantages. In this study, we evaluated the safety and efficacy of PBT for pediatric patients treated in Japan. A retrospective observational study in pediatric patients who received PBT was performed. All patients aged < 20 years old who underwent PBT from January 1983 to August 2014 at four sites in Japan were enrolled in the study. There were 343 patients in the study. The median follow-up periods were 22.6 months (0.4–374.3 months) for all patients and 30.6 months (0.6–374.3 months) for survivors. The estimated 1-, 3-, 5-, and 10-year survival rates were 82.7% (95% CI: 78.5–87.0%), 67.4% (61.7–73.2%), 61.4% (54.8–67.9%), and 58.7% (51.5–65.9%), respectively. Fifty-two events of toxicity ≥ grade 2 occurred in 43 patients. Grade 4 toxicities of myelitis, visual loss (two cases), cerebral vascular disease, and tissue necrosis occurred in five patients. This study provides preliminary results for PBT in pediatric patients in Japan. More experience and follow-up with this technique are required to establish the efficacy of PBT in this patient population.
  • Takahiro Yamada, Naoki Miyamoto, Taeko Matsuura, Seishin Takao, Yusuke Fujii, Yuka Matsuzaki, Hidenori Koyano, Masumi Umezawa, Hideaki Nihongi, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS 32 (7) 932 -937 2016年07月 [査読無し][通常論文]
     
    Purpose: To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system. Methods: A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase. The gated irradiation efficiency depends on the timer value, T-w. To find the optimum Tw value, gated irradiation efficiency was evaluated for each configurable T-w value. 271 gate signal data sets from 58 patients were used for the simulation. Results: The highest mean efficiency 0.52 was obtained in T-W = 0.2 s. The irradiation efficiency was approximately 21% higher than at T-W = 0 s, which corresponds to ordinary synchrotron operation. The irradiation efficiency was improved in 154 (57%) of the 271 cases. The irradiation efficiency was reduced in 117 cases because the T-W value was insufficient or the function introduced an unutilized wait time for the next gate-on signal in the flat top phase. In the actual treatment of a patient with a hepatic tumor at T-w = 0.2 s, 4.48 GyE irradiation was completed within 250 s. In contrast, the treatment time of ordinary synchrotron operation was estimated to be 420 s. Conclusions: The results suggest that the multiple gated-irradiation function has potential to improve the gated irradiation efficiency and to reduce the treatment time. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
  • Kimitoshi Kubo, Hiroshi Kawakami, Masaki Kuwatani, Mutsumi Nishida, Kazumichi Kawakubo, Shuhei Kawahata, Yoko Taya, Yoshimasa Kubota, Toraji Amano, Hiroki Shirato, Naoya Sakamoto BMC GASTROENTEROLOGY 16 2016年07月 [査読無し][通常論文]
     
    Background: Obstructive jaundice has been reported to influence liver elasticity, independent of liver fibrosis. The aim of our prospective study was to evaluate the changes in liver elasticity, before and after biliary drainage, in patients with obstructive jaundice, and to evaluate the correlation between elasticity measures and serum markers of liver fibrosis. Methods: This is a prospective cohort study of 20 patients with obstructive jaundice. Liver elasticity was assessed by Transient Elastography (TE) and Virtual Touch (TM) Quantification (VTQ). Serum total bilirubin (T-Bil) level was measured before biliary drainage (Day 0), with measures repeated at 2 days (Day 2) and 7 days (Day 7) after biliary drainage. Serum levels of the following markers of liver fibrosis were also obtained on Day 0 and Day 7: hyaluronic acid (HA), procollagen-III-peptide (P-III-P). Results: T-Bil, TE, and VTQ for the left (VTQ-L) and right (VTQ-R) lobes of the liver were all elevated before biliary drainage, with respective levels, measured at Day 0, of 11.9 +/- 1.5 mg/dl, 12.1 +/- 0.9 kPa, 2.23 +/- 0.10 m/s, and 1.85 +/- 0. 10 m/s. All values decreased on Day 7 after drainage: T-Bil, 4.7 +/- 1.0 mg/dl (P < 0.001); TE, 7.6 +/- 0.6 kPa (P < 0.001); VTQ-L, 1.53 +/- 0.08 m/s (P < 0.001); and VTQ-R, 1.30 +/- 0.05 m/s (P < 0.001). Similar changes were observed in serum markers of liver fibrosis. Liver elasticity measures correlated with serum levels of T-Bil, P-III-P, and HA (r = 0.35-0.67, P < 0.001). Conclusions: This study confirmed decreases in liver elasticity, measured by TE and VTQ, after biliary drainage. Measures of liver elasticity correlated to levels of T-Bil and serum markers of liver fibrosis.
  • Kenichiro Maeda, Hironobu Yasui, Taeko Matsuura, Tohru Yamamori, Motofumi Suzuki, Masaki Nagane, Jin-Min Nam, Osamu Inanami, Hiroki Shirato JOURNAL OF RADIATION RESEARCH 57 (3) 307 -311 2016年06月 [査読無し][通常論文]
     
    Variations in relative biological effectiveness (RBE) from a fixed value of 1.1 are critical in proton beam therapy. To date, studies estimating RBE at multiple positions relative to the spread-out Bragg peak (SOBP) have been predominantly performed using passive scattering methods, and limited data are available for spot-scanning beams. Thus, to investigate the RBE of spot-scanning beams, Chinese hamster fibroblast V79 cells were irradiated using the beam line at the Hokkaido University Hospital Proton Therapy Center. Cells were placed at six different depths, including the entrance of the proton beam and the proximal and distal part of the SOBP. Surviving cell fractions were analyzed using colony formation assay, and cell survival curves were obtained by the curve fitted using a linear-quadratic model. RBE10 and RBE37 were 1.15 and 1.21 at the center of the SOBP, respectively. In contrast, the distal region showed higher RBE values (1.50 for RBE10 and 1.85 for RBE37). These results are in line with those of previous studies conducted using passive scattering proton beams. Taken together, these data strongly suggest that variations in RBE should be considered during treatment planning for spot-scanning beams as well as for passive scattering proton beams.
  • Toshiyuki Hamada, Kenneth Sutherland, Masayori Ishikawa, Naoki Miyamoto, Sato Honma, Hiroki Shirato, Ken-ichi Honma NATURE COMMUNICATIONS 7 2016年06月 [査読無し][通常論文]
     
    Clock genes are expressed throughout the body, although how they oscillate in unrestrained animals is not known. Here, we show an in vivo imaging technique that enables long-term simultaneous imaging of multiple tissues. We use dual-focal 3D tracking and signal-intensity calibration to follow gene expression in a target area. We measure circadian rhythms of clock genes in the olfactory bulb, right and left ears and cortices, and the skin. In addition, the kinetic relationship between gene expression and physiological responses to experimental cues is monitored. Under stable conditions gene expression is in phase in all tissues. In response to a long-duration light pulse, the olfactory bulb shifts faster than other tissues. In Cry1(-/-) Cry2(-/-) arrhythmic mice circadian oscillation is absent in all tissues. Thus, our system successfully tracks circadian rhythms in clock genes in multiple tissues in unrestrained mice.
  • Rie Mimura, Fumi Kato, Khin Khin Tha, Kohsuke Kudo, Yosuke Konno, Noriko Oyama-Manabe, Tatsuya Kato, Hidemichi Watari, Noriaki Sakuragi, Hiroki Shirato Japanese journal of radiology 34 (3) 229 -37 2016年03月 [査読無し][通常論文]
     
    PURPOSE: This study aimed to evaluate whether histogram analysis of the apparent diffusion coefficient (ADC) of a solid tumor component could distinguish borderline ovarian tumors from ovarian carcinoma. MATERIALS AND METHODS: Sixteen pathologically proven borderline tumors and 21 carcinomas were retrospectively examined. Magnetic resonance (1.5-T) image data sets were coregistered, and the solid components of each tumor were semiautomatically segmented. ADC histograms of the solid components were extracted; modes, minimums, means, and 10th, 25th, 50th, 75th, and 90th percentiles of the histograms were compared between the two tumor types, and receiver-operating characteristic (ROC) analysis was performed. RESULTS: The mode, minimum, mean, 10th, 25th, 50th, and 75th percentile ADC values of solid components of borderline tumors were significantly larger than those of carcinomas. Among these, the 10th percentile values had the lowest p value (p = 0.0003). At ROC analysis, the area under the curve (AUC) in the 10th percentile was the greatest (0.854), and the best cutoff value in the 10th percentile provided the highest specificity (93.8 %). CONCLUSIONS: ADC histograms of solid tumor components facilitated the distinction between borderline ovarian tumors and carcinoma. The 10th percentile ADC values had the best diagnostic performance.
  • Taeko Matsuura, Yusuke Fujii, Seishin Takao, Takahiro Yamada, Yuka Matsuzaki, Naoki Miyamoto, Taisuke Takayanagi, Shinichiro Fujitaka, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki PHYSICS IN MEDICINE AND BIOLOGY 61 (4) 1515 -1531 2016年02月 [査読無し][通常論文]
     
    Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the proton's range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial marker's trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT.
  • Yi Cui, Khin Khin Tha, Shunsuke Terasaka, Shigeru Yamaguchi, Jeff Wang, Kohsuke Kudo, Lei Xing, Hiroki Shirato, Ruijiang Li RADIOLOGY 278 (2) 546 -553 2016年02月 [査読無し][通常論文]
     
    Purpose: To develop and independently validate prognostic imaging biomarkers for predicting survival in patients with glioblastoma on the basis of multiregion quantitative image analysis. Materials and Methods: This retrospective study was approved by the local institutional review board, and informed consent was waived. A total of 79 patients from two independent cohorts were included. The discovery and validation cohorts consisted of 46 and 33 patients with glioblastoma from the Cancer Imaging Archive (TCIA) and the local institution, respectively. Preoperative T1-weighted contrast material-enhanced and T2-weighted fluid-attenuation inversion recovery magnetic resonance (MR) images were analyzed. For each patient, we semiautomatically delineated the tumor and performed automated intratumor segmentation, dividing the tumor into spatially distinct subregions that demonstrate coherent intensity patterns across multiparametric MR imaging. Within each subregion and for the entire tumor, we extracted quantitative imaging features, including those that fully capture the differential contrast of multimodality MR imaging. A multivariate sparse Cox regression model was trained by using TCIA data and tested on the validation cohort. Results: The optimal prognostic model identified five imaging biomarkers that quantified tumor surface area and intensity distributions of the tumor and its subregions. In the validation cohort, our prognostic model achieved a concordance index of 0.67 and significant stratification of overall survival by using the log-rank test (P = .018), which outperformed conventional prognostic factors, such as age (concordance index, 0.57; P = .389) and tumor volume (concordance index, 0.59; P = .409). Conclusion: The multiregion analysis presented here establishes a general strategy to effectively characterize intratumor heterogeneity manifested at multimodality imaging and has the potential to reveal useful prognostic imaging biomarkers in glioblastoma. (C) RSNA, 2015
  • N. Fujima, D. Yoshida, T. Sakashita, A. Homma, A. Tsukahara, K. K. Tha, K. Kudo, H. Shirato AMERICAN JOURNAL OF NEURORADIOLOGY 37 (2) 342 -348 2016年02月 [査読無し][通常論文]
     
    Forty-one patients with head and neck squamous cell carcinoma were evaluated by using pseudocontinuous ASL. Quantitative tumor blood flow was calculated at the pretreatment and the early treatment periods. Pretreatment tumor blood flow in patients in the treatment failure group was significantly lower than that in patients in the local control group. The use of the percentage change of tumor blood flow combined with the percentage change of tumor volume had high diagnostic accuracy for predicting local control. BACKGROUND AND PURPOSE: For the assessment of the treatment response in non-surgical treatment, tumor blood flow provides the functional information of the tumor which is different from the morphological information such as tumor volume. The purpose of this study was to evaluate the diagnostic value of tumor blood flow values obtained by pseudocontinuous arterial spin-labeling in patients with head and neck squamous cell carcinoma. MATERIALS AND METHODS: Forty-one patients with head and neck squamous cell carcinoma were evaluated by using pseudocontinuous arterial spin-labeling. Quantitative tumor blood flow was calculated at the pretreatment and the early treatment periods in all the patients, and the percentage change of tumor blood flow between the two was calculated. At the early treatment period, based on their tumor volume reduction rate, we divided the patients into stable disease and partial response groups for a subgroup analysis. The local control or failure was confirmed either by histopathology or by radiologic evaluation within the follow-up. RESULTS: Pretreatment tumor blood flow in patients in the failure group was significantly lower than that in patients in the local control group. In the subgroup analysis of patients with stable disease, the percentage change of tumor blood flow was significantly larger (due to the tumor blood flow increase from pretreatment value) in the local control group than in the failure group. In addition, in patients with a partial response, the percentage change of tumor blood flow was significantly smaller (due to the tumor blood flow decrease from the pretreatment value) in the local control group than in the failure group. The accuracy for determination of the local control group or the failure group in pretreatment tumor blood flow was 0.83 and that in the combination use of the percentage change of tumor blood flow and tumor volume in the early treatment period was 0.93. CONCLUSIONS: Tumor blood flow obtained by pseudocontinuous arterial spin-labeling can be useful for the determination of local control. The combined use of the percentage change of tumor blood flow and tumor volume had particularly high diagnostic accuracy.
  • Keiichi Harada, Norio Katoh, Ryusuke Suzuki, Yoichi M. Ito, Shinichi Shimizu, Rikiya Onimaru, Tetsuya Inoue, Naoki Miyamoto, Hiroki Shirato PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS 32 (2) 305 -311 2016年02月 [査読無し][通常論文]
     
    Purpose: We investigated the usefulness of four-dimensional computed tomography (4DCT) performed before stereotactic body radiation therapy (SBRT) in determining the internal margins for peripheral lung tumors. Methods and Materials: The amplitude of the movement of a fiducial marker near a lung tumor measured using the maximum intensity projection (MIP) method in 4DCT imaging was acquired before the SBRT (Amp(CT)) and compared with the mean amplitude of the marker movement during SBRT (Amp(mean)) and with the maximum amplitude of the marker movement during SBRT (Amp(max)) using a real-time tumortracking radiotherapy (RTRT) system with 22 patients. Results: There were no significant differences between the means of the Amp(mean) and the means of the Amp(CT) in all directions (LR, P = 0.45; CC, P = 0.80; AP, P = 0.65). The means of the Amp(max) were significantly larger than the means of the Amp(CT) in all directions (LR, P < 0.01; CC, P = 0.03; AP, P < 0.01). In the lower lobe, the mean difference of the Amp(CT) from the mean of the Amp(max) was 5.7 +/- 8.0 mm, 12.5 +/- 16.7 mm, and 6.8 +/- 8.5 mm in the LR, CC, and AP directions, respectively. Conclusions: Acquiring 4DCT MIP images before the SBRT treatment is useful to establish the mean amplitude for a patient during SBRT but it underestimates the maximum amplitude during actual SBRT. Caution must be paid to determine the margin with the 4DCT especially for tumors at the lower lobe where it is of the potentially greatest benefit. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd.
  • Seishin Takao, Naoki Miyamoto, Taeko Matsuura, Rikiya Onimaru, Norio Katoh, Tetsuya Inoue, Kenneth Lee Sutherland, Ryusuke Suzuki, Hiroki Shirato, Shinichi Shimizu INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 94 (1) 172 -180 2016年01月 [査読無し][通常論文]
     
    Purpose: To investigate the frequency and amplitude of baseline shift or drift (shift/drift) of lung tumors in stereotactic body radiation therapy (SBRT), using a real-time tumor-tracking radiation therapy (RTRT) system. Methods and Materials: Sixty-eight patients with peripheral lung tumors were treated with SBRT using the RTRT system. One of the fiducial markers implanted near the tumor was used for the real-time monitoring of the intrafractional tumor motion every 0.033 seconds by the RTRT system. When baseline shift/drift is determined by the system, the position of the treatment couch is adjusted to compensate for the shift/drift. Therefore, the changes in the couch position correspond to the baseline shift/drift in the tumor motion. The frequency and amount of adjustment to the couch positions in the left-right (LR), cranio-caudal (CC), and antero-posterior (AP) directions have been analyzed for 335 fractions administered to 68 patients. Results: The average change in position of the treatment couch during the treatment time was 0.45 +/- 2.23 mm (mean +/- standard deviation), -1.65 +/- 5.95 mm, and 1.50 +/- 2.54 mm in the LR, CC, and AP directions, respectively. Overall the baseline shift/drift occurs toward the cranial and posterior directions. The incidence of baseline shift/drift exceeding 3 mm was 6.0%, 15.5%, 14.0%, and 42.1% for the LR, CC, AP, and for the square-root of sum of 3 directions, respectively, within 10 minutes of the start of treatment, and 23.0%, 37.6%, 32.5%, and 71.6% within 30 minutes. Conclusions: Real-time monitoring and frequent adjustments of the couch position and/or adding appropriate margins are suggested to be essential to compensate for possible underdosages due to baseline shift/drift in SBRT for lung cancers. (C) 2016 Elsevier Inc. All rights reserved.
  • Jun Furusawa, Akihiro Homma, Rikiya Onimaru, Tomohiro Sakashita, Daisuke Yoshida, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda Journal of Otolaryngology of Japan 119 (5) 782 -783 2016年 [査読無し][通常論文]
  • Takashi Ohno, Kohsuke Kudo, Greg Zaharchuk, Noriyuki Fujima, Hiroki Shirato JAPANESE JOURNAL OF RADIOLOGY 34 (1) 28 -34 2016年01月 [査読無し][通常論文]
     
    The purpose of the present study was to determine optimal threshold of vascular pixel elimination (VPE) for CT perfusion (CTP) and to assess diagnostic accuracy of CTP by comparing with xenon enhanced CT (XeCT) in moyamoya disease. Twenty-three patients underwent XeCT and CTP. Cerebral blood flow (CBF) images were generated for XeCT and CTP using nine types of software. Region of interest (ROI) measurement was performed on XeCT-CBF and CTP-CBF. Linear regression analysis was performed between XeCT-CBF and CTP-CBF in all software, without and with VPE. The Pearson correlation coefficient was calculated, and an optimal threshold was determined based on maximum correlation coefficients. Correlation coefficients at various VPE thresholds including data of no-VPE were compared with each other. The maximum correlation coefficient at the optimal threshold was also compared. Optimal thresholds varied among software types (0.8-2.2 and 7-14 ml/100 g in relative and absolute VPE, respectively). There were significant differences between correlation coefficients at a range of VPE thresholds compared to no-VPE in most software types. There were significant differences in maximum correlation coefficient at optimal threshold among various software types. Optimal threshold of VPE for CTP could be determined and diagnostic accuracy of CTP varied among software types in moyamoya disease.
  • Fumi Kato, Kohsuke Kudo, Hiroko Yamashita, Jeff Wang, Mitsuchika Hosoda, Kanako C. Hatanaka, Rie Mimura, Noriko Oyama-Manabe, Hiroki Shirato EUROPEAN JOURNAL OF RADIOLOGY 85 (1) 96 -102 2016年01月 [査読無し][通常論文]
     
    Purpose: To compare the morphology and minimum apparent diffusion coefficient (ADC) values among breast cancer subtypes. Methods: Ninety-three patients, who underwent breast MRI and collectively had 98 pathologically proven invasive carcinomas, were enrolled. Morphology was evaluated according to BIRADS-MRI. Minimum ADC was measured. Morphology and minimum ADC were compared among subtypes. Multivariate logistic regression analyses were used to identify the characteristics associated with different subtypes. Results: Oval/round shape was significantly associated with triple-negative (TN) cancer (TN vs. non-TN: 90.9% vs. 45.2%; p = 0.0123). Rim enhancement was significantly less frequent in Luminal A (Luminal A vs. non-Luminal A: 34.2% vs. 76.1%; p = 0.0003). The minimum ADC of Luminal A was significantly higher than that of Luminal B (HER2-negative) (834 vs. 748 x 10(-6) mm(2)/s; p <0.025). The minimum ADC of the TN-special type was significantly higher than that of TN-ductal (997 vs. 702 x 10-6 mm2/s; p <0.025). On the multivariate analysis comparing the characteristics associated with Luminal A vs. Luminal B (HER2-negative), the internal enhancement characteristics of the mass and minimum ADC were significant factors. Conclusion: Morphology and minimum ADC would be useful in distinguishing breast cancer subtypes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Jun Furusawa, Satoshi Kano, Takatsugu Mizumachi, Satoshi Iizuka, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 20 (6) 1081 -1085 2015年12月 [査読無し][通常論文]
     
    Background Pyriform sinus squamous cell carcinoma (SCC) has one of the worst prognoses of all upper aerodigestive tract cancers. Improving clinical outcomes for patients with hypopharyngeal SCC has been particularly challenging for head and neck surgeons and oncologists. Methods We investigated 30 patients with pyriform sinus SCC to verify the effectiveness of weekly cisplatin chemotherapy with concurrent radiotherapy. Cisplatin was administered at a dose of 40 mg/m(2) on weeks 1, 2, 3, 5, 6, and 7 during definitive radiotherapy with the aim of preserving the larynx. Results All 30 patients achieved definitive radiotherapy at a median dose of 70 Gy (range 64-70 Gy). Cisplatin was administrated concomitantly a median of five times (range 2-6 times). Persistent or recurrent primary disease was observed in four patients (13 %). Persistent or recurrent nodal metastasis was observed in five patients (17 %). Nine salvage surgeries were performed for eight patients, of whom seven survived without any evidence of disease. Post-operative complications were observed in two patients (22 %). The 5-year overall survival and locoregional control rates were 87 and 96 %, respectively. The 5-year laryngeal preservation rate was 74 %. Conclusions The regimen of weekly cisplatin CRT may be effective for pyriform sinus SCC; however, there were problems with strong selection bias in the current study due to the large number of T2 patients. Salvage surgery was safe and was able to improve the survival rate. This chemoradiation regimen was considered successful in preserving laryngeal function.
  • Rikiya Onimaru, Kazutoshi Hida, Naoki Takeda, Shunsuke Onodera, Yukiko Nishikawa, Takashi Mori, Hiroki Shirato JAPANESE JOURNAL OF RADIOLOGY 33 (12) 757 -763 2015年12月 [査読無し][通常論文]
     
    We retrospectively evaluated the efficacy of three-dimensional conformal radiotherapy (3D-CRT) for spinal schwannoma. Nine patients with spinal schwannoma were treated with 3D-CRT. All patients had a paravertebral or intraosseous component. Tumor sizes ranged from 0.8 to 8.7 cm, with a median of 3.5 cm. The prescribed dose was 50 Gy in 25 fractions at the isocenter, except for 1 patient who received 66 Gy in 33 fractions for a large sacral tumor. The follow-up period ranged from 20 to 137 months, with a median of 72 months. Tumor shrinkage within 3 mm occurred in 4 patients and tumor expansion within 3 mm occurred in 3. One tumor showed neither expansion nor shrinkage at the last follow-up. One patient experienced transient expansion by 8 mm in diameter at 12 months after the completion of radiotherapy (35-43 mm), and then the tumor size remained unchanged for 7 years. No severe late toxicity a parts per thousand yen grade 3 was observed. Only 1 of 9 tumors showed transit expansion over 3 mm after 3D-CRT, and severe late radiation toxicity was not observed. Use of 3D-CRT should be considered a treatment option for spinal schwannoma.
  • Jun Furusawa, Akihiro Homma, Rikiya Onimaru, Tomohiro Sakashita, Daisuke Yoshida, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda AURIS NASUS LARYNX 42 (6) 443 -448 2015年12月 [査読無し][通常論文]
     
    Objective: We retrospectively assessed the indications for superselective intra-arterial infusion of cisplatin with concomitant radiotherapy (RADPLAT) in patients with hypopharyngeal cancer (HPC). Methods: Between April 2000 and March 2013,41 previously untreated patients received superselective intra-arterial infusion of cisplatin (100-120 mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65-70 Gy). Results: During the median follow-up period of 5.5 years, a statistically significant difference in the 5-year overall survival was noted between patients with N0-1 (n = 14) and N2b-3 disease (n = 27). One-half of deaths were observed to be the result of distant metastasis. The 5-year local control and overall survival were significantly better in patients with unilateral than in those with bilateral primary tumors. All the patients with T4b disease (n = 3) died of disease within 2 years. Conclusion: Indications for RADPLAT in patients with HPC were defined as patients with unilateral tumors staged as T3-4a and N0-1. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Motoaki Yasuda, Tomoyuki Hatanaka, Hiroki Shirato, Takeshi Nishioka Oncology Letters 10 (5) 3171 -3176 2015年11月 [査読無し][通常論文]
     
    The present study demonstrated the acquisition of additional malignant characteristics in irradiated mouse fibrosarcoma cells compared with the parent cells. Several reporter assays indicated that hypoxia-inducible factor (HIF)-1 alpha, activator protein-1 and Ets-dependent transcription were activated in irradiated cells. The cis-elements in the 5'-untranslated region (UTR) of these transcription factors plays a major role in their expression in surviving irradiated cancer cells. By contrast, there were no evident differences between the 3'-UTR-dependent repression demonstrated by parent cells and irradiated cells. A small population of parental fibrosarcoma cells was also found to exhibit the same enhanced 5'-UTR-dependent HIF-1 alpha expression as that demonstrated by irradiated cells. These observations may indicate that high-dose X-ray irradiation affects the majority of proliferating cancer cells, but not the cancer stem cells (CSCs), and an increased CSC population may explain the progressive phenotypes of the irradiated cells. It appears likely that the transcription factors that maintain stemness are regulated by the same 5'-UTR-dependent mechanism.
  • Yasutaka Sugano, Masahiro Mizuta, Seishin Takao, Hiroki Shirato, Kenneth L. Sutherland, Hiroyuki Date MEDICAL PHYSICS 42 (11) 6203 -6210 2015年11月 [査読無し][通常論文]
     
    Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose-volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose-volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose-volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8-32 fractions with a daily dose of 2.2-6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose-volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation. (C) 2015 American Association of Physicists in Medicine.
  • Masumi Umezawa, Futaro Ebina, Yusuke Fujii, Koji Matsuda, Kazuo Hiramoto, Kikuo Umegaki, Hiroki Shirato Hitachi Review 64 506 -513 2015年11月01日 [査読無し][通常論文]
     
    OVERVIEW: The use of particle beams in treating cancer, both in Japan and overseas, is growing in recognition of their ability to precisely target the dose of radiation on the cancerous tumor while minimizing the impact on surrounding organs. In particular, it is anticipated that particle therapy using scanning irradiation will become mainstream in the future. Having led the world in the commercialization of this form of treatment, Hitachi has also been working on the development of compact particle therapy systems that have been designed specifically to use this method. In 2009, as part of the "Advanced Radiation Therapy Project Real-time Tumor-tracking with Molecular Imaging Technique" funded by the FIRST Program as a national project launched in partnership with Hokkaido University, Hitachi jointly developed and commercialized a scanning irradiation technique that can track moving organs, and that incorporated a tumor-tracking radiotherapy system developed by Hokkaido University. Hitachi intends to utilize these new technical developments to help encourage the wider adoption of particle therapy.
  • Noriyuki Fujima, Hiroyuki Kameda, Akiko Tsukahara, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato EUROPEAN JOURNAL OF RADIOLOGY 84 (11) 2187 -2193 2015年11月 [査読無し][通常論文]
     
    Objectives: To investigate the diagnostic value of tumor blood flow (TBF) obtained with pseudocontinuous arterial spin labeling (pCASL) for the differentiation of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the nasal or sinonasal cavity. Methods: Thirty-three patients with SCC and 6 patients with ML in the nasal or sinonasal cavity were retrospectively analyzed. Quantitative TBF values were obtained using whole-tumor region of interest (ROI) from pCASL data. The histogram analysis of TBF values within the tumor ROI was also performed by calculating the coefficient of variation (CV), kurtosis, and skewness. The mean TBF value, histogram CV, kurtosis and skewness of the patients with SCC were compared with those of the ML patients. The diagnostic accuracy to differentiate SCC from ML was also calculated by receiver operating characteristic (ROC) curve analysis. In addition, multiple logistic regression models were also performed to determine their independent predictive value, and diagnostic accuracy with the combined use of these parameters. Results: Between the SCC and ML groups, significant differences were observed in mean TBF, CV, and kurtosis, but not in skewness. In ROC curve analysis, the diagnostic accuracy values for the differentiation of SCC from ML in mean TBF, CV, and kurtosis were all 0.87, respectively. Multiple logistic regression models revealed TBF and CV were respectively independent predictive value. With the combination of these parameters, the diagnostic accuracy was elevated to 0.97. Conclusions: The TBF value and its histogram analysis obtained with pCASL can help differentiate SCC and ML. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Akihiro Homma, Yuji Nakamaru, Tomohiro Sakashita, Rikiya Onimaru, Shunsuke Terasaka, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiromitsu Hatakeyama, Jun Furusawa, Takatsugu Mizumachi, Satoshi Kano, Hiroki Shirato, Satoshi Fukuda AURIS NASUS LARYNX 42 (5) 377 -381 2015年10月 [査読無し][通常論文]
     
    Objective: Here we report our experience of patients with squamous cell carcinoma (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of treatment outcomes. Methods: A retrospective analysis was performed using data from 25 consecutive patients treated between 2000 and 2012. Four patients were diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease. No patient had lymph node metastasis. Results: Twelve patients were treated with surgery with/without radiotherapy and with/without chemotherapy. Of these, 4 underwent endoscopic surgery without an open approach and 3 required an anterior skull base approach. Thirteen were treated with radiotherapy; 1 with radiotherapy alone, and 4 and 8 with intravenous and intra-arterial chemotherapy, respectively. The 5-yr overall survival for T1-3, T4a, and T4b disease was 53.9%, 71.4%, and 29.0%, respectively. The 5-yr disease-specific survival for T1-3, T4a, and T4b disease was 74.1%, 71.4%, and 29.0%, respectively. Conclusion: Our treatment policy for patients with SCC of NC&ES, which basically follows the NCCN guideline, was considered to be appropriate. However, several points in terms of surgery and nonsurgical approach remain to be solved through further research. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Yusuke Sakuhara, Saori Nishio, Ken Morita, Daisuke Abo, Yu Hasegawa, Noriaki Yuasa, Toshio Mochizuki, Takeshi Soyama, Koji Oba, Hiroki Shirato, Kohsuke Kudo Radiology 277 (1) 277 -85 2015年10月 [査読無し][通常論文]
     
    PURPOSE: To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) with ethanol in symptomatic patients with enlarged polycystic kidney disease. MATERIALS AND METHODS: This prospective study was institutional review board approved and was planned for patients with symptoms related to enlarged polycystic kidney disease, such as a markedly distended abdomen, gastroesophageal reflux, and abdominal pain. At the time of TAE, all patients were undergoing dialysis therapy for chronic renal failure, and their urinary volume had decreased to less than 500 mL per day. Bilateral renal TAE with absolute ethanol was performed, and changes in kidney volume, clinical symptoms, laboratory data, and complications were evaluated after TAE. The differences in patients' kidney volumes, clinical symptoms, abdominal circumference, and dry weights before and after TAE were analyzed with a mixed effect model. RESULTS: Fifteen patients (seven men and eight women; mean age, 57.7 years ± 5.3 [standard deviation]) were treated. Among the 15 patients, the follow-up period was 24 months in 13 patients, 6 months in one patient, and 3 months in one patient. The mean kidney volume was 3380 mL before renal TAE, and at 3, 12, and 24 months after TAE, it significantly decreased to 60.9%, 39.8%, and 32.1% of the pretherapeutic value, respectively (P < .001). All patients reported improved clinical symptoms within 3 months after TAE (P < .001). Abdominal circumferences were significantly decreased after TAE (P < .001). The dry weights also continued to significantly decreased until 6 months after TAE (P < .001), at which point they began to slightly increase until 24 months after TAE. Abdominal pain, nausea, and inflammatory response developed in all patients after TAE, but these symptoms improved with conservative treatment. Abscess formation was found in one kidney, and drainage catheter placement was performed. No major complications related to TAE occurred in the remaining patients. CONCLUSION: Renal contraction therapy by TAE with ethanol injection appears to be a safe and effective treatment in patients with symptomatic enlarged polycystic kidney disease.
  • N. Fujima, Y. Nakamaru, T. Sakashita, A. Homma, A. Tsukahara, K. Kudo, H. Shirato DENTOMAXILLOFACIAL RADIOLOGY 44 (9) 2015年09月 [査読無し][通常論文]
     
    Objectives: To investigate the diagnostic value of tumour blood flow (TBF) obtained with pseudocontinuous arterial spin labelling for the differentiation of squamous cell carcinoma (SCC) and inverted papilloma (IP) in the nasal or sinonasal cavity. Methods: We retrospectively analysed the cases of 33 patients with SCC and 8 patients with IF in the nasal or sinonasal cavity. Pseudocontinuous arterial spin labelling scanning was performed for all patients using a 3.0-T MR unit. Quantitative TBF values were measured by two neuroradiologists by respectively delineating the whole-tumour regions of interest, and the mean of them was determined as TBF value in each patient. Additionally, the presence of imaging findings of convoluted cerebriform pattern (CCP) on MR T-2 weighted images was determined in all patients. As a subgroup analysis, patients with IF were divided into aggressive and non-aggressive IPs depending on their progression range. First, an intraclass correlation coefficient (ICC) of TBF values between two neuroradiologists was determined. Next, a statistical comparison of the TBF value by a Mann-Whitney U test between the patients with SCC and IP was performed. Additionally, the comparison by an ANOVA with a post hoc test of Tukey's method among the SCC, non-aggressive IF and aggressive IP groups was also performed. If significance was observed, the diagnostic accuracy to differentiate SCCs from IPs was calculated. Diagnostic accuracy by CCP findings alone and by the combination of CCP findings and TBF were also assessed. Results: The ICC of TBF values between two neuroradiologists was 0.82. The mean TBF values in the patients with SCC, all patients with IP, those with aggressive IP and those with non-aggressive IP were 141.2 +/- 33.1, 77.8 +/- 31.5, 109.4 +/- 16.7 and 58.8 +/- 19.9 ml 100 g(-1) min(-1), respectively. A significant difference was observed between SCC and IP (p < 0.001), SCC and non-aggressive IP (p < 0.01) and non-aggressive IP and aggressive IP (p < 0.01). The diagnostic accuracy values obtained with receiver operating characteristic curve analysis for the differentiation of SCC from IF and for SCC from non-aggressive IP were 0.90 and 0.92, respectively. The diagnostic accuracy was elevated (0.95 from 0.88) by adding the TBF value to CCP findings. Conclusions: The pseudocontinuous arterial spin labelling technique can be a useful non-invasive diagnostic tool to differentiate SCC from IP in nasal or sinonasal cavity.
  • Fumi Kato, Noriko Oyama-Manabe, Yusuke Sakuhara, Suzuko Mito, Masato Takahashi, Tetsuro Sakamoto, Mitsuchika Hosoda, Satoshi Terae, Hiroki Shirato BREAST CANCER 22 (5) 475 -479 2015年09月 [査読無し][通常論文]
     
    Background Breast MRI protocols have been improved by using a combination of dynamic scans for bilateral breasts and high-resolution imaging for a single breast which can be obtained during dynamic scans by recent technological advances. The purpose of this study was to compare high-resolution imaging during dynamic scans (HR-intra) with high-resolution imaging obtained post dynamic scans (HR-post). Methods Fifty-five women with pathologically proven breast cancer who underwent breast dynamic scans at 3-T MRI from February to September 2009 were enrolled in this study. Tumoral contrasts to the background breast tissue were compared by three radiologists independently in a blinded fashion. Results of visual assessment were categorized into three groups as follows: HR-intra being better (IB), equal (E), and HR-post being better (PB). The contrast to noise ratio (CNR) of the tumor and the signal to noise ratio of the normal breast gland (SNR) were compared between HR-intra and HR-post. Results Two patients were excluded because of poor MR imaging quality. Three radiologists separately categorized 64.2, 79.2, and 77.4 % of lesions as IB. The CNR of the tumor of HR-intra (mean +/- SD = 6.9 +/- 4.0) was significantly higher than that of HR-post (6.0 +/- 3.7, p < 0.0001). The SNR of the normal breast gland of HR-intra (9.5 +/- 1.7) was significantly lower than that of HR-post (10.0 +/- 1.9, p < 0.0001). Conclusion HR-intra during dynamic MRI provided earlier and better tumor to normal breast gland contrast than HR-post.
  • Rikiya Onimaru, Shinichi Shimizu, Hiroki Shirato, Masayori Ishikawa Stereotactic Body Radiation Therapy: Principles and Practices 217 -224 2015年08月06日 [査読無し][通常論文]
  • Hiroki Shirato, Rikiya Onimaru, Shinichi Shimizu, Naoki Miyamoto, Ruijiang Li, Albert C. Koong, Masahiro Mizuta Stereotactic Body Radiation Therapy: Principles and Practices 239 -250 2015年08月06日 [査読無し][通常論文]
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Jun Furusawa, Satoshi Kano, Takatsugu Mizumachi, Satoshi Iizuka, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda ACTA OTO-LARYNGOLOGICA 135 (8) 853 -858 2015年08月 [査読無し][通常論文]
     
    Conclusion: Grade >= 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well. Objectives: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation. Method: This study retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities. In the BRT group, an initial cetuximab loading dose of 400 mg/m(2) was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m(2) of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m(2) weekly during the definitive radiotherapy. Results: The BRT group had a higher incidence of Grade >= 3 radiation dermatitis than did the CRT group (43% vs 3%, respectively, p < 0.01). The incidence rate of Grade >= 3 mucositis/stomatitis was 64.3% and 41.4% in the BRT and CRT group, respectively (p = 0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p = 0.2053).
  • Quynh-Thu Le, Hiroki Shirato, Amato J. Giaccia, Albert C. Koong CLINICAL CANCER RESEARCH 21 (15) 3393 -3401 2015年08月 [査読無し][通常論文]
     
    Rapid advancements in radiotherapy and molecularly targeted therapies have resulted in the development of potential paradigm-shifting use of radiotherapy in the treatment of cancer. In this review, we discuss some of the most promising therapeutic approaches in the field of radiation oncology. These strategies include the use of highly targeted stereotactic radiotherapy and particle therapy as well as combining radiotherapy with agents that modulate the DNA damage response, augment the immune response, or protect normal tissues. (C)2015 AACR.
  • Hidefumi Aoyama, Masao Tago, Hiroki Shirato JAMA ONCOLOGY 1 (4) 457 -464 2015年07月 [査読無し][通常論文]
     
    IMPORTANCE It remains uncertain whether treatment with stereotactic radiosurgery (SRS) alone can be safely applied to all patient populations with 1 to 4 brain metastases (BMs) exhibiting heterogeneous prognoses. OBJECTIVE To investigate the feasibility of SRS alone for patients with different prognoses determined by the diagnosis-specific Graded Prognostic Assessment (DS-GPA). DESIGN, SETTING, AND PARTICIPANTS A secondary analysis (performed in September 2014) of the Japanese Radiation Oncology Study Group (JROSG) 99-1, a phase 3 randomized trial, comparing SRS alone and whole-brain radiotherapy (WBRT) + SRS conducted in 1999 to 2003. Among a total of 132 patients, 88 with non-small-cell lung cancer (NSCLC) and 1 to 4 BMs were included and poststratified by DS-GPA scores to avoid potential bias from BMs from different primary cancer types. The median follow-up time was 8.05 months. INTERVENTIONS The WBRT schedule was 30 Gy in 10 fractions over 2 to 2.5 weeks. The mean SRS dose was 21.9 Gy in SRS alone and 16.6 Gy in WBRT + SRS. MAIN OUTCOMES AND MEASURES The primary end point was overall survival (OS), and the secondary end points included brain tumor recurrence (BTR), salvage treatment, and radiation toxic effects. RESULTS Forty-seven patients had a favorable prognosis, with DS-GPA scores of 2.5 to 4.0 (26 SRS-alone and 21 WBRT + SRS [DS-GPA 2.5-4.0 group]), and 41 had an unfavorable prognosis, with DS-GPA scores of 0.5 to 2.0 (19 SRS-alone and 22 WBRT + SRS [DS-GPA 0.5-2.0 group]). Significantly better OS was observed in the DS-GPA 2.5-4.0 group in WBRT + SRS vs the SRS alone, with a median survival time of 16.7 (95% CI, 7.5-72.9) months vs 10.6 (95% CI, 7.7-15.5) months (P = .04) (hazard ratio [HR], 1.92; 95% CI, 1.01-3.78). However, no such difference was observed in the DS-GPA 0.5-2.0 group (HR, 1.05; 95% CI, 0.55-1.99) (P =.86). This benefit could be explained by the differing BTR rates, in that the prevention against BTR by WBRT had a more significant impact in the DS-GPA 2.5-4.0 group (HR, 8.31; 95% CI, 3.05-29.13) (P < .001) vs the DS-GPA 0.5-2.0 group (HR, 3.57; 95% CI, 1.02-16.49) (P = .04). CONCLUSIONS AND RELEVANCE Despite the current trend of using SRS alone, the important role of WBRT for patients with BMs from NSCLC with a favorable prognosis should be considered. Our findings should be validated through appropriately designed prospective studies.
  • Takatsugu Mizumachi, Akihiro Homma, Tomohiko Kakizaki, Tomohiro Sakashita, Satoshi Kano, Hiromitsu Hatakeyama, Kazuhiko Tsuchiya, Koichi Yasuda, Rikiya Onimaru, Hiroki Shirato, Jun Taguchi, Yasushi Shimizu, Ichiro Kinoshita, Hirotoshi Akita, Satoshi Fukuda INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 20 (3) 431 -437 2015年06月 [査読無し][通常論文]
     
    The aim of this study was to evaluate the feasibility of induction docetaxel, cisplatin, and 5-fluorouracil chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Between 2010 and 2013, 30 patients with Stage IV HNSCC were treated in Hokkaido University Hospital with three cycles of induction chemotherapy (docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2), day 1; and 5-fluorouracil 750 mg/m(2)/day 120 h continuous infusion, every 3 weeks) followed by concurrent weekly cisplatin (40 mg/m(2), on weeks 1, 2, 3, 5, 6 and 7) chemoradiotherapy. Three courses of induction chemotherapy were performed in 25 patients (83 %) with grade 3-4 toxicities during induction chemotherapy observed in 22 patients (73 %). The major toxicities were hematologic, with 22 cases (73 %) showing grade 3-4 neutropenia. Radiotherapy was completed (70 Gy) in 29 patients (97 %), while a total of 19 patients (63 %) completed five (13 patients) or six (6 patients) courses of chemotherapy. During concurrent chemoradiotherapy, no grade 4 hematological toxicities were observed. Grade 4 dermatitis was observed in one patient, and grade 3 mucositis was observed in 12 patients. There were no treatment-related deaths during the induction chemotherapy or concurrent chemoradiotherapy. The 1- and 2-year progression-free survival rates and the 1- and 2-year overall survival rates were 86 %, 72 %, and 89 %, 81 %, respectively. Sequential therapy composed of induction chemotherapy followed by concurrent weekly cisplatin chemoradiotherapy is feasible, showing encouraging results in patients with locally advanced HNSCC. Concurrent weekly cisplatin chemoradiotherapy following induction chemotherapy appears to be a suitable alternative to three-weekly high-dose cisplatin therapy.
  • Jun Kunimatsu, Naoki Miyamoto, Masayori Ishikawa, Hiroki Shirato, Masaki Tanaka Frontiers in Systems Neuroscience 9 2015年04月24日 [査読無し][通常論文]
     
    Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans.
  • Noriyuki Fujima, Kohsuke Kudo, Akiko Tsukahara, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Khin Khin Tha, Hiroki Shirato JOURNAL OF MAGNETIC RESONANCE IMAGING 41 (4) 983 -+ 2015年04月 [査読無し][通常論文]
     
    PurposeTo investigate the feasibility of tumor blood flow (TBF) measurement in head and neck squamous cell carcinoma (HNSCC) using pseudo-continuous arterial spin labeling (pCASL) in a comparison with dynamic contrast-enhanced (DCE) perfusion. Materials and MethodsWe prospectively scanned 18 patients with HNSCC using 3T magnetic resonance imaging (MRI) with both pCASL and DCE perfusion. Quantitative TBF value in the whole-tumor region of interest (ROI), and regional TBF in the ROIs of the central and peripheral areas in the tumor were respectively measured. Relative TBF value in the whole-tumor ROI was also calculated. We determined the correlation and agreement between each measured TBF by pCASL and DCE perfusion using Pearson's correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman analysis. ResultsIn the whole-tumor ROIs, significant correlation was observed between the absolute TBF values (r=0.72, P<0.01), with an ICC of 0.72; moreover, higher correlation was observed in the relative TBF (r=0.79). The correlation was higher in the peripheral ROI (r=0.70) than the central ROI (r=0.65), with an ICC of 0.62 and 0.54, respectively. Bland-Altman plots revealed the underestimation of TBF by pCASL in central ROIs. ConclusionTBF measurement by pCASL was feasible in patients with HNSCC. J. Magn. Reson. Imaging 2015;41:983-991. (c) 2014 Wiley Periodicals, Inc.
  • Noriyuki Fujima, Kohsuke Kudo, Akiko Tsukahara, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Khin K.hin Tha, Hiroki Shirato Journal of magnetic resonance imaging : JMRI 41 983 -991 2015年04月01日 [査読無し][通常論文]
     
    © 2014 Wiley Periodicals, Inc. PURPOSE: To investigate the feasibility of tumor blood flow (TBF) measurement in head and neck squamous cell carcinoma (HNSCC) using pseudo-continuous arterial spin labeling (pCASL) in a comparison with dynamic contrast-enhanced (DCE) perfusion. MATERIALS AND METHODS: We prospectively scanned 18 patients with HNSCC using 3T magnetic resonance imaging (MRI) with both pCASL and DCE perfusion. Quantitative TBF value in the whole-tumor region of interest (ROI), and regional TBF in the ROIs of the central and peripheral areas in the tumor were respectively measured. Relative TBF value in the whole-tumor ROI was also calculated. We determined the correlation and agreement between each measured TBF by pCASL and DCE perfusion using Pearson's correlation coefficients, intraclass correlation coefficients (ICC), and Bland-Altman analysis. RESULTS: In the whole-tumor ROIs, significant correlation was observed between the absolute TBF values (r = 0.72, P  <  0.01), with an ICC of 0.72; moreover, higher correlation was observed in the relative TBF (r = 0.79). The correlation was higher in the peripheral ROI (r = 0.70) than the central ROI (r = 0.65), with an ICC of 0.62 and 0.54, respectively. Bland-Altman plots revealed the underestimation of TBF by pCASL in central ROIs. CONCLUSION: TBF measurement by pCASL was feasible in patients with HNSCC. J. Magn. Reson. Imaging 2015;41:1-1. © 2014 Wiley Periodicals, Inc.
  • Takashi Mori, Rikiya Onimaru, Shunsuke Onodera, Kazuhiko Tsuchiya, Koichi Yasuda, Hiromitsu Hatakeyama, Hiroyuki Kobayashi, Shunsuke Terasaka, Akihiro Homma, Hiroki Shirato RADIATION ONCOLOGY 10 2015年04月 [査読無し][通常論文]
     
    Background: Olfactory neuroblastoma (ONB) is a rare tumor originating from olfactory epithelium. Here we retrospectively analyzed the long-term treatment outcomes and toxicity of radiotherapy for ONB patients for whom computed tomography (CT) and three-dimensional treatment planning was conducted to reappraise the role of radiotherapy in the light of recent advanced technology and chemotherapy. Methods: Seventeen patients with ONB treated between July 1992 and June 2013 were included. Three patients were Kadish stage B and 14 were stage C. All patients were treated with radiotherapy with or without surgery or chemotherapy. The radiation dose was distributed from 50 Gy to 66 Gy except for one patient who received 40 Gy preoperatively. Results: The median follow-up time was 95 months (range 8-173 months). The 5-year overall survival (OS) and relapse-free survival (RFS) rates were estimated at 88% and 74%, respectively. Five patients with stage C disease had recurrence with the median time to recurrence of 59 months (range 7-115 months). Late adverse events equal to or above Grade 2 in CTCAE v4.03 were observed in three patients. Conclusion: Multimodal therapy including radiotherapy with precise treatment planning based on CT simulation achieved an excellent local control rate with acceptable toxicity and reasonable overall survival for patients with ONB.
  • Masayori Ishikawa, Naomi Nagase, Taeko Matsuura, Junichi Hiratsuka, Ryusuke Suzuki, Naoki Miyamoto, Kenneth Lee Sutherland, Katsuhisa Fujita, Hiroki Shirato JOURNAL OF RADIATION RESEARCH 56 (2) 372 -381 2015年03月 [査読無し][通常論文]
     
    The scintillator with optical fiber (SOF) dosimeter consists of a miniature scintillator mounted on the tip of an optical fiber. The scintillator of the current SOF dosimeter is a 1-mm diameter hemisphere. For a scintillation dosimeter coupled with an optical fiber, measurement accuracy is influenced by signals due to Cerenkov radiation in the optical fiber. We have implemented a spectral filtering technique for compensating for the Cerenkov radiation effect specifically for our plastic scintillator-based dosimeter, using a wavelength-separated counting method. A dichroic mirror was used for separating input light signals. Individual signal counting was performed for high-and low-wavelength light signals. To confirm the accuracy, measurements with various amounts of Cerenkov radiation were performed by changing the incident direction while keeping the Ir-192 source-to-dosimeter distance constant, resulting in a fluctuation of <5%. Optical fiber bending was also addressed; no bending effect was observed for our wavelength-separated SOF dosimeter.
  • Noriyuki Miyamoto, Satoshi Yabusaki, Keita Sakamoto, Yasuka Kikuchi, Rie Mimura, Fumi Kato, Noriko Oyama-Manabe, Bunya Takahashi, Takeshi Soyama, Daisuke Abo, Yusuke Sakuhara, Kohsuke Kudo, Hiroki Shirato, Toru Nakamura, Takahiro Tsuchikawa, Keisuke Okamura, Satoshi Hirano JAPANESE JOURNAL OF RADIOLOGY 33 (2) 59 -66 2015年02月 [査読無し][通常論文]
     
    To determine whether the preoperative pancreatic apparent diffusion coefficient (ADC) can be used to predict the development of postoperative pancreatic anastomotic failure (PAF). We retrospectively examined the cases of 79 patients who underwent pancreatic head resection between January 2010 and October 2013. The patients underwent 1.5-T MR imaging including diffusion-weighted imaging before surgery. The main pancreatic duct diameter (MPD), the pancreatic parenchymal thickness (PT), and the ADC of the pancreatic remnant parenchyma were measured. Two radiologists blinded to the patients' outcomes performed the measurements. The imaging parameters were compared between the patients who developed PAF and those who did not. The cut-off ADC for the development of PAF was calculated with a receiver operating characteristic analysis. The imaging parameters were highly correlated between the two observers. The MPD and PT did not differ significantly among the patients. The mean pancreatic ADCs were significantly higher in the patients with PAF than in those without PAF. An ADC higher than 1.50 x 10(-3) mm(2)/s (Az = 0.719, observer-1) or 1.35 x 10(-3) mm(2)/s (Az = 0.752, observer-2) was optimal for predicting the development of postoperative PAF. Measuring the preoperative non-tumorous pancreatic ADC may be useful for the prediction of a postoperative PAF.
  • Shigeru Yamaguchi, Kenji Hirata, Sadahiro Kaneko, Hiroyuki Kobayashi, Tohru Shiga, Kentaro Kobayashi, Rikiya Onimaru, Hiroki Shirato, Nagara Tamaki, Shunsuke Terasaka, Kiyohiro Houkin Acta Neurochirurgica 157 (2) 187 -194 2015年02月 [査読無し][通常論文]
     
    © 2014, Springer-Verlag Wien. Background: Although histological diagnosis is indispensable in treating primary central nervous system lymphoma (PCNSL), we sometimes face an intractable situation in which tissue can be obtained only from a deep-seated brain lesion. In place of a histological diagnosis, the diagnostic adequacy of the combined use of 18 F-FDG PET and corticosteroid administration for PCNSL located in a deep-seated brain structure is reported.Methods: Patients with a deep-seated tumor were treated as having PCNSL without histological confirmation, based on the following criteria: (1) there was no evidence of systemic malignancy; (2) the tumor showed an extremely high FDG uptake relative to normal gray matter on pretreatment 18 F-FDG PET; (3) the tumor decreased in size 1 week after diagnostic therapy by corticosteroid administration on contrast-enhanced T1-weighted magnetic resonance imaging (MRI). FDG uptake of the lesion was evaluated by the maximum of standardized uptake values (SUVmax) and tumor-to-normal ratio of the SUV (T/N ratio). The extent of the tumor reduction was calculated by volumetric analysis for the treatment response to corticosteroid administration.Results: Ten patients (4 males and 6 females) matched these criteria. On pretreatment 18 F-FDG PET, mean SUVmax in the tumor was 24.8 (8.75–60.75), and mea n T/N ratio was 3.24 (2.17–5.12). The extent of tumor volume reduction was shown to be 21 to 68 % 1 week after diagnostic therapy by corticosteroids. Mean total dose and duration of corticosteroids were 719 mg as prednisolone and 6.5 days, respectively. Nine patients achieved complete response and one patient achieved partial response on MRI after standard treatment for PCNSL with high-dose methotrexate and/or whole-brain irradiation.Conclusion: Although the value of biopsy is universal, combining 18 F-FDG PET and corticosteroid administration is an important alternative method that may lead to the diagnosis of deep-seated PCNSLs in cases with intractable histopathological confirmations.
  • Magdalena Bazalova-Carter, Moiz Ahmad, Taeko Matsuura, Seishin Takao, Yuto Matsuo, Rebecca Fahrig, Hiroki Shirato, Kikuo Umegaki, Lei Xing MEDICAL PHYSICS 42 (2) 900 -907 2015年02月 [査読無し][通常論文]
     
    Purpose: To demonstrate the feasibility of proton-induced x-ray fluorescence CT (pXFCT) imaging of gold in a small animal sized object by means of experiments and Monte Carlo (MC) simulations. Methods: First, proton-induced gold x-ray fluorescence (pXRF) was measured as a function of gold concentration. Vials of 2.2 cm in diameter filled with 0%-5% Au solutions were irradiated with a 220 MeV proton beam and x-ray fluorescence induced by the interaction of protons, and Au was detected with a 3x3 mm(2) CdTe detector placed at 90 degrees. with respect to the incident proton beam at a distance of 45 cm from the vials. Second, a 7-cm diameter water phantom containing three 2.2-diameter vials with 3%-5% Au solutions was imaged with a 7-mm FWHM 220 MeV proton beam in a first generation CT scanning geometry. X-rays scattered perpendicular to the incident proton beam were acquired with the CdTe detector placed at 45 cm from the phantom positioned on a translation/ rotation stage. Twenty one translational steps spaced by 3 mm at each of 36 projection angles spaced by 10. were acquired, and pXFCT images of the phantom were reconstructed with filtered back projection. A simplified geometry of the experimental data acquisition setup was modeled with the MC TOPAS code, and simulation results were compared to the experimental data. Results: A linear relationship between gold pXRF and gold concentration was observed in both experimental and MC simulation data (R-2 > 0.99). All Au vials were apparent in the experimental and simulated pXFCT images. Specifically, the 3% Au vial was detectable in the experimental [contrast-to-noise ratio (CNR) = 5.8] and simulated (CNR = 11.5) pXFCT image. Due to fluorescence x-ray attenuation in the higher concentration vials, the 4% and 5% Au contrast were underestimated by 10% and 15%, respectively, in both the experimental and simulated pXFCT images. Conclusions: Proton-induced x-ray fluorescence CT imaging of 3%-5% gold solutions in a small animal sized water phantom has been demonstrated for the first time by means of experiments and MC simulations. (C) 2015 American Association of Physicists in Medicine.
  • Naoki Miyamoto, Masayori Ishikawa, Kenneth Sutherland, Ryusuke Suzuki, Taeko Matsuura, Chie Toramatsu, Seishin Takao, Hideaki Nihongi, Shinichi Shimizu, Kikuo Umegaki, Hiroki Shirato JOURNAL OF RADIATION RESEARCH 56 (1) 186 -196 2015年01月 [査読無し][通常論文]
     
    In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory-gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low-dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some trajectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within +/- 2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction.
  • Seiichiro Ishihara, Motoaki Yasuda, Akihiro Ishizu, Masayori Ishikawa, Hiroki Shirato, Hisashi Haga Oncotarget 6 (7) 4602 -4614 2015年 [査読無し][通常論文]
     
    Radiotherapy is effective for treating various types of tumors. However, some cancer cells survive after irradiation and repopulate tumors with highly malignant phenotypes that correlate with poor prognosis. It is not known how cancer cells survive and generate malignant tumors after irradiation. Here, we show that activating transcription factor 5 (ATF5) promotes radioresistance and malignancy in cancer cells after irradiation. In the G1-S phase of the cell cycle, cancer cells express high levels of ATF5, which promotes cell cycle progression and thereby increases radioresistance. Furthermore, ATF5 increases malignant phenotypes, such as cell growth and invasiveness, in cancer cells in vitro and in vivo. We have identified a new mechanism for the regeneration of highly malignant tumors after irradiation and shown that ATF5 plays a key role in the process.
  • Kinya Ishizaka, Fumi Kato, Satoshi Terae, Suzuko Mito, Noriko Oyama-Manabe, Tamotsu Kamishima, Mitsuhiro Nakanishi, Hiroyuki Sugimori, Hiroyuki Hamaguchi, Hiroki Shirato Radiological physics and technology 8 (1) 4 -12 2015年01月 [査読無し][通常論文]
     
    In this study, we aimed to compare fat-suppression homogeneity on breast MR imaging by using dual-source parallel radiofrequency excitation and image-based shimming (DS-IBS) with single-source radiofrequency excitation with volume shim (SS-Vol) at 3 Tesla. Twenty patients were included. Axial three-dimensional T1-weighted turbo-field-echo breast images with DS-IBS and SS-Vol were obtained. Fat suppression was scored with four grade points. The contrast of the pectoral muscle and the fat in each breast area was obtained in the head medial, head lateral, foot medial, and foot lateral areas. The axillary space was calculated and compared between DS-IBS and SS-Vol. The average DS-IBS score was significantly higher than that of SS-Vol. The mean contrasts of fat in the foot lateral areas and axillary spaces on DS-IBS images were significantly higher than on SS-Vol images.
  • H. Shirato Japanese Journal of Clinical Radiology 60 1565 -1570 2015年01月01日 [査読無し][通常論文]
  • Akihiro Homma, Tomohiro Sakashita, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Yuji Nakamaru, Daisuke Yoshida, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda ACTA OTO-LARYNGOLOGICA 135 (9) 950 -954 2015年 [査読無し][通常論文]
     
    Conclusions: Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery. Objective: To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck. Patients and methods: Between 2001-2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100-120 mg/m(2)/ week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy). Results: Five patients had tumors arising in the base of the tongue, two in the maxillary sinus, and the remaining two in the nasopharynx. The median follow-up period was 9 years 7 months (9; 7) (range = 4; 6-12; 5), and the 5-year local control (LC), overall survival (OS), and disease-free survival rates were 88.9%, 88.9%, and 55.6%, respectively. The 10-year OS rate was 57.1%, but all patients who remained alive for over 10 years are still alive with disease. Primary tumor recurrence was observed in five of the nine patients, with the median time to recurrence being 6 years (range = 4-9 years). Five of the nine patients had distant metastasis, and of these three patients also had primary recurrence.
  • Rikiya Onimaru, Hiroki Shirato, Taro Shibata, Masahiro Hiraoka, Satoshi Ishikura, Katsuyuki Karasawa, Yukinori Matsuo, Masaki Kokubo, Yoshiyuki Shioyama, Haruo Matsushita, Yoshinori Ito, Hiroshi Onishi Radiotherapy and Oncology 116 (2) 276 -280 2015年 [査読無し][通常論文]
     
    © 2015 Elsevier Ireland Ltd. Purpose To estimate the maximum tolerated dose (MTD) and to determine the recommended dose (RD) of stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinoma (NSCLC) with target volume (PTV) < 100 cc. Materials and methods The continual reassessment method (CRM) was used to determine the dose level that patients should be assigned to and to estimate the MTD. Dose limiting toxicity (DLT) was grade 3 radiation pneumonitis (RP) within 180 days after the start of SBRT, grade 2 RP was used as a surrogate DLT. The RD was equal to the MTD. The dose was prescribed at D95 of the PTV. Results Fifteen patients were accrued. Only 1 experienced grade 2 RP at 60 Gy in 4 fractions. It was difficult to fulfill the dose constraints at 60 Gy in 4 fractions, and the maximum dose level assigned by CRM was changed to 55 Gy in 4 fractions. The lower limit of 95% of the credible interval exceeded the adjacent level, and the RD was determined as 55 Gy in 4 fractions. Conclusions The RD of SBRT for peripheral T2N0M0 NSCLC with PTV < 100 cc was determined to be 55 Gy in 4 fractions.
  • Jeff Wang, Fumi Kato, Noriko Oyama-Manabe, Ruijiang Li, Yi Cui, Khin Khin Tha, Hiroko Yamashita, Kohsuke Kudo, Hiroki Shirato PloS one 10 (11) e0143308 2015年 [査読無し][通常論文]
     
    OBJECTIVES: To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE) MRI at 3.0 Tesla in identifying "triple-negative" breast cancers. MATERIALS AND METHODS: In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC) using cross-validation. RESULTS: Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (p<0.01). Similar improvements were seen in nearly all subtype classification tasks undertaken. Notably, amongst the most discriminating features for predicting triple-negative cancers were textures of background parenchymal enhancement. CONCLUSIONS: Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype. Prospective validation studies are warranted to confirm these findings and determine potential implications.
  • Noriyuki Fujima, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Akiko Tsukahara, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato MAGNETIC RESONANCE IMAGING 32 (10) 1206 -1213 2014年12月 [査読無し][通常論文]
     
    Purpose: To investigate the correlation between perfusion-related parameters obtained with intravoxel incoherent motion (IVIM) and classical perfusion parameters obtained with dynamic contrast-enhanced (DCE) magnetic resonance imaging in patients with head and neck squamous cell carcinoma (HNSCC), and to compare direct and asymptotic fitting, the pixel-by-pixel approach, and a region of interest (ROI)-based approach respectively for IVIM parameter calculation. Materials and methods: Seventeen patients with HNSCC were included in this retrospective study. All magnetic resonance (MR) scanning was performed using a 3 T MR unit. Acquisition of IVIM was performed using single-shot spin-echo echo-planar imaging with three orthogonal gradients with 12 b-values (0, 10, 20, 30, 50, 80, 100, 200, 400, 800, 1000, and 2000). Perfusion-related parameters of perfusion fraction 'f' and the pseudo-diffusion coefficient 'D*' were calculated from IVIM data by using least square fitting with the two fitting methods of direct and asymptotic fitting, respectively. DCE perfusion was performed in a total of 64 dynamic phases with a 3.2-s phase interval. The two-compartment exchange model was used for the quantification of tumor blood volume (TBV) and tumor blood flow (TBF). Each tumor was delineated with a polygonal ROI for the calculation of f, f center dot D* performed using both the pixel-by-pixel approach and the ROI-based approach. In the pixel-by-pixel approach, after fitting each pixel to obtain f, f center dot D* maps, the mean value in the delineated ROI on these maps was calculated. In the ROI-based approach, the mean value of signal intensity was calculated within the ROI for each b-value in IVIM images, and then fitting was performed using these values. Correlations between fin a total of four combinations (direct or asymptotic fitting and pixel-by-pixel or ROI-based approach) and TBV were respectively analyzed using Pearson's correlation coefficients. Correlations between f center dot D* and TBF were also similarly analyzed. Results: In all combinations of f and TBV, f center dot D* and TBF, there was a significant correlation. In the comparison of f and TBV, a moderate correlation was observed only between f obtained by direct fitting with the pixel-by-pixel approach, whereas a good correlation was observed in the comparisons using the other three combinations. In the comparison of f center dot D* and TBF, a good correlation was observed only with f center dot D* obtained by asymptotic fitting with the ROI-based approach. In contrast, moderate correlations were observed in the comparisons using the other three combinations. Conclusion: IVIM was found to be feasible for the analysis of perfusion-related parameters in patients with HNSCC. Especially, the combination of asymptotic fitting with the ROI-based approach was better correlated with DCE perfusion. (C) 2014 Elsevier Inc. All rights reserved.
  • Shunsuke Onodera, Hidefumi Aoyama, Khin Khin Tha, Naoki Hashimoto, Atsuhito Toyomaki, Satoshi Terae, Hiroki Shirato JOURNAL OF NEURO-ONCOLOGY 120 (2) 311 -319 2014年11月 [査読無し][通常論文]
     
    To investigate whether the neurocognitive function at 4 months could be a relevant primary endpoint in clinical trials dealing with brain metastases, we created a Japanese neurocognitive battery and examined the changes in patients' neurocognitive function for 1 year after their brain radiotherapy. In this prospective pilot study, we enrolled 27 patients (20 patients who received whole-brain radiation therapy [WBRT] and seven who received stereotactic irradiation [STI] alone) between March 2009 and December 2010. The follow-up neurocognitive data at 4, 8 and 12 months were available in 22 (17 WBRT, 5 STI), 19 patients (14 WBRT, 5 STI) and 13 patients (9 WBRT, 4 STI), respectively. Among the patients who received WBRT, significant deterioration in delayed memory compared to the baseline (p = 0.04) was observed at 4 months, and at 8 months, significant improvements were observed in immediate memory compared to the baseline (p = 0.008) and 4-months scores (p = 0.005). At 12 months, however, the immediate memory scores had returned to the baseline. Similar trends were observed in other functions (delayed memory, attention and executive functions). In these patients, the correlations between 4-months scores of neurocognitive functions and 12-months scores were significant in immediate memory (gamma = 0.68, p = 0.004), delayed memory (gamma = 0.738, p = 0.023) and attention (gamma = 0.817, p = 0.007). Among the patients who received STI, no significant changes were observed in any functions. These results suggest that 4-months changes in neurocognitive functions were transient but could also be a premonitory index for predicting the neurocognitive function 1 year or later after brain radiation therapy.
  • Noriyuki Fujima, Kohsuke Kudo, Daisuke Yoshida, Akihiro Homma, Tomohiro Sakashita, Akiko Tsukahara, Khin Khin Tha, Yuri Zaitsu, Satoshi Terae, Hiroki Shirato JOURNAL OF MAGNETIC RESONANCE IMAGING 40 (4) 920 -928 2014年10月 [査読無し][通常論文]
     
    Purpose: To evaluate the feasibility of arterial spin-labeling (ASL) in head and neck cancer for noninvasive measurement of tumor blood flow (TBF), by comparing 1) the TBF change before and after the treatment, and 2) posttreatment TBF and its reduction rate between residual and nonresidual tumors after treatment. Materials and Methods: Twenty-two patients with head and neck cancer were evaluated using ASL on 3.0-T magnetic resonance imaging (MRI) before and after nonsurgical treatment. A pulsed ASL sequence with Look-Locker readout was used to calculate quantitative TBF. TBF reduction rates between pre- and posttreatment values were also calculated. Residual tumors were confirmed when present with either histopathologically or clinical follow-up. Results: Pre- and posttreatment mean TBF values were 121.4 +/- 27.8 (standard deviation) and 24.9 +/- 14.9 mL/100g/min, respectively. Pre-and posttreatment TBF differed significantly. Posttreatment TBF was significantly higher in patients with residual tumors (five patients, 46.9 +/- 7.1 mL/100g/min) than in those without (17 patients, 18.4 +/- 9.2 mL/100g/min). The TBF reduction rate was significantly lower in patients with residual tumors (0.540.55 +/- 0.120.12) than in those without (0.85 +/- 0.06). Conclusion: ASL allows quantitative assessment of TBF in head and neck cancer. ASL may be useful for noninvasive assessment of tumor viability in head and neck cancer.
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Jun Furusawa, Daisuke Yoshida, Noriyuki Fujima, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY 271 (10) 2767 -2770 2014年10月 [査読無し][通常論文]
     
    The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100-120 mg/m(2) superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3 % (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2 % (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer.
  • Rie Yamazaki, Rikiya Onimaru, Norio Katoh, Tetsuya Inoue, Takeshi Nishioka, Hiroki Shirato, Hiroyuki Date Radiological Physics and Technology 7 (2) 284 -289 2014年07月 [査読無し][通常論文]
     
    Our purpose in this study was to evaluate the variation in calculated doses caused by respiration in stereotactic body radiotherapy (SBRT) of the lung. The study targeted ten patients who underwent SBRT for lung tumors. CT images were acquired during free breathing and in the inhalation and exhalation phases. We compared the CT image at inhalation with the image at exhalation so as to measure the change in lung volume, variation in the CT value, and displacement of the chest wall. The lung volume change was shown to be correlated with the maximum of the chest wall motion and with the variation in the CT value. A statistically significant difference was observed in the CT values between inhalation and exhalation (p < 0.05). The total dose variation at the isocenter was confined within ±2 %. However, the dose from individual beams can vary significantly when the chest wall moves more than 10 mm in natural breathing. © 2014 Japanese Society of Radiological Technology and Japan Society of Medical Physics.
  • Yasuka Kikuchi, Noriko Oyama-Manabe, Masanao Naya, Osamu Manabe, Yuuki Tomiyama, Tsukasa Sasaki, Chietsugu Katoh, Kohsuke Kudo, Nagara Tamaki, Hiroki Shirato European radiology 24 (7) 1547 -56 2014年07月 [査読無し][通常論文]
     
    OBJECTIVES: This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against (15)O-H₂O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients. METHODS: Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7). RESULTS: Correlation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 ± 0.8) was significantly lower than that in the validation group (5.2 ± 1.8) (P = 0.0011). CONCLUSIONS: We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP. KEY POINTS: • MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. • MBF and CFR showed good correlation between dynamic CTP and PET. • Lower CFR was well demonstrated in CAD patients by dynamic CTP.
  • S. Shimizu, T. Matsuura, M. Umezawa, K. Hiramoto, N. Miyamoto, K. Umegaki, H. Shirato PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS 30 (5) 555 -558 2014年07月 [査読無し][通常論文]
     
    Purpose: Spot-scanning proton beam therapy (PBT) can create good dose distribution for static targets. However, there exists larger uncertainty for tumors that move due to respiration, bowel gas or other internal circumstances within the patients. We have developed a real-time tumor-tracking radiation therapy (RTRT) system that uses an X-ray linear accelerator gated to the motion of internal fiducial markers introduced in the late 1990s. Relying on more than 10 years of clinical experience and big log data, we established a real-time image gated proton beam therapy system dedicated to spot scanning. Materials and methods: Using log data and clinical outcomes derived from the clinical usage of the RTRT system since 1999, we have established a library to be used for in-house simulation for tumor targeting and evaluation. Factors considered to be the dominant causes of the interplay effects related to the spot scanning dedicated proton therapy system are listed and discussed. Results/conclusions: Total facility design, synchrotron operation cycle, and gating windows were listed as the important factors causing the interplay effects contributing to the irradiation time and motion-induced dose error. Fiducial markers that we have developed and used for the RTRT in X-ray therapy were suggested to have the capacity to improve dose distribution. Accumulated internal motion data in the RTRT system enable us to improve the operation and function of a Spot-scanning proton beam therapy (SSPT) system. A real-time-image gated SSPT system can increase accuracy for treating moving tumors. The system will start clinical service in early 2014. (C) 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
  • Teiji Nishio, Hiroki Shirato, Masayori Ishikawa, Yuki Miyabe, Satoshi Kito, Yuichirou Narita, Rikiya Onimaru, Satoshi Ishikura, Yoshinori Ito, Masahiro Hiraoka JOURNAL OF RADIATION RESEARCH 55 (3) 600 -607 2014年05月 [査読無し][通常論文]
     
    A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was <= 0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.
  • Roshan Mahabir, Mishie Tanino, Aiman Elmansuri, Lei Wang, Taichi Kimura, Tamio Itoh, Yusuke Ohba, Hiroshi Nishihara, Hiroki Shirato, Masumi Tsuda, Shinya Tanaka NEURO-ONCOLOGY 16 (5) 671 -685 2014年05月 [査読無し][通常論文]
     
    Ionizing irradiation is an effective treatment for malignant glioma (MG); however, a higher rate of recurrence with more aggressive phenotypes is a vital issue. Although epithelial-mesenchymal transition (EMT) is involved in irradiation-induced cancer progression, the role for such phenotypic transition in MG remains unknown. To investigate the mechanism of irradiation-dependent tumor progression in MG, we performed immunohistochemistry (IHC) and qRT-PCR using primary and recurrent MG specimens, MG cell lines, and primary culture cells of MG. siRNA technique was used for MG cell lines. In 22 cases of clinically recurrent MG, the expression of the mesenchymal markers vimentin and CD44 was found to be increased by IHC. In paired identical MG of 7 patients, the expression of collagen, MMPs, and YKL-40 were also elevated in the recurrent MGs, suggesting the The Cancer Genome Atlas-based mesenchymal subtype. Among EMT regulators, sustained elevation of Snail was observed in MG cells at 21 days after irradiation. Cells exhibited an upregulation of migration, invasion, numbers of focal adhesion, and MMP-2 production, and all of these mesenchymal features were abrogated by Snail knockdown. Intriguingly, phosphorylation of ERK1/2 and GSK-3 were increased after irradiation in a Snail-dependent manner, and TGF- was elevated in both fibroblasts and macrophages but not in MG cells after irradiation. It was noteworthy that irradiated cells also expressed stemness features such as SOX2 expression and tumor-forming potential in vivo. We here propose a novel concept of glial-mesenchymal transition after irradiation in which the sustained Snail expression plays an essential role.
  • Shigeru Yamaguchi, Shunsuke Terasaka, Hiroyuki Kobayashi, Katsuyuki Asaoka, Hiroaki Motegi, Hiroshi Nishihara, Hiromi Kanno, Rikiya Onimaru, Yoichi M. Ito, Hiroki Shirato, Kiyohiro Houkin PLOS ONE 9 (5) 2014年05月 [査読無し][通常論文]
     
    Background: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy.Methods: We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy.Results: Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3-5 resection, preoperative Karnofsky Performance status, <= 70%, and MIB-1 labeling index >= 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group.Conclusion: We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy.
  • Motoaki Yasuda, Tomoyuki Hatanaka, Hiroki Shirato, Takeshi Nishioka Biochemical and Biophysical Research Communications 447 (4) 638 -643 2014年05月 [査読無し][通常論文]
     
    In the present study, we demonstrated the reciprocal regulation of hypoxia-inducible factor 1 alpha (HIF1A) gene expression via untranslated region-(UTR) dependent mechanisms. A 151 nucleotide sequence found in the HIF1A 5′-UTR is sufficient for significant translational up-regulation. On the other hand, the 3′-UTR of HIF1A has been implicated in mRNA degradation. In the non-metastatic breast cancer cell line MCF7, the 3′-UTR-dependent down-regulatory machinery predominates over the 5′-UTR-dependent up-regulation of HIF1A. However, 5′-UTR-dependent up-regulation is dominant among metastatic cell lines (MDA-MB453, U87MG). It is therefore likely that the predominance of 5′-UTR-dependent translational enhancement of HIF1A is critical for the malignant phenotype of cancer cells. PTBP-1, but not HuR, is a candidate RNA binding protein for the translational control of HIF1A. © 2014 Elsevier Inc. All rights reserved.
  • Shinichi Shimizu, Kentaro Nishioka, Ryusuke Suzuki, Nobuo Shinohara, Satoru Maruyama, Takashige Abe, Rumiko Kinoshita, Norio Katoh, Rikiya Onimaru, Hiroki Shirato RADIATION ONCOLOGY 9 2014年05月 [査読無し][通常論文]
     
    Background: We prospectively assessed the utility of intensity-modulated radiation therapy (IMRT) with urethral dose reduction and a small margin between the clinical target volume (CTV) and the planning target volume (PTV) for patients with localized prostate cancer. Methods: The study population was 110 patients in low- (14.5%), intermediate- (41.8%), and high-risk (43.6%) categories. Three gold fiducial markers were inserted into the prostate. A soft guide-wire was used to identify the urethra when computed tomography (CT) scan for treatment planning was performed. A dose constraint of V70 < 10% was applied to the urethral region. Margins between the CTV-PTV were set at 3 mm in all directions. Patients were treated with 70 Gy IMRT in 30 fractions (D95 of PTV) over 7.5 weeks. The patient couch was adjusted to keep the gold markers within 2.0 mm from their planned positions with the use of frequent on-line verification. Results: The median follow-up period was 31.3 (3.2 to 82.1) months. The biochemical relapse-free survival (bRFS) rates at 3 years were 100%, 93.8% and 89.5% for the low-, intermediate-, and high-risk patients, respectively. The incidences of acute adverse events (AEs) were 45.5% and 0.9% for grades 1 and 2, respectively. The late AEs were grade 1 cystitis in 10.0% of the patients, rectal bleeding in 7.3%, and urinary urgency in 6.4%. Only three patients (2.7%) developed grade 2 late AEs. Conclusions: On-line image guidance with precise correction of the table position during radiotherapy achieved one of the lowest AEs rates with a bRFS equal to the highest in the literature.
  • F. Kato, R. Mimura, K. Kudo, N. Manabe, T. Fujiwara, H. Sugimori, M. Hosoda, H. Yamashita, H. Shirato Japanese Journal of Clinical Radiology 59 (4) 558 -562 2014年04月 [査読無し][通常論文]
     
    We investigated usefulness of the slice selection gradient reversal (SSGR) method in diffusion weighed imaging (DWI) using 3-tesla breast MRI. Thirty-four women with 42 breast tumors were studied. Image quality and lesion detectability were compared between DWI with and without SSGR. DWI with SSGR had higher image quality with little artifact and higher detectability of the lesions than DWI without SSGR. Image quality and lesion detectability were improved on DWI using SSGR.
  • Tomohiro Sakashita, Akihiro Homma, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Jun Furusawa, Daisuke Yoshida, Noriyuki Fujima, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Fumiyuki Suzuki, Satoshi Fukuda BRITISH JOURNAL OF ORAL & MAXILLOFACIAL SURGERY 52 (4) 323 -328 2014年04月 [査読無し][通常論文]
     
    Our aim was to evaluate the feasibility of salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy. We retrospectively analysed the records of 61 patients with cancer of the maxillary sinus who were treated in this way. Chemotherapy comprised 100-120 mg/m(2) superselective intra-arterial infusions of cisplatin given a median of 4 times weekly (range 2-5). Concurrent radiotherapy was given in a median dose of 65 Gy (range 24-70 Gy). Persistent or recurrent cancer of the maxillary sinus was found in 17 patients, of whom 11 had salvage surgery. The disease was controlled in 8 of the 11, and 7 of the 11 survived with no evidence of disease. Their 5-year overall survival was 61%. Two of the 11 developed serious operative complications. Salvage surgery for patients with persistent or recurrent cancer of the maxillary sinus treated by superselective chemoradiotherapy is both safe and successful. Salvage surgery is a good option when this sort of persistent or recurrent cancer is followed up after the regimen of chemoradiotherapy described. (C) 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
  • Shinichi Shimizu, Naoki Miyamoto, Taeko Matsuura, Yusuke Fujii, Masumi Umezawa, Kikuo Umegaki, Kazuo Hiramoto, Hiroki Shirato PLOS ONE 9 (4) 2014年04月 [査読無し][通常論文]
     
    Purpose: A proton beam therapy (PBT) system has been designed which dedicates to spot-scanning and has a gating function employing the fluoroscopy-based real-time-imaging of internal fiducial markers near tumors. The dose distribution and treatment time of the newly designed real-time-image gated, spot-scanning proton beam therapy (RGPT) were compared with free-breathing spot-scanning proton beam therapy (FBPT) in a simulation. Materials and Methods: In-house simulation tools and treatment planning system VQA (Hitachi, Ltd., Japan) were used for estimating the dose distribution and treatment time. Simulations were performed for 48 motion parameters (including 8 respiratory patterns and 6 initial breathing timings) on CT data from two patients, A and B, with hepatocellular carcinoma and with clinical target volumes 14.6 cc and 63.1 cc. The respiratory patterns were derived from the actual trajectory of internal fiducial markers taken in X-ray real-time tumor-tracking radiotherapy (RTRT). Results: With FBPT, 9/48 motion parameters achieved the criteria of successful delivery for patient A and 0/48 for B. With RGPT 48/48 and 42/48 achieved the criteria. Compared with FBPT, the mean liver dose was smaller with RGPT with statistical significance (p<0.001); it decreased from 27% to 13% and 28% to 23% of the prescribed doses for patients A and B, respectively. The relative lengthening of treatment time to administer 3 Gy (RBE) was estimated to be 1.22 (RGPT/FBPT: 138 s/113 s) and 1.72 (207 s/120 s) for patients A and B, respectively. Conclusions: This simulation study demonstrated that the RGPT was able to improve the dose distribution markedly for moving tumors without very large treatment time extension. The proton beam therapy system dedicated to spot-scanning with a gating function for real-time imaging increases accuracy with moving tumors and reduces the physical size, and subsequently the cost of the equipment as well as of the building housing the equipment.
  • Emi Hirano, Hiroshi Fuji, Tsuyoshi Onoe, Vinay Kumar, Hiroki Shirato, Koichi Kawabuchi JOURNAL OF RADIATION RESEARCH 55 (2) 320 -327 2014年03月 [査読無し][通常論文]
     
    Background: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. Methods: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. Results: The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. Conclusions: Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.
  • Takatsugu Mizumachi, Akihiro Homma, Tomohiro Sakashita, Satoshi Kano, Hiromitsu Hatakeyama, Kazuhiko Tsuchiya, Kouichi Yasuda, Rikiya Onimaru, Hiroki Shirato, Satoshi Fukuda Japanese Journal of Head and Neck Cancer 40 (1) 66 -70 2014年 [査読無し][通常論文]
     
    The most common chemoradiotherapy regimen is high-dose (100 mg/m2) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. A recent study demonstrated that HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) patients showed good prognosis. Here, we reviewed the efficacy of concomitant weekly cisplatin and radiotherapy in patients with OPSCC. Twenty-two patients with untreated OPSCC were enrolled and evaluated at our institution from July 2006 to June 2012. Weekly cisplatin (40 mg/m2) was given at weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. The presence of HPV was analyzed using the multiplex PCR method. Median follow-up time was 38.6 months for surviving patients. Of the 22 oropharyngeal carcinomas, 13 (59%) were HPV-positive. Twenty-one patients (95.4%) received the full dose of radiotherapy. Over the course of the chemotherapy, 14 patients (63.6%) received more than 200 mg/m2 cisplatin. The acute and late toxicity was manageable in all cases. HPV-positive patients had better three-year overall survival rates (92.3% vs 66.7%) than HPV-negative patients. For HPV-positive patients, 1 of 13 died of distant metastasis, whereas for HPV-negative patients, 1 of 9 died of local recurrence and 2 of 9 died of distant metastasis. Because of its favorable outcome and lower toxicity, concomitant weekly cisplatin and radiotherapy appears to be a suitable treatment for HPV-positive OPSCC.
  • Kazuhiko Tsuchiya, Rumiko Kinoshita, Shinichi Shimizu, Kentaro Nishioka, Keiichi Harada, Noboru Nishikawa, Ryusuke Suzuki, Hiroki Shirato Radiological Physics and Technology 7 (1) 67 -72 2014年 [査読無し][通常論文]
     
    We sought to investigate whether intensity-modulated radiotherapy (IMRT) has a dosimetric advantage compared to the standard wedged tangential technique (SWT) for whole-breast radiotherapy (WBRT) in Asian women with relatively small breast volume. Computed tomography images of 25 Asian patients with early-stage breast cancer (right 15, left 10) used for WBRT planning were examined. After contouring the target volumes and bilateral lungs and, for left-side treatment, the heart, 4 plans were made for each patient: namely, SWT, tangential-field IMRT (T-IMRT), 3-field IMRT (3F-IMRT), and 4-field IMRT (4F-IMRT). The prescribed dose was 5000 cGy. The median planning target volume (PTV) for WBRT was 552.6 cc (range 288.8-1518.4 cc). Compared to SWT, (1) T-IMRT achieved significant improvement for dose homogeneity in the PTV (p < 0.001) and the dose received by 2 % (D2) of the PTV (p < 0.001). T-IMRT also reduced the bilateral lung mean dose (p < 0.001) and the ipsilateral lung volume which received more than 20 Gy (V20) (p = 0.01). (2) 3F-IMRT resulted in a significant increase in the mean dose to the ipsilateral lung (p < 0.001) and to the contralateral lung (p < 0.001). (3) 4F-IMRT also resulted in a significant increase in the mean dose to the ipsilateral lung (p < 0.001) and to the contralateral lung (p < 0.001). Tangential-field IMRT provided an improved dose distribution compared with SWT for WBRT in Asian women with a relatively small breast volume. © Japanese Society of Radiological Technology and Japan Society of Medical Physics 2013.
  • Hiroshi Kawakami, Daisuke Abo, Kazumichi Kawakubo, Masaki Kuwatani, Yuki Yoshino, Yoshimasa Kubota, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Yusuke Sakuhara, Hiroki Shirato, Naoya Sakamoto ENDOSCOPY 46 E460 -E461 2014年 [査読無し][通常論文]
  • Jeff Wang, Fumi Kato, Kohsuke Kudo, Hiroko Yamashita, Hiroki Shirato Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 8539 334 -340 2014年 [査読無し][通常論文]
     
    Early classification of breast cancers by molecular subtype allows for expeditious characterization of the disease and selection of appropriate treatment options. This ability is especially a concern for "triple- negative" cancers, which lack expression of the three cell surface receptors that most breast cancer hormonal therapies target, tend to be the most aggressive/metastatic compared to other subtypes, have lymph node involvement at diagnoses, and have relatively poor prognoses. In this study, we aim to develop predictive models using Dynamic Contrast-Enhanced (DCE) MRI-extracted features to identify triple-negative cancers and axillary lymph node metastasis at the time of diagnostic imaging. Using only morphological, pharmacokinetic, densitometric, statistical, textural, and textural kinetic features obtained from DCE-MRI, we were able to classify 91.3% of 69 lesions correctly for triple-negative status with a sensitivity of 55.6%, a specificity of 96.7, and an AUC of 0.889 71.6% of lesions correctly for lymph node metastasis with a sensitivity of 50.0%, a specificity of 82.2%, and an AUC of 0.677. © 2014 Springer International Publishing.
  • Shinichi Shimizu, Kazuhiko Tsuchiya, Seishin Takao, Hiroki Shirato [Hokkaido igaku zasshi] The Hokkaido journal of medical science 89 25 -28 2014年01月01日 [査読無し][通常論文]
     
    Cancer is the most major cause of death in Japan recently. In this symposium, we explained advanced treatment technology for cancer treatment, now used and that will be used in near future at the Hokkaido University Hospital. Intensity Moderated Radiation Therapy (IMRT) and Proton Beam Therapy (PBT) are considered to be the most promising and advanced technologies for cancer treatment. Various kinds of radiation treatment equipment and methods have been developed and constructed at the Hokkaido University. One of the most worlds wide famous one is the real time tumor tracking radiotherapy system. The FIRST (Funding for World-Leading Innovative R & D on Science and Technology) Program has been supporting us to produce cutting-edge technology. We hope that this symposium would help the audience to understand the latest technology for cancer treatment especially in the field of radiation therapy and also we wish the audience would recognize the importance of the research aspect that have been performed at Hokkaido University and its Hospital.
  • Yuichi Hirata, Naoki Miyamoto, Morihito Shimizu, Mitsuhiro Yoshida, Kazuo Hiramoto, Yoshiaki Ichikawa, Shuji Kaneko, Tsuyoshi Sasagawa, Masahiro Hiraoka, Hiroki Shirato Synthesiology 7 238 -246 2014年01月01日 [査読無し][通常論文]
     
    © 2014, National Institute of Advanced Industrial Science and Technology(AIST). In radiation therapy for cancer, there are possibilities of changing of positions of the affected area during irradiation due to respiration of a patient. In order to enhance effects of irradiation for the affected area and minimize damages to the surrounding normal tissues, four dimensional radiotherapy (4DRT), which can take into account time variation of the three-dimensional position of the affected area, has been recently developed, and has been achieving significant therapeutic effect. We have proposed the International Electrotechnical Commission (IEC) standards including technical requirements of the safety aspects of the systems which realize this 4DRT, taking into account the time variation. The reason for the proposal is that international standardization will be very effective to ensure safety of 4DRT, and international standards of IEC will have compelling force if regulatory agencies refer to them. The purpose of this paper is to summarize the analysis of the strategy in a precedent endeavor toward international standardization of the 4DRT systems, for which demands are increasing. The main point of the strategy is forming an international consensus by bringing together the opinions of specialists from various fields from a clinical point of view, focusing on the international standardization of the technical requirements of the safety aspects of the 4DRT. Based on such a strategy, we will promote developing new standards by evaluating the overall safety of the 4DRT systems for further expanding use, in addition to updating existing standards of particular equipment which constitute the 4DRT systems.
  • Kentaro Nishioka, Shinichi Shimizu, Nobuo Shinohara, Yoichi M. Ito, Takashige Abe, Satoru Maruyama, Rumiko Kinoshita, Keiichi Harada, Noboru Nishikawa, Naoki Miyamoto, Rikiya Onimaru, Hiroki Shirato JAPANESE JOURNAL OF CLINICAL ONCOLOGY 44 (1) 28 -35 2014年01月 [査読無し][通常論文]
     
    The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than 2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65. Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients quality of life.
  • A. Homma, T. Sakashita, D. Yoshida, R. Onimaru, K. Tsuchiya, F. Suzuki, K. Yasuda, H. Hatakeyama, J. Furusawa, T. Mizumachi, S. Kano, N. Inamura, S. Taki, H. Shirato, S. Fukuda BRITISH JOURNAL OF CANCER 109 (12) 2980 -2986 2013年12月 [査読無し][通常論文]
     
    Background: The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma of maxillary sinus (SCC-MS). Methods: Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120mgm(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy). Results: One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n-5), brain necrosis (n-1), and ocular/ visual problems (n = 14) were observed as late adverse reactions. Conclusion: We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.
  • Satoshi Tanabe, Miyako Myojin, Shinichi Shimizu, Masaharu Fujino, Hiroaki Takahashi, Hiroki Shirato, Yoichi M. Ito, Masayori Ishikawa, Masao Hosokawa Journal of Radiation Research 54 (6) 1085 -1094 2013年11月 [査読無し][通常論文]
     
    Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy ( plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0 1 RP (RPG≤1) group and the Grade 2 5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients Grade 3, n = 3 Grade 4, n = 3 Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (< 55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP. © The Author 2013. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology.
  • Nobuo Shinohara, Satoru Maruyama, Shinichi Shimizu, Kentaro Nishioka, Takashige Abe, Kanako C-Hatanaka, Koji Oba, Katsuya Nonomura, Hiroki Shirato Journal of radiation research 54 (6) 1095 -101 2013年11月01日 [査読無し][通常論文]
     
    The purpose of this study was to compare the quality of life (QOL) in patients with localized prostate cancer (PC) after intensity-modulated radiation therapy assisted with a fluoroscopic real-time intensity-modulated radiation therapy (RT-IMRT) tumor-tracking system versus the QOL after radical prostatectomy (RP). Between 2003 and 2006, 71 patients were enrolled in this longitudinal prospective study. Each patient was allowed to decide which treatment modality they would receive. Of the 71 patients, 23 patients underwent RT-IMRT, while 48 opted for RP. No patient received neo-adjuvant or adjuvant hormone therapy. The global QOL and disease-specific-QOL were evaluated before treatment and again at 1, 3 and 5 years after treatment. There was no significant difference in the background characteristics between the two groups. The 5-year biochemical progression-free survival was 90% in the RT-IMRT and 79% in the RP group. In the RT-IMRT group, there was no significant deterioration of the global QOL or disease-specific QOL through 5 years post-treatment. In the RP group, the urinary function, sexual function, and sexual bother indicators significantly deteriorated after treatment. Urinary and sexual function was significantly better in the RT-IMRT group at 1, 3 and 5 years post-treatment compared to the RP group. RT-IMRT may be a preferable treatment for localized PC because of similar efficacy to RP but better post-treatment QOL.
  • Yukie Shimizu, Khin Khin Tha, Akihiro Iguchi, Yuko Cho, Atsushi Yoshida, Noriyuki Fujima, Akiko Tsukahara, Hiroki Shirato, Satoshi Terae The neuroradiology journal 26 (5) 514 -9 2013年10月 [査読無し][通常論文]
     
    Posterior reversible encephalopathy syndrome (PRES) is characterized by reversible vasogenic edema affecting the subcortical white matter of bilateral occipital and parietal lobes. We describe a case of isolated posterior fossa involvement of PRES which occurred during remission induction chemotherapy for T-cell acute lymphoblastic leukemia. Both the brainstem and cerebellum were extensively involved, but the supratentorial structures were completely spared. The follow-up magnetic resonance images revealed reversibility of most lesions. The knowledge of atypical radiological features of PRES is essential for prompt diagnosis.
  • Rumiko Kinoshita, Jin-Min Nam, Yoichi M. Ito, Kanako C. Hatanaka, Ari Hashimoto, Haruka Handa, Yutaro Otsuka, Shigeru Hashimoto, Yasuhito Onodera, Mitsuchika Hosoda, Shunsuke Onodera, Shinichi Shimizu, Shinya Tanaka, Hiroki Shirato, Mishie Tanino, Hisataka Sabe PLOS ONE 8 (10) 2013年10月 [査読無し][通常論文]
     
    A major problem of current cancer research and therapy is prediction of tumor recurrence after initial treatment, rather than the simple biological characterization of the malignancy and proliferative properties of tumors. Breast conservation therapy (BCT) is a well-approved, standard treatment for patients with early stages of breast cancer, which consists of lumpectomy and whole-breast irradiation. In spite of extensive studies, only 'age' and 'Ki-67 positivity' have been identified to be well correlated with local recurrence after BCT. An Arf6 pathway, activated by GEP100 under receptor tyrosine kinases (RTKs) and employs AMAP1 as its effector, is crucial for invasion and metastasis of some breast cancer cells. This pathway activates beta 1 integrins and perturbs E-cadherin-based adhesions, hence appears to be integral for epithelial-mesenchymal transdifferentiation (EMT). We here show that expression of the Arf6 pathway components statistically correlates with rapid local recurrence after BCT. We retrospectively analyzed four hundred seventy-nine patients who received BCT in Hokkaido University Hospital, and found 20 patients had local recurrence. We then analyzed pathological samples of patients who experienced local recurrence by use of Kaplan-Meier analysis, Stepwise regression analysis and the t-test, coupled with immunostaining, and found that co-overexpression of GEP100 and AMAP1 correlates with rapidity of the local recurrence. Their margin-status, node-positivity, and estrogen receptor (ER)-or progesterone receptor (PgR)positivity did not correlated with the rapidity. This study is the first to show that expression of a certain set of proteins correlates with the rapidity of local recurrence. Our results are useful not only for prediction, but highlight the possibility of developing novel strategies to block local recurrence. We also discuss why mRNAs encoding these proteins have not been identified to correlate with local recurrence by previous conventional gene expression profiling analyses.
  • Yasuka Kikuchi, Noriko Oyama-Manabe, Osamu Manabe, Masanao Naya, Yoichi M Ito, Kanako C Hatanaka, Hiroyuki Tsutsui, Satoshi Terae, Nagara Tamaki, Hiroki Shirato European journal of nuclear medicine and molecular imaging 40 (9) 1337 -44 2013年09月 [査読無し][通常論文]
     
    PURPOSE: To investigate the specific imaging findings of multidetector row CT (MDCT) and PET/CT with(18)F-FDG in cardiac dominant diffuse large B-cell lymphoma (DLBCL) in comparison with other cardiac tumours. METHODS: Five patients with DLBCL and 12 patients with other cardiac tumours including pericardial tumours were retrospectively reviewed. Among the patients with other cardiac tumours, seven had metastatic tumours, three had benign tumours, and two had other malignant cardiac tumours. The location of the cardiac mass, the encasement of the coronary artery surrounded by the mass, and pericardial effusion were evaluated using MDCT. The disease activity of the cardiac tumour was also evaluated by PET/CT. RESULTS: Four of the five DLBCL patients had primarily right-sided cardiac lesions, which was seen significantly more frequently in DLBCL than in other cardiac tumours (p = 0.028). All cardiac DLBCL lesions were located around the atrioventricular groove and encased the coronary arteries. ECG-gated cardiac MDCT showed that there was no apparent stenosis of the coronary arteries. Large amounts of pericardial effusion were seen in all DLBCL patients. PET/CT revealed significantly higher FDG uptake in DLBCL than in other cardiac malignant tumours, with no overlap (p = 0.0007). CONCLUSION: The combination of a right-sided cardiac mass with a large pericardial effusion and no apparent stenosis of the encased coronary artery revealed by MDCT and a high maximum standard uptake value were the specific findings in cardiac dominant DLBCL.
  • Hiroki Shirato Journal of the Institute of Electronics, Information and Communication Engineers 96 708 -712 2013年09月01日 [査読無し][通常論文]
  • Xue Li, Seiichiro Ishihara, Motoaki Yasuda, Takeshi Nishioka, Takeomi Mizutani, Masayori Ishikawa, Kazushige Kawabata, Hiroki Shirato, Hisashi Haga PLoS ONE 8 (8) 2013年08月 [査読無し][通常論文]
     
    Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as a contributor to the limited benefit of radiotherapy; however, its mechanism is still unclear. We previously showed that subcloned lung adenocarcinoma A549 cells (P cells), which survived 10 Gy IR (IR cells), acquired high invasiveness in vitro. Here, we tried to identify the mechanism by which IR cells increase their invasiveness by examining altered gene expression and signaling pathways in IR cells compared with those in P cells. To simulate the microenvironment in vivo, cells were embedded in a three-dimensional (3D) collagen type I gel, in which the IR cells were elongated, while the P cells were spherical. The integrin expression pattern was surveyed, and expression levels of the integrin α2 and β1 subunits were significantly elevated in IR cells. Knockdown of α2 expression or functional blockade of integrin α2β1 resulted in a round morphology of IR cells, and abrogated their invasion in the collagen matrix, suggesting the molecule's essential role in cell spread and invasion in 3D collagen. Epidermal growth factor receptor (EGFR) also presented enhanced expression and activation in IR cells. Treatment with EGFR tyrosine kinase inhibitor, PD168393, decreased the ratio of elongated cells and cell invasiveness. Signaling molecules, including extracellular signal-regulated kinase-1/2 (Erk1/2) and Akt, exhibited higher activation in IR cells. Inhibition of Akt activation by treating with phosphoinositide 3-kinase (PI3K) inhibitor LY294002 decreased IR cell invasion, whereas inhibition of Erk1/2 activation by mitogen-activated protein kinase kinase (MEK) inhibitor U0126 did not. Our results show that integrin α2β1 and EGFR cooperatively promote higher invasiveness of IR-survived lung cancer cells, mediated in part by the PI3K/Akt signaling pathway, and might serve as alternative targets in combination with radiotherapy. © 2013 Li et al.
  • Jin Min Nam, Kazi M. Ahmed, Sylvain Costes, Hui Zhang, Yasuhito Onodera, Adam B. Olshen, Kanako C. Hatanaka, Rumiko Kinoshita, Masayori Ishikawa, Hisataka Sabe, Hiroki Shirato, Catherine C. Park, Catherine C. Park Breast Cancer Research 15 (4) 2013年07月25日 [査読無し][通常論文]
     
    Introduction: Ductal carcinoma in situ (DCIS) is characterized by non-invasive cancerous cell growth within the breast ducts. Although radiotherapy is commonly used in the treatment of DCIS, the effect and molecular mechanism of ionizing radiation (IR) on DCIS are not well understood, and invasive recurrence following radiotherapy remains a significant clinical problem. This study investigated the effects of IR on a clinically relevant model of Akt-driven DCIS and identified possible molecular mechanisms underlying invasive progression in surviving cells.Methods: We measured the level of phosphorylated-Akt (p-Akt) in a cohort of human DCIS specimens by immunohistochemistry (IHC) and correlated it with recurrence risk. To model human DCIS, we used Akt overexpressing human mammary epithelial cells (MCF10A-Akt) which, in three-dimensional laminin-rich extracellular matrix (lrECM) and in vivo, form organotypic DCIS-like lesions with lumina expanded by pleiomorphic cells contained within an intact basement membrane. In a population of cells that survived significant IR doses in three-dimensional lrECM, a malignant phenotype emerged creating a model for invasive recurrence.Results: P-Akt was up-regulated in clinical DCIS specimens and was associated with recurrent disease. MCF10A-Akt cells that formed DCIS-like structures in three-dimensional lrECM showed significant apoptosis after IR, preferentially in the luminal compartment. Strikingly, when cells that survived IR were repropagated in three-dimensional lrECM, a malignant phenotype emerged, characterized by invasive activity, up-regulation of fibronectin, α5β1-integrin, matrix metalloproteinase-9 (MMP-9) and loss of E-cadherin. In addition, IR induced nuclear translocation and binding of nuclear factor-kappa B (NF-κB) to the β1-integrin promoter region, associated with up-regulation of α5β1-integrins. Inhibition of NF-κB or β1-integrin signaling abrogated emergence of the invasive activity.Conclusions: P-Akt is up-regulated in some human DCIS lesions and is possibly associated with recurrence. MCF10A-Akt cells form organotypic DCIS-like lesions in three-dimensional lrECM and in vivo, and are a plausible model for some forms of human DCIS. A population of Akt-driven DCIS-like spheroids that survive IR progresses to an invasive phenotype in three-dimensional lrECM mediated by β1-integrin and NF-κB signaling. © 2013 Nam et al.; licensee BioMed Central Ltd.
  • Taeko Matsuura, Naoki Miyamoto, Shinichi Shimizu, Yusuke Fujii, Masumi Umezawa, Seishin Takao, Hideaki Nihongi, Chie Toramatsu, Kenneth Sutherland, Ryusuke Suzuki, Masayori Ishikawa, Rumiko Kinoshita, Kenichiro Maeda, Kikuo Umegaki, Hiroki Shirato MEDICAL PHYSICS 40 (7) 2013年07月 [査読無し][通常論文]
     
    Purpose: In spot-scanning proton therapy, the interplay effect between tumor motion and beam delivery leads to deterioration of the dose distribution. To mitigate the impact of tumor motion, gating in combination with repainting is one of the most promising methods that have been proposed. This study focused on a synchrotron-based spot-scanning proton therapy system integrated with real-time tumor monitoring. The authors investigated the effectiveness of gating in terms of both the delivered dose distribution and irradiation time by conducting simulations with patients' motion data. The clinically acceptable range of adjustable irradiation control parameters was explored. Also, the relation between the dose error and the characteristics of tumor motion was investigated. Methods: A simulation study was performed using a water phantom. A gated proton beam was irradiated to a clinical target volume (CTV) of 5 x 5 x 5 cm(3), in synchronization with lung cancer patients' tumor trajectory data. With varying parameters of gate width, spot spacing, and delivered dose per spot at one time, both dose uniformity and irradiation time were calculated for 397 tumor trajectory data from 78 patients. In addition, the authors placed an energy absorber upstream of the phantom and varied the thickness to examine the effect of changing the size of the Bragg peak and the number of required energy layers. The parameters with which 95% of the tumor trajectory data fulfill our defined criteria were accepted. Next, correlation coefficients were calculated between the maximum dose error and the tumor motion characteristics that were extracted from the tumor trajectory data. Results: With the assumed CTV, the largest percentage of the data fulfilled the criteria when the gate width was +/- 2 mm. Larger spot spacing was preferred because it increased the number of paintings. With a prescribed dose of 2 Gy, it was difficult to fulfill the criteria for the target with a very small effective depth (the sum of an assumed energy absorber's thickness and the target depth in the phantom) because of the sharpness of the Bragg peak. However, even shallow targets could be successfully irradiated by employing an adequate number of paintings and by placing an energy absorber of sufficient thickness to make the effective target depth more than 12 cm. The authors also observed that motion in the beam direction was the main cause of dose distortion, followed by motion in the lateral plane perpendicular to the scan direction. Conclusions: The results suggested that by properly adjusting irradiation control parameters, gated proton spot-scanning beam therapy can be robust to target motion. This is an important first step toward establishing treatment plans in real patient geometry. (C) 2013 American Association of Physicists in Medicine.
  • Kentaro Nishioka, Shinichi Shimizu, Rumiko Kinoshita, Tetsuya Inoue, Shunsuke Onodera, Koichi Yasuda, Keiichi Harada, Yukiko Nishikawa, Rikiya Onimaru, Hiroki Shirato RADIATION ONCOLOGY 8 2013年07月 [査読無し][通常論文]
     
    Background: In-room cone-beam computerized tomography (CBCT) imaging is a promising method to reduce setup errors, especially in organs such as the bladder that often have large intrafractional variations due to organ movement. CBCT image quality is limited by low contrast and imaging artifacts, but few data have been reported about inter-observer variability of bladder boundary delineation on CBCT. The aim of this work was to analyze and evaluate the inter-observer contouring uncertainties of bladder boundary delineation on CBCT images in a prospective fashion. Methods: Five radiation oncologists contoured 10 bladders using the CBCT datasets of consecutive 10 patients (including 4 females) who were irradiated to the pelvic region. Prostates were also contoured in male patients. Patients who had had prostatectomy were excluded. The coefficient of variation (COV), conformity index (CIgen), and coordinates of center-of-mass (COM) of the bladder and prostate were calculated for each patient. Results: The mean COV for the bladder and prostate was 0.08 and 0.20, respectively. The mean CIgen of the bladder and prostate was 0.81 and 0.66, respectively. The root mean square (RMS) of the inter-observer standard deviation (s) of the COM displacement in the left-right (LR) and anterior-posterior (AP) direction was 0.79, 0.87 and 0.54 for the bladder and 0.63, 0.99 and 1.72 for the prostate. Regarding the mean COV and CIgen for the bladder, the differences between males and females were not significant. Conclusions: Inter-observer variability for bladder delineation on CBCT images was substantially small regardless of gender. We believe that our results support the applicability of CBCT in adaptive radiotherapy for bladder cancer.
  • Kouji Nakamura, Reika Okamura, Norihiro Satoh, Hiroki Shirato, Kazunori Yasuda Japanese Pharmacology and Therapeutics 41 2013年06月25日 [査読無し][通常論文]
  • T. Matsuura, Y. Fujii, R. Fujimoto, M. Umezawa, N. Miyamoto, K. Sutherland, S. Takao, H. Nihongi, C. Toramatsu, S. Shimizu, K. U. Megaki, H. Shirato Medical Physics 40 (6) 308 2013年06月 [査読無し][通常論文]
     
    Purpose: To mitigate the impact of tumor motion in spot‐scanning proton beam therapy, the gating technique has been considered as a powerful tool. Although residual tumor motion of a few millimeters of gate volume can still cause a dose error, the error can be minimized by repainting. However, a larger number of paintings also results in the prolongation of treatment time. We propose a method which improves the dose uniformity while minimally increasing the number of paintings. Methods: Lateral beam tracking was applied in conjunction with gating. A simulation study was performed using the VQA treatment planning system (Hitachi Ltd., Japan) to assess the effectiveness of this method. A gated proton beam provided by a synchrotron was irradiated to spherical clinical target volumes (CTVs) with a diameter of 5 cm located at 10 cm and 15 cm depth in a heterogeneous phantom. The system delay time was 66 ms. Gate width was set to 2 mm. Rigid motion was assumed for CTVs which were shifted in synchronization with 20 patients' tumor trajectory data. A dose of 2 Gy was prescribed with the minimum repainting scheme. The cases that fulfilled the ICRU 50 criteria (CTVmax < 107% and CTVmin > 95%) were accepted. Results: When only gating was used, 12 and 16 out of 20 cases were accepted for targets at 10 cm and 15 cm depth, respectively. On the other hand, when beam tracking was also applied, all cases were accepted for both target depths. Conclusion: The results suggest that the application of lateral beam tracking in gate volume can improve the dose uniformity without (or minimally) increasing the number of paintings. A simulation including non‐rigid patient motion will be considered in the future. © 2013, American Association of Physicists in Medicine. All rights reserved.
  • M. Ishikawa, S. Tanabe, S. Yamaguchi, N. Ukon, T. Yamanaka, K. Sutherland, N. Miyamoto, R. Suzuki, N. Katoh, K. Yasuda, H. Shirato Medical Physics 40 (6) 162 2013年06月 [査読無し][通常論文]
     
    Purpose: Molecular imaging is one of the important modalities in delineating tumors particularly in radiotherapy treatment planning. If the real‐time tumor position can be detected using molecular imaging during radiotherapy, it may be helpful for gated irradiation. A feasibility study on a beam gating system for radiotherapy using real‐time molecular imaging was conducted by the prototype and simulating a parallel plane PET system. Methods: Assuming that the motion of the positron source is constrained to the central plane, the source position can be calculated from a cross point of the Line of Response (LOR) and the central plane between detector surfaces. If a positron source is located at the ISO center, distribution of the cross points might be blurred due to random/scattered coincidence. Center Located Ratio (CLR) was defined as a ratio of LORs passing through the ISO center divided by the entire LORs. When dislocation for perpendicular direction is occurred, a distribution of cross points will be spread out and associated decrease of CLR value will be expected. Results: The behavior between real measurement and simulation was similar on proto‐type experiments, however, the Result from simulation for demonstrator might be different from actual measurement. RTRT system recognizes the position of a gold marker in the rate of 30 fps using two X‐ray television systems. It is shown that 15,000 events per second will be needed for an appropriate gating irradiation to recognize discrepancy over 2mm of time resolution in the parallel plane PET system demonstrator. Conclusion: A feasibility study was carried out to verify the potential for gating irradiation of tumors with real‐time molecular imaging using a parallel plane PET system. For an parallel plane PET system demonstrator, the possibility of detecting the tumor position with an accuracy of 2 mm from the ISO center with 500 events. This research was a part of the “Innovation COE Program for Future Drug Discovery and Medical Care” project and partially supported by the Grant‐in‐Aid for Project for Developing Innovation Systems of the Japanese Ministry of Education, Culture, Sports, Science and Technology. © 2013, American Association of Physicists in Medicine. All rights reserved.
  • Kimihiro Ogisu, Kohsuke Kudo, Makoto Sasaki, Ken Sakushima, Ichiro Yabe, Hidenao Sasaki, Satoshi Terae, Mitsuhiro Nakanishi, Hiroki Shirato Neuroradiology 55 (6) 719 -24 2013年06月 [査読無し][通常論文]
     
    INTRODUCTION: Neuromelanin-sensitive MRI has been reported to be used in the diagnosis of Parkinson's disease (PD), which results from loss of dopamine-producing cells in the substantia nigra pars compacta (SNc). In this study, we aimed to apply a 3D turbo field echo (TFE) sequence for neuromelanin-sensitive MRI and to evaluate the diagnostic performance of semi-automated method for measurement of SNc volume in patients with PD. METHODS: We examined 18 PD patients and 27 healthy volunteers (control subjects). A 3D TFE technique with off-resonance magnetization transfer pulse was used for neuromelanin-sensitive MRI on a 3T scanner. The SNc volume was semi-automatically measured using a region-growing technique at various thresholds (ranging from 1.66 to 2.48), with the signals measured relative to that for the superior cerebellar peduncle. Receiver operating characteristic (ROC) analysis was performed at all thresholds. Intra-rater reproducibility was evaluated by intraclass correlation coefficient (ICC). RESULTS: The average SNc volume in the PD group was significantly smaller than that in the control group at all the thresholds (P < 0.01, student t test). At higher thresholds (>2.0), the area under the curve of ROC (Az) increased (0.88). In addition, we observed balanced sensitivity and specificity (0.83 and 0.85, respectively). At lower thresholds, sensitivity tended to increase but specificity reduced in comparison with that at higher thresholds. ICC was larger than 0.9 when the threshold was over 1.86. CONCLUSIONS: Our method can distinguish the PD group from the control group with high sensitivity and specificity, especially for early stage of PD.
  • Tetsuya Inoue, Norio Katoh, Rikiya Onimaru, Shinichi Shimizu, Kazuhiko Tsuchiya, Ryusuke Suzuki, Jun Sakakibara-Konishi, Naofumi Shinagawa, Satoshi Oizumi, Hiroki Shirato Radiation Oncology 8 (1) 2013年03月21日 [査読無し][通常論文]
     
    Background: To clarify the clinical outcomes of two dose schedule of stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) using a real-time tumor-tracking radiation therapy (RTRT) system in single institution.Methods: Using a superposition algorithm, we administered 48 Gy in 4 fractions at the isocenter in 2005-2006 and 40 Gy in 4 fractions to the 95% volume of PTV in 2007-2010 with a treatment period of 4 to 7 days. Target volume margins were fixed irrespective of the tumor amplitude.Results: In total, 109 patients (79 T1N0M0 and 30 T2N0M0). With a median follow-up period of 25 months (range, 4 to 72 months), the 5-year local control rate (LC) was 78% and the 5-year overall survival rate (OS) was 64%. Grade 2, 3, 4, and 5 radiation pneumonitis (RP) was experienced by 15 (13.8%), 3 (2.8%), 0, and 0 patients, respectively. The mean lung dose (MLD) and the volume of lung receiving 20 Gy (V20) were significantly higher in patients with RP Grade 2/3 than in those with RP Grade 0/1 (MLD p = 0.002, V20 p = 0.003). There was no correlation between larger maximum amplitude of marker movement and larger PTV (r = 0.137), MLD (r = 0.046), or V20 (r = 0.158).Conclusions: SBRT using the RTRT system achieved LC and OS comparable to other SBRT studies with very low incidence of RP, which was consistent with the small MLD and V20 irrespective of tumor amplitude. For stage I NSCLC, SBRT using RTRT was suggested to be reliable and effective, especially for patients with large amplitude of tumor movement. © 2013 Inoue et al.; licensee BioMed Central Ltd.
  • Chie Toramatsu, Norio Katoh, Shinichi Shimizu, Hideaki Nihongi, Taeko Matsuura, Seishin Takao, Naoki Miyamoto, Ryusuke Suzuki, Kenneth Sutherland, Rumiko Kinoshita, Rikiya Onimaru, Masayori Ishikawa, Kikuo Umegaki, Hiroki Shirato RADIATION ONCOLOGY 8 2013年03月 [査読無し][通常論文]
     
    Background: We performed a dosimetric comparison of spot-scanning proton therapy (SSPT) and intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma (HCC) to investigate the impact of tumor size on the risk of radiation induced liver disease (RILD). Methods: A number of alternative plans were generated for 10 patients with HCC. The gross tumor volumes (GTV) varied from 20.1 to 2194.5 cm(3). Assuming all GTVs were spherical, the nominal diameter was calculated and ranged from 3.4 to 16.1 cm. The prescription dose was 60 Gy for IMRT or 60 cobalt Gy-equivalents for SSPT with 95% planning target volume (PTV) coverage. Using IMRT and SSPT techniques, extensive comparative planning was conducted. All plans were evaluated by the risk of RILD estimated using the Lyman-normal-tissue complication probability model. Results: For IMRT the risk of RILD increased drastically between 6.3-7.8 cm nominal diameter of GTV. When the nominal diameter of GTV was more than 6.3 cm, the average risk of RILD was 94.5% for IMRT and 6.2% for SSPT. Conclusions: Regarding the risk of RILD, HCC can be more safely treated with SSPT, especially if its nominal diameter is more than 6.3 cm.
  • Seiichiro Ishihara, Motoaki Yasuda, Takeshi Nishioka, Takeomi Mizutani, Kazushige Kawabata, Hiroki Shirato, Hisashi Haga FEBS LETTERS 587 (6) 732 -736 2013年03月 [査読無し][通常論文]
     
    Radiotherapy is one of the major treatment modalities for malignancies. However, cells surviving irradiation often display high levels of invasiveness. This study shows that irradiation-tolerant lung adenocarcinoma demonstrates high invasive capability depending on dephosphorylation of the myosin regulatory light chain (MRLC). In a collagen gel overlay condition, low-invasive subclones of lung adenocarcinoma (A549P-3) showed a round morphology and diphosphorylation of MRLC. In contrast, irradiation-tolerant A549P-3 cells (A549P-3IR) displayed high invasiveness and a lower level of MRLC diphosphorylation. In addition, inhibition of MRLC phosphatase activity decreased the invasive activity. These findings suggest that A549P-3IR cells acquire high invasiveness through MRLC dephosphorylation. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
  • Shozo Okamoto, Tohru Shiga, Koichi Yasuda, Yoichi M. Ito, Keiichi Magota, Katsuhiko Kasai, Yuji Kuge, Hiroki Shirato, Nagara Tamaki JOURNAL OF NUCLEAR MEDICINE 54 (2) 201 -207 2013年02月 [査読無し][通常論文]
     
    Tumor hypoxia is well known to be radiation resistant. F-18-fluoromisonidazole (F-18-FMISO) PET has been used for noninvasive evaluation of hypoxia. Quantitative evaluation of F-18-FMISO uptake is thus expected to play an important role in the planning of dose escalation radiotherapy. However, the reproducibility of F-18-FMISO uptake has remained unclarified. We therefore investigated the reproducibility of tumor hypoxia by using quantitative analysis of F-18-FMISO uptake. Methods: Eleven patients with untreated head and neck cancer underwent 2 F-18-FMISO PET/CT scans (F-18-FMISO1 and F-18-FMISO2) with a 48-h interval prospectively. All images were acquired at 4 h after F-18-FMISO injection for 10 min. The maximum standardized uptake (SUVmax), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of F-18-FMISO uptake were statistically compared between the 2 F-18-FMISO scans by use of intraclass correlation coefficients (ICCs). The hypoxic volume was calculated as the area with a TBR of greater than or equal to 1.5 or the area with a TMR of greater than or equal to 1.25 to assess differences in hypoxic volume between the 2 F-18-FMISO scans. The distances from the maximum uptake locations of the F-18-FMISO1 images to those of the F-18-FMISO2 images were measured to evaluate the locations of F-18-FMISO uptake. Results: The SUVmax (mean +/- SD) for F-18-FMISO1 and F-18-FMISO2 was 3.16 +/- 1.29 and 3.02 +/- 1.12, respectively, with the difference between the 2 scans being 7.0% +/- 4.6%. The TBRs for F-18-FMISO1 and F-18-FMISO2 were 2.98 +/- 0.83 and 2.97 +/- 0.64, respectively, with a difference of 9.9% +/- 3.3%. The TMRs for F-18-FMISO1 and F-18-FMISO2 were 2.25 +/- 0.71 and 2.19 +/- 0.67, respectively, with a difference of 7.1% +/- 5.3%. The ICCs for SUVmax, TBR, and TMR were 0.959, 0.913, and 0.965, respectively. The difference in hypoxic volume based on TBR was 1.8 +/- 1.8 mL, and the difference in hypoxic volume based on TMR was 0.9 +/- 1.3 mL, with ICCs of 0.986 and 0.996, respectively. The maximum uptake locations of the F-18-FMISO1 images were different from those of the F-18-FMISO2 images and were within the full width at half maximum of the PET/CT scanner, except in 1 case. Conclusion: The values for F-18-FMISO PET uptake and hypoxic volume in head and neck tumors between the 2 F-18-FMISO scans were highly reproducible. Such high reproducibility of tumor hypoxia is promising for accurate radiation planning.
  • Eric W. Pepin, Huanmei Wu, Hiroki Shirato Medical Physics 40 (10) 2013年 [査読無し][通常論文]
     
    Purpose: To simulate and evaluate the use of dynamic multileaf collimators (dMLC) in respiratory gating to compensate for baseline drift. Methods: Tumor motion tracking data from 30 lung tumors over 322 treatment fractions was analyzed with the finite state model. A dynamic respiratory gating window was established in real-time by determining the average positions during the previous two end-of-expiration breathing phases and centering the dMLC aperture on a weighted average of these positions. A simulated dMLC with physical motion constraints was used in dynamic gating treatment simulations. Fluence maps were created to provide a statistical description of radiation delivery for each fraction. Duty cycle was also calculated for each fraction. Results: The average duty cycle was 2.3% greater under dynamic gating conditions. Dynamic gating also showed higher fluences and less tumor obstruction. Additionally, dynamic gating required fewer beam toggles and each delivery period was longer on average than with static gating. Conclusions: The use of dynamic gating showed better performance than static gating and the physical constraints of a dMLC were shown to not be an impediment to dynamic gating. © 2013 American Association of Physicists in Medicine.
  • Atsushi Yoshida, Khin Khin Tha, Noriyuki Fujima, Yuri Zaitsu, Daisuke Yoshida, Akiko Tsukahara, Shunsuke Onodera, Hiroki Shirato, Satoshi Terae JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 37 (1) 84 -90 2013年01月 [査読無し][通常論文]
     
    Objective: This study aimed to compare the diagnostic performance in the detection of brain metastases between contrast-enhanced T1-weighted volume isotropic turbo spin echo acquisition (T1-VISTA) and 3-dimensional T1-weighted fluid-attenuated inversion recovery (3D-T1-FLAIR) imaging at 3 T.Methods: Two neuroradiologists selected 129 true (metastases) and 70 false (vessels and artifacts) lesions on the contrast-enhanced T1-VISTA and 3D-T1-FLAIR images of 14 cancer patients with hyperintense brain lesions. Four blinded neuroradiologists distinguished between the true and false lesions, using a 5-point confidence rating scale. The receiver operating characteristic analysis was performed to compare the diagnostic performance. Contrast-to-noise ratio of the true lesions was also compared between the 2 sequences by using paired t tests.Results: For lesions less than 3 mm, the area under curve and sensitivity achieved by T1-VISTA imaging were significantly greater than 3D-T1-FLAIR imaging. The contrast-to-noise ratio was also significantly greater with T1-VISTA imaging.Conclusions: The contrast-enhanced T1-VISTA imaging is better suited than 3D-T1-FLAIR imaging, for detection of small metastases.
  • Masumi Umezawa, Rintaro Fujimoto, Tooru Umekawa, Yuusuke Fujii, Taisuke Takayanagi, Futaro Ebina, Takamichi Aoki, Yoshihiko Nagamine, Koji Matsuda, Kazuo Hiramoto, Taeko Matsuura, Naoki Miyamoto, Hideaki Nihongi, Kikuo Umegaki, Hiroki Shirato AIP Conference Proceedings 1525 360 -363 2013年 [査読無し][通常論文]
     
    Hokkaido University and Hitachi Ltd. have started joint development of the Gated Spot Scanning Proton Therapy with Real-Time Tumor-Tracking System by integrating real-time tumor tracking technology (RTRT) and the proton therapy system dedicated to discrete spot scanning techniques under the "Funding Program for World-Leading Innovative R& D on Science and Technology (FIRST Program)". In this development, we have designed the synchrotron-based accelerator system by using the advantages of the spot scanning technique in order to realize a more compact and lower cost proton therapy system than the conventional system. In the gated irradiation, we have focused on the issues to maximize irradiation efficiency and minimize the dose errors caused by organ motion. In order to understand the interplay effect between scanning beam delivery and target motion, we conducted a simulation study. The newly designed system consists of the synchrotron, beam transport system, one compact rotating gantry treatment room with robotic couch, and one experimental room for future research. To improve the irradiation efficiency, the new control function which enables multiple gated irradiations per synchrotron cycle has been applied and its efficacy was confirmed by the irradiation time estimation. As for the interplay effect, we confirmed that the selection of a strict gating width and scan direction enables formation of the uniform dose distribution. © 2013 AIP Publishing LLC.
  • Rie Yamazaki, Seiko Nishioka, Hiroyuki Date, Hiroki Shirato, Takao Koike, Takeshi Nishioka RADIATION ONCOLOGY 7 2012年12月 [査読無し][通常論文]
     
    Background: The use of stereotactic body radiotherapy (SBRT) is rapidly increasing. Presently, the most accurate method uses fiducial markers implanted near the tumor. A shortcoming of this method is that the beams turn off during the majority of the respiratory cycle, resulting in a prolonged treatment time. Recent advances in collimation technology have enabled continuous irradiation to a moving tumor. However, the lung is a dynamic organ characterized by inhalation exhalation cycles, during which marker/tumor geometry may change (i.e., misalignment), resulting in under-dosing to the tumor. Findings: Eight patients with lung cancer who were candidates for stereotactic radiotherapy were examined with 4D high-resolution CT. As a marker surrogate, virtual bronchoscopy using the pulmonary artery (VBPA) was conducted. To detect possible marker/tumor misalignment during the respiration cycle, the distance between the peripheral bronchus, where a marker could be implanted, and the center of gravity of a tumor were calculated for each respiratory phase. When the respiration cycle was divided into 10 phases, the median value was significantly larger for the 30%-70% respiratory phases compared to that for the 10% respiratory phase (P<0.05, Mann-Whitney U-test). Conclusions: These results demonstrate that physiological aspect must be considered when continuous tumor tracking is applied to a moving tumor. To minimize an "additional" internal target volume (ITV) margin, a marker should be placed approximately 2.5 cm from the tumor.
  • N. Miyamoto, M. Ishikawa, K. Sutherland, R. Suzuki, T. Matsuura, S. Takao, C. Toramatsu, H. Nihongi, S. Shimizu, R. Onimaru, K. Umegaki, H. Shirato Medical Physics 39 (6) 3661 -3662 2012年06月 [査読無し][通常論文]
     
    Purpose: In the real‐time tumor‐tracking radiotherapy system, fiducial markers are detected by X‐ray fluoroscopy. The fluoroscopic parameters should be optimized as low as possible in order to reduce unnecessary imaging dose. However, the fiducial markers could not be recognized due to effect of statistical noise in low dose imaging. Image processing is envisioned to be a solution to improve image quality and to maintain tracking accuracy. In this study, a recursive image filter adapted to target motion is proposed. Methods: A fluoroscopy system was used for the experiment. A spherical gold marker was used as a fiducial marker. About 450 fluoroscopic images of the marker were recorded. In order to mimic respiratory motion of the marker, the images were shifted sequentially. The tube voltage, current and exposure duration were fixed at 65 kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube current was 100 mA as high dose imaging. A pattern recognition score (PRS) ranging from 0 to 100 and image registration error were investigated by performing template pattern matching to each sequential image. The results with and without image processing were compared. Results: In low dose imaging, theimage registration error and the PRS without the image processing were 2.15±1.21 pixel and 46.67±6.40, respectively. Those with the image processing were 1.48±0.82 pixel and 67.80±4.51, respectively. There was nosignificant difference in the image registration error and the PRS between the results of low dose imaging with the image processing and that of high dose imaging without the image processing. Conclusions: The results showed that the recursive filter was effective in order to maintain marker tracking stability and accuracy in low dose fluoroscopy. © 2012, American Association of Physicists in Medicine. All rights reserved.
  • Norio Katoh, Koichi Yasuda, Tohru Shiga, Masakazu Hasegawa, Rikiya Onimaru, Shinichi Shimizu, Gerard Bengua, Masayori Ishikawa, Nagara Tamaki, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 82 (4) E671 -E676 2012年03月 [査読無し][通常論文]
     
    Purpose: We compared two treatment planning methods for stereotactic boost for treating nasopharyngeal carcinoma (NPC): the use of conventional whole-body bismuth germanate (BGO) scintillator positron emission tomography (PETCONVWB) versus the new brain (BR) PET system using semiconductor detectors (PETNEWBR). Methods and Materials: Twelve patients with NPC were enrolled in this study. [F-18]Fluorodeoxyglucose-PET images were acquired using both the PETNEWBR and the PETCONVWB system on the same day. Computed tomography (CT) and two PET data sets were transferred to a treatment planning system, and the PETCONVWB and PETNEWBR images were coregistered with the same set of CT images. Window width and level values for all PET images were fixed at 3000 and 300, respectively. The gross tumor volume (GTV) was visually delineated on PET images by using either PETCONVWB (GTV(CONV)) images or PETNEWBR (GTV(NEW)) images. Assuming a stereotactic radiotherapy boost of 7 ports, the prescribed dose delivered to 95% of the planning target volume (PTV) was set to 2000 cGy in 4 fractions. Results: The average absolute volume (+/- standard deviation [SD]) of GTV(NEW) was 15.7 ml (+/- 9.9) ml, and that of GTV(CONV) was 34.0 (+/- 20.5) ml. The average GTV(NEW) was significantly smaller than that of GTV(CONV) (p = 0.0006). There was no statistically significant difference between the maximum dose (p = 0.0585) and the mean dose (p = 0.2748) of PTV. The radiotherapy treatment plan based on the new gross tumor volume (PLAN(NEW)) significantly reduced maximum doses to the cerebrum and cerebellum (p = 0.0418) and to brain stem (p = 0.0041). Conclusion: Results of the present study suggest that the new brain PET system using semiconductor detectors can provide more accurate tumor delineation than the conventional whole-body BGO PET system and may be an important tool for functional and molecular radiotherapy treatment planning. (C) 2012 Elsevier Inc.
  • T. Matsuura, K. Maeda, K. Sutherland, T. Takayanagi, S. Shimizu, S. Takao, H. Nihongi, C. Toramatsu, N. Miyamoto, Y. Nagamine, R. Fujimoto, K. Umegaki, H. Shirato Medical Physics 39 (6) 3872 2012年 [査読無し][通常論文]
     
    Purpose: In spot scanning proton therapy, accurate patient positioning before and during treatment is essential. A small gold ball marker is suitable as a fiducial for prostate treatment. However, it has been pointed out that the marker causes dose shadowing because the protons are scattered with their energy quickly diminished. In this research we explore the possibility that the biological effect of dose shadowing can be mitigated with a limited number of fields. Methods: The proton dose distribution in prostate was simulated using Geant4. The simulations include the Hokkaido University spot scanning nozzle and a water phantom positioned isocentrically. The PTV was delineated at the center of the phantom and a gold ball of 2 mm in diameter was placed at the middle of the PTV. The plan was created by single‐field optimization and each of the following beam arrangements was investigated; (1) single lateral field (2) two lateral fields (3) two lateral + one anterior fields (4) four‐field box. The dose prescription was D95 = 74 GyE (37 fr). The minimum dose and tumor control probability (TCP) were compared for the four beam arrangements. Results: For (1)–(4), the minimum dose values were 55%, 77%, 78%, and 84% of the prescribed dose, respectively. The reduction of the TCP values from those in the absence of the gold marker were 50%, 2%, 1.1%, and 0.7%, using the TCP model by Wang et al. (Int.J.Radiat.Oncol.Biol.Phys. 55, 2003) and 2%, 0.7%, 0.5%, and 0.4%, using the biological parameters in Levegrün et al. (Int.J.RadiatOncol.Biol.Phys. 51, 2001), respectively. Conclusions: Although dose shadowing by the gold marker is locally non‐negligible, the size of the affected domain is tiny. It was found that with a minimum number of fields, the TCP nearly recovers to the value without the gold marker. © 2012, American Association of Physicists in Medicine. All rights reserved.
  • C. Toramatsu, T. Matsuura, H. Nihongi, S. Takao, N. Miyamoto, S. Shimizu, R. Kinoshita, K. Umegaki, H. Shirato Medical Physics 39 3821 -3822 2012年01月01日 [査読無し][通常論文]
     
    Purpose: To investigate the possibility of using a single spot scanning proton beam to treat superficial lesions. Methods: A cylindrical phantom with a simulated superficial target (it seated 0.5–4cm depth from the surface, volume: 270cm 3 ) was created in Eclipse treatment planning system. Three proton plans were generated: (a) a single AP uniform scanning beam with aperture and range compensator; (b) a single AP spot scanning beam with a pre‐absorber. The location and thickness of the pre‐absorber were calculated using Geant4 to Monte Carlo code to make use of the available spot scanning beams to get a conformal plan. (c) a five‐beam spot scanning beam plan using multi‐field optimization. The prescription is 54 cobalt grey equivalent (CGE) which covers 95% of the target. The target coverage, lateral penumbra at 2 and 4cm depth in water, the doses to normal tissue (phantom‐target) and skin (2mm from the surface) were evaluated and compared for three plans. Results: The mean doses to the target are comparable within 2.4% for all three plans. The conformity indices (at 95%) are 1.36, 1.04 and 0.98 for plan (a), (b) and (c) respectively. The lateral penumbra (80% to 20%) for plan (a), (b) are both 0.73 cm, while it is 3.75 cm for plan (c). The skin dose which received more than 40 (CGE) from plan (a) is 10% higher than that of other two plans. Plan (c) has 70% higher mean doses to normal tissue than that of plan (a) and (b). Conclusions: Each plan provides good coverage of target. And in this study, it showed that, with a properly designed pre‐absorber, it is possible to use a single spot scanning beam to treat superficial lesion. The plan provides good target coverage and maintains normal tissue sparing in the mean time. © 2012, American Association of Physicists in Medicine. All rights reserved.
  • Naoki Miyamoto, Kenneth Sutherland, Ryusuke Suzuki, Taeko Matsuura, Chie Toramatsu, Seishin Takao, Hideaki Nihongi, Rumiko Kinoshita, Shinichi Shimizu, Rikiya Onimaru, Kikuo Umegaki, Hiroki Shirato, Masayori Ishikawa Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8316 2012年 [査読無し][通常論文]
     
    In the real-time tumor-tracking radiotherapy (RTRT) system, the fiducial markers are inserted in or near the target tumor in order monitor the respiratory-induced motion of tumors. During radiation treatment, the markers are detected by continuous fluoroscopy operated at 30 frames/sec. The marker position is determined by means of a template pattern matching technique which is based on the normalized cross correlation. With high tube voltage, large current and long exposure, the fiducial marker will be recognized accurately, however, the radiation dose due to X-ray fluoroscopy increases. On the other hand, by decreasing the fluoroscopy parameter settings, the fiducial marker could be lost because the effect of statistical noise is increased. In the respiratory-gated radiotherapy, the error of the image guidance will induce the reduction of the irradiation efficiency and accuracy. In order to track the marker stably and accurately in low dose fluoroscopy, we propose the application of a recursive filter. The effectiveness of the image processing is investigated by tracking the static marker and the dynamic marker. The results suggest that the stability and the accuracy of the marker tracking can be improved by applying the recursive image filter in low dose imaging. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).
  • Yae Harada, Kenji Hirata, Hiroyuki Kobayashi, Reiko Usui, Tohru Shiga, Satoshi Terae, Hiroki Shirato, Nagara Tamaki CLINICAL NUCLEAR MEDICINE 37 (1) 110 -111 2012年01月 [査読無し][通常論文]
     
    A 31-year-old woman presenting with tonic seizures was radiologically investigated using CT, MR imaging, and positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and C-11 methionine (MET). Initial CT, C-11 MET PET, and F-18 FDG PET suggested a low-grade tumor such as oligodendroglial tumor. However, MR imaging findings strongly suggested venous infarction. We chose observation rather than surgical intervention. Two months later, self-regression of the lesion confirmed the diagnosis of venous infarction. Therefore, to avoid unnecessary invasive operations, we should keep in mind that high C-11 MET accumulation does not always signify a tumoral lesion but is sometimes the result of vascular pathology.
  • Cancer Sci. 103 2012年 [査読無し][通常論文]
  • R. Kinoshita, S. Shimizu, K. Tsuchiya, N. Kato, H. Shirato, H. Taguchi, M. Takahashi, H. Takahashi Japanese Journal of Clinical Radiology 56 1813 -1818 2011年12月10日 [査読無し][通常論文]
     
    Between 1988 and 2008, 489 patients received breast conservation therapy at Hokkaido University. Among them, we identified and analyzed 20 ipsilateral breast tumor recurrences.75% of recurrence was occurred in the same quadrant of the primary tumor. Twelve patients received mastectomy, seven patients received local tumor excision.17 of 20 patients are alive without disease. Salvage breast-conserving therapy may be feasible for certain condition.
  • Yuri Zaitsu, Kohsuke Kudo, Satoshi Terae, Rie Yazu, Kinya Ishizaka, Noriyuki Fujima, Khin K Tha, E Mark Haacke, Makoto Sasaki, Hiroki Shirato Radiology 261 (3) 930 -6 2011年12月 [査読無し][通常論文]
     
    PURPOSE: To develop a map to detect changes in oxygen extraction fraction (OEF) utilizing susceptibility-weighted (SW) phase images and to correlate such changes in OEF with those in cerebral blood flow (CBF). MATERIALS AND METHODS: The study protocol was approved by the institutional review board, and written informed consent was obtained from all subjects. Eight healthy volunteers (mean age ± standard deviation, 29.8 years ± 4.6) were included in the study. Subjects were evaluated by using SW imaging, and the change in OEF was calculated by subtracting the image at baseline from one of the images obtained during six different conditions, including two at resting state, three different types of respiratory challenges, and one drug challenge with acetazolamide. Arterial spin labeling was carried out to measure CBF, while SW imaging was used to generate maps of change in OEF in response to a given condition. Statistical tests included one-way analysis of variance and Dunnett multiple comparisons to compare among the six conditions the magnitude of change from baseline for both OEF and CBF, by using the OEF change at resting state (resting 1) as the control. RESULTS: Hyperventilation caused a statistically significant decrease in CBF (-29.3%, P < .001) and an increase in OEF (+5.2%, P < .001) compared with the control, resting 1 (+2.2%, -0.7%, respectively). Acetazolamide caused a significant increase in CBF (+39.7%, P < .001) and a decrease in OEF (-3.4%, P = .040). Carbogen also induced a CBF increase (+16.2%); however, the change was not significant (P = .090), even though OEF decreased significantly (-4.2%, P = .003). Oxygen administration resulted in a significant CBF decrease (-27.2%, P < .001), whereas OEF showed no significant difference (-0.6%, P > .99). CONCLUSION: Maps of changes in OEF generated from SW phase images revealed changes in OEF corresponding to anticipated changes in CBF induced by various conditions; SW phase imaging might, in the future, be applied to evaluate cerebrovascular and other cerebral disorders in which changes in oxygen metabolism are important for planning therapeutic strategies.
  • Hiroshi Onishi, Hiroki Shirato, Yasushi Nagata, Masahiro Hiraoka, Masaharu Fujino, Kotaro Gomi, Katsuyuki Karasawa, Kazushige Hayakawa, Yuzuru Niibe, Yoshihiro Takai, Tomoki Kimura, Atsuya Takeda, Atsushi Ouchi, Masato Hareyama, Masaki Kokubo, Takuyo Kozuka, Takuro Arimoto, Ryusuke Hara, Jun Itami, Tsutomu Araki INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81 (5) 1352 -1358 2011年12月 [査読無し][通常論文]
     
    Purpose: To review treatment outcomes for stereotactic body radiotherapy (SBRT) in medically operable patients with Stage I non small-cell lung cancer (NSCLC), using a Japanese multi-institutional database. Patients and Methods: Between 1995 and 2004, a total of 87 patients with Stage I NSCLC (median age, 74 years; T1N0M0, n = 65; T2N0M0, n = 22) who were medically operable but refused surgery were treated using SBRT alone in 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. Total dose was 45-72.5 Gy at the isocenter, administered in 3-10 fractions. Median calculated biological effective dose was 116 Gy (range, 100-141 Gy). Data were collected and analyzed retrospectively. Results: During follow-up (median, 55 months), cumulative local control rates for T1 and T2 tumors at 5 years after SBRT were 92% and 73%, respectively. Pulmonary complications above Grade 2 arose in 1 patient (1.1%). Five-year overall survival rates for Stage IA and IB subgroups were 72% and 62%, respectively. One patient who developed local recurrences safely underwent salvage surgery. Conclusion: Stereotactic body radiotherapy is safe and promising as a radical treatment for operable Stage NSCLC. The survival rate for SBRT is potentially comparable to that for surgery. (C) 2011 Elsevier Inc.
  • Noriko Oyama-Manabe, Naoki Ishimori, Hiroyuki Sugimori, Marc Van Cauteren, Kohsuke Kudo, Osamu Manabe, Tomoyuki Okuaki, Tamotsu Kamishima, Yoichi M Ito, Hiroyuki Tsutsui, Khin Khin Tha, Satoshi Terae, Hiroki Shirato European radiology 21 (11) 2362 -8 2011年11月 [査読無し][通常論文]
     
    OBJECTIVES: To investigate whether subendocardial and transmural myocardial infarction can be identified and differentiated using the peak circumferential and longitudinal strains measured by fast strain-encoded (SENC). METHODS: Nineteen patients with ischemic heart diseases underwent imaging with fast SENC and late gadolinium enhancement (LGE) MRI at 3 T. Fast SENC measurements were performed in three short-axis slices (basal, mid-ventricular and apical levels) and one long-axis view (four-chamber) to assess peak longitudinal and circumferential systolic strains. RESULTS: All patients showed myocardial infarction with an average of 7 positive LGE segments. A total of 304 segments for longitudinal strains (LS) and 114 segments for circumferential strains (CS) could be analysed. Positive LGE segments showed lower peak CS and LS compared with the no LGE segments (P < 0.0001 for both). Segments with subendocardial infarction showed reduced CS and LS compared with the no LGE segments (P < 0.0001 for both). There was a significant difference in CS between subendocardial and transmural infarct segments (P = 0.03), but no significant difference in LS between them (P = 0.64). CONCLUSIONS: Fast SENC can identify old myocardial infarction and differentiate subendocardial from transmural infarction.
  • Shinichi Shimizu, Yasuhiro Osaka, Nobuo Shinohara, Ataru Sazawa, Kentaro Nishioka, Ryusuke Suzuki, Rikiya Onimaru, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81 (4) E393 -E399 2011年11月 [査読無し][通常論文]
     
    Purpose: Interportal adjustment was applied to patients with prostate cancer using three fiducial markers and two sets of fluoroscopy in a real-time tumor-tracking radiotherapy (RTRT) system. The incidence of table position adjustment required to keep intrafractional uncertainty within 2.0 mm was investigated in this study. Methods and Materials: The coordinates of the center of gravity of the three fiducial markers were measured at the start of every portal irradiation in intensity-modulated radiotherapy (IMRT) with seven ports. The table position was adjusted to the planned position if the discrepancy was larger than 2.0 mm in the anterior-posterior (AP), cranial-caudal (CC), or left-right (LR) directions. In total, we analyzed 4,541 observations in 20 patients who received 70 Gy in 30 fractions (7.6 times a day on average). Results: The incidence of table position adjustment at 10 minutes from the initial setup of each treatment was 14.2%, 12.3%, and 5.0% of the observations in the AP, CC, and LR directions, respectively. The accumulated incidence of the table position adjustment was significantly higher at 10 minutes than at 2 minutes for AP (p = 0.0033) and CC (p = 0.0110) but not LR (p = 0.4296). An adjustment greater than 5 mm was required at least once in the treatment period in 11 (55%) patients. Conclusions: Interportal adjustment of table position was required in more than 10% of portal irradiations during the 10-minute period after initial setup to maintain treatment accuracy within 2.0 mm. (C) 2011 Elsevier Inc.
  • Jun Sakakibara-Konishi, Satoshi Oizumi, Ichiro Kinoshita, Naofumi Shinagawa, Junko Kikuchi, Mototsugu Kato, Tetsuya Inoue, Norio Katoh, Rikiya Onimaru, Hiroki Shirato, Hirotoshi Dosaka-Akita, Masaharu Nishimura LUNG CANCER 74 (2) 248 -252 2011年11月 [査読無し][通常論文]
     
    Introduction: Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT). Patients and methods: Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m(2) followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5 mg/m(2) per level. Results: Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m(2) and 45 mg/m(2)), carboplatin (AUC = 2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m(2) and carboplatin, AUC = 2). At Level 2 (paclitaxel, 45 mg/m(2) and carboplatin, AUC = 2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m(2) and 40 mg/m(2), respectively. Conclusions: This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m(2) at AUC = 2, respectively. Further studies are warranted to evaluate the efficacy of this regimen. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Seishin Takao, Shigeru Tadano, Hiroshi Taguchi, Koichi Yasuda, Rikiya Onimaru, Masayori Ishikawa, Gerard Bengua, Ryusuke Suzuki, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 81 (3) 871 -879 2011年11月 [査読無し][通常論文]
     
    Purpose: To establish a method for the accurate acquisition and analysis of the variations in tumor volume, location, and three-dimensional (3D) shape of tumors during radiotherapy in the era of image-guided radiotherapy. Methods and Materials: Finite element models of lymph nodes were developed based on computed tomography (CT) images taken before the start of treatment and every week during the treatment period. A surface geometry map with a volumetric scale was adopted and used for the analysis. Six metastatic cervical lymph nodes, 3.5 to 55.1 cm before treatment, in 6 patients with head and neck carcinomas were analyzed in this study. Three fiducial markers implanted in mouthpieces were used for the fusion of CT images. Changes in the location of the lymph nodes were measured on the basis of these fiducial markers. Results: The surface geometry maps showed convex regions in red and concave regions in blue to ensure that the characteristics of the 3D tumor geometries are simply understood visually. After the irradiation of 66 to 70 Gy in 2 Gy daily doses, the patterns of the colors had not changed significantly, and the maps before and during treatment were strongly correlated (average correlation coefficient was 0.808), suggesting that the tumors shrank uniformly, maintaining the original characteristics of the shapes in all 6 patients. The movement of the gravitational center of the lymph nodes during the treatment period was everywhere less than +/-5 mm except in 1 patient, in whom the change reached nearly 10 mm. Conclusions: The surface geometry map was useful for an accurate evaluation of the changes in volume and 3D shapes of metastatic lymph nodes. The fusion of the initial and follow-up CT images based on fiducial markers enabled an analysis of changes in the location of the targets. Metastatic cervical lymph nodes in patients were suggested to decrease in size without significant changes in the 3D shape during radiotherapy. The movements of the gravitational center of the lymph nodes were almost all less than +/-5 mm. (C) 2011 Elsevier Inc.
  • Y. Morimoto, Y. Ueno, W. Takeuchi, S. Kojima, K. Matsuzaki, T. Ishitsu, K. Umegaki, Y. Kiyanagi, N. Kubo, C. Katoh, T. Shiga, H. Shirato, N. Tamaki IEEE TRANSACTIONS ON NUCLEAR SCIENCE 58 (5) 2181 -2189 2011年10月 [査読無し][通常論文]
     
    Targeting improved spatial resolution, a three-dimensional positron-emission-tomography (PET) scanner employing CdTe semiconductor detectors and using depth-of-interaction (DOI) information was developed, and its physical performance was evaluated. This PET scanner is the first to use semiconductor detectors dedicated to the human brain and head-and-neck region. Imaging performance of the scanner used for (18)F-fluorodeoxy glucose (FDG) scans of phantoms and human brains was evaluated. The gantry of the scanner has a 35.0-cm-diameter patient port, the trans-axial field of view (FOV) is 31.0 cm, and the axial FOV is 24.6 cm. The energy resolution averaged over all detector channels and timing resolution were 4.1% and 6.8 ns (each in FWHM), respectively. Spatial resolution measured at the center of FOV was 2.3-mm FWHM-which is one of the best resolutions achieved by human PET scanners. Noise-equivalent count ratio (NEC2R) has a maximum in the energy window of 390 to 540 keV and is 36 kcps/Bq/cm(3) at 3.7 kBq/cm(3). The sensitivity of the system according to NEMA 1994 was 25.9 cps/Bq/cm(3). Scatter fraction of the scanner is 37% for the energy window of 390 to 540 keV and 23% for 450 to 540 keV. Images of a hot-rod phantom and images of brain glucose metabolism show that the structural accuracy of the images obtained with the semiconductor PET scanner is higher than that possible with a conventional Bismuth Germanium Oxide (BGO) PET scanner. In addition, the developed scanner permits better delineation of the head-and-neck cancer. These results show that the semiconductor PET scanner will play a major role in the upcoming era of personalized medicine.
  • Takashi Yokota, Shintaro Kinugawa, Koichi Okita, Kagami Hirabayashi, Tadashi Suga, Masaaki Hattori, Yoshinao Nakagawa, Noriko Oyama-Manabe, Hiroki Shirato, Hiroyuki Tsutsui HYPERTENSION RESEARCH 34 (9) 1029 -1034 2011年09月 [査読無し][通常論文]
     
    Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex-and activity-matched control subjects to assess the aerobic capacity. We performed (31)phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO(2); 34.1 +/- 6.2 vs. 41.4 +/- 8.4 ml kg(-1) min(-1), P < 0.05) and anaerobic threshold (AT; 18.0 +/- 2.4 vs. 23.1 +/- 3.7 ml kg(-1) min(-1), P < 0.01) adjusted by lean body mass were lower in MetS patients than control subjects. Phosphocreatine (PCr) loss during exercise was 1.5-fold greater in MetS, suggesting reduced intramuscular oxidative capacity. PCr loss was inversely correlated with peak VO(2) (r = -0.64) and AT (r = -0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO(2) (r = -0.47) and AT (r = -0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r = 0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism. Hypertension Research (2011) 34, 1029-1034; doi: 10.1038/hr.2011.78; published online 14 July 2011
  • Naoki Miyamoto, Masayori Ishikawa, Gerard Bengua, Kenneth Sutherland, Ryusuke Suzuki, Suguru Kimura, Shinichi Shimizu, Rikiya Onimaru, Hiroki Shirato PHYSICS IN MEDICINE AND BIOLOGY 56 (15) 4803 -4813 2011年08月 [査読無し][通常論文]
     
    In the real-time tumor-tracking radiotherapy system, fluoroscopy is used to determine the real-time position of internal fiducial markers. The pattern recognition score (PRS) ranging from 0 to 100 is computed by a template pattern matching technique in order to determine the marker position on the fluoroscopic image. The PRS depends on the quality of the fluoroscopic image. However, the fluoroscopy parameters such as tube voltage, current and exposure duration are selected manually and empirically in the clinical situation. This may result in an unnecessary imaging dose from the fluoroscopy or loss of the marker because of too much or insufficient x-ray exposure. In this study, a novel optimization method is proposed in order to minimize the fluoroscopic dose while keeping the image quality usable for marker tracking. The PRS can be predicted in a region where the marker appears to move in the fluoroscopic image by the proposed method. The predicted PRS can be utilized to judge whether the marker can be tracked with accuracy. In this paper, experiments were performed to show the feasibility of the PRS prediction method under various conditions. The predicted PRS showed good agreement with the measured PRS. The root mean square error between the predicted PRS and the measured PRS was within 1.44. An experiment using a motion controller and an anthropomorphic chest phantom was also performed in order to imitate a clinical fluoroscopy situation. The result shows that the proposed prediction method is expected to be applicable in a real clinical situation.
  • Akihiro Homma, Naoya Inamura, Nobuhiko Oridate, Seigo Suzuki, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda JAPANESE JOURNAL OF CLINICAL ONCOLOGY 41 (8) 980 -986 2011年08月 [査読無し][通常論文]
     
    Objective: The most common chemoradiotherapy regimen is high-dose (100 mg/m(2)) three-weekly cisplatin with concomitant radiotherapy; however, this protocol is associated with acute and late toxicities. Here, we reviewed the dose intensity and toxicity for concomitant weekly cisplatin and radiotherapy in patients with head and neck cancer. Methods: Fifty-three patients with untreated head and neck cancer were enrolled and evaluated at our institution from April 2006 to April 2010. Weekly cisplatin (40 mg/m(2)) was given on weeks 1, 2, 3, 5, 6 and 7 with radiotherapy, which comprised a standard dose of 70 Gy delivered in 35 daily fractions over 7 weeks. Results: Fifty-one patients (96.2%) received the full dose of radiotherapy, while the course was disrupted by adverse events in two. Over the course of the chemotherapy, 31 patients (58.5%) received more than 200 mg/m(2) cisplatin. The toxicity was manageable in all except one patient, who died of sepsis after completing treatment. The 2-year overall survival rate and local progression-free rate for all patients were 93.7% and 88.0%, respectively. The primary site showed a complete response in 52 patients (98.1%) and a partial response in 1 patient (1.9%). The primary disease was well controlled by chemoradiotherapy in 47 patients (88.7%). Conclusions: Weekly cisplatin could be easier to manage than three-weekly cisplatin, because patients can be monitored more regularly for toxicity allowing the schedule to be altered if required. This regimen appears to be a suitable alternative to three-weekly high-dose cisplatin with concomitant radiotherapy.
  • Kentaro Kobayashi, Khin Khin Tha, Satoshi Terae, Yuki Iijima, Kenichi Katabami, Yosuke Minami, Shinji Uegaki, Satoshi Gando, Hiroki Shirato JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 35 (4) 498 -500 2011年07月 [査読無し][通常論文]
     
    We report a case of heat stroke in which detection of brain injury was improved by high b-value diffusion-weighted imaging (DWI). High b-value DWI revealed moderate to marked hyperintensity at/around bilateral dentate nuclei and part of thalami. Apparent diffusion coefficient maps revealed apparent diffusion coefficient decrease of the dentate lesions. Routine DWI showed only mild hyperintensity of part of dentate lesions. High b-value DWI could be valuable for improved detection of heat stroke-induced brain injury.
  • Satoshi Kano, Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Jun Furusawa, Tomohiro Sakashita, Daisuke Yoshida, Rikiya Onimaru, Hiroki Shirato, Satoshi Fukuda ORAL ONCOLOGY 47 (7) 665 -670 2011年07月 [査読無し][通常論文]
     
    The treatment of base of tongue (BOT) cancer is highly controversial with differing options according to individual institutions, or the primary surgical or radiation therapy bias. We aimed to determine patient outcomes and discuss technical aspects following treatment with concurrent radiation therapy and targeted cisplatin chemotherapy (RADPLAT). We utilized RADPLAT for the definitive treatment of patients with BOT cancers. The 5-year local control and overall survival rate was 92.3% and 90.9% for all patients, respectively, and all surviving patients achieved normal swallowing without a feeding-tube and normal speech without tracheostoma after treatment. Our study found that RADPLAT gave excellent survival rates and organ functions for patients with BOT cancers. We consider that BOT cancer is a good indication for RADPLAT and that the angiographic technique and patient selection are keys to success. (C) 2011 Elsevier Ltd. All rights reserved.
  • Makoto Chuma, Hiroshi Taguchi, Yoshiya Yamamoto, Shinichi Shimizu, Mitsuru Nakanishi, Koji Ogawa, Takuya Sho, Hiromasa Horimoto, Tomoe Kobayashi, Masato Nakai, Katsumi Terashita, Yusuke Sakuhara, Daisuke Abo, Yoko Tsukuda, Seiji Tsunematsu, Shuhei Hige, Mototsugu Kato, Hiroki Shirato, Masahiro Asaka JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 26 (7) 1123 -1132 2011年07月 [査読無し][通常論文]
     
    Background and Aim: To evaluate the efficacy of intra-arterial 5-fluorouracil (5-FU) and subcutaneous interferon (IFN) combined with image-guided radiation therapy (IGRT) in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: Twenty HCC patients with PVTT were treated with 5-FU and IFN combined with image-guided radiation therapy (IGRT) (IGRT group), and as controls, 20 patients with PVTT were treated with 5-FU and IFN alone (non-IGRT group). Overall survival (OS) time, response rates, time to progression (TTP) and safety were compared across groups. Results: Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) of PVTT were 5%, 55%, 40% and 0% in the IGRT group and 0%, 30%, 35% and 35%, in the non-IGRT group, respectively. CR, PR, SD, and PD of the whole tumor were 0%, 35%, 45% and 20% in the IGRT group and 0%, 30%, 35% and 35%, in the non-IGRT group, respectively. Overall median survival was significantly longer in the IGRT group (12.0 months 95% confidence interval [CI], 9.3-17.6 months) than in the non-IGRT group (9.1 months [95% Cl, 5.5-11.1 months]) (P = 0.041). TTP was significantly longer in the IGRT group (6.9 months [95% CI, 5.6-10.2 months]) than in the non-IGRT group (4.0 months [95% Cl, 3.3-6.4 months]) (P = 0.034). Conclusions: The response rates, median OS time and TTP in patients with advanced HCC with PVTT who received this novel combination therapy of intra-arterial 5-FU and subcutaneous IFN with TORT are encouraging, and this combination therapy warrants further investigation.
  • Fumi Kato, Tamotsu Kamishima, Ken Morita, Natalia S. Muto, Syozou Okamoto, Tokuhiko Omatsu, Noriko Oyama, Satoshi Terae, Kakuko Kanegae, Katsuya Nonomura, Hiroki Shirato EUROPEAN JOURNAL OF RADIOLOGY 79 (1) 15 -20 2011年07月 [査読無し][通常論文]
     
    Purpose: To evaluate the speed and precision of split renal volume (SRV) measurement, which is the ratio of unilateral renal volume to bilateral renal volume, using a newly developed software for computed tomographic (CT) volumetry and to investigate the usefulness of SRV for the estimation of split renal function (SRF) in kidney donors. Method: Both dynamic CT and renal scintigraphy in 28 adult potential living renal donors were the subjects of this study. We calculated SRV using the newly developed volumetric software built into a PACS viewer (n-SRV), and compared it with SRV calculated using a conventional workstation, ZIOSOFT (z-SRV). The correlation with split renal function (SRF) using 99mTc-DMSA scintigraphy was also investigated. Results: The time required for volumetry of bilateral kidneys with the newly developed software (16.7 +/- 3.9 s) was significantly shorter than that of the workstation (102.6 +/- 38.9 s, p < 0.0001). The results of n-SRV (49.7 +/- 4.0%) were highly consistent with those of z-SRV (49.9 +/- 3.6%), with a mean discrepancy of 0.12 +/- 0.84%. The SRF also agreed well with the n-SRV, with a mean discrepancy of 0.25 +/- 1.65%. The dominant side determined by SRF and n-SRV showed agreement in 26 of 28 cases (92.9%). Conclusion: The newly developed software for CT volumetry was more rapid than the conventional workstation volumetry and just as accurate, and was suggested to be useful for the estimation of SRF and thus the dominant side in kidney donors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • E. Pepin, H. wu, H. Shirato Medical Physics 38 (6) 3480 2011年06月 [査読無し][通常論文]
     
    Purpose: To analyze and evaluate the necessity and use of dynamic gating techniques for compensation of baseline shift during respiratory‐gated radiation therapy of lung tumors. Methods: Motion tracking data from 30 lung tumors over 592 treatment fractions were analyzed for baseline shift. The finite state model (FSM) was used to identify the end‐of‐exhale (EOE) breathing phase throughout each treatment fraction. Using duty cycle as an evaluation metric, several methods of end‐of‐exhale dynamic gating were compared: An a posteriori ideal gating window, a predictive trend‐line‐ based gating window, and a predictive weighted point‐based gating window. These methods were evaluated for each of several gating window types: Superior/inferior (SI) gating, anterior/posterior beam, lateral beam, and 3D gating. Results: In the absence of dynamic gating techniques, SI gating gave a 39.6% duty cycle. The ideal SI gating window yielded a 41.5% duty cycle. The weight‐based method of dynamic SI gating yielded a duty cycle of 36.2%. The trend‐line‐based method yielded a duty cycle of 34.0%. Conclusions: Dynamic gating was not broadly beneficial due to a breakdown of the FSM's ability to identify the EOE phase. When the EOE phase was well defined, dynamic gating showed an improvement over static‐window gating. © 2011, American Association of Physicists in Medicine. All rights reserved.
  • J. Lewis, S. Friesen, J. Rottmann, S. Nishioka, H. Shirato, R. Berbeco, F. Hacker Medical Physics 38 (6) 3856 -+ 2011年06月 [査読無し][通常論文]
     
    Purpose: To evaluate the effect of an adaptive gating system on treatment accuracy and delivery time as compared to gating based only on an external surrogate. Methods: Two studies were designed to simulate the process of treatment planning, patient setup, and treatment delivery for 1) external surrogate‐based; and 2) adaptive gating. External surrogate‐based gating used only chestwall motion to generate the respiratory gating signal, while adaptive gating updates the external/internal correlation periodically based on the location of implanted fiducial markers. Lung tumor trajectories with corresponding chestwall motions acquired from 8 patients with multiple days of radiation treatments. A total of 20,026 seconds of data from 163 treatment beams was used. The average target miss percentage is defined to be the percentage of beam‐on time that the target is thought to be within the gating window but is actually outside of it. The average duty cycle is defined as the beam‐on time divided by the sum of beam‐on and beam‐off time. Results: The average target miss percentage for adaptive gating was 17.6% (range: 8.0–23.6%) and 22.6% (range: 8.1–44.5%) without adaptation. The magnitude of the average miss was 1.7 mm (range: 0.6–4.8 mm) with adaptation and 1.8 mm (range: 0.6–4.3 mm) without adaptation. The average miss percentage for misses of over 5 mm was 0.6 % (range: 0.0–3.3%) for adaptive gating and 0.9 % (range: 0.0–3.7%) without adaptation, suggesting that additional planning margins of 5 mm would mitigate most gating errors with either method. The average duty cycle using adaptive gating was 33% (range: 23–39%), compared to 45% (range: 35–57%) without adaptation. Conclusion: We have shown that adaptive gating can improve the accuracy of gated treatments, at the cost of longer treatment times. However, both adaptive and non‐adaptive techniques perform well if an additional planning margin of 5 mm is used. © 2011, American Association of Physicists in Medicine. All rights reserved.
  • Tamotsu Kamishima, Kazuhide Tanimura, Masato Shimizu, Megumi Matsuhashi, Jun Fukae, Yujiro Kon, Hiromi Hagiwara, Akihiro Narita, Yuko Aoki, Naoki Kosaka, Tatsuya Atsumi, Hiroki Shirato, Satoshi Terae SKELETAL RADIOLOGY 40 (6) 745 -755 2011年06月 [査読無し][通常論文]
     
    To compare quantitative magnetic resonance imaging (MRI) and power Doppler ultrasonography (PDUS) with conventional measures of disease activity in rheumatoid arthritis (RA) patients treated with the anti-interleukin 6 (anti-IL 6) receptor antibody tocilizumab in terms of responsiveness at a few months to disease activity and ability to predict structural damage at 1 year. A cohort of patients with RA (n = 29) was evaluated clinically including disease activity score 28 (DAS28) and by semiquantitative (SQ-) and quantitative (Q-) PDUS (bilateral metacarpophalangeal joints) and MRI (one hand and wrist) at initiation of treatment with anti-IL 6 receptor antibody agents and after 2 and 5 months. Conventional radiography for both hands and wrists was performed at baseline and at 12 months. Responsiveness was assessed by standardized response means (SRM). Areas under the curve (AUC) for measures at baseline, 2 and 5 months were correlated with structural damage at 1 year. Among the laboratory and clinical parameters, DAS28-ESR was the most responsive with a large effect size of SRM. Structural damage progressions for radiography and MR erosion were correlated with AUC of MR bone erosion and Q-PDUS, respectively. In the evaluation of disease activity in RA patients in the first few months after starting anti-IL 6 receptor antibody tocilizumab treatment, the semiquantitative MR bone erosion score of the hand and quantitative value for power Doppler signal in the finger joint were both responsive and predictive of structural damage progression at 1 year.
  • Eric W. Pepin, Huanmei Wu, Hiroki Shirato MEDICAL PHYSICS 38 (4) 1912 -1918 2011年04月 [査読無し][通常論文]
     
    Purpose: To analyze and evaluate the necessity and use of dynamic gating techniques for compensation of baseline shift during respiratory-gated radiation therapy of lung tumors. Methods: Motion tracking data from 30 lung tumors over 592 treatment fractions were analyzed for baseline shift. The finite state model (FSM) was used to identify the end-of-exhale (EOE) breathing phase throughout each treatment fraction. Using duty cycle as an evaluation metric, several methods of end-of-exhale dynamic gating were compared: An a posteriori ideal gating window, a predictive trend-line-based gating window, and a predictive weighted point-based gating window. These methods were evaluated for each of several gating window types: Superior/inferior (SI) gating, anterior/posterior beam, lateral beam, and 3D gating. Results: In the absence of dynamic gating techniques, SI gating gave a 39.6% duty cycle. The ideal SI gating window yielded a 41.5% duty cycle. The weight-based method of dynamic SI gating yielded a duty cycle of 36.2%. The trend-line-based method yielded a duty cycle of 34.0%. Conclusions: Dynamic gating was not broadly beneficial due to a breakdown of the FSM's ability to identify the EOE phase. When the EOE phase was well defined, dynamic gating showed an improvement over static-window gating. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3556588]
  • Natalia Sayuri Muto, Tamotsu Kamishima, Ardene A. Harris, Fumi Kato, Yuya Onodera, Satoshi Terae, Hiroki Shirato EUROPEAN JOURNAL OF RADIOLOGY 78 (1) 151 -156 2011年04月 [査読無し][通常論文]
     
    Purpose: To evaluate the relationship between renal cortical volume, measured by an automatic contouring software, with body mass index (BMI), age and renal function. Materials and methods: The study was performed in accordance to the institutional guidelines at our hospital. Sixty-four patients (34 men, 30 women), aged 19 to 79 years had their CT scans for diagnosis or follow-up of hepatocellular carcinoma retrospectively examined by a computer workstation using a software that automatically contours the renal cortex and the renal parenchyma. Body mass index and estimated glomerular filtration rate (eGFR) were calculated based on data collected. Statistical analysis was done using the Student t-test, multiple regression analysis, and intraclass correlation coefficient (ICC). Results: The ICC for total renal and renal cortical volumes were 0.98 and 0.99, respectively. Renal volume measurements yielded a mean cortical volume of 105.8 cm(3) +/- 28.4 SD, mean total volume of 153 cm(3) +/- 39 SD and mean medullary volume of 47.8 cm(3) +/- 19.5 SD. The correlation between body weight/height/BMI and both total renal and cortical volumes presented r = 0.6, 0.6 and 0.4, respectively, p < 0.05, while the correlation between renal cortex and age was r = -0.3, p < 0.05. eGFR showed correlation with renal cortical volume r = 0.6, p < 0.05. Conclusion: This study demonstrated that renal cortical volume had a moderate positive relationship with BMI, moderate negative relationship with age, and a strong positive relationship with the renal function, and provided a new method to routinely produce volumetric assessment of the kidney. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Yuya Onodera, Noriko Nishoka, Koichi Yasuda, Noriyuki Fujima, Mylin Torres, Tamotsu Kamishima, Noriko Ooyama, Rikiya Onimaru, Satoshi Terae, Satoshi Ooizumi, Masaharu Nishimura, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 79 (5) 1408 -1413 2011年04月 [査読無し][通常論文]
     
    Purpose: For lung cancer patients with poor pulmonary function because of emphysema or fibrosis, it is important to predict the amplitude of internal tumor motion to minimize the irradiation of the functioning lung tissue before undergoing stereotactic body radiotherapy. Methods and Materials: Two board-certified diagnostic radiologists independently assessed the degree of pulmonary emphysema and fibrosis on computed tomography scans in 71 patients with peripheral lung tumors before real-time tumor-tracking radiotherapy. The relationships between the computed tomography findings of the lung parenchyma and the motion of the fiducial marker near the lung tumor were investigated. Of the 71 patients, 30 had normal pulmonary function, and 29 had obstructive pulmonary dysfunction (forced expiratory volume in 1 s/forced vital capacity ratio of < 70%), 6 patients had constrictive dysfunction (percentage of vital capacity < 80%), and 16 had mixed dysfunction. Results: The upper region was associated with smaller tumor motion, as expected (p = .0004), and the presence of fibrosis (p = .088) and pleural tumor contact (p = .086) were weakly associated with tumor motion. The presence of fibrotic changes in the lung tissue was associated with smaller tumor motion in the upper region (p <.05) but not in the lower region. The findings of emphysema and pulmonary function tests were not associated with tumor motion. Conclusion: Tumors in the upper lung region with fibrotic changes have smaller motion than those in the upper region of the lungs without fibrotic changes. The tumor motion in the lower lung region was not significantly different between patients with and without lung fibrosis. Emphysema was not associated with the amplitude of tumor motion. (C) 2011 Elsevier Inc.
  • Kohsuke Kudo, Makoto Sasaki, Leif Ostergaard, Soren Christensen, Ikuko Uwano, Masako Suzuki, Kuniaki Ogasawara, Hiroki Shirato, Akira Ogawa JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 31 (3) 908 -912 2011年03月 [査読無し][通常論文]
     
    The time-to-maximum of the tissue residue function (T-max) perfusion index has proven very predictive of infarct growth in large clinical trials, yet its dependency on simple tracer delays remains unknown. Here, we determine the dependency of computed tomography (CT) perfusion (CTP) T-max estimates on tracer delay using a range of deconvolution techniques and digital phantoms. Digital phantom data sets simulating the tracer delay were created from CTP data of six healthy individuals, in which time frames of the left cerebral hemisphere were shifted forward and backward by up to +/- 5 seconds. These phantoms were postprocessed with three common singular value decomposition (SVD) deconvolution algorithms-standard SVD (sSVD), block-circulant SVD (bSVD), and delay-corrected SVD (dSVD)-with an arterial input function (AIF) obtained from the right middle cerebral artery (MCA). The T-max values of the left hemisphere were compared among different tracer delays and algorithms by a region of interest-based analysis. The T-max values by sSVD were positively correlated with 'positive shifts' but unchanged with 'negative shifts,' those by bSVD had an excellent positive linear correlation with both positive and negative shifts, and those by dSVD were relatively constant, although slightly increased with the positive shifts. The T-max is a parameter highly dependent on tracer delays and deconvolution algorithm. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 908-912; doi:10.1038/jcbfm.2010.169; published online 22 September 2010
  • Noriko Oyama, Daisuke Goto, Yoichi M Ito, Naoki Ishimori, Rie Mimura, Tomoo Furumoto, Fumi Kato, Hiroyuki Tsutsui, Nagara Tamaki, Satoshi Terae, Hiroki Shirato Japanese journal of radiology 29 (2) 104 -9 2011年02月 [査読無し][通常論文]
     
    PURPOSE: The aim of this study was to assess a method for measuring epicardial fat volume (EFV) by means of a single-slice area measurement. We investigated the relation between a single-slice fat area measurement and total EFV. METHODS AND METHODS: A series of 72 consecutive patients (ages 65 ± 11 years; 36 men) who had undergone cardiac computed tomography (CT) on a 64-slice multidetector scanner with prospective electrocardiographic triggering were retrospectively reviewed. Pixels in the pericardium with a density range from -230 to -30 Hounsfield units were considered fat, giving the per-slice epicardial fat area (EFA). The EFV was estimated by the summation of EFAs multiplied by the slice thickness. We investigated the relation between total EFV and each EFA. RESULTS: EFAs measured at several anatomical landmarks-right pulmonary artery, origins of the left main coronary artery, right coronary artery, coronary sinus-all correlated with the EFV (r = 0.77-0.92). The EFA at the LMCA level was highly reproducible and showed an excellent correlation with the EFV (r = 0.92). CONCLUSION: The EFA is significantly correlated with the EFV. The EFA is a simple, quick method for representing the time-consuming EFV, which has been used as a predictive indicator of cardiovascular diseases.
  • Takahiro Yamada, Gen Nishimura, Keiichiro Nishida, Hideaki Sawai, Tokuhiko Omatsu, Taichi Kimura, Hiroshi Nishihara, Rina Shono, Shigeki Shimada, Mamoru Morikawa, Masato Mizushima, Takashi Yamada, Kazutoshi Cho, Shinya Tanaka, Hiroki Shirato, Hisanori Minakami JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 37 (2) 151 -155 2011年02月 [査読無し][通常論文]
     
    We present a case of short-rib polydactyly syndrome (SRPs) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRP encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). As accurate prenatal diagnosis of SRP is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of 'short-rib dysplasia group' on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as short-rib dysplasia group led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias.
  • Satoshi Yamaguchi, Masayori Ishikawa, Gerard Bengua, Kenneth Sutherland, Teiji Nishio, Satoshi Tanabe, Naoki Miyamoto, Ryusuke Suzuki, Hiroki Shirato PHYSICS IN MEDICINE AND BIOLOGY 56 (4) 965 -977 2011年02月 [査読無し][通常論文]
     
    A feasibility study of a novel PET-based molecular image guided radiation therapy (m-IGRT) system was conducted by comparing PET-based digitally reconstructed planar image (PDRI) registration with radiographic registration. We selected a pair of opposing parallel-plane PET systems for the practical implementation of this system. Planar images along the in-plane and cross-plane directions were reconstructed from the parallel-plane PET data. The in-plane and cross-plane FWHM of the profile of 2 mm diameter sources was approximately 1.8 and 8.1 mm, respectively. Therefore, only the reconstructed in-plane image from the parallel-plane PET data was used in the PDRI registration. In the image registration, five different sizes of (18)F cylindrical sources (diameter: 8, 12, 16, 24, 32 mm) were used to determine setup errors. The data acquisition times were 1, 3 and 5 min. Image registration was performed by five observers to determine the setup errors from PDRI registration and radiographic registration. The majority of the mean registration errors obtained from the PDRI registration were not significantly different from those obtained from the radiographic registration. Acquisition time did not appear to result in significant differences in the mean registration error. The mean registration error for the PDRI registration was found to be 0.93 +/- 0.33 mm. This is not statistically different from the radiographic registration which had a mean registration error of 0.92 +/- 0.27 mm. Our results suggest that m-IGRT image registration using PET-based reconstructed planar images along the in-plane direction is feasible for clinical use if PDRI registration is performed at two orthogonal gantry angles.
  • Rikiya Onimaru, Koichi Yasuda, Norio Katoh, Hiroki Shirato, Tohru Shiga, Shozo Okamoto, Nagara Tamaki, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda Japanese Journal of Head and Neck Cancer 37 (3) 376 -380 2011年 [査読無し][通常論文]
     
    Positron emission tomography (PET) can obtain functional information about tumors. There are some reports that intensity modulated radiation therapy (IMRT) planning was made using hypoxic imaging information obtained by PET. We used a semiconductor PET which was developed by the Department of Nuclear Medicine in Hokkaido University, where hypoxic imaging by [18F] fluoromisonidazole (FMISO) PET is available. We are investigating a dose escalation planning study of IMRT using FMISO PET imaging, and report on the usage of PET for radiotherapy in Hokkaido University.
  • Power Doppler signal calibration using capillary phantom for pannus vascularity in rheumatoid finger joint. A pilot study.
    Clin Exp Rheumatol 1057 2011年 [査読無し][通常論文]
  • Long-term outcomes of fractionated stereotactic radiotherapy for intracranial skull base benign meningiomas in single institution.a-Naumoff type) by three-dimensional helical computed tomography.
    Jpn J Clin Oncol. 462 2011年 [査読無し][通常論文]
  • Detection of patient setup errors with a portal image - DRR registration software application.
    J Appl Clin Med Phys 3492 2011年 [査読無し][通常論文]
  • Noriyuki Fujima, Kohsuke Kudo, Satoshi Terae, Kinya Ishizaka, Rie Yazu, Yuri Zaitsu, Khin Khin Tha, Daisuke Yoshida, Akiko Tsukahara, Mark E. Haacke, Makoto Sasaki, Hiroki Shirato NEUROIMAGE 54 (1) 344 -349 2011年01月 [査読無し][通常論文]
     
    Susceptibility-weighted imaging (SWI) has been used for quantitative and non-invasive measurement of blood oxygen saturation in the brain. In this study, we used SWI for quantitative measurement of oxygen saturation in the spinal vein to look for physiological- or caffeine-induced changes in venous oxygenation. SWI measurements were obtained for 5 healthy volunteers using 1.5-T MR units, under 1) 3 kinds of physiological load (breath holding, Bh; hyperventilation, Hv; and inspiration of highly concentrated oxygen. Ox) and 2) caffeine load. Oxygen saturation in the anterior spinal vein (ASV) was calculated. We evaluated changes in oxygen saturation induced by physiological load. We also evaluated the time-course of oxygen saturation after caffeine intake. For the physiological load measurements, the average oxygen saturation for the 5 subjects was significantly lower in Hv (0.75) and significantly higher in Bh (0.84) when compared with control (0.80). There was no significant difference between Ox (0.81) and control. Oxygen saturation gradually decreased after caffeine intake. The average values of oxygen saturation were 0.79 (0 min), 0.76 (20 min), 0.74 (40 min), and 0.73 (60 min), respectively. We demonstrated a significant difference in oxygen saturation at 40 and 60 min after caffeine intake when compared with 0 min. In conclusion, we demonstrated the feasibility of using SWI for non-invasive measurement of oxygen saturation in the spinal vein. We showed changes in oxygen saturation under physiological as well as caffeine load and suggest that this method is a useful tool for the clinical evaluation of spinal cord oxygenation. (C) 2010 Elsevier Inc. All rights reserved.
  • Rikiya Onimaru, Masakazu Hasegawa, Kouichi Yasuda, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda, Hiroki Shirato JAPANESE JOURNAL OF CLINICAL ONCOLOGY 41 (1) 103 -109 2011年01月 [査読無し][通常論文]
     
    We retrospectively investigated treatment outcomes in patients with glottic T1 carcinoma treated with 65 Gy in 26 fractions four times a week and discuss the importance of the overall treatment time. Two hundred one patients with glottic T1 carcinoma were evaluated. Sixty-five Gray in 26 fractions were delivered for 200 patients, whereas 1 patient received 62.5 Gy in 25 fractions. We delivered radiotherapy once daily four times a week in this period, for a weekly dose of 10 Gy. Weekdays except Wednesday were treatment days. The overall survival rate was 96.8 +/- 1.3% (standard error) at 3 years and 90.8 +/- 2.2% at 5 years. The local control rate was 91.9 +/- 2.0% at 3 years and 89.8 +/- 2.3% at 5 years. In patients with an overall treatment time equal to or longer than 47 days, the local control rate was 82.6 +/- 6.0% at both 3 and 5 years. In the patients with overall treatment time equal to or less than 46 days, the local control rate was 94.6 +/- 1.9% at 3 years and 91.8 +/- 2.4% at 5 years. There was a significant difference between these two groups (P = 0.0349). A severe late radiation reaction occurred in one patient. He experienced severe laryngeal edema that required tracheotomy at 6 months after the completion of radiotherapy. The tracheotomy was closed at 14 months after completion of radiotherapy. Overall treatment time seems to be an important factor for a good local control rate for glottic T1N0 carcinoma even when treated with slight hypofractionation.
  • Tamotsu Kamishima, Kazuhide Tanimura, Yuko Aoki, Naoki Kosaka, Masato Shimizu, Megumi Matsuhashi, Jun Fukae, Yujiro Kon, Satoshi Terae, Hiroki Shirato SKELETAL RADIOLOGY 40 (1) 65 -74 2011年01月 [査読無し][通常論文]
     
    To determine an optimal threshold in a simplified 3D-based volumetry of abnormal signals in rheumatoid wrists utilizing contrast and non-contrast MR data, and investigate the feasibility and reliability of this method. MR images of bilateral hands of 15 active rheumatoid patients were assessed before and 5 months after the initiation of tocilizumab infusion protocol. The volumes of abnormal signals were measured on STIR and post-contrast fat-suppressed T1-weighted images. Three-dimensional volume rendering of the images was used for segmentation of the wrist by an MR technologist and a radiologist. Volumetric data were obtained with variable thresholding (1, 1.25, 1.5, 1.75, and 2 times the muscle signal), and were compared to clinical data and semiquantitative MR scoring (RAMRIS) of the wrist. Intra- and interobserver variability and time needed for volumetry measurements were assessed. The volumetric data correlated favorably with clinical parameters almost throughout the pre-determined thresholds. Interval differences in volumetric data correlated favorably with those of RAMRIS when the threshold was set at more than 1.5 times the muscle signal. The repeatability index was lower than the average of the interval differences in volumetric data when the threshold was set at 1.5-1.75 for STIR data. Intra- and interobserver variability for volumetry was 0.79-0.84. The time required for volumetry was shorter than that for RAMRIS. These results suggest that a simplified MR volumetric data acquisition may provide gross estimates of disease activity when the threshold is set properly. Such estimation can be achieved quickly by non-imaging specialists and without contrast administration.
  • Magn Reson Med Sci 10 (2) 129 -132 2011年 [査読無し][通常論文]
  • ISHIZAKA Kinya, OYAMA Noriko, MITO Suzuko, SUGIMORI Hiroyuki, NAKANISHI Mitsuhiro, OKUAKI Tomoyuki, SHIRATO Hiroki, TERAE Satoshi Magn Reson Med Sci 10 (1) 41 -48 2011年 [査読無し][通常論文]
  • NISHIOKA Takeshi, YASUDA Motoaki, TAKESHIMA Tsuguhide, HAGA Hisashi, MIYAI Yusuke, SHIBATA Ken-ichiro, YAMAZAKI Rie, SHIRATO Hiroki, TEDUKA Masahiro, DATE Hiroyuki Cell Struct Funct. 36 (1) 13 -20 2011年 [査読無し][通常論文]
  • Noriyuki Fujima, Kohsuke Kudo, Satoshi Terae, Kinya Ishizaka, Rie Yazu, Yuri Zaitsu, Khin Khin Tha, Daisuke Yoshida, Akiko Tsukahara, Mark E. Haacke, Makoto Sasaki, Hiroki Shirato NEUROIMAGE 54 (1) 344 -349 2011年01月 [査読無し][通常論文]
     
    Susceptibility-weighted imaging (SWI) has been used for quantitative and non-invasive measurement of blood oxygen saturation in the brain. In this study, we used SWI for quantitative measurement of oxygen saturation in the spinal vein to look for physiological- or caffeine-induced changes in venous oxygenation. SWI measurements were obtained for 5 healthy volunteers using 1.5-T MR units, under 1) 3 kinds of physiological load (breath holding, Bh; hyperventilation, Hv; and inspiration of highly concentrated oxygen. Ox) and 2) caffeine load. Oxygen saturation in the anterior spinal vein (ASV) was calculated. We evaluated changes in oxygen saturation induced by physiological load. We also evaluated the time-course of oxygen saturation after caffeine intake. For the physiological load measurements, the average oxygen saturation for the 5 subjects was significantly lower in Hv (0.75) and significantly higher in Bh (0.84) when compared with control (0.80). There was no significant difference between Ox (0.81) and control. Oxygen saturation gradually decreased after caffeine intake. The average values of oxygen saturation were 0.79 (0 min), 0.76 (20 min), 0.74 (40 min), and 0.73 (60 min), respectively. We demonstrated a significant difference in oxygen saturation at 40 and 60 min after caffeine intake when compared with 0 min. In conclusion, we demonstrated the feasibility of using SWI for non-invasive measurement of oxygen saturation in the spinal vein. We showed changes in oxygen saturation under physiological as well as caffeine load and suggest that this method is a useful tool for the clinical evaluation of spinal cord oxygenation. (C) 2010 Elsevier Inc. All rights reserved.
  • S. Takao, S. Tadano, H. Taguchi, H. Shirato IFMBE Proceedings 31 IFMBE 1483 -1486 2010年10月22日 [査読無し][通常論文]
     
    This study proposes a computational simulation method to calculate therapeutic outcomes in radiotherapy for head and neck carcinoma. As a tumor shrinks due to radiation exposure, it was possible to express the radiotherapeutic effects in terms of tumor volume changes and geometric distortion. The shrinking was assumed to conform to the deformation of solid body. The relationships between radiation energy and tumor deformation were estimated from solid mechanics equations. The simulation model was applied to six clinical cases of lymph node metastasis in patients with head and neck carcinoma. Three-dimensional solid models of tumors were constructed based on computed tomography (CT) images taken before the start of treatment. Follow up CT images were also taken weekly during the treatment period, to evaluate the changes in tumor volumes. The values of parameters prescribing tumor radiosensitivity or growth rates of tumor cells were identified so that the calculated results fit the clinical results. The simulated results represented the tumor decreases well in all cases. Average differences between measured and calculated tumor volume for all the cases were less than 10%. In conclusions, simulation results show that the simulation model can be applied to a variety of clinical cases by determining the tumor parameters appropriately. © 2010 International Federation for Medical and Biological Engineering.
  • Tamotsu Kamishima, Yuichiro Fujieda, Tatsuya Atsumi, Rie Mimura, Takao Koike, Satoshi Terae, Hiroki Shirato AMERICAN JOURNAL OF ROENTGENOLOGY 195 (4) W287 -W292 2010年10月 [査読無し][通常論文]
     
    OBJECTIVE. The purpose of this article is to examine the feasibility of whole-body joint MRI for detecting systemic joint synovitis and for analyzing the relationship between the hands and systemic joint involvement in patients with unclassified arthritis who later develop early rheumatoid arthritis (RA). MATERIALS AND METHODS. The study included 17 patients (five men and 12 women; median age, 65 years [range, 38-77 years]; median symptom duration, 3 months [range, 1-6 months]). MRI of the systemic joints was performed for patients with unclassified arthritis without radiographic evidence of RA and who were diagnosed as having RA according to 1987 revised classification criteria within 2 years. RESULTS. The chosen 4-point scale for image quality was moderate to excellent. MRI findings of systemic joints were in accordance with joint swelling and tenderness (chi-square test, p < 0.0001). Sixty percent (45/75) of hand joints and 67% (12/18) of systemic joints other than hands showed MR synovitis without swelling. With regard to the correlation of MRI findings between hands and joints other than hands, there was a statistically significant positive correlation in the joint count (r = 0.5514 and p = 0.0218) and semiquantitative value of hand synovitis (r = 0.5382 and p = 0.0258). CONCLUSION. Whole-body joint MRI in early RA is feasible in terms of image quality and agreement with the results of clinical examination. MRI may be more sensitive for depicting synovitis-positive joints than clinical examination. Estimation of the systemic burden of synovitis detected by MRI may be possible via MRI of the hands.
  • Michalis Aristophanous, Joerg Rottmann, Sang-June Park, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco PHYSICS IN MEDICINE AND BIOLOGY 55 (15) 4321 -4333 2010年08月 [査読無し][通常論文]
     
    The purpose of this study is to investigate the effect that image-guided adaptation of the gating window during treatment could have on the residual tumor motion, by simulating different gated radiotherapy techniques. There are three separate components of this simulation: (1) the 'Hokkaido Data', which are previously measured 3D data of lung tumor motion tracks and the corresponding 1D respiratory signals obtained during the entire ungated radiotherapy treatments of eight patients, (2) the respiratory gating protocol at our institution and the imaging performed under that protocol and (3) the actual simulation in which the Hokkaido Data are used to select tumor position information that could have been collected based on the imaging performed under our gating protocol. We simulated treatments with a fixed gating window and a gating window that is updated during treatment. The patient data were divided into different fractions, each with continuous acquisitions longer than 2 min. In accordance to the imaging performed under our gating protocol, we assume that we have tumor position information for the first 15 s of treatment, obtained from kV fluoroscopy, and for the rest of the fractions the tumor position is only available during the beam-on time from MV imaging. The gating window was set according to the information obtained from the first 15 s such that the residual motion was less than 3 mm. For the fixed gating window technique the gate remained the same for the entire treatment, while for the adaptive technique the range of the tumor motion during beam-on time was measured and used to adapt the gating window to keep the residual motion below 3 mm. The algorithm used to adapt the gating window is described. The residual tumor motion inside the gating window was reduced on average by 24% for the patients with regular breathing patterns and the difference was statistically significant (p-value = 0.01). The magnitude of the residual tumor motion depended on the regularity of the breathing pattern suggesting that image-guided adaptive gating should be combined with breath coaching. The adaptive gating window technique was able to track the exhale position of the breathing cycle quite successfully. Out of a total of 53 fractions the duty cycle was greater than 20% for 42 fractions for the fixed gating window technique and for 39 fractions for the adaptive gating window technique. The results of this study suggest that real-time updating of the gating window can result in reliably low residual tumor motion and therefore can facilitate safe margin reduction.
  • Gerben R. Borst, Masayori Ishikawa, Jasper Nijkamp, Michael Hauptmann, Hirk Shirato, Gerard Bengua, Rikiya Onimaru, A. de Josien Bois, Joos V. Lebesque, Jan-Jakob Sonke INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 77 (5) 1596 -1603 2010年08月 [査読無し][通常論文]
     
    Purpose: To evaluate the linear quadratic (LQ) model for hypofractionated radiotherapy within the context of predicting radiation pneumonitis (RP) and to investigate the effect if a linear (L) model in the high region (LQL model) is used. Methods and Materials: The radiation doses used for 128 patients treated with hypofractionated radiotherapy were converted to the equivalent doses given in fractions of 2 Gy for a range of alpha/beta ratios (1 Gy to infinity) according to the LQ(L) model. For the LQL model, different cut-off values between the LQ model and the linear component were used. The Lyman model parameters were fitted to the events of RP grade 2 or higher to derive the normal tissue complication probability (NTCP). The lung dose was calculated as the mean lung dose and the percentage of lung volume (V) receiving doses higher than a threshold dose of xGy (V(x)). Results: The best NTCP fit was found if the mean lung dose, or V(x), was calculated with an alpha/beta ratio of 3 Gy. The NTCP fit of other alpha/beta ratios and the LQL model were worse but within the 95% confidence interval of the NTCP fit of the LQ model with an alpha/beta ratio of 3 Gy. The V(50) NTCP fit was better than the NTCP fit of lower threshold doses. Conclusions: For high fraction doses, the LQ model with an alpha/beta ratio of 3 Gy was the best method for converting the physical lung dose to predict RP. (C) 2010 Elsevier Inc.
  • Tetsuya Inoue, Norio Katoh, Hidefumi Aoyama, Rikiya Onimaru, Hiroshi Taguchi, Shunsuke Onodera, Satoshi Yamaguchi, Hiroki Shirato JAPANESE JOURNAL OF CLINICAL ONCOLOGY 40 (8) 788 -794 2010年08月 [査読無し][通常論文]
     
    Several recent studies have shown that oligometastatic disease has curative potential, although it was previously considered to signal a patient's last stage of life. Stereotactic body radiotherapy has been available for extra-cranial metastases in addition to stereotactic cranial radiotherapy for brain metastases. The aim of the present study was to retrospectively evaluate the clinical outcomes of stereotactic radiotherapy for patients with oligometastatic lesions. Between 1999 and 2008, 41 patients with five or fewer detectable metastases were treated with stereotactic radiotherapy at our institution. The treated oligometastatic lesions were in the brain, lung and adrenal glands. With a median follow-up period of 20 months, the 3-year overall survival, progression-free survival, local control and distant control rates were 39%, 20%, 80% and 35%, respectively, and the respective 5-year rates were 28%, 20%, 80% and 35%. The median survival time was 24 months. According to interval to recurrence, the 3- and 5-year overall survival rates were 19% and 10%, respectively, for patients with < 12 months (n = 18), compared with 53% and 40% for those with >= 12 months (n = 23) (P = 0.006). Precise stereotactic radiotherapy was effective in controlling oligometastatic lesions for patients with a median survival time of 24 months. Interval to recurrence may impact the overall survival rate and should be included in the stratification criteria in a prospective randomized trial to investigate the benefits of stereotactic radiotherapy for patients with oligometastases.
  • Gerben R. Borst, Masayori Ishikawa, Jasper Nijkamp, Michael Hauptmann, Hirk Shirato, Gerard Bengua, Rikiya Onimaru, A. de Josien Bois, Joos V. Lebesque, Jan-Jakob Sonke INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 77 (5) 1596 -1603 2010年08月 [査読無し][通常論文]
     
    Purpose: To evaluate the linear quadratic (LQ) model for hypofractionated radiotherapy within the context of predicting radiation pneumonitis (RP) and to investigate the effect if a linear (L) model in the high region (LQL model) is used. Methods and Materials: The radiation doses used for 128 patients treated with hypofractionated radiotherapy were converted to the equivalent doses given in fractions of 2 Gy for a range of alpha/beta ratios (1 Gy to infinity) according to the LQ(L) model. For the LQL model, different cut-off values between the LQ model and the linear component were used. The Lyman model parameters were fitted to the events of RP grade 2 or higher to derive the normal tissue complication probability (NTCP). The lung dose was calculated as the mean lung dose and the percentage of lung volume (V) receiving doses higher than a threshold dose of xGy (V(x)). Results: The best NTCP fit was found if the mean lung dose, or V(x), was calculated with an alpha/beta ratio of 3 Gy. The NTCP fit of other alpha/beta ratios and the LQL model were worse but within the 95% confidence interval of the NTCP fit of the LQ model with an alpha/beta ratio of 3 Gy. The V(50) NTCP fit was better than the NTCP fit of lower threshold doses. Conclusions: For high fraction doses, the LQ model with an alpha/beta ratio of 3 Gy was the best method for converting the physical lung dose to predict RP. (C) 2010 Elsevier Inc.
  • Hiroki Shirato, Yoshio Hishikawa Japanese Journal of Clinical Radiology 55 841 -842 2010年07月01日 [査読無し][通常論文]
  • Ardene Harris, Tamotsu Kamishima, Hong Yi Hao, Fumi Kato, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato EUROPEAN JOURNAL OF RADIOLOGY 75 (1) E97 -E101 2010年07月 [査読無し][通常論文]
     
    Objective: The present research was conducted to establish the normal splenic volume in adults using a novel and fast technique. The relationship between splenic volume and age, gender, and anthropometric parameters was also examined. Materials and methods: The splenic volume was measured in 230 consecutive patients who underwent computed tomography (CT) scans for various indications. Patients with conditions that have known effect on the spleen size were not included in this study. A new technique using volumetric software to automatically contour the spleen in each CT slice and quickly calculate splenic volume was employed. Inter- and intra-observer variability were also examined. Results: The average splenic volume of all the subjects was 127.4 +/- 62.9 cm(3), ranging from 22 to 417 cm(3). The splenic volume (S) correlated with age (A) (r = -0.33, p < 0.0001), body weight (W) (r = 0.35, p < 0.0001), body mass index (r = 0.24, p < 0.0001) and body surface area (BSA) (r = 0.31, p < 0.0001). The age-adjusted splenic volume index correlated with gender (p = 0.0089). The formulae S = W[6.47A((-0,31))] and S = BSA[278A((-0,36))] were derived and can be used to estimate the splenic volume. Inter- and intra-observer variability were 6.4 +/- 9.8% and 2.8 +/- 3.5% respectively. Conclusion: Of the anthropometric parameters, the splenic volume was most closely linked to body weight. The automatically contouring software as well as formulae can be used to obtain the volume of the spleen in regular practice. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
  • Takeshi Nishioka, Masaharu Fujino, Akihiro Homma, Tetsuro Yamashita, Akira Sato, Keiichi Ohmori, Kenichi Obinata, Hiroki Shirato, Kenichi Notani, Masamichi Nishio YONSEI MEDICAL JOURNAL 51 (4) 557 -561 2010年07月 [査読無し][通常論文]
     
    Purpose: Deciding on treatment carcinoma of the tongue when the tumor has a thickness of 1.5 cm or more is difficult. Surgery often requires wide resection and re-construction, leading to considerable functional impairment. A cesium implant is an attractive option, but according to the Manchester System, a two plane implant is needed. Materials and Methods: According to the textbook, a tumor is sandwiched between the needles, which are implanted at the edge of the tumor. This may cause an unnecessarily high dose to the outer surface of the tongue, which sometimes leads to a persistent ulcer. To avoid this complication, we invented a modified implantation method, and applied the method to five consecutive patients. Results: With a minimum follow-up of 2 years, all primary tumors in 5 consecutive patients have been controlled. No complications occurred in soft tissue of the tongue or in the mandible. Conclusion: Our modified Manchester System was feasible and effective for tumors that has a thickness of 1.5 cm or more.
  • Eric W. Pepin, Huanmei Wu, George A. Sandison, Mark Langer, Hiroki Shirato PHYSICS IN MEDICINE AND BIOLOGY 55 (12) 3325 -3337 2010年06月 [査読無し][通常論文]
     
    The treatment of lung cancer with radiation therapy is hindered by respiratory motion. Real-time adjustments to compensate for this motion are hampered by mechanical system latencies and imaging-rate restrictions. To better understand tumour motion behaviour for adaptive image-guided radiation therapy of lung cancer, the volume of a tumour's motion space was investigated. Motion data were collected by tracking an implanted fiducial using fluoroscopy at 30 Hz during treatment sessions. A total of 637 treatment fractions from 31 tumours were used in this study. For each fraction, data points collected from three consecutive breathing cycles were used to identify instantaneous tumour location. A convex hull was created over these data points, defining the tumour motion envelope. The study sought a correlation between the tumour location in the lung and the convex hull's volume and shape. It was found that tumours located in the upper apex had smaller motion envelopes (<50 mm(3)), whereas tumours located near the chest wall or diaphragm had larger envelopes (>70 mm(3)). Tumours attached to fixed anatomical structures had small motion spaces. Three general shapes described the tumour motion envelopes: 50% of motion envelopes enclosed largely 1D oscillation, 38% enclosed an ellipsoid path, 6% enclosed an arced path and 6% were of hybrid shape. This location-space correlation suggests it may be useful in developing a predictive model, but more work needs to be done to verify it.
  • Gerard Bengua, Masayori Ishikawa, Kenneth Sutherland, Kenji Horita, Rie Yamazaki, Katsuhisa Fujita, Rikiya Onimaru, Noriwo Katoh, Tetsuya Inoue, Shunsuke Onodera, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 77 (2) 630 -636 2010年06月 [査読無し][通常論文]
     
    Purpose: To evaluate the effectiveness of the stereotactic body frame (SBF), with or without a diaphragm press or a breathing cycle monitoring device (Abches), in controlling the range of lung tumor motion, by tracking the real-time position of fiducial markers. Methods and Materials: The trajectories of gold markers in the lung were tracked with the real-time tumor-tracking radiotherapy system. The SBF was used for patient immobilization and the diaphragm press and Abches were used to actively control breathing and for self-controlled respiration, respectively. Tracking was performed in five setups, with and without immobilization and respiration control. The results were evaluated using the effective range, which was defined as the range that includes 95% of all the recorded marker positions in each setup. Results: The SBF, with or without a diaphragm press or Abches, did not yield effective ranges of marker motion which were significantly different from setups that did not use these materials. The differences in the effective marker ranges in the upper lobes for all the patient setups were less than 1mm. Larger effective ranges were obtained for the markers in the middle or lower lobes. Conclusion: The effectiveness of controlling respiratory-induced organ motion by using the SBF+diaphragm press or SBF + Abches patient setups were highly dependent on the individual patient reaction to the use of these materials and the location of the markers. They may be considered for lung tumors in the lower lobes, but are not necessary for tumors in the upper lobes. (C) 2010 Elsevier Inc.
  • Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, Hiroki Shirato, Takeshi Nishioka BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 396 (3) 651 -655 2010年06月 [査読無し][通常論文]
     
    Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin beta 1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin beta 1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin beta 1-dependent phenotype, and integrin beta 1 might be a potentially effective therapeutic target in combination with radiotherapy. (C) 2010 Elsevier Inc. All rights reserved.
  • Gerard Bengua, Masayori Ishikawa, Kenneth Sutherland, Kenji Horita, Rie Yamazaki, Katsuhisa Fujita, Rikiya Onimaru, Noriwo Katoh, Tetsuya Inoue, Shunsuke Onodera, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 77 (2) 630 -636 2010年06月 [査読無し][通常論文]
     
    Purpose: To evaluate the effectiveness of the stereotactic body frame (SBF), with or without a diaphragm press or a breathing cycle monitoring device (Abches), in controlling the range of lung tumor motion, by tracking the real-time position of fiducial markers. Methods and Materials: The trajectories of gold markers in the lung were tracked with the real-time tumor-tracking radiotherapy system. The SBF was used for patient immobilization and the diaphragm press and Abches were used to actively control breathing and for self-controlled respiration, respectively. Tracking was performed in five setups, with and without immobilization and respiration control. The results were evaluated using the effective range, which was defined as the range that includes 95% of all the recorded marker positions in each setup. Results: The SBF, with or without a diaphragm press or Abches, did not yield effective ranges of marker motion which were significantly different from setups that did not use these materials. The differences in the effective marker ranges in the upper lobes for all the patient setups were less than 1mm. Larger effective ranges were obtained for the markers in the middle or lower lobes. Conclusion: The effectiveness of controlling respiratory-induced organ motion by using the SBF+diaphragm press or SBF + Abches patient setups were highly dependent on the individual patient reaction to the use of these materials and the location of the markers. They may be considered for lung tumors in the lower lobes, but are not necessary for tumors in the upper lobes. (C) 2010 Elsevier Inc.
  • Noriko Oyama, Daisuke Goto, Tsukasa Sasaki, Hiroyuki Tsutsui, Nagara Tamaki, Satoshi Terae, Hiroki Shirato JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY 4 (3) 218 -220 2010年05月 [査読無し][通常論文]
     
    Electrocardiographic-gated 64-slice multidetector computed tomography (MDCT) was performed on a 30-year-old man who presented with a complete endocardial cushion defect (ECD) and severe pulmonary hypertension diagnosed when he was 3 years old. Multiplanar reconstruction image showed the common atrium without an atrial septum, a large ventricular septum defect, and a small right ventricle due to a complete atrioventricular canal defect. Three-dimensional CT volume-rending imaging showed a patent ductus arteriosus, dilation of the ascending aorta, and an anomalous-origin right coronary artery. This patient also had heterotaxy syndrome with polysplenia and azygos continuation. MDCT proved to be a good noninvasive imaging method for the evaluation of ECD associated with cardiac as well as extracardiac abnormalities. (C) 2010 Society of Cardiovascular Computed Tomography. All rights reserved.
  • Rie Mimura, Tamotsu Kamishima, Kanako C. Kubota, Fumihito Nakano, Ichiro Yabe, Hidenao Sasaki, Satoru Maruyama, Nobuo Shinohara, Ardene A. Harris, Hironori Haga, Hiroki Shirato, Satoshi Terae JAPANESE JOURNAL OF RADIOLOGY 28 (4) 309 -313 2010年05月 [査読無し][通常論文]
     
    A 62-year-old man was referred to us after unsuccessful treatment of bilateral weakness in his upper and lower extremities with paresthesia in both lower extremities. Computed tomography (CT) revealed soft tissue masses in the left kidney along the capsule and paraaortic region that were of relatively low attenuation with accompanying granular calcifications. Pathological diagnosis of the biopsy specimen was extramedullary plasmacytoma accompanied by extramedullary hematopoiesis and amyloid deposition. Although the CT findings correlated well with the pathological results, the case was extremely atypical for extramedullary plasmacytoma in respect to location and the accompaniment with extramedullary hematopoiesis.
  • Khin K Tha, Satoshi Terae, Ichiro Yabe, Tamaki Miyamoto, Hiroyuki Soma, Yuri Zaitsu, Noriyuki Fujima, Kohsuke Kudo, Hidenao Sasaki, Hiroki Shirato Radiology 255 (2) 563 -9 2010年05月 [査読無し][通常論文]
     
    PURPOSE: To determine whether diffusion-tensor (DT) imaging can demonstrate microstructural white matter abnormalities of multiple system atrophy (MSA) and to correlate these imaging findings with clinical signs and symptoms. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. DT imaging was performed in 16 patients with MSA with predominant cerebellar symptoms (MSA-C) (mean age, 60.0 years + or - 5.1 [standard deviation]; range, 51-69 years) and 16 age-matched healthy subjects. Fractional anisotropy (FA) and mean diffusivity (MD) were compared voxel-by-voxel between the two groups by using a two-sample t test. Overlap maps were created to illustrate areas with FA and MD alterations. Correlation between DT imaging indexes and Barthel index score, scale for assessment and rating of ataxia (SARA) score, severity of orthostatic hypotension, age of disease onset, and disease duration was tested by using Spearman rank or Pearson product-moment correlation analysis. T2-weighted and proton density-weighted images of the patients were visually assessed. RESULTS: Widespread areas of FA reduction and MD elevation were observed in supra- and infratentorial white matter structures in patients with MSA (P < .05, false discovery rate corrected). Significant correlation (P < .01) between DT imaging indexes and Barthel index score, SARA score, severity of orthostatic hypotension, and disease duration was observed for multiple areas with FA and/or MD alterations. T2-weighted and proton density-weighted images showed no significant abnormality in supratentorial white matter. CONCLUSION: DT imaging may help identify the microstructural white matter abnormalities of MSA-C. DT imaging may be useful for severity assessment of MSA-C.
  • T. Kamishima, N. Kitamura, M. Amemiya, K. Ishizaka, F. Kato, K. Yasuda, H. Shirato, S. Terae CLINICAL RADIOLOGY 65 (5) 387 -390 2010年05月 [査読無し][通常論文]
  • Tamotsu Kamishima, Akira Sagawa, Kazuhide Tanimura, Masato Shimizu, Megumi Matsuhashi, Masahide Shinohara, Hiromi Hagiwara, Mihoko Henmi, Akihiro Narita, Satoshi Terae, Hiroki Shirato SKELETAL RADIOLOGY 39 (5) 457 -465 2010年05月 [査読無し][通常論文]
     
    To determine the timing for follow-up study of power Doppler ultrasonography (PDUS) by evaluating the response of finger joint synovitis in patients with rheumatoid arthritis (RA) to treatment including infliximab, an antitumor necrosis factor alpha agent. Bilateral second/third metacarpo-phalangeal (MCP) joints and second proximal inter-phalangeal (PIP) joints (total of six joints) in 21 patients (18 women and three men; median age 53 years) with chronic active RA were assessed by PDUS before and after 2 weeks, 6 weeks, 14 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks of infliximab infusion. Pulse Doppler settings were standardized for each patient and optimized for the detection of synovial blood flow by adjustment of color gain, pulse repetition, and flow optimization. Power Doppler signal was graded for each joint [joint grade for power Doppler (JGPD) signals], and the sum of the grades of six joints was defined as the PDUS index [joint index for power Doppler signals (JIPD)] at each visit. PDUS and clinical parameters [28-joint disease activity score (DAS28), health assessment questionnaire, and C-reactive protein (CRP) level] were independently assessed and compared with baseline values. The American College of Rheumatology (ACR) core set responders and non-responders at week 54 were compared for clinical parameters and PDUS index at each visit. Fourteen patients completed the planned treatment for 1 year, while six patients dropped out for various reasons and one died suddenly. PDUS was performed a total of 146 times on 467 joints. DAS28 was assessed 127 times. Both DAS28 and JIPD had decreased at the follow-up. Comparative analysis between DAS28 and PDUS was available 125 times. The transverse correlation between the PDUS index and DAS28 was not significant throughout the follow-up period. When responders and non-responders were discriminated at week 54, a logistic regression model for the binary endpoint of responder vs non-responder, with PDUS index as explanatory variable at time point 0, and follow-up revealed statistical significance from week 38 and on. PDUS reflected infliximab's effect on pannus vascular signals; this effect was observed as early as 2 weeks after treatment had begun. Also, the responders to treatment at 54 weeks tended to have fewer JIPD than non-responders in the follow-up period. PDUS may be performed at week 38 or later to foresee the response to the treatment at week 54.
  • Tsuguhide Takeshima, Kenji Chamoto, Daiko Wakita, Takayuki Ohkuri, Yuji Togashi, Hiroki Shirato, Hidemitsu Kitamura, Takashi Nishimura CANCER RESEARCH 70 (7) 2697 -2706 2010年04月 [査読無し][通常論文]
     
    Radiation therapy is one of the primary treatment modalities for cancer along with chemotherapy and surgical therapy. The main mechanism of the tumor reduction after irradiation has been considered to be damage to the tumor DNA. However, we found that tumor-specific CTL, which were induced in the draining lymph nodes (DLN) and tumor tissue of tumor-bearing mice, play a crucial role in the inhibition of tumor growth by radiation. Indeed, the therapeutic effect of irradiation was almost completely abolished in tumor-bearing mice by depleting CD8(+) T cells through anti-CD8 monoclonal antibody administration. In mice whose DLN were surgically ablated or genetically defective (Aly/Aly mice), the generation of tetramer(+) tumor-specific CTL at the tumor site was greatly reduced in parallel with the attenuation of the radiation-induced therapeutic effect against the tumor. This indicates that DLN are essential for the activation and accumulation of radiation-induced CTL, which are essential for inhibition of the tumor. A combined therapy of local radiation with Th1 cell therapy augmented the generation of tumor-specific CTL at the tumor site and induced a complete regression of the tumor, although radiation therapy alone did not exhibit such a pronounced therapeutic effect. Thus, we conclude that the combination treatment of local radiation therapy and Th1 cell therapy is a rational strategy to augment antitumor activity mediated by tumor-specific CTL. Cancer Res; 70(7); 2697-706. (C) 2010 AACR.
  • Noriyuki Fujima, Kohsuke Kudo, Satoshi Terae, Kazutoshi Hida, Kinya Ishizaka, Yuri Zaitsu, Takeshi Asano, Daisuke Yoshida, Khin Khin Tha, E. Mark Haacke, Makoto Sasaki, Hiroki Shirato RADIOLOGY 254 (3) 891 -899 2010年03月 [査読無し][通常論文]
     
    Purpose: To evaluate the efficacy of susceptibility-weighted (SW) magnetic resonance (MR) imaging for the assessment of the post-treatment change in oxygen saturation in the draining vein in patients with spinal arteriovenous malformation (AVM). Materials and Methods: The study protocol was approved by the institutional review board, and written informed consent was obtained from all subjects. SW imaging was performed in 11 patients with spinal AVM before and after surgical or endovascular treatment. Eleven healthy subjects were included as a control group. A four-grade response scale was used for the visual assessment of the anterior spinal vein (ASV). For quantitative analysis, the phase value of the ASV was measured and oxygen saturation was calculated. Nonparametric multigroup comparison for visual assessment and one-way analysis of variance for quantitative measurement of oxygen saturation were used as statistical tests for comparison among three groups (pretreatment patients, posttreatment patients, and control subjects). Results: Complete shunt occlusion in all patients was confirmed by using conventional angiography. For visual assessment, the average score of the pretreatment group was significantly less than that of the posttreatment and control groups. For quantitative analysis, the average oxygen saturation of the pretreatment group was significantly higher than that of the posttreatment and control groups, while no significant difference was observed between the posttreatment and control groups. Conclusion: After treatment, normalization of increased oxygen saturation was noninvasively observed by using SW imaging in patients with spinal AVM. SW imaging can be a useful tool for the assessment of treatment efficacy in patients with spinal AVM. (C)RSNA, 2010
  • citations
    J Obstet Gynaecol Res. 1 2010年 [査読無し][通常論文]
  • Yuri Zaitsu, Satoshi Terae, Kohsuke Kudo, Khin Khin Tha, Mineji Hayakawa, Noriyuki Fujima, Daisuke Yoshida, Akiko Tsukahara, Hiroki Shirato Journal of computer assisted tomography 34 (1) 107 -12 2010年01月 [査読無し][通常論文]
     
    Cerebral fat embolism (CFE) causes microinfarcts, vasogenic edema, and petechiae in the brain. Conventional magnetic resonance imaging has been reported to effectively visualize microinfarcts and vasogenic edema in CFE, but not petechiae. We report 3 cases of CFE in which susceptibility-weighted imaging distinctly demonstrated multiple minute hypointense foci in the brain, which were interpreted as petechiae, susceptibility-weighted imaging is a useful adjunct to conventional magnetic resonance imaging for the evaluation of CFE.
  • Evaluation of the need for simultaneous orthogonal gated setup imaging.
    J Appl Clin Med Phys. 3203 2010年 [査読無し][通常論文]
  • Kenneth Sutherland, Satoshi Miyajima, Hiroyuki Date, Hiroki Shirato, Masayori Ishikawa, Masao Murakami, Mitsuru Yamagiwa, Paul Bolton, Toshiki Tajima Radiological Physics and Technology 3 (1) 16 -22 2010年01月 [査読無し][通常論文]
     
    The results of Monte Carlo calculated dose distributions of proton treatment of ocular melanoma are presented. An efficient spot scanning method utilizing active energy modulation, which also minimizes the number of target spots was developed. We simulated various parameter values for the particle energy spread and the pencil beam diameter in order to determine values suitable for medical treatment. We found that a 2.5-mm-diameter proton beam with a 5% Gaussian energy spread was suitable for treatment of ocular melanoma while preserving vision for the typical case that we simulated. The energy spectra and the required proton current were also calculated and are reported. The results are intended to serve as a guideline for a new class of low-cost, compact accelerators. © 2009 Japanese Society of Radiological Technology and Japan Society of Medical Physics.
  • NAKAYAMA Jun, MIYASAKA Kazuo, OMATSU Tokuhiko, ONODERA Yuuya, TERAE Satoshi, MATSUNO Yoshihiro, CHO Yasushi, HIDA Yasuhiro, KAGA Kichizo, SHIRATO Hiroki J Comput Assist Tomogr 34 (1) 1 -8 2010年 [査読無し][通常論文]
  • Hee Chul Park, Shinichi Shimizu, Akio Yonesaka, Kazuhiko Tsuchiya, Yasuhiko Ebina, Hiroshi Taguchi, Norio Katoh, Rumiko Kinoshita, Masayori Ishikawa, Noriaki Sakuragi, Hiroki Shirato YONSEI MEDICAL JOURNAL 51 (1) 93 -99 2010年01月 [査読無し][通常論文]
     
    Purpose: The purpose of this study is to evaluate the clinical results of treatment with a high dose of 3-dimensional conformal boost (3DCB) using a real-time tracking radiation therapy (RTRT) system in cervical cancer patients. Materials and Methods: Between January 2001 and December 2004, 10 patients with cervical cancer were treated with a high dose 3DCB using RTRT system. Nine patients received whole pelvis radiation therapy (RT) with a median dose of 50 Gy (range, 40-50 Gy) before the 3DCB. The median dose of the 3DCB was 30 Gy (range, 25-30 Gy). Eight patients received the 3DCB twice a week with a daily fraction of 5 Gy. The determined endpoints were tumor response, overall survival, local failure free survival, and distant metastasis free survival. The duration of survival was calculated from the time of the start of radiotherapy. Results: All patients were alive at the time of analysis and the median follow-up was 17.6 months (range, 4.9-27.3 months). Complete response was achieved in nine patients and one patient had a partial response. The 1- and 2-year local failure free survival was 78.8% and 54%, respectively. The 1- and 2-year distant metastasis free survival was 90% and 72%, respectively. Late toxicity of a grade 2 rectal hemorrhage was seen in one patient. A subcutaneous abscess was encountered in one patient. Conclusion: the use of the high dose 3DCB in the treatment of cervical cancer is safe and feasible where intracavitary brachytherapy (ICBT) is unable to be performed. The escalation of the 3DCB dose is currently under evaluation.
  • Kohsuke Kudo, Makoto Sasaki, Kei Yamada, Suketaka Momoshima, Hidetsuna Utsunomiya, Hiroki Shirato, Kuniaki Ogasawara RADIOLOGY 254 (1) 200 -209 2010年01月 [査読無し][通常論文]
     
    Purpose: To examine the variability in the qualitative and quantitative results of computed tomographic (CT) perfusion imaging generated from identical source data of stroke patients by using commercially available software programs provided by various CT manufacturers. Materials and Methods: Institutional review board approval and informed consent were obtained. CT perfusion imaging data of 10 stroke patients were postprocessed by using five commercial software packages, each of which had a different algorithm: singular-value decomposition (SVD), maximum slope (MS), inverse filter (IF), box modulation transfer function (bMTF), and by using custom-made original software with standard (sSVD) and block-circulant (bSVD) SVD methods. Areas showing abnormalities in cerebral blood flow (CBF), mean transit time (MTT), and cerebral blood volume (CBV) were compared with each other and with the final infarct areas. Differences among the ratios of quantitative values in the final infarct areas and those in the unaffected side were also examined. Results: The areas with CBF or MTT abnormalities and the ratios of these values significantly varied among software, while those of CBV were stable. The areas with CBF or MTT abnormalities analyzed by using SVD or bMTF corresponded to those obtained with delay-sensitive sSVD, but overestimated the final infarct area. The values obtained from software by using MS or IF corresponded well with those obtained from the delay-insensitive bSVD and the final infarct area. Given the similarities between CBF and MTT, all software were separated in two groups (ie, sSVD and bSVD). The ratios of CBF or MTTs correlated well within both groups, but not across them. Conclusion: CT perfusion imaging maps were significantly different among commercial software even when using identical source data, presumably because of differences in tracer-delay sensitivity. (C) RSNA, 2010
  • Kinya Ishizaka, Kohsuke Kudo, Noriyuki Fujima, Yuri Zaitsu, Rie Yazu, Khin Khin Tha, Satoshi Terae, E. Mark Haacke, Makoto Sasaki, Hiroki Shirato JOURNAL OF MAGNETIC RESONANCE IMAGING 31 (1) 32 -38 2010年01月 [査読無し][通常論文]
     
    Purpose: To evaluate the visualization of the spinal veins using susceptibility-weighted imaging (SWI). Materials and Methods: A 1.5-T magnet equipped with a spine matrix coil was used. Axial SWI scans of 20 healthy volunteers were obtained with a three-dimensional fast low-angle shot (3D-FLASH) sequence. Maximum intensity projection (MIP) of the phase images were reconstructed and five MIP images (at the levels of T11, T11/12, T12, T12/L1, and L1) were selected for the evaluation. The anterior median vein (AMV), posterior median vein (PMV), anterior radiculomedullary vein (ARV), posterior radiculomedullary vein (PRV), and sulcal vein (SV) were evaluated using a 4-grade scale (0, none; 1, weak; 2, moderate: and 3, prominent). Results: The AMV was detected in all the subjects (100%). The detection rates of the other veins were lower: PMV, 65%: right ARV. 45%: left ARV, 15%; right PRV. 10%; left PRV, 30%; and SV, 0%. The average scores for AMV, PMV, right ARV. left ARV, right PRV, left PRV, and SV were 0.98, 0.24, 0.20, 0.08, 0.08, 0.14, and 0, respectively. Conclusion: SWI of the spine is feasible. The extrinsic spinal veins can be visualized by SWI without using contrast materials.
  • Kohsuke Kudo, Makoto Sasaki, Kei Yamada, Suketaka Momoshima, Hidetsuna Utsunomiya, Hiroki Shirato, Kuniaki Ogasawara RADIOLOGY 254 (1) 200 -209 2010年01月 [査読無し][通常論文]
     
    Purpose: To examine the variability in the qualitative and quantitative results of computed tomographic (CT) perfusion imaging generated from identical source data of stroke patients by using commercially available software programs provided by various CT manufacturers. Materials and Methods: Institutional review board approval and informed consent were obtained. CT perfusion imaging data of 10 stroke patients were postprocessed by using five commercial software packages, each of which had a different algorithm: singular-value decomposition (SVD), maximum slope (MS), inverse filter (IF), box modulation transfer function (bMTF), and by using custom-made original software with standard (sSVD) and block-circulant (bSVD) SVD methods. Areas showing abnormalities in cerebral blood flow (CBF), mean transit time (MTT), and cerebral blood volume (CBV) were compared with each other and with the final infarct areas. Differences among the ratios of quantitative values in the final infarct areas and those in the unaffected side were also examined. Results: The areas with CBF or MTT abnormalities and the ratios of these values significantly varied among software, while those of CBV were stable. The areas with CBF or MTT abnormalities analyzed by using SVD or bMTF corresponded to those obtained with delay-sensitive sSVD, but overestimated the final infarct area. The values obtained from software by using MS or IF corresponded well with those obtained from the delay-insensitive bSVD and the final infarct area. Given the similarities between CBF and MTT, all software were separated in two groups (ie, sSVD and bSVD). The ratios of CBF or MTTs correlated well within both groups, but not across them. Conclusion: CT perfusion imaging maps were significantly different among commercial software even when using identical source data, presumably because of differences in tracer-delay sensitivity. (C) RSNA, 2010
  • Kinya Ishizaka, Kohsuke Kudo, Noriyuki Fujima, Yuri Zaitsu, Rie Yazu, Khin Khin Tha, Satoshi Terae, E. Mark Haacke, Makoto Sasaki, Hiroki Shirato JOURNAL OF MAGNETIC RESONANCE IMAGING 31 (1) 32 -38 2010年01月 [査読無し][通常論文]
     
    Purpose: To evaluate the visualization of the spinal veins using susceptibility-weighted imaging (SWI). Materials and Methods: A 1.5-T magnet equipped with a spine matrix coil was used. Axial SWI scans of 20 healthy volunteers were obtained with a three-dimensional fast low-angle shot (3D-FLASH) sequence. Maximum intensity projection (MIP) of the phase images were reconstructed and five MIP images (at the levels of T11, T11/12, T12, T12/L1, and L1) were selected for the evaluation. The anterior median vein (AMV), posterior median vein (PMV), anterior radiculomedullary vein (ARV), posterior radiculomedullary vein (PRV), and sulcal vein (SV) were evaluated using a 4-grade scale (0, none; 1, weak; 2, moderate: and 3, prominent). Results: The AMV was detected in all the subjects (100%). The detection rates of the other veins were lower: PMV, 65%: right ARV. 45%: left ARV, 15%; right PRV. 10%; left PRV, 30%; and SV, 0%. The average scores for AMV, PMV, right ARV. left ARV, right PRV, left PRV, and SV were 0.98, 0.24, 0.20, 0.08, 0.08, 0.14, and 0, respectively. Conclusion: SWI of the spine is feasible. The extrinsic spinal veins can be visualized by SWI without using contrast materials.
  • Seishin Takao, S. Tadano, H. Taguchi, H. Shirato IFMBE Proceedings 23 2083 -2087 2009年12月01日 [査読無し][通常論文]
     
    In Radiotherapy, shapes of tumors are important information to determine irradiation area and energy. In this study a simulation method is proposed to calculate changes of tumor geometry during radiotherapy. Relationships between tumor geometry and the amount of radiation energy were estimated from fundamental equations in solid mechanics as a mechanical analogy. Parameters between the radiotherapeutic effect and the geometric factor were defined as reduction resistance and reduction ratio. The values of these parameters were initially determined based on a widely-used radiobiological model (Linear-Quadratic model) and then revised by comparing with the change of actual tumor shape. To simulate uneven tumor shrinkage, the values of reduction resistance were varied depending on the tumor heterogeneity. Finite element models of tumors were constructed from CT images taken before the start of radiotherapy. For precise assessment of therapeutic effect, it would be useful to examine tumor morphological features. Three-dimensional (3D) tumor shape was represented in twodimensional (2D) map like a global map. Distances from origin (center of gravity of the tumor) to surface were visually indicated by colors in this map. Tumor volumes were indicated by sizes of the maps. Tumors in head and neck were analyzed in this study. Simulation results of tumor geometries were compared with actual tumor geometries and found to have similar tendencies. The 2D color maps enabled to evaluate the 3D morphological features of the tumors. Therefore this study provides the methodology to evaluate changes of 3D tumor geometry during radiotherapy. © 2009 International Federation of Medical and Biological Engineering.
  • Kentaro Nishioka, Daisuke Abo, Hidefumi Aoyama, Yasushi Furuta, Rikiya Onimaru, Shunsuke Onodera, Yutaka Sawamura, Masayori Ishikawa, Satoshi Fukuda, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 (5) 1415 -1419 2009年12月 [査読無し][通常論文]
     
    Purpose: Although the effectiveness of stereotactic radiosurgery for nonacoustic schwannomas is currently being assessed, there have been few studies on the efficacy of stereotactic radiotherapy (SRT) for these tumors. We investigated the long-term outcome of SRT for nonacoustic intracranial nerve schwannomas. Methods and Materials: Seventeen patients were treated between July 1994 and December 2006. Of these patients, 7 had schwannomas located in the jugular foramen, 5 in the trigeminal nerve, 4 in the facial nerve, and I in the oculomotor nerve. Radiotherapy was used as an initial treatment without surgery in 10 patients (59 %) and after initial subtotal resection in the remaining patients. The tumor volume ranged from 0.3 to 31.3 mL (mean, 8.2 mL). The treatment dose was 40 to 54 Gy in 20 to 26 fractions. The median follow-up period was 59.5 months (range, 7.4-122.6 months). Local control was defined as stable or decreased tumor size on follow-up magnetic resonance imaging. Results: Tumor size was decreased in 3 patients, stable in 13, and increased in I after SRT. Regarding neurologic symptoms, 8 patients (47 %) had improvement and 9 patients were unchanged. One patient had an increase in tumor size and received microsurgical resection at 32 months after irradiation. No patient had worsening of pre-existing neurologic symptoms or development of new cranial nerve deficits at the last follow-up. Conclusions: SRT is an effective alternative to surgical resection for patients with nonacoustic intracranial nerve schwannomas with respect to not only long-term local tumor control but also neuro-functional preservation. (C) 2009 Elsevier Inc.
  • Tamotsu Kamishima, Noriko Nishioka, Hiroshi Kataoka, Jun Fukae, Tatsuya Atsumi, Ardene A. Harris, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato European Journal of Radiology Extra 72 (2) e87 -e90 2009年11月 [査読無し][通常論文]
     
    In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare and there is no report on CT and MR imaging findings of predominant tubulointerstitial lupus nephritis. Herein, we describe the case of a 48-year-old woman with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis with an emphasis on CT and MR imaging findings. CT demonstrated multiple wedge-shaped areas or streaky zones of lesser enhancement that extend from the papilla to the renal cortex. MR images revealed relatively clear corticomedullary junction with slightly irregular cortex on T1-weighted images, and wed-shaped areas of decreased signal intensity corresponding CT findings increased signal intensity in the central parenchyma on T2-weighted image. The enhancement effect was weak and delayed in the central parenchyma on dynamic MR images after bolus administration of contrast. These imaging features seemed to reflect the tubulointerstitial dysfunction and infiltration in this case. © 2009 Elsevier Ireland Ltd. All rights reserved.
  • Tetsuya Inoue, Shinichi Shimizu, Rikiya Onimaru, Atsuya Takeda, Hiroshi Onishi, Yasushi Nagata, Tomoki Kimura, Katsuyuki Karasawa, Takuro Arimoto, Masato Hareyama, Elki Kikuchi, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 (3) 683 -687 2009年11月 [査読無し][通常論文]
     
    Purpose: Image-guided biopsy occasionally fails to diagnose small lung lesions, which are highly suggestive of primary lung cancer. The aim of the present study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) for small lung lesions that were clinically diagnosed as primary lung cancer without pathologic confirmation. Methods and Materials: A total of 115 patients were treated with SBRT in 12 institutions. Tumor size ranged from 5 to 45 mm in diameter, with a median of 20 mm. Results: The 3-year and 5-year overall survival rates for patients with a tumor size <= 20 mm in diameter (it = 58) were both 89.8%, compared with 60.7% and 53.1% for patients with tumors >20 mm (n = 57) (p < 0.0005), respectively. Local progression occurred in 2 patients (3.4%) with a tumor size <= 20 mm and in 3 patients (5.3%) with tumors >20 mm. Among the patients with a tumor size <= 20 mm, Grade 2 pulmonary complications were observed in 2 (3.4%), but no Grade 3 to 5 toxicity was observed. In patients with a tumor size >20 mm, Grades 2, 3, and 5 toxicity were observed in 5 patients (8.8%), 3 patients (5.3%), and 1 patient (1.8%), respectively. Conclusion: In patients with a tumor <= 20 mm in diameter, SBRT was reasonably safe in this retrospective study. The clinical implications of the high local control rate depend on the accuracy of clinical/radiologic diagnosis for small lung lesions and are to be carefully evaluated in a prospective study. (C) 2009 Elsevier Inc.
  • Tadashi Shimizu, Yusuke Sakuhara, Daisuke Abo, Yu Hasegawa, Yoshihisa Kodama, Hideho Endo, Hiroki Shirato, Kazuo Miyasaka JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 16 (6) 816 -823 2009年11月 [査読無し][通常論文]
     
    To assess the mid-term results of MR-guided percutaneous cryoablation for small hepatocellular carcinoma (HCC). Using an argon-based cryoablation system, MR-guided percutaneous cryoablation was performed. The number of tumors was three or fewer. The maximum diameter of tumors was less than 5 cm when solitary and no more than 3 cm when multiple. The Kaplan-Meier method was used to calculate the survival of patients. Among 15 patients, 16 tumors were treated. The maximum tumor diameter ranged from 1.2 to 4.5 cm, with a mean of 2.5 +/- A 0.8 cm (mean +/- A standard deviation). The volume of iceballs measured on MR-images was greater than that of the tumors in all cases. The follow-up period ranged from 10 to 52 months, with a mean of 36.6 +/- A 12.1 months. One-year and 3-year overall survival were 93.8 and 79.3%, respectively. The complete ablation rate was 80.8% at 3 years. Immediate complications were pneumothorax, hemothorax, and pleural effusion. An ablation zone was not absorbed and content exuded from a scar of the probe tract 4 months after cryoablation in one patient. MR-guided percutaneous cryoablation appears to be a feasible modality and potentially good option for the treatment of small HCC.
  • Tetsuya Inoue, Shinichi Shimizu, Rikiya Onimaru, Atsuya Takeda, Hiroshi Onishi, Yasushi Nagata, Tomoki Kimura, Katsuyuki Karasawa, Takuro Arimoto, Masato Hareyama, Elki Kikuchi, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 (3) 683 -687 2009年11月 [査読無し][通常論文]
     
    Purpose: Image-guided biopsy occasionally fails to diagnose small lung lesions, which are highly suggestive of primary lung cancer. The aim of the present study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) for small lung lesions that were clinically diagnosed as primary lung cancer without pathologic confirmation. Methods and Materials: A total of 115 patients were treated with SBRT in 12 institutions. Tumor size ranged from 5 to 45 mm in diameter, with a median of 20 mm. Results: The 3-year and 5-year overall survival rates for patients with a tumor size <= 20 mm in diameter (it = 58) were both 89.8%, compared with 60.7% and 53.1% for patients with tumors >20 mm (n = 57) (p < 0.0005), respectively. Local progression occurred in 2 patients (3.4%) with a tumor size <= 20 mm and in 3 patients (5.3%) with tumors >20 mm. Among the patients with a tumor size <= 20 mm, Grade 2 pulmonary complications were observed in 2 (3.4%), but no Grade 3 to 5 toxicity was observed. In patients with a tumor size >20 mm, Grades 2, 3, and 5 toxicity were observed in 5 patients (8.8%), 3 patients (5.3%), and 1 patient (1.8%), respectively. Conclusion: In patients with a tumor <= 20 mm in diameter, SBRT was reasonably safe in this retrospective study. The clinical implications of the high local control rate depend on the accuracy of clinical/radiologic diagnosis for small lung lesions and are to be carefully evaluated in a prospective study. (C) 2009 Elsevier Inc.
  • Tadashi Shimizu, Yusuke Sakuhara, Daisuke Abo, Yu Hasegawa, Yoshihisa Kodama, Hideho Endo, Hiroki Shirato, Kazuo Miyasaka JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 16 (6) 816 -823 2009年11月 [査読無し][通常論文]
     
    To assess the mid-term results of MR-guided percutaneous cryoablation for small hepatocellular carcinoma (HCC). Using an argon-based cryoablation system, MR-guided percutaneous cryoablation was performed. The number of tumors was three or fewer. The maximum diameter of tumors was less than 5 cm when solitary and no more than 3 cm when multiple. The Kaplan-Meier method was used to calculate the survival of patients. Among 15 patients, 16 tumors were treated. The maximum tumor diameter ranged from 1.2 to 4.5 cm, with a mean of 2.5 +/- A 0.8 cm (mean +/- A standard deviation). The volume of iceballs measured on MR-images was greater than that of the tumors in all cases. The follow-up period ranged from 10 to 52 months, with a mean of 36.6 +/- A 12.1 months. One-year and 3-year overall survival were 93.8 and 79.3%, respectively. The complete ablation rate was 80.8% at 3 years. Immediate complications were pneumothorax, hemothorax, and pleural effusion. An ablation zone was not absorbed and content exuded from a scar of the probe tract 4 months after cryoablation in one patient. MR-guided percutaneous cryoablation appears to be a feasible modality and potentially good option for the treatment of small HCC.
  • Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Shigenari Taki, Takeshi Asano, Daisuke Yoshida, Rikiya Onimaru, Takeshi Nishioka, Hiroki Shirato, Satoshi Fukuda CANCER 115 (20) 4705 -4714 2009年10月 [査読無し][通常論文]
     
    BACKGROUND: The current study aimed to evaluate the efficacy of superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with advanced cancer of the nasal cavity and paranasal sinuses. METHODS: Between October 1999 and December 2006, 47 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional external-beam radiotherapy (65-70 grays), RESULTS: There were 7 patients (14.9%) diagnosed with T3, 22 (46.8%) with T4a, and 18 (38.3%) with T4b disease. During the median follow-up period of 4.6 years, the 5-year local progression-free survival rate was 78.4% for all patients (n=47), 69.0% for patients with T4b disease (n=18), and 83.2% for patients with <T4b disease (n=29). The 5-year overall survival rate was 69.3% for all patients, 61.1% for patients with T4b disease, and 71.1% for patients with < T4b disease. RADPLAT was feasible in 45 patients (95.7%). No patient died as a result of treatment toxicity or had a cerebrovascular accident. Osteonecrosis (n=7), brain necrosis (n=2), and ocular/visual problems (n=16) were observed as late adverse reactions. CONCLUSIONS: Although a single institution experience, the results of the current study suggest that RADPLAT can cure the majority of patients with advanced cancer of the nasal cavity and paranasal sinuses, as well as preserve organs. Late adverse reactions should be monitored in future studies. Cancer 2009;115:4705-14. (C) 2009 American Cancer Society.
  • Yasushi Nagata, Masahiro Hiraoka, Takashi Mizowaki, Yuichiro Narita, Yukinori Matsuo, Yoshiki Norihisa, Hiroshi Onishi, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 (2) 343 -347 2009年10月 [査読無し][通常論文]
     
    Purpose: To recognize the current status of stereotactic body radiotherapy (SBRT) in Japan, using a nationwide survey conducted by the Japan 3-D Conformal External Beam Radiotherapy Group. Methods and Materials: The questionnaire was sent by mail to 117 institutions. Ninety-four institutions (80%) responded by the end of November 2005. Fifty-three institutions indicated that they have already started SBRT, and 38 institutions had been reimbursed by insurance. Results: A total of 1111 patients with histologically confirmed lung cancer were treated. Among these patients, 637 had TIN0M0 and 272 had T2N0M0 lung cancer. Metastatic lung cancer was found in 702 and histologically unconfirmed lung tumor in 291 patients. Primary liver cancer was found in 207 and metastatic liver cancer in 76 patients. The most frequent schedule used for primary lung cancer was 48Gy in 4 fractions at 22 institutions (52%), followed by 50Gy in 5 fractions at I I institutions (26%) and 60Gy in 8 fractions at 4 institutions (10%). The tendency was the same for metastatic lung cancer. The average number of personnel involved in SBRT was 1.8 radiation oncologists, including 1.1 certified radiation oncologists, 2.8 technologists, 0.7 nurses, and 0.6 certified quality assurance personnel and 0.3 physicists. The most frequent amount of time for treatment planning was 61-120min, for quality assurance was 50-60min, and for treatment was 30min. There were 14 (0.6% of all cases) reported Grade 5 complications: 11 cases of radiation pneumonitis, 2 cases of hemoptysis, and 1 case of radiation esophagitis. Conclusion: The current status of SBRT in Japan was surveyed. (C) 2009 Elsevier Inc.
  • Tamotsu Kamishima, Akiko Hasegawa, Kanako C. Kubota, Naomi Oizumi, Norimasa Iwasaki, Akio Minami, Satoru Sasaki, Yuhei Yamamoto, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato JAPANESE JOURNAL OF RADIOLOGY 27 (8) 328 -332 2009年10月 [査読無し][通常論文]
     
    Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report two cases of intravenous pyogenic granuloma localized in the finger, giving details of the magnetic resonance imaging (MRI) findings. These two cases had similar locations in fingers and identical MRI findings. The differential diagnoses of this rare entity are also discussed.
  • Shinichi Shimizu, Masao Hosokawa, Kazuo Itoh, Masahiro Fujita, Hiroaki Takahashi, Hiroki Shirato INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 14 (5) 421 -425 2009年10月 [査読無し][通常論文]
     
    We aimed to determine the appropriateness of adding 18F-fluorodeoxyglucose (FDG)-positronemission tomography (PET) to computed tomography (CT) and other pre-existing diagnostic imaging modalities for detecting subclinical lymph node metastasis of esophageal cancer, by comparing images from these modalities with the results of histopathological analysis. Twenty patients who received radical surgery for squamous cell carcinoma of the esophagus were examined by PET-CT, and endoscopic ultrasound (EUS) examination before surgery. Based on these diagnostic modalities, the clinical target volume (CTV) was set as the gross tumor volume (GTV) plus a 1-cm margin. Histopathological diagnosis was performed in all patients immediately after resection. Fifty-three (3.0%) of 1764 nodes in the 20 patients were histopathologically positive for cancer cells. The CTV was not adequate to cover these histopathologically detected positive lymph nodes in 8 of 20 patients on CT, 5 of 20 on CT+EUS, 7 of 20 on PET-CT, and 5 of 20 on PET-CT+EUS. The detection rate of subclinical lymph node metastasis did not improve with the use of PET-CT, for either the cervical and supraclavicular, mediastinal, or abdominal regions. It is not recommended to use FDG-PET or PET-CT alone as a diagnostic tool to determine CTV if pathologically involved lymphatic regions are to be included in the CTV in the treatment protocol. The accuracy of PET-CT must be further improved in order to better detect positive nodes and improve the definition of the CTV.
  • A. A. Harris, T. Kamishima, T. Horita, T. Atsumi, N. Fujita, T. Omatsu, Y. Onodera, S. Terae, T. Koike, H. Shirato LUPUS 18 (12) 1119 -1120 2009年10月 [査読無し][通常論文]
  • Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Shigenari Taki, Takeshi Asano, Daisuke Yoshida, Rikiya Onimaru, Takeshi Nishioka, Hiroki Shirato, Satoshi Fukuda CANCER 115 (20) 4705 -4714 2009年10月 [査読無し][通常論文]
     
    BACKGROUND: The current study aimed to evaluate the efficacy of superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with advanced cancer of the nasal cavity and paranasal sinuses. METHODS: Between October 1999 and December 2006, 47 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional external-beam radiotherapy (65-70 grays), RESULTS: There were 7 patients (14.9%) diagnosed with T3, 22 (46.8%) with T4a, and 18 (38.3%) with T4b disease. During the median follow-up period of 4.6 years, the 5-year local progression-free survival rate was 78.4% for all patients (n=47), 69.0% for patients with T4b disease (n=18), and 83.2% for patients with <T4b disease (n=29). The 5-year overall survival rate was 69.3% for all patients, 61.1% for patients with T4b disease, and 71.1% for patients with < T4b disease. RADPLAT was feasible in 45 patients (95.7%). No patient died as a result of treatment toxicity or had a cerebrovascular accident. Osteonecrosis (n=7), brain necrosis (n=2), and ocular/visual problems (n=16) were observed as late adverse reactions. CONCLUSIONS: Although a single institution experience, the results of the current study suggest that RADPLAT can cure the majority of patients with advanced cancer of the nasal cavity and paranasal sinuses, as well as preserve organs. Late adverse reactions should be monitored in future studies. Cancer 2009;115:4705-14. (C) 2009 American Cancer Society.
  • Yasushi Nagata, Masahiro Hiraoka, Takashi Mizowaki, Yuichiro Narita, Yukinori Matsuo, Yoshiki Norihisa, Hiroshi Onishi, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 75 (2) 343 -347 2009年10月 [査読無し][通常論文]
     
    Purpose: To recognize the current status of stereotactic body radiotherapy (SBRT) in Japan, using a nationwide survey conducted by the Japan 3-D Conformal External Beam Radiotherapy Group. Methods and Materials: The questionnaire was sent by mail to 117 institutions. Ninety-four institutions (80%) responded by the end of November 2005. Fifty-three institutions indicated that they have already started SBRT, and 38 institutions had been reimbursed by insurance. Results: A total of 1111 patients with histologically confirmed lung cancer were treated. Among these patients, 637 had TIN0M0 and 272 had T2N0M0 lung cancer. Metastatic lung cancer was found in 702 and histologically unconfirmed lung tumor in 291 patients. Primary liver cancer was found in 207 and metastatic liver cancer in 76 patients. The most frequent schedule used for primary lung cancer was 48Gy in 4 fractions at 22 institutions (52%), followed by 50Gy in 5 fractions at I I institutions (26%) and 60Gy in 8 fractions at 4 institutions (10%). The tendency was the same for metastatic lung cancer. The average number of personnel involved in SBRT was 1.8 radiation oncologists, including 1.1 certified radiation oncologists, 2.8 technologists, 0.7 nurses, and 0.6 certified quality assurance personnel and 0.3 physicists. The most frequent amount of time for treatment planning was 61-120min, for quality assurance was 50-60min, and for treatment was 30min. There were 14 (0.6% of all cases) reported Grade 5 complications: 11 cases of radiation pneumonitis, 2 cases of hemoptysis, and 1 case of radiation esophagitis. Conclusion: The current status of SBRT in Japan was surveyed. (C) 2009 Elsevier Inc.
  • Tamotsu Kamishima, Akiko Hasegawa, Kanako C. Kubota, Naomi Oizumi, Norimasa Iwasaki, Akio Minami, Satoru Sasaki, Yuhei Yamamoto, Tokuhiko Omatsu, Yuya Onodera, Satoshi Terae, Hiroki Shirato JAPANESE JOURNAL OF RADIOLOGY 27 (8) 328 -332 2009年10月 [査読無し][通常論文]
     
    Intravenous pyogenic granuloma is a rare solitary form of lobular capillary hemangioma that usually occurs in the veins of the neck and upper extremities. We report two cases of intravenous pyogenic granuloma localized in the finger, giving details of the magnetic resonance imaging (MRI) findings. These two cases had similar locations in fingers and identical MRI findings. The differential diagnoses of this rare entity are also discussed.
  • Shinichi Shimizu, Masao Hosokawa, Kazuo Itoh, Masahiro Fujita, Hiroaki Takahashi, Hiroki Shirato INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 14 (5) 421 -425 2009年10月 [査読無し][通常論文]
     
    We aimed to determine the appropriateness of adding 18F-fluorodeoxyglucose (FDG)-positronemission tomography (PET) to computed tomography (CT) and other pre-existing diagnostic imaging modalities for detecting subclinical lymph node metastasis of esophageal cancer, by comparing images from these modalities with the results of histopathological analysis. Twenty patients who received radical surgery for squamous cell carcinoma of the esophagus were examined by PET-CT, and endoscopic ultrasound (EUS) examination before surgery. Based on these diagnostic modalities, the clinical target volume (CTV) was set as the gross tumor volume (GTV) plus a 1-cm margin. Histopathological diagnosis was performed in all patients immediately after resection. Fifty-three (3.0%) of 1764 nodes in the 20 patients were histopathologically positive for cancer cells. The CTV was not adequate to cover these histopathologically detected positive lymph nodes in 8 of 20 patients on CT, 5 of 20 on CT+EUS, 7 of 20 on PET-CT, and 5 of 20 on PET-CT+EUS. The detection rate of subclinical lymph node metastasis did not improve with the use of PET-CT, for either the cervical and supraclavicular, mediastinal, or abdominal regions. It is not recommended to use FDG-PET or PET-CT alone as a diagnostic tool to determine CTV if pathologically involved lymphatic regions are to be included in the CTV in the treatment protocol. The accuracy of PET-CT must be further improved in order to better detect positive nodes and improve the definition of the CTV.
  • Noriko Oyama, Tomonori Ooka, Tsukasa Sasaki, Suguru Kubota, Yuya Onodera, Yoshiro Matsui, Satoshi Terae, Hiroki Shirato Journal of Cardiovascular Computed Tomography 3 (5) 346 -347 2009年09月 [査読無し][通常論文]
     
    We diagnosed unroofed coronary sinus preoperatively by the 3D volume rendering and endocardial views with 64-slice MDCT, and those clearly showed the defect of the roof of the coronary sinus and the relationship with the surrounding structure. MDCT is a good non-invasive tool for the evaluation of unroofed coronary sinus, and the reconstructed endocardial view is useful for preoperative surgical planning. © 2009 Society of Cardiovascular Computed Tomography.
  • Noriko Oyama, Tomonori Ooka, Tsukasa Sasaki, Suguru Kubota, Yuya Onodera, Yoshiro Matsui, Satoshi Terae, Hiroki Shirato Journal of Cardiovascular Computed Tomography 3 (5) 346 -347 2009年09月 [査読無し][通常論文]
     
    We diagnosed unroofed coronary sinus preoperatively by the 3D volume rendering and endocardial views with 64-slice MDCT, and those clearly showed the defect of the roof of the coronary sinus and the relationship with the surrounding structure. MDCT is a good non-invasive tool for the evaluation of unroofed coronary sinus, and the reconstructed endocardial view is useful for preoperative surgical planning. © 2009 Society of Cardiovascular Computed Tomography.
  • Takeshi Nishioka, Seiko Nishioka, Masaki Kawahara, Shigeru Tanaka, Hiroki Shirato, Ken Nishi, Tadao Hiromura JAPANESE JOURNAL OF RADIOLOGY 27 (7) 285 -289 2009年08月 [査読無し][通常論文]
     
    Purpose. Four-dimensional (4D) radiotherapy, in particular respiration gating for the treatment of lung tumors, is gaining popularity. Its utility for other sites, however, has not been investigated fully. The purpose of this study was to see whether 4D therapy is feasible for liver tumors. Material and methods. Six patients (five with hepatomas and one with metastatic liver tumor) had a fiducial, gold marker 1.5 mm in diameter implanted in the vicinity of their liver tumors. The inner and external (i.e., upper abdominal wall) respiratory movements were simultaneously recorded using a real-time tumor-tracking radiotherapy system and respiration monitor equipment applied to the mid to upper abdomen. Results. The fluctuations from the baseline position of liver tumors were small; the mean absolute value was 3.92 +/- 1.94 mm. The mean right-left, anteroposterior, and craniocaudal total movements were 4.19 +/- 2.46, 7.23 +/- 2.96, and 15.98 +/- 6.02 mm, respectively. The phase shift was negligible. Conclusion. Liver tumors may be suitable for respiration-gated radiotherapy, and they may become curable with 4D radiotherapy.
  • Takeshi Nishioka, Seiko Nishioka, Masaki Kawahara, Shigeru Tanaka, Hiroki Shirato, Ken Nishi, Tadao Hiromura JAPANESE JOURNAL OF RADIOLOGY 27 (7) 285 -289 2009年08月 [査読無し][通常論文]
     
    Purpose. Four-dimensional (4D) radiotherapy, in particular respiration gating for the treatment of lung tumors, is gaining popularity. Its utility for other sites, however, has not been investigated fully. The purpose of this study was to see whether 4D therapy is feasible for liver tumors. Material and methods. Six patients (five with hepatomas and one with metastatic liver tumor) had a fiducial, gold marker 1.5 mm in diameter implanted in the vicinity of their liver tumors. The inner and external (i.e., upper abdominal wall) respiratory movements were simultaneously recorded using a real-time tumor-tracking radiotherapy system and respiration monitor equipment applied to the mid to upper abdomen. Results. The fluctuations from the baseline position of liver tumors were small; the mean absolute value was 3.92 +/- 1.94 mm. The mean right-left, anteroposterior, and craniocaudal total movements were 4.19 +/- 2.46, 7.23 +/- 2.96, and 15.98 +/- 6.02 mm, respectively. The phase shift was negligible. Conclusion. Liver tumors may be suitable for respiration-gated radiotherapy, and they may become curable with 4D radiotherapy.
  • Keishiro Suzuki, Takeshi Nishioka, Akihiro Homma, Kazuhiko Tsuchiya, Motoaki Yasuda, Hidefumi Aoyama, Rikiya Onimaru, Nagara Tamaki, Hiroki Shirato JAPANESE JOURNAL OF RADIOLOGY 27 (6) 237 -242 2009年07月 [査読無し][通常論文]
     
    Purpose. The aim of this study was to determine if the standardized uptake value (SUV) of fluorodeoxyglucose positron emission tomography (FDG-PET) for head and neck cancer can predict the outcome of radiotherapy and if the SUV is correlated with histological grade, mitosis, and apoptosis. Materials and methods. The study included 45 head and neck cancer patients who underwent FDG-PET scanning before radiotherapy. The maximum SUV (SUVmax) of their primary lesions were measured. Biopsy was performed in all patients to determine the histological diagnosis. Altogether, 14 biopsy specimens were available for mitotic and apoptotic cell counts. Results. The mean SUVmax of T3 tumors was significantly higher than that of T1 (P = 0.01) and T2 (P = 0.011) tumors. The mean SUVmax of stage II disease was significantly lower than that of stage III (P = 0.028) and stage IV (P = 0.007) disease. There was a tendency toward a better locoregional control rate and disease-free survival for the lower SUV group using a cutoff value of 5.5. For 41 patients with squamous cell carcinoma or undifferentiated carcinoma, SUVmax did not reflect the histological grade. There was no correlation between the SUVmax and the mitotic/apoptotic status. Conclusion. SUVmax may correlate with the T classification and stage, but there was no predictive value for outcome of radiation therapy. Neither histological grading nor mitotic/apoptotic status is correlated with SUVmax.
  • R. Berbeco, S. Nishioka, H. Shirato Medical Physics 36 (6) 2490 -+ 2009年06月 [査読無し][通常論文]
     
    Purpose: As many clinics would prefer to use a pair of kV radiographs for gated patient setup, it is important to quantify the possible errors that could occur due to the non‐simultaneity of the acquisitions. Method and Materials: The data set from 11 patients includes internal and external coordinates acquired at 30Hz during multi‐fraction SBRT treatments. We simulated a gated setup procedure which included an AP radiograph, followed by a lateral radiograph. The time interval between the two radiographic acquisitions was set to a minimum of 30 seconds based on our clinical experience. The setup position is derived from a combination of both the initial (AP) and the second (LAT) image in the following way: [formula omitted]. The 3D error is then the magnitude of the vector from the initial position to the setup position. The calculation was done for every exhale phase in the data for which there was another one at least 30 seconds later at an amplitude within 2 mm from the first. In all, 1908 data points were analyzed. Results: The 3D error is found to be less than 2 mm for 91% of the data points and less than 3 mm for 97% of the data. The maximum error found was 7.5 mm. 97.5% of the second acquisitions could be completed within 35 seconds of the first. The maximum time interval found was 42 seconds. No correlation was found between the length of the time interval and the 3D error. Conclusion: When acquiring gated radiographs for patient setup, no large setup errors should be expected if those images are not taken simultaneously. Conflict of Interest: This work was sponsored, in part, by a grant from Varian Medical Systems, Inc. © 2009, American Association of Physicists in Medicine. All rights reserved.
  • Tamotsu Kamishima, Toru Harabayashi, Syuhei Ishikawa, Kanako C. Kubota, Katsuya Nonomura, Tokuhiko Omatsu, Yuya Onodera, Hiroki Shirato, Satoshi Terae JAPANESE JOURNAL OF RADIOLOGY 27 (5) 225 -228 2009年06月 [査読無し][通常論文]
     
    Echinococcosis is a parasitic infection of humans caused by the larval stage of the tapeworm Echinococcus. Primary alveolar echinococcosis of the adrenal gland is rare. We report a case of alveolar hydatid disease of the adrenal gland that presented as a multiloculated cystic mass without calcification. The lesion was purely cystic in nature, suggesting that it was at an early stage of development.
  • Gerben R. Borst, Masayori Ishikawa, Jasper Nijkamp, Michael Hauptmann, Hiroki Shirato, Rikiya Onimaru, Michel M. van den Heuvel, Jose Belderbos, Joos V. Lebesque, Jan-Jakob Sonke RADIOTHERAPY AND ONCOLOGY 91 (3) 307 -313 2009年06月 [査読無し][通常論文]
     
    Purpose: We evaluated the relationship between the mean lung dose (MLD) and the incidence of radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT), and compared this with conventional fractionated radiation therapy (CFRT). Materials and methods: For both SBRT (n=128) and CFRT (n=142) patients, RP grade >= 2 was scored. Toxicity models predicting the probability of RP as a function of the MLD were fitted Using Maximum log likelihood analysis. The MLD was NTD (Normalized Total Dose) corrected using an alpha/beta ratio of 3 Gy. Results: SBRT patients were treated with 6-12 Gy per fraction with a median MLD of 6.4 Gy (range: 1.5-6.5 Gy). CFRT patients were treated with 2 Gy or 2.25 Gy per fraction, the median MLD was 13.2 Gy (range: 3.0-23.0 Gy). The crude incidence rates of RP were 10.9% and 17.6% for the SBRT and CFRT patients, respectively. A significant close-response relationship for RP was found after SBRT, which was not significantly different from the dose-response relationship for CFRT (p = 0.18). Conclusion: We derived a significant dose-response relationship between the risk of RP and the MLD for SBRT from the clinical data. This relation was not significantly different from the dose-response relation for CFRT, although statistical analysis was hampered by the low number of patients in the high dose range. D 2009 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 91 (2009) 307-313
  • Tamotsu Kamishima, Toru Harabayashi, Syuhei Ishikawa, Kanako C. Kubota, Katsuya Nonomura, Tokuhiko Omatsu, Yuya Onodera, Hiroki Shirato, Satoshi Terae JAPANESE JOURNAL OF RADIOLOGY 27 (5) 225 -228 2009年06月 [査読無し][通常論文]
     
    Echinococcosis is a parasitic infection of humans caused by the larval stage of the tapeworm Echinococcus. Primary alveolar echinococcosis of the adrenal gland is rare. We report a case of alveolar hydatid disease of the adrenal gland that presented as a multiloculated cystic mass without calcification. The lesion was purely cystic in nature, suggesting that it was at an early stage of development.
  • Gerben R. Borst, Masayori Ishikawa, Jasper Nijkamp, Michael Hauptmann, Hiroki Shirato, Rikiya Onimaru, Michel M. van den Heuvel, Jose Belderbos, Joos V. Lebesque, Jan-Jakob Sonke RADIOTHERAPY AND ONCOLOGY 91 (3) 307 -313 2009年06月 [査読無し][通常論文]
     
    Purpose: We evaluated the relationship between the mean lung dose (MLD) and the incidence of radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT), and compared this with conventional fractionated radiation therapy (CFRT). Materials and methods: For both SBRT (n=128) and CFRT (n=142) patients, RP grade >= 2 was scored. Toxicity models predicting the probability of RP as a function of the MLD were fitted Using Maximum log likelihood analysis. The MLD was NTD (Normalized Total Dose) corrected using an alpha/beta ratio of 3 Gy. Results: SBRT patients were treated with 6-12 Gy per fraction with a median MLD of 6.4 Gy (range: 1.5-6.5 Gy). CFRT patients were treated with 2 Gy or 2.25 Gy per fraction, the median MLD was 13.2 Gy (range: 3.0-23.0 Gy). The crude incidence rates of RP were 10.9% and 17.6% for the SBRT and CFRT patients, respectively. A significant close-response relationship for RP was found after SBRT, which was not significantly different from the dose-response relationship for CFRT (p = 0.18). Conclusion: We derived a significant dose-response relationship between the risk of RP and the MLD for SBRT from the clinical data. This relation was not significantly different from the dose-response relation for CFRT, although statistical analysis was hampered by the low number of patients in the high dose range. D 2009 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 91 (2009) 307-313
  • Tamotsu Kamishima, Kazuhide Tanimura, Mihoko Henmi, Akihiro Narita, Fumihiko Sakamoto, Satoshi Terae, Hiroki Shirato SKELETAL RADIOLOGY 38 (5) 467 -472 2009年05月 [査読無し][通常論文]
     
    The objective of this study was to assess interobserver uncertainties in power Doppler (PD) examination of the fingers of patients with rheumatoid arthritis (RA), by separating the source of the discrepancy into (1) acquisition of the images and (2) criteria for assessment of the images. Twenty patients who had been diagnosed with RA were enrolled in this study. Ultrasound examinations were performed by one inexperienced and two experienced sonographers. Interobserver variation was measured using a conventional semiquantitative image grading scale. Interobserver variation of the quantitative PD (QPD) index (the summation of the colored pixels in a region of interest) was also assessed. The agreement was higher between the two experienced sonographers (kappa value of 0.8) than between experienced and inexperienced sonographers (kappa value, 0.6-0.7) in the semiquantitative image grading scale. Results suggest that the difference in the assessment on the image grading scale was due more to the difference in the acquisition of the images than to variations in the grading criteria between sonographers. An excellent relationship was noted between the image grading scale and the QPD index for Doppler signal with a Spearman's coefficient of rank correlation of 0.83 (P < 0.0001). Interobserver discrepancies in the image grading and QPD index methods were due more to the difference in the acquisition of the image than to the grading criteria used. The QPD index seems to be as reliable as the image grading scale with reasonable interobserver agreement between experienced sonographers.
  • Kenji Chamoto, Tsuguhide Takeshima, Daiko Wakita, Takayuki Ohkuri, Shigeru Ashino, Tokuhiko Omatsu, Hiroki Shirato, Hidemitsu Kitamura, Yuji Togashi, Takashi Nishimura CANCER SCIENCE 100 (5) 934 -939 2009年05月 [査読無し][通常論文]
     
    Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG + OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG + OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG + OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG + OVA-liposome allowed the augmented induction of OVA-tetramer(+) LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (Cancer Sci 2009; 100: 934-939).
  • Noriyuki Miyamoto, Kazuhide Hiramatsu, Kazuhiko Tsuchiya, Yukihiko Sato, Satoshi Terae, Hiroki Shirato Japanese Journal of Radiology 27 (4) 185 -193 2009年05月 [査読無し][通常論文]
     
    Purpose: The purpose of this study was to assess the usefulness of contrast harmonic sonography with a newly developed sonographic contrast agent as a means of guidance for percutaneous radiofrequency (RF) ablation of hepatocellular carcinoma (HCC). Materials and methods: A total of 52 consecutive HCC lesions in 42 patients with HCC who underwent percutaneous RF ablation were included in this study. Altogether, 40 lesions in 35 patients were untreated HCC, and 12 lesions in 7 patients were local tumor progression of an HCC that had already been treated by other methods. We investigated tumors by Kupffer-phase imaging and vascular-phase imaging after reinjection. We performed RF ablation guided by Sonazoid-enhanced sonography using Kupffer-phase imaging and vascular-phase imaging after reinjection. Results: Conventional sonography identified 30 (57%) of 52 HCCs, whereas Sonazoid-enhanced sonography detected 50 (96%) of 52 HCCs (P < 0.01, McNemar's χ2 test). Complete ablation was achieved at a single session in 48 of 50 tumors. Conclusion: Sonazoid-enhanced sonography is a useful technique for guiding RF ablation of HCCs, even when treating local progression of a previously treated HCC. © 2009 Japan Radiological Society.
  • Tamotsu Kamishima, Kazuhide Tanimura, Mihoko Henmi, Akihiro Narita, Fumihiko Sakamoto, Satoshi Terae, Hiroki Shirato SKELETAL RADIOLOGY 38 (5) 467 -472 2009年05月 [査読無し][通常論文]
     
    The objective of this study was to assess interobserver uncertainties in power Doppler (PD) examination of the fingers of patients with rheumatoid arthritis (RA), by separating the source of the discrepancy into (1) acquisition of the images and (2) criteria for assessment of the images. Twenty patients who had been diagnosed with RA were enrolled in this study. Ultrasound examinations were performed by one inexperienced and two experienced sonographers. Interobserver variation was measured using a conventional semiquantitative image grading scale. Interobserver variation of the quantitative PD (QPD) index (the summation of the colored pixels in a region of interest) was also assessed. The agreement was higher between the two experienced sonographers (kappa value of 0.8) than between experienced and inexperienced sonographers (kappa value, 0.6-0.7) in the semiquantitative image grading scale. Results suggest that the difference in the assessment on the image grading scale was due more to the difference in the acquisition of the images than to variations in the grading criteria between sonographers. An excellent relationship was noted between the image grading scale and the QPD index for Doppler signal with a Spearman's coefficient of rank correlation of 0.83 (P < 0.0001). Interobserver discrepancies in the image grading and QPD index methods were due more to the difference in the acquisition of the image than to the grading criteria used. The QPD index seems to be as reliable as the image grading scale with reasonable interobserver agreement between experienced sonographers.
  • Kenji Chamoto, Tsuguhide Takeshima, Daiko Wakita, Takayuki Ohkuri, Shigeru Ashino, Tokuhiko Omatsu, Hiroki Shirato, Hidemitsu Kitamura, Yuji Togashi, Takashi Nishimura CANCER SCIENCE 100 (5) 934 -939 2009年05月 [査読無し][通常論文]
     
    Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG + OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG + OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG + OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG + OVA-liposome allowed the augmented induction of OVA-tetramer(+) LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (Cancer Sci 2009; 100: 934-939).
  • M. Ishikawa, G. Bengua, K. L. Sutherland, J. Hiratsuka, N. Katoh, S. Shimizu, H. Aoyama, K. Fujita, R. Yamazaki, K. Horita, H. Shirato PHYSICS IN MEDICINE AND BIOLOGY 54 (7) 2079 -2092 2009年04月 [査読無し][通常論文]
     
    The purpose of this study was to develop a novel scintillation dosimeter for in vivo dosimetry in Ir-192 brachytherapy via the pulse-counting mode. The new dosimeter was made from a plastic scintillator shaped into a hemisphere of diameter 1 mm and connected to the tip of a plastic optical fiber. The relationship between pulse counts and absorbed dose was derived based on the assumption that scintillation photons from the incident gamma ray are proportional to the absorbed dose. An equation for the conversion of pulse counts to water-equivalent dose was deduced wherein the pulse height spectrum from scintillation photons was assumed to be exponential. To confirm its accuracy, the dose rate distribution in a water phantom was measured by the present dosimeter and this was compared with Monte Carlo simulations, resulting in a discrepancy of less than 1.97%. It was found that the dosimeter has a wide dynamic range of linearity up to an order of magnitude of almost 10(3), including corrections for loss of counts due to pile-up.
  • Ataru Sazawa, Nobuo Shinohara, Toru Harabayashi, Takashige Abe, Hiroki Shirato, Katsuya Nonomura INTERNATIONAL JOURNAL OF UROLOGY 16 (4) 410 -412 2009年04月 [査読無し][通常論文]
     
    Patients with an adrenal tumor usually undergo laparoscopic adrenalectomy. However, an alternative treatment approach might be needed in some patients with adrenal metastasis from malignancy or with severe complications. Real-time tracking radiotherapy (RTRT) with a gold marker is considered one of the feasible treatment options because this system can reduce the adverse effects of organ movement such as that in the adrenal gland or kidney. A 64-year-old patient with hormone refractory prostate cancer presented with clinically isolated adrenal metastasis. The patient underwent RTRT treatment with an implanted gold marker in the right adrenal metastasis. There were no adverse events. Although disease progression with elevated prostate-specific antigen occurred 8 months later, there was no further growth of the right adrenal metastasis before he died. From our experience, RTRT with an implanted gold marker might be feasible for the treatment of isolated adrenal metastasis from malignancies including prostate cancer.
  • Ataru Sazawa, Nobuo Shinohara, Toru Harabayashi, Takashige Abe, Hiroki Shirato, Katsuya Nonomura International Journal of Urology 16 (4) 410 -412 2009年04月 [査読無し][通常論文]
     
    Patients with an adrenal tumor usually undergo laparoscopic adrenalectomy.However, an alternative treatment approach might be needed in some patients with adrenal metastasis from malignancy or with severe complications. Real-time tracking radiotherapy (RTRT) with a gold marker is considered one of the feasible treatment options because this system can reduce the adverse effects of organ movement such as that in the adrenal gland or kidney. A 64-year-old patient with hormone refractory prostate cancer presented with clinically isolated adrenal metastasis. The patient underwent RTRT treatment with an implanted gold marker in the right adrenal metastasis. There were no adverse events. Although disease progression with elevatedprostate-specific antigen occurred 8 months later, there was no further growth of the right adrenal metastasis before he died. From our experience, RTRT with an implanted gold marker might be feasible for the treatment of isolated adrenal metastasis from malignancies including prostate cancer. © 2008 The Japanese Urological Association.
  • Kohsuke Kudo, Makoto Sasaki, Kuniaki Ogasawara, Satoshi Terae, Shigeru Ehara, Hiroki Shirato RADIOLOGY 251 (1) 241 -249 2009年04月 [査読無し][通常論文]
     
    Institutional review board approval and informed consent were obtained. The purpose was to evaluate the differences in tracer delay-induced effects of various deconvolution algorithms for computed tomographic (CT) perfusion imaging by using digital phantoms created from actual source data. Three methods of singular value decomposition (SVD) were evaluated. For standard SVD (sSVD), the delays induced significant errors in cerebral blood flow and mean transit time. In contrast, for block-circulant SVD (bSVD), these values remained virtually unchanged, whereas for delay-corrected SVD (dSVD), mild changes were observed. bSVD was superior to sSVD and dSVD for avoiding the tracer delay-induced effects in CT perfusion imaging. (C) RSNA, 2009
  • Fumiyuki Suzuki, Akihiro Homma, Nobuhiko Oridate, Seigo Suzuki, Takathugu Mizumachi, Satoshi Kanou, Shigenari Taki, Naoya Inamura, Satoshi Fukuda, Rikiya Onimaru, Masakazu Hasegawa, Hiroki Shirato, Yasushi Furuta Toukeibu Gan 35 (4) 344 -349 2009年 [査読無し][通常論文]
     
    Complication rates for salvage surgery after concurrent chemoradiotherapy (CCRT) have been reported to be high. From 1995 to 2008, 131 patients with laryngeal cancer and 107 with hypopharyngeal cancer underwent CCRT at Hokkaido University Hospital, Japan. Of the 131 patients with laryngeal cancer, a local recurrence developed in 43 (33%), of whom 38 (88%) underwent salvage surgery. The local control rate after salvage surgery was 79% (30/38). On the other hand, a local recurrence developed in 30 (28%) of 107 patients with hypopharyngeal cancer, of whom only 10 (33%) underwent salvage surgery, the local control rate after which was 60% (6/10). In 34 patients who underwent salvage laryngectomy or laryngopharyngectomy in our hospital (laryngeal cancer 28, hypopharyngeal cancer 6), overall wound complications, major wound complications and pharyngocutaneous fistulas were observed in 53%, 29% and 26%, respectively. CCRT can cause difficulties in wound healing and wound complications, such as infection or pharyngocutaneous fistulas. To reduce the incidence of wound complications, we have taken steps including appropriate skin incisions, preservation of the strap muscles, thyroid glands and major veins, and pectoralis major myofascial flap transfer to reinforce the primary pharyngeal closure (pharyngeal interposition graft). High incidences of wound complications and poor wound recovery in patients undergoing salvage surgery following CCRT should be taken into account before the initiation of CCRT, and emphasis should be placed on taking steps to prevent wound complications associated with salvage surgery. © 2009, Japan Society for Head and Neck Cancer. All rights reserved.
  • H. Wu, C. He, Q. Zhao, R. Berbeco, H. Shirato, S. Nishioka Medical Physics 36 2502 -2503 2009年01月01日 [査読無し][通常論文]
     
    Purpose: Reliable correlation between internal tumor and external marker motion is important for effective radiation treatment based on external signal, such as external gating and the CyberKnife Synchrony System. This study is to analyze the internal/external correlation stabilities by calculating the missed tumor volume. Methods and Materials: Internal tumor and external marker motion of eight patients with multiple fractions were acquired simultaneous at 30Hz. Internal signal is the 3D tumor motion and external signal is the 1D motion of abdominal surface. The internal/external correlation was constructed using the first 3 breathing cycles. The correlated tumor position was calculated based on this correlation model with external signal. The missed tumor volume was calculated based on the distance between the internal and the correlated positions at each acquired data point. The inter‐patient, inter‐fractional, and intra‐fractional variations of the missed volume percentage were analyzed. Results: The results of a solid sphere tumor with different sizes were performed based on the true patient motion data. For a sphere tumor with 20mm diameter, the average missed volume percentage averaged over all treatment fractions of one patient was between 5.14% and 15.3%. The percentages changed from one fraction to another. The daily percentages varied from 3% to 6.5% for the patient with the smallest average patient‐wide missed percentage. The intra‐fraction motion changed from one breathing cycle to another. In one fraction of a patient, the average cycle percentages changed from 6% to 26%. Even within the same breathing cycle, the missed percentages changed greatly from one breathing state to another, with larger values (∼30%) at the inhale and exhale states and smaller value (∼3%) at the end‐of‐exhale state. Conclusions: Strong correlations between internal and external motion exist but change overtime. Verification and updating the correlation in real‐time delivery is required for effective treatment. © 2009, American Association of Physicists in Medicine. All rights reserved.
  • E. Pepin, H. wu, G. Sandison, M. Langer, H. Shirato Medical Physics 36 2726 2009年01月01日 [査読無し][通常論文]
     
    Purpose: To develop a Hidden Markov Model (HMM) of tumor motion behavior for use in adaptive image‐guided radiation therapy (IGRT) to overcome the beam delivery system's inherent mechanical and imaging‐rate latency. As input to the HMM we investigated clinically defined parameters and tumor motion characteristics. Method and Materials: Motion data from 43 lung tumors were collected by tracking an implanted fiducial using a fluoroscopic real‐time tracking system. Data on a total of 1297 radiotherapy fractions were collected and for 637 fractions a convex hull was created over the data points for three consecutive breathing cycles. Statistical analysis led to the removal of outlier points, then the volumes of the hulls were calculated and their shapes visually examined. Tumor location in the lung as defined by bronchial segments was related to the volume and shape of the tumor movement envelope. Results: Outlier points were removed based on data density and tumor velocity limits. It was found that tumors located in the upper apex had smaller volume of movement envelope ( < 50 mm≈3), whereas tumors located near the chest wall or diaphragm were larger ( > 70 mm≈3). Tumors attached to fixed anatomical structures had a small volume of movement envelope ( < 30 mm≈3). Three general shapes described the tumor motion envelopes. Envelope volume and shape was inter‐fractionally consistent. Fifty percent of tumors exhibited largely 1D oscillation; Thirty‐eight percent of tumors had motion enclosed by an ellipsoid envelop with few data points in the center region, six percent of tumors moved in an arc‐like defining a concave shaped movement envelope, and six percent defined a movement envelope that was of hybrid shape. Conclusions: The location‐space correlation and the inter‐fractional consistency of the movement envelope shapes will, in part, inform the development of a HMM to predict lung tumor motion for real‐time beam adjustments in IGRT. © 2009, American Association of Physicists in Medicine. All rights reserved.
  • Noriko Nishioka, Tamotsu Kamishima, Tatsuya Masuko, Kanako C. Kubota, Miki Komatsu, Norimasa Iwasaki, Takayuki Nojima, Tomoo Itoh, Ardene A. Harris, Akio Minami, Hiroki Shirato European Journal of Radiology Extra 69 (1) e33 -e36 2009年01月 [査読無し][通常論文]
     
    Nodular fasciitis is a benign, usually self-limiting proliferation of myofibroblasts, arising from the fascia. In this article, a case of nodular fasciitis in the elbow joint of a 29-year-old man is presented. The nodular lesion developed from the synovial joint capsule in the elbow and histological and immunohistochemical studies revealed myofibroblastic proliferation. Only 13 cases of intra-articular nodular fasciitis have been reported in English literature. The present report describes the first case in which intra-articular nodular fasciitis occurs in the elbow joint of a patient. Additionally, magnetic resonance imaging findings of intra-articular nodular fasciitis are discussed along with a review of previous articles. © 2008 Elsevier Ireland Ltd. All rights reserved.
  • Rikiya Onimaru, Masakazu Hasegawa, Koichi Yasuda, Rumiko Kinoshita, Hiroki Shirato, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda Toukeibu Gan 35 (3) 245 -249 2009年 [査読無し][通常論文]
     
    We evaluated the clinical outcome of 37 patients who had received intensity modulated radiation therapy (IMRT) in Hokkaido University Hospital from May 2002 to December 2007. Thirteen patients had nasopharyngeal cancer, 19 had oropharyngeal cancer, 3 had hypopharyngeal cancer, 1 had maxillary sinus cancer, and 1 had oral cancer. One patient who had oropharyngeal cancer died of pharyngeal abscess which was a treatment-related complication. Three patients died of other cancers. One patient with nasopharyngeal cancer had local recurrence. In patients with oropharyngeal cancer, recurrence at the primary site occurred in 3 patients, and residual/recurrence at neck lymph nodes occurred in 2 patients. One patient with hypopharyngeal cancer had residual neck lymph node metastasis. Some patients experienced severe reactions to the radiation. One patient had pharyngeal abscess and died of this treatment complication. One patient who had nasopharyngeal cancer experienced hearing loss and angle closure glaucoma. © 2009, Japan Society for Head and Neck Cancer. All rights reserved.
  • Tetsuya Inoue, R. Onimaru, S. Shimizu, H. Aoyama, H. Shirato Japanese Journal of Clinical Radiology 54 (5) 625 -630 2009年 [査読無し][通常論文]
     
    Recently stereotactic body radiotherapy (SBRT) for small lung cancer has been performed safely and effectively. Image-guided biopsy occasionally fails to diagnose small lung lesions, which are highly suggestive of primary lung cancer. Retrospective study showed SBRT for small lung lesions that were clinically diagnosed as primary lung cancer without pathological confirmation was safe and effective. Prospective study is under construction.
  • Seishin Takao, Shigeru Tadano, Hiroshi Taguchi, Hiroki Shirato Journal of Biomechanical Science and Engineering 4 (2) 221 -229 2009年 [査読無し][通常論文]
     
    Precise assessment of therapeutic response in radiotherapy has been an important issue in the field of radiation oncology. This study proposed a methodology to evaluate therapeutic response based on tumor geometries. Three-dimensional (3D) tumor shapes were obtained from follow-up CT scans taken once a week throughout the treatment period. Tumor geometries were represented in two-dimensional (2D) surface geometry maps. These maps indicated the distances from the tumor center to surface at each azimuthal and horizontal angle by colors, in order to represent the characteristics of tumor morphologies. This method was applied to three clinical cases of head and neck cancer. The changes of tumor geometries could be represented visually and quantitatively using surface geometry maps. These maps provided valuable information about tumors for accurate diagnosis of tumor response to radiotherapy. Copyright © 2009 by The Japan Society of Mechanical Engineers.
  • Seishin Takao, Shigeru Tadano, Hiroshi Taguchi, Hiroki Shirato Journal of Biomechanical Science and Engineering 4 (4) 576 -588 2009年 [査読無し][通常論文]
     
    A new simulation method was developed that considered a tumor as a solid body and therapeutic response as deformation of the tumor using mechanical analogy. As radiation exposure to the tumor was related to the external force to the solid body, the geometrical change of the tumor could be estimated from fundamental equations in solid mechanics. A change in tumor volume was calculated using finite element (FE) method. The FE models were constructed from CT images of patients before the radiotherapy. The initial radiotherapeutic parameters of tumor radioresistance and repopulation rate were determined based on a linear-quadratic model and then revised by the comparison with actual tumor volume change. Three patients with uterine cervix carcinoma were applied in this method. Simulation results well showed tendencies of tumor volume changes with radiotherapy. In addition, this method could provide the appropriate value of radiotherapeutic parameters for individual case. In conclusion, our approach could calculate three-dimensional tumor deformation during the course of radiotherapy and will provide useful information for more effective treatment.
  • MIYAMOTO Noriyuki, HIRAMATSU Kazuhide, TSUCHIYA Kazuhiko, SATO Yukihiko, TERAE Satoshi, SHIRATO Hiroki Jpn J Radiol 27 (4) 185 -193 2009年 [査読無し][通常論文]
  • Tohru Shiga, Yuichi Morimoto, Naoki Kubo, Norio Katoh, Chietsugu Katoh, Wataru Takeuchi, Reiko Usui, Kenji Hirata, Shinichi Kojima, Kikuo Umegaki, Hiroki Shirato, Nagara Tamaki JOURNAL OF NUCLEAR MEDICINE 50 (1) 148 -155 2009年01月 [査読無し][通常論文]
     
    An autoradiography method revealed intratumoral inhomogeneity in various solid tumors. It is becoming increasingly important to estimate intratumoral inhomogeneity. However, with low spatial resolution and high scatter noise, it is difficult to detect intratumoral inhomogeneity in clinical settings. We developed a new PET system with CdTe semiconductor detectors to provide images with high spatial resolution and low scatter noise. Both phantom images and patients' images were analyzed to evaluate intratumoral inhomogeneity. Methods: This study was performed with a cold spot phantom that had 6-mm-diameter cold sphenoid defects, a dual-cylinder phantom with an adjusted concentration of 1:2, and an "H"-shaped hot phantom. These were surrounded with water. Phantom images and (18)F-FDG PET images of patients with nasopharyngeal cancer were compared with conventional bismuth germanate PET images. Profile curves for the phantoms were measured as peak-to-valley ratios to define contrast. Intratumoral inhomogeneity and tumor edge sharpness were evaluated on the images of the patients. Results: The contrast obtained with the semiconductor PET scanner (1.53) was 28% higher than that obtained with the conventional scanner (1.20) for the 6-mm-diameter cold sphenoid phantom. The contrast obtained with the semiconductor PET scanner (1.43) was 27% higher than that obtained with the conventional scanner (1.13) for the dual-cylinder phantom. Similarly, the 2-mm cold region between 1-mm hot rods was identified only by the new PET scanner and not by the conventional scanner. The new PET scanner identified intratumoral inhomogeneity in more detail than the conventional scanner in 6 of 10 patients. The tumor edge was sharper on the images obtained with the new PET scanner than on those obtained with the conventional scanner. Conclusion: These phantom and clinical studies suggested that this new PET scanner has the potential for better identification of intratumoral inhomogeneity, probably because of its high spatial resolution and low scatter noise.
  • Keishiro Suzuki, Yukinori Hirasawa, Yuji Yaegashi, Hideki Miyamoto, Hiroki Shirato JOURNAL OF TELEMEDICINE AND TELECARE 15 (8) 414 -418 2009年 [査読無し][通常論文]
     
    We developed a web-based, remote radiation treatment planning system which allowed staff at an affiliated hospital to obtain support from a fully staffed central institution. Network security was based on a firewall and a virtual private network (VPN). Client computers were installed at a cancer centre, at a university hospital and at a staff home. We remotely operated the treatment planning computer using the Remote Desktop function built in to the Windows operating system. Except for the initial setup of the VPN router, no special knowledge was needed to operate the remote radiation treatment planning system. There was a time lag that seemed to depend on the volume of data traffic on the Internet, but it did not affect smooth operation. The initial cost and running cost of the system were reasonable.
  • Takeshi Nishioka, Yusuke Miyai, Hisashi Haga, Kazushige Kawabata, Hiroki Shirato, Akihiro Homma, Kenichiro Shibata, Motoaki Yasuda CELL STRUCTURE AND FUNCTION 34 (1) 17 -22 2009年 [査読無し][通常論文]
     
    Purpose: To find a new molecule that affects p53-dependent radiosensitivity.Methods and Materials: A mouse sarcoma cell line, QRsP(p53+/+), was used. From this cell line, we established a radiosensitive clone and a radioresistant one. Colony assay, p53 gene transfer, a luciferase assay for p53 and p21, animal transplantation experiment, and DNA array analyses were performed.Results: Microarray showed marked reduction of a transcription factor, ATF5, both in vitro and in vivo for the radiosensitive clone. Interestingly, flow cytometric analysis demonstrated marked apoptosis for the radiosensitive clone by p53 cloned adenovirus infection. Luciferase reporter assay revealed that ATF5 suppressed the transactivational activity of p53 and p63. By ATF5 gene transfer, the radiosensitive clone regained resistance to both ionizing-radiation and Ad-p53 infection-induced cell death. Surprisingly, time-lapse cell migration observation revealed greater cell motility for ATF5-transfected radiosensitive clone.Conclusions: It seems likely that ATF5 is a potent repressor of p53 and elevated expression of ATF5 in a tumor may relate to enhanced malignant phenotypes, such as radioresistance or greater cell motility.
  • Cell Struct Funct. 34 (2) 89 -96 2009年 [査読無し][通常論文]
  • Int J Radiat Oncol Biol Phys. 75(5) 1415 -1419 2009年 [査読無し][通常論文]
  • Tohru Shiga, Yuichi Morimoto, Naoki Kubo, Norio Katoh, Chietsugu Katoh, Wataru Takeuchi, Reiko Usui, Kenji Hirata, Shinichi Kojima, Kikuo Umegaki, Hiroki Shirato, Nagara Tamaki JOURNAL OF NUCLEAR MEDICINE 50 (1) 148 -155 2009年01月 [査読無し][通常論文]
     
    An autoradiography method revealed intratumoral inhomogeneity in various solid tumors. It is becoming increasingly important to estimate intratumoral inhomogeneity. However, with low spatial resolution and high scatter noise, it is difficult to detect intratumoral inhomogeneity in clinical settings. We developed a new PET system with CdTe semiconductor detectors to provide images with high spatial resolution and low scatter noise. Both phantom images and patients' images were analyzed to evaluate intratumoral inhomogeneity. Methods: This study was performed with a cold spot phantom that had 6-mm-diameter cold sphenoid defects, a dual-cylinder phantom with an adjusted concentration of 1:2, and an "H"-shaped hot phantom. These were surrounded with water. Phantom images and (18)F-FDG PET images of patients with nasopharyngeal cancer were compared with conventional bismuth germanate PET images. Profile curves for the phantoms were measured as peak-to-valley ratios to define contrast. Intratumoral inhomogeneity and tumor edge sharpness were evaluated on the images of the patients. Results: The contrast obtained with the semiconductor PET scanner (1.53) was 28% higher than that obtained with the conventional scanner (1.20) for the 6-mm-diameter cold sphenoid phantom. The contrast obtained with the semiconductor PET scanner (1.43) was 27% higher than that obtained with the conventional scanner (1.13) for the dual-cylinder phantom. Similarly, the 2-mm cold region between 1-mm hot rods was identified only by the new PET scanner and not by the conventional scanner. The new PET scanner identified intratumoral inhomogeneity in more detail than the conventional scanner in 6 of 10 patients. The tumor edge was sharper on the images obtained with the new PET scanner than on those obtained with the conventional scanner. Conclusion: These phantom and clinical studies suggested that this new PET scanner has the potential for better identification of intratumoral inhomogeneity, probably because of its high spatial resolution and low scatter noise.
  • Keishiro Suzuki, Yukinori Hirasawa, Yuji Yaegashi, Hideki Miyamoto, Hiroki Shirato JOURNAL OF TELEMEDICINE AND TELECARE 15 (8) 414 -418 2009年 [査読無し][通常論文]
     
    We developed a web-based, remote radiation treatment planning system which allowed staff at an affiliated hospital to obtain support from a fully staffed central institution. Network security was based on a firewall and a virtual private network (VPN). Client computers were installed at a cancer centre, at a university hospital and at a staff home. We remotely operated the treatment planning computer using the Remote Desktop function built in to the Windows operating system. Except for the initial setup of the VPN router, no special knowledge was needed to operate the remote radiation treatment planning system. There was a time lag that seemed to depend on the volume of data traffic on the Internet, but it did not affect smooth operation. The initial cost and running cost of the system were reasonable.
  • Takeshi Nishioka, Yusuke Miyai, Hisashi Haga, Kazushige Kawabata, Hiroki Shirato, Akihiro Homma, Kenichiro Shibata, Motoaki Yasuda CELL STRUCTURE AND FUNCTION 34 (1) 17 -22 2009年 [査読無し][通常論文]
     
    Purpose: To find a new molecule that affects p53-dependent radiosensitivity.Methods and Materials: A mouse sarcoma cell line, QRsP(p53+/+), was used. From this cell line, we established a radiosensitive clone and a radioresistant one. Colony assay, p53 gene transfer, a luciferase assay for p53 and p21, animal transplantation experiment, and DNA array analyses were performed.Results: Microarray showed marked reduction of a transcription factor, ATF5, both in vitro and in vivo for the radiosensitive clone. Interestingly, flow cytometric analysis demonstrated marked apoptosis for the radiosensitive clone by p53 cloned adenovirus infection. Luciferase reporter assay revealed that ATF5 suppressed the transactivational activity of p53 and p63. By ATF5 gene transfer, the radiosensitive clone regained resistance to both ionizing-radiation and Ad-p53 infection-induced cell death. Surprisingly, time-lapse cell migration observation revealed greater cell motility for ATF5-transfected radiosensitive clone.Conclusions: It seems likely that ATF5 is a potent repressor of p53 and elevated expression of ATF5 in a tumor may relate to enhanced malignant phenotypes, such as radioresistance or greater cell motility.
  • Kaori Tsutsumi, Masumi Tsuda, Natsuka Yazawa, Hirotaka Nakamura, Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Rie Yamazaki, Hiroki Shirato, Hideaki Kawaguchi, Takeshi Nishioka, Yusuke Ohba Cell Struct Funct. 34 (2) 89 -96 2009年 [査読無し][通常論文]
  • Huanmei Wu, Qingya Zhao, Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang PHYSICS IN MEDICINE AND BIOLOGY 53 (24) 7137 -7150 2008年12月 [査読無し][通常論文]
     
    Precise localization of mobile tumor positions in real time is critical to the success of gated radiotherapy. Tumor positions are usually derived from either internal or external surrogates. Fluoroscopic gating based on internal surrogates, such as implanted fiducial markers, is accurate however requiring a large amount of imaging dose. Gating based on external surrogates, such as patient abdominal surface motion, is non-invasive however less accurate due to the uncertainty in the correlation between tumor location and external surrogates. To address these complications, we propose to investigate an approach based on hybrid gating with dynamic internal/external correlation updates. In this approach, the external signal is acquired at high frequency (such as 30 Hz) while the internal signal is sparsely acquired (such as 0.5 Hz or less). The internal signal is used to validate and update the internal/external correlation during treatment. Tumor positions are derived from the external signal based on the newly updated correlation. Two dynamic correlation updating algorithms are introduced. One is based on the motion amplitude and the other is based on the motion phase. Nine patients with synchronized internal/external motion signals are simulated retrospectively to evaluate the effectiveness of hybrid gating. The influences of different clinical conditions on hybrid gating, such as the size of gating windows, the optimal timing for internal signal acquisition and the acquisition frequency are investigated. The results demonstrate that dynamically updating the internal/external correlation in or around the gating window will reduce false positive with relatively diminished treatment efficiency. This improvement will benefit patients with mobile tumors, especially greater for early stage lung cancers, for which the tumors are less attached or freely floating in the lung.
  • Yasushi Furuta, Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Keishiro Suzuki, Takeshi Nishioka, Hiroki Shirato, Satoshi Fukuda INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 13 (6) 521 -527 2008年12月 [査読無し][通常論文]
     
    Surgical complication rates of total laryngectomy vary according to the preoperative treatments performed and patient factors. Wound complications after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were analyzed. Eighty-six patients who had undergone total laryngectomy for laryngeal cancer at Hokkaido University Hospital, Japan, between 1990 and 2006 were divided into three groups according to preoperative treatments received: group I (n = 35) without radiotherapy (RT) or CCRT, group II (n = 17) RT alone, and group III (n = 34) low-dose CCRT. Salvage total laryngectomy was performed as a consequence of residual or recurrent disease after completion of the treatments. Wound complications such as pharyngocutaneous fistulas, bleeding, infections, and skin necrosis were retrospectively analyzed in each group. A considerable (not statistically significant) difference in the incidence of major wound complications was observed between groups I and III (11.4% vs 29.4%, P = 0.078), but not between groups II and III. In stage III/IV patients, a significant increase in the incidence of wound complications was observed in group III compared to group I. Pharyngocutaneous fistulas were the most common complication, occurring in 8/34 (23.5%) of the group III patients. Additional pharyngeal reconstruction surgery was performed in 5 of the 8 (62.5%) group III patients with pha ryngocutaneous fistulas, while no such patients (0/3) in group I required reconstruction surgery. There was an increased risk of wound complications in patients undergoing salvage laryngectomy following CCRT. Patients who developed pharyngocutaneous fistulas after CCRT tended to require surgical reintervention for repair. These findings should be taken into account before the initiation of CCRT and salvage surgery.
  • Huanmei Wu, Qingya Zhao, Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang PHYSICS IN MEDICINE AND BIOLOGY 53 (24) 7137 -7150 2008年12月 [査読無し][通常論文]
     
    Precise localization of mobile tumor positions in real time is critical to the success of gated radiotherapy. Tumor positions are usually derived from either internal or external surrogates. Fluoroscopic gating based on internal surrogates, such as implanted fiducial markers, is accurate however requiring a large amount of imaging dose. Gating based on external surrogates, such as patient abdominal surface motion, is non-invasive however less accurate due to the uncertainty in the correlation between tumor location and external surrogates. To address these complications, we propose to investigate an approach based on hybrid gating with dynamic internal/external correlation updates. In this approach, the external signal is acquired at high frequency (such as 30 Hz) while the internal signal is sparsely acquired (such as 0.5 Hz or less). The internal signal is used to validate and update the internal/external correlation during treatment. Tumor positions are derived from the external signal based on the newly updated correlation. Two dynamic correlation updating algorithms are introduced. One is based on the motion amplitude and the other is based on the motion phase. Nine patients with synchronized internal/external motion signals are simulated retrospectively to evaluate the effectiveness of hybrid gating. The influences of different clinical conditions on hybrid gating, such as the size of gating windows, the optimal timing for internal signal acquisition and the acquisition frequency are investigated. The results demonstrate that dynamically updating the internal/external correlation in or around the gating window will reduce false positive with relatively diminished treatment efficiency. This improvement will benefit patients with mobile tumors, especially greater for early stage lung cancers, for which the tumors are less attached or freely floating in the lung.
  • Yasushi Furuta, Akihiro Homma, Nobuhiko Oridate, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Keishiro Suzuki, Takeshi Nishioka, Hiroki Shirato, Satoshi Fukuda INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 13 (6) 521 -527 2008年12月 [査読無し][通常論文]
     
    Surgical complication rates of total laryngectomy vary according to the preoperative treatments performed and patient factors. Wound complications after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were analyzed. Eighty-six patients who had undergone total laryngectomy for laryngeal cancer at Hokkaido University Hospital, Japan, between 1990 and 2006 were divided into three groups according to preoperative treatments received: group I (n = 35) without radiotherapy (RT) or CCRT, group II (n = 17) RT alone, and group III (n = 34) low-dose CCRT. Salvage total laryngectomy was performed as a consequence of residual or recurrent disease after completion of the treatments. Wound complications such as pharyngocutaneous fistulas, bleeding, infections, and skin necrosis were retrospectively analyzed in each group. A considerable (not statistically significant) difference in the incidence of major wound complications was observed between groups I and III (11.4% vs 29.4%, P = 0.078), but not between groups II and III. In stage III/IV patients, a significant increase in the incidence of wound complications was observed in group III compared to group I. Pharyngocutaneous fistulas were the most common complication, occurring in 8/34 (23.5%) of the group III patients. Additional pharyngeal reconstruction surgery was performed in 5 of the 8 (62.5%) group III patients with pha ryngocutaneous fistulas, while no such patients (0/3) in group I required reconstruction surgery. There was an increased risk of wound complications in patients undergoing salvage laryngectomy following CCRT. Patients who developed pharyngocutaneous fistulas after CCRT tended to require surgical reintervention for repair. These findings should be taken into account before the initiation of CCRT and salvage surgery.
  • Daisuke Abo, Satoshi Terae, Yuichiro Fukasawa, Hideyuki Seki, Yu Hasegawa, Yusuke Sakuhara, Tadashi Shimizu, Hiroki Shirato JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 32 (6) 890 -892 2008年11月 [査読無し][通常論文]
     
    A splenic mass was found in an asymptomatic 76-year-old woman who had been treated with steroids for autoimmune hepatitis. The lesion was found to be hyperechoic on ultrasound examination, hypovascular on angiography, low attenuating on postcontrast computed tomography, isointense to splenic parenchyma on precontrast T1- and T2-weightcd images, and showed inhomogeneous enhancement on gadolinium-enhanced T1-weighted images. Splenic peliosis should be considered when diagnosing tumorlike conditions of the spleen because of its potential to cause splenic rupture.
  • Yuuta Kamoshima, Yutaka Sawamura, Jun Ikeda, Hiroki Shirato, Hidefumi Aoyama JOURNAL OF NEURO-ONCOLOGY 90 (2) 205 -211 2008年11月 [査読無し][通常論文]
     
    Central nervous system (CNS) germinoma is a curable tumor and its recurrence rate after initial therapy may be approximately 10% or higher. This study elucidates the time-course of recurrence and results of salvage therapy. Twenty-five patients with recurrent germinoma treated at Hokkaido University Hospital were retrospectively reviewed. The median age at initial treatment was 12 years (range: 8-37). All patients had been tumor-free for at least 6 months after the initial treatment. The median follow-up period was 134 months (range: 44-338). The median age at first recurrence was 18 years and the median time to the first recurrence was 50 months. Among the patients, 9 (36%) had the first recurrence at 60 months or later. The latest recurrence in a patient occurred 230 months after the initial treatment. The results of salvage therapy were estimated in all 25 patients. Seventeen patients (68%) were salvaged and were tumor-free at the final observation. The remaining 8 patients died of disease. At first recurrence, 11 patients were treated using radiation therapy with or without surgery and 7 out of the 11 patients died due to the recurrent tumor. On the other hand, 13 patients who received salvage chemotherapy and radiotherapy were tumor-free at the last follow-up. In conclusion, late recurrence is not a rare event in patients with CNS germinoma. To identify a true cure rate of this disease, a 10-year or longer observation period may be required. As a salvage therapy, platinum-based chemotherapy followed by wide-field low-dose radiation therapy appears to be effective.
  • Daisuke Abo, Satoshi Terae, Yuichiro Fukasawa, Hideyuki Seki, Yu Hasegawa, Yusuke Sakuhara, Tadashi Shimizu, Hiroki Shirato JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY 32 (6) 890 -892 2008年11月 [査読無し][通常論文]
     
    A splenic mass was found in an asymptomatic 76-year-old woman who had been treated with steroids for autoimmune hepatitis. The lesion was found to be hyperechoic on ultrasound examination, hypovascular on angiography, low attenuating on postcontrast computed tomography, isointense to splenic parenchyma on precontrast T1- and T2-weightcd images, and showed inhomogeneous enhancement on gadolinium-enhanced T1-weighted images. Splenic peliosis should be considered when diagnosing tumorlike conditions of the spleen because of its potential to cause splenic rupture.
  • Yuuta Kamoshima, Yutaka Sawamura, Jun Ikeda, Hiroki Shirato, Hidefumi Aoyama JOURNAL OF NEURO-ONCOLOGY 90 (2) 205 -211 2008年11月 [査読無し][通常論文]
     
    Central nervous system (CNS) germinoma is a curable tumor and its recurrence rate after initial therapy may be approximately 10% or higher. This study elucidates the time-course of recurrence and results of salvage therapy. Twenty-five patients with recurrent germinoma treated at Hokkaido University Hospital were retrospectively reviewed. The median age at initial treatment was 12 years (range: 8-37). All patients had been tumor-free for at least 6 months after the initial treatment. The median follow-up period was 134 months (range: 44-338). The median age at first recurrence was 18 years and the median time to the first recurrence was 50 months. Among the patients, 9 (36%) had the first recurrence at 60 months or later. The latest recurrence in a patient occurred 230 months after the initial treatment. The results of salvage therapy were estimated in all 25 patients. Seventeen patients (68%) were salvaged and were tumor-free at the final observation. The remaining 8 patients died of disease. At first recurrence, 11 patients were treated using radiation therapy with or without surgery and 7 out of the 11 patients died due to the recurrent tumor. On the other hand, 13 patients who received salvage chemotherapy and radiotherapy were tumor-free at the last follow-up. In conclusion, late recurrence is not a rare event in patients with CNS germinoma. To identify a true cure rate of this disease, a 10-year or longer observation period may be required. As a salvage therapy, platinum-based chemotherapy followed by wide-field low-dose radiation therapy appears to be effective.
  • Yusuke Sakuhara, Yoshihisa Kodama, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Tokuhiko Omatsu, Tamotsu Kamishika, Yuya Onodera, Satoshi Terae, Hiroki Shirato ABDOMINAL IMAGING 33 (5) 563 -570 2008年09月 [査読無し][通常論文]
     
    Background: To evaluate the vascular supply of regions of the pancreas on computed tomography (CT) during arteriography with selective catheterization. Methods: Thirteen patients were included. In each patient we performed conventional arteriography followed by CT during arteriography of each of the arteries: the superior mesenteric artery (SMA), gastroduodenal artery (GDA), and splenic artery (SPA). The regions of the pancreas that were most enhanced on CT during arteriography were considered to be the areas receiving the greatest infusion of blood from the selected artery. Results: In all 13 patients, the uncinate process, the superior head, and the tail of the pancreas were predominantly supplied by the SMA, GDA, and SPA, respectively. The inferior head of the pancreas was predominantly supplied by the SMA in five patients, the GDA in nine patients, and both the SMA and GDA in one patient. The body of the pancreas was predominantly supplied by the SMA, GDA, and SPA in seven, two, and ten patients, respectively. Conclusions: The uncinate process predominantly infused by the SMA, the superior head by the GDA, and the tail by the SPA. The patterns of the vascular supply of the inferior head and the body vary from patient to patient.
  • Yusuke Sakuhara, Yoshihisa Kodama, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Tokuhiko Omatsu, Tamotsu Kamishika, Yuya Onodera, Satoshi Terae, Hiroki Shirato ABDOMINAL IMAGING 33 (5) 563 -570 2008年09月 [査読無し][通常論文]
     
    Background: To evaluate the vascular supply of regions of the pancreas on computed tomography (CT) during arteriography with selective catheterization. Methods: Thirteen patients were included. In each patient we performed conventional arteriography followed by CT during arteriography of each of the arteries: the superior mesenteric artery (SMA), gastroduodenal artery (GDA), and splenic artery (SPA). The regions of the pancreas that were most enhanced on CT during arteriography were considered to be the areas receiving the greatest infusion of blood from the selected artery. Results: In all 13 patients, the uncinate process, the superior head, and the tail of the pancreas were predominantly supplied by the SMA, GDA, and SPA, respectively. The inferior head of the pancreas was predominantly supplied by the SMA in five patients, the GDA in nine patients, and both the SMA and GDA in one patient. The body of the pancreas was predominantly supplied by the SMA, GDA, and SPA in seven, two, and ten patients, respectively. Conclusions: The uncinate process predominantly infused by the SMA, the superior head by the GDA, and the tail by the SPA. The patterns of the vascular supply of the inferior head and the body vary from patient to patient.
  • Catherine Coolens, Steve Webb, H. Shirato, K. Nishioka, Phil M. Evans PHYSICS IN MEDICINE AND BIOLOGY 53 (16) 4317 -4330 2008年08月 [査読無し][通常論文]
     
    In order to reduce the sensitivity of radiotherapy treatments to organ motion, compensation methods are being investigated such as gating of treatment delivery, tracking of tumour position, 4D scanning and planning of the treatment, etc. An outstanding problem that would occur with all these methods is the assumption that breathing motion is reproducible throughout the planning and delivery process of treatment. This is obviously not a realistic assumption and is one that will introduce errors. A dynamic internal margin model (DIM) is presented that is designed to follow the tumour trajectory and account for the variability in respiratory motion. The model statistically describes the variation of the breathing cycle over time, i. e. the uncertainty in motion amplitude and phase reproducibility, in a polar coordinate system from which margins can be derived. This allows accounting for an additional gating window parameter for gated treatment delivery as well as minimizing the area of normal tissue irradiated. The model was illustrated with abdominal motion for a patient with liver cancer and tested with internal 3D lung tumour trajectories. The results confirm that the respiratory phases around exhale are most reproducible and have the smallest variation in motion amplitude and phase (approximately 2 mm). More importantly, the margin area covering normal tissue is significantly reduced by using trajectory- specific margins (as opposed to conventional margins) as the angular component is by far the largest contributor to the margin area. The statistical approach to margin calculation, in addition, offers the possibility for advanced online verification and updating of breathing variation as more data become available.
  • Koichi Yasuda, Hiroshi Taguchi, Yutaka Sawamura, Jun Ikeda, Hidefumi Aoyama, Kenji Fujieda, Nobuaki Ishii, Masaaki Kashiwamura, Yoshinobu Iwasaki, Hiroki Shirato JAPANESE JOURNAL OF CLINICAL ONCOLOGY 38 (7) 486 -492 2008年07月 [査読無し][通常論文]
     
    Objective: The current study was conducted to evaluate the effects of low-dose craniospinal irradiation (CSI) combined with chemotherapy on non-metastatic embryonal tumors in the central nervous system (CNS), including medulloblastoma and supra-tentorial primitive neuroectodermal tumors (ST-PNET). Methods: All patients were treated according to the following protocol. After surgery, the patients <= 5 years old received 18 Gy and the patients > 5 years old received 24 Gy CSI. The dose to the primary tumor bed was 39.6-54 Gy. Chemotherapy consisted of ifosfamide, cisplatin and etoposide (ICE chemotherapy). Results: Sixteen patients aged 0.5-20.4 (median 6.1) years were enrolled and followed for 11-165 (median 112) months. Both 5-year actuarial overall survival (OAS) and progression-free survival (PFS) were 81% (95% confidence interval (CI): 62-100%) for the 16 patients. Both 5-year OAS and PFS were 82% (CI: 59-100%) for the patients with medulloblastoma and 80% (CI: 45-100%) for the patients with ST-PNET. Both 5-year OAS and PFS were 75% for the eight patients <= 5 years old and 88% for the eight patients > 5 years old. Both 5-year OAS and PFS were 100% for six average-risk patients (3 years or older, total resection and posterior fossa) and 70% for 10 poor-risk patients (others). The median total intellectual quotient at the last follow-up was 85 (ranging from 48 to 103) in 12 patients who were followed for 3-145 (median 49) months. Eight patients received hormone replacement therapy. Conclusion: Low-dose CSI and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the CNS.
  • Koichi Yasuda, Hiroshi Taguchi, Yutaka Sawamura, Jun Ikeda, Hidefumi Aoyama, Kenji Fujieda, Nobuaki Ishii, Masaaki Kashiwamura, Yoshinobu Iwasaki, Hiroki Shirato JAPANESE JOURNAL OF CLINICAL ONCOLOGY 38 (7) 486 -492 2008年07月 [査読無し][通常論文]
     
    Objective: The current study was conducted to evaluate the effects of low-dose craniospinal irradiation (CSI) combined with chemotherapy on non-metastatic embryonal tumors in the central nervous system (CNS), including medulloblastoma and supra-tentorial primitive neuroectodermal tumors (ST-PNET). Methods: All patients were treated according to the following protocol. After surgery, the patients <= 5 years old received 18 Gy and the patients > 5 years old received 24 Gy CSI. The dose to the primary tumor bed was 39.6-54 Gy. Chemotherapy consisted of ifosfamide, cisplatin and etoposide (ICE chemotherapy). Results: Sixteen patients aged 0.5-20.4 (median 6.1) years were enrolled and followed for 11-165 (median 112) months. Both 5-year actuarial overall survival (OAS) and progression-free survival (PFS) were 81% (95% confidence interval (CI): 62-100%) for the 16 patients. Both 5-year OAS and PFS were 82% (CI: 59-100%) for the patients with medulloblastoma and 80% (CI: 45-100%) for the patients with ST-PNET. Both 5-year OAS and PFS were 75% for the eight patients <= 5 years old and 88% for the eight patients > 5 years old. Both 5-year OAS and PFS were 100% for six average-risk patients (3 years or older, total resection and posterior fossa) and 70% for 10 poor-risk patients (others). The median total intellectual quotient at the last follow-up was 85 (ranging from 48 to 103) in 12 patients who were followed for 3-145 (median 49) months. Eight patients received hormone replacement therapy. Conclusion: Low-dose CSI and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the CNS.
  • D. Ruan, J. Fessler, J. Balter, R. Berbeco, S. Nishioka, H. Shirato Medical Physics 35 (6) 2893 2008年06月 [査読無し][通常論文]
     
    Purpose: To infer internal respiration‐induced tumor motion from external surrogate. To systematically resolve mapping ambiguity caused by breathing hysteresis. Method and Materials: We propose a state‐augmentation approach to capture system dynamics. Concatenating real‐time surrogate observations with their time‐delayed records describes the state information in a higher‐dimensional state space. In such space, inhale and exhale “stages” are naturally separated due to the incorporated velocity contents. Any existing inference model migrates effortlessly into this framework. We illustrate the idea with simple polynomial inference models, and derive a closed‐form solution for optimal choice of model parameters. Choice of lag length is demonstrated empirically to be robust and may be chosen offline. This approach is tested on synchronized recordings of internal tumor trajectories and external fiducial marker readouts from eight lung patients (multiple fractions and readings) with a Mitsubishi real‐time radiotherapy (RTRT) system. Internal recording is obtained by fluoroscopic tracking of implanted 1.5mm‐diameter gold ball bearings around the tumor and external surrogates measure relative abdominal skin positions. Results: Examination of trajectories in the augmented state‐space suggests the existence of a consistent and unambiguous inference map. Empirical tests with clinical data show that using state augmentation decreases the 3D RMSE from 2.01mm to 1.74mm with the linear model and 1.93mm to 1.63 with the quadratic model. Paired student‐t tests with P‐values on the order of 10e‐13 indicate statistical significance of the improvement. Conclusion: We proposed a simple state‐augmentation approach to implicitly incorporate the hysteretic internal‐external response pattern into the estimation framework with any existing inference model. For the general class of correspondence models that are linear in their parameters, closed‐form solutions for the optimal parameter values and the error evaluations are derived. Tests with clinical data demonstrate statistically significant improvement over direct models. This work is sponsored by NIH P01‐CA59827 and Barbour Scholarship. © 2008, American Association of Physicists in Medicine. All rights reserved.
  • H. Wu, Q. Zhao, R. Berbeco, H. Shirato, S. Nishioka, S. Jiang Medical Physics 35 (6) 2697 -+ 2008年06月 [査読無し][通常論文]
     
    Purpose: The effectiveness of gated radiotherapy dependents on the precise localization of tumor positions in real‐time during the treatment. Two widely used gating approaches are internal gating and external gating. Internal gating is accurate but invasive and radiation dose to the patients is a big concern. External gating is non‐invasive but less accurate. We have proposed a new gating approach to combine the advantages and minimize the disadvantages of internal and external gating. Method and Materials: In our new approach, the external signal is acquired at high frequency while the internal signal is acquired at very low frequency. Algorithms are designed to decide the optimal x‐ray imaging time and update the internal/external correlation in real‐time, which will be used to derive the internal tumor position. A simulation system has been implemented to evaluate hybrid gating using the synchronized internal/external signals acquired during patient treatment. Results: Two dynamic correlation updating algorithms are introduced: based on amplitude and a piecewise linear model. Two assessment metrics, gating duty cycle and target coverage, have been defined to quantitatively evaluate the simulation results. The influences of different clinical scenarios for hybrid gating, including the gating window size, x‐ray imaging frequency, and the timing for internal signal acquisition, has been investigated. Our results demonstrated that dynamically updating the internal/external correlation in or around the gating window will improve the target coverage (by ∼14%) with relatively diminished duty cycle (by ∼10%). Conclusion: The developed hybrid gating technique has higher accuracy than external gating at a cost of much lower x‐ray imaging dose than internal gating. This improvement will benefit patients with mobile tumors, especially greater for early stage lung cancers, for which the tumors are less attached or freely floating in the lung with more movement. © 2008, American Association of Physicists in Medicine. All rights reserved.
  • R. Mcmahon, L. Papiez, R. Berbeco, S. Nishioka, H. Shirato Medical Physics 35 (6) 2638 -+ 2008年06月 [査読無し][通常論文]
     
    Purpose: We have developed a real‐time MLC control algorithm that allows for delivery of dynamic‐MLC (DMLC) IMRT to targets exhibiting 2D rigid motion in the beam's eye view (BEV). Method and Materials: The control algorithm consists of two components: 1) Construction of baseline DMLC leaf trajectories, and 2) real‐time control loop. The synchronized baseline leaf trajectories are constructed using target motion data that is collected prior to delivery. Only target motion that is aligned with leaf travel is included in this step. To account for target motion in the BEV that is not aligned with leaf travel, we have implemented a real‐time leaf‐pair switching mechanism, which allows the MLC to track motion along this axis in discrete increments of the leaf width. Using patient data, 36 target trajectories were constructed. One of these trajectories was used to construct the baseline leaf trajectories, and the others were used to simulate a 35 fraction IMRT treatment. Errors were analyzed using difference maps and a distance‐to‐agreement analysis. Results: The results indicate that 2D tracking resulted in deliveries that were superior to both no tracking and 1D tracking. A 160ms system lag time produced errors that were approximately equal those that resulted from ignoring one component of motion altogether. Additional results show that the algorithm's performance is very insensitive to the level of agreement between the target motion collected prior to delivery, and the motion observed during delivery. Conclusion: Over the course of a fractionated IMRT treatment, the MLC tracking algorithm is able to accurately compensate for 2D rigid target motion in the BEV. The performance of the algorithm is insensitive to the difference between the target motion measured during planning and the motion that actually occurs during delivery. © 2008, American Association of Physicists in Medicine. All rights reserved.
  • D. Ruan, J. A. Fessler, J. M. Balter, R. I. Berbeco, S. Nishioka, H. Shirato PHYSICS IN MEDICINE AND BIOLOGY 53 (11) 2923 -2936 2008年06月 [査読無し][通常論文]
     
    It is important to monitor tumor movement during radiotherapy. Respiration-induced motion affects tumors in the thorax and abdomen (in particular, those located in the lung region). For image-guided radiotherapy (IGRT) systems, it is desirable to minimize imaging dose, so external surrogates are used to infer the internal tumor motion between image acquisitions. This process relies on consistent correspondence between the external surrogate signal and the internal tumor motion. Respiratory hysteresis complicates the external/internal correspondence because two distinct tumor positions during different breathing phases can yield the same external observation. Previous attempts to resolve this ambiguity often subdivided the data into inhale/exhale stages and restricted the estimation to only one of these directions. In this study, we propose a new approach to infer the internal tumor motion from external surrogate signal using state augmentation. This method resolves the hysteresis ambiguity by incorporating higher-order system dynamics. It circumvents the segmentation of the internal/external trajectory into different phases, and estimates the inference map based on all the available external/internal correspondence pairs. Optimization of the state augmentation is investigated. This method generalizes naturally to adaptive on-line algorithms.
  • Norio Katoh, Rikiya Onimaru, Yusuke Sakuhara, Daisuke Abo, Shinichi Shimizu, Hiroshi Taguchi, Yoshiaki Watanabe, Nobuo Shinohara, Masayori Ishikawa, Hiroki Shirato RADIOTHERAPY AND ONCOLOGY 87 (3) 418 -424 2008年06月 [査読無し][通常論文]
     
    Purpose: To investigate the three-dimensional movement of internal fiducial markers near the adrenal tumors using a real-time tumor-tracking radiotherapy (RTRT) system and to examine the feasibility of high-dose hypofractionated radiotherapy for the adrenal tumors. Materials and methods: The subjects considered in this study were 10 markers of the 9 patients treated with RTRT. A total of 72 days in the prone position and 61 treatment days in the supine position for nine of the 10 markers were analyzed. All but one patient were prescribed 48 Gy in eight fractions at the isocenter. Results: The average absolute amplitude of the marker movement in the prone position was 6.1 +/- 4.4 mm (range 2.3-14.4), 11.1 +/- 7.1 mm (3.5-25.2), and 7.0 +/- 3.5 mm (3.9-12.5) in the left-right (LR), craniocaudal (CC), and anterior-posterior (AP) directions, respectively. The average absolute amplitude in the supine position was 3.4 +/- 2.9 mm (0.6-9.1), 9.9 +/- 9.8 mm (1.1-27.1), and 5.4 +/- 5.2 mm (1.7-26.6) in the LR, CC, and AP directions, respectively. Of the eight markers, which were examined in both the prone and supine positions, there was no significant difference in the average absolute amplitude between the two positions. No symptomatic adverse effects were observed within the median follow-up period of 16 months (range 5-21 months). The actuarial freedom-from-local-progression rate was 100% at 12 months. Conclusions: Three-dimensional motion of a fiducial marker near the adrenal tumors was detected. Hypofractionated RTRT for adrenal tumors was feasible for patients with metastatic tumors. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
  • Norio Katoh, Rikiya Onimaru, Yusuke Sakuhara, Daisuke Abo, Shinichi Shimizu, Hiroshi Taguchi, Yoshiaki Watanabe, Nobuo Shinohara, Masayori Ishikawa, Hiroki Shirato RADIOTHERAPY AND ONCOLOGY 87 (3) 418 -424 2008年06月 [査読無し][通常論文]
     
    Purpose: To investigate the three-dimensional movement of internal fiducial markers near the adrenal tumors using a real-time tumor-tracking radiotherapy (RTRT) system and to examine the feasibility of high-dose hypofractionated radiotherapy for the adrenal tumors. Materials and methods: The subjects considered in this study were 10 markers of the 9 patients treated with RTRT. A total of 72 days in the prone position and 61 treatment days in the supine position for nine of the 10 markers were analyzed. All but one patient were prescribed 48 Gy in eight fractions at the isocenter. Results: The average absolute amplitude of the marker movement in the prone position was 6.1 +/- 4.4 mm (range 2.3-14.4), 11.1 +/- 7.1 mm (3.5-25.2), and 7.0 +/- 3.5 mm (3.9-12.5) in the left-right (LR), craniocaudal (CC), and anterior-posterior (AP) directions, respectively. The average absolute amplitude in the supine position was 3.4 +/- 2.9 mm (0.6-9.1), 9.9 +/- 9.8 mm (1.1-27.1), and 5.4 +/- 5.2 mm (1.7-26.6) in the LR, CC, and AP directions, respectively. Of the eight markers, which were examined in both the prone and supine positions, there was no significant difference in the average absolute amplitude between the two positions. No symptomatic adverse effects were observed within the median follow-up period of 16 months (range 5-21 months). The actuarial freedom-from-local-progression rate was 100% at 12 months. Conclusions: Three-dimensional motion of a fiducial marker near the adrenal tumors was detected. Hypofractionated RTRT for adrenal tumors was feasible for patients with metastatic tumors. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
  • Rumiko Kinoshita, Shinichi Shimizu, Hiroshi Taguchi, Norio Katoh, Masaharu Fujino, Rikiya Onimaru, Hidefumi Aoyama, Fumi Katoh, Tokuhiko Omatsu, Masayori Ishikawa, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 (3) 931 -934 2008年03月 [査読無し][通常論文]
     
    Purpose: To evaluate the three-dimensional intrafraction motion of the breast during tangential breast irradiation using a real-time tracking radiotherapy (RT) system with a high-sampling frequency. Methods and Materials: A total of 17 patients with breast cancer who had received breast conservation RT were included in this study. A 2.0-mm gold marker was placed on the skin near the nipple of the breast for RT. A fluoroscopic real-time tumor-tracking RT system was used to monitor the marker. The range of motion of each patient was calculated in three directions. Results: The mean standard deviation of the range of respiratory motion was 1.0 +/- 0.6 mm (median, 0.9; 95% confidence interval [CI] of the marker position, 0.4-2.6), 1.3 +/- 0.5 mm (median, 1.1; 95 % CI, 0.5-2.5), and 2.6 +/- 1.4 (median, 2.3; 95 % CI, 1.0-6.9) for the right-left, craniocaudal, and anteroposterior direction, respectively. No correlation was found between the range of motion and the body mass index or respiratory function. The mean +/- standard deviation of the absolute value of the baseline shift in the right-left, craniocaudal, and anteroposterior direction was 0.2 +/- 0.2 mm (range, 0.0-0.8 mm), 0.3 +/- 0.2 mm (range, 0.0-0.7 mm), and 0.8 +/- 0.7 mm (range, 0.1-1.8 mm), respectively. Conclusion: Both the range of motion and the baseline shift were within a few millimeters in each direction. As long as the conventional wedge-pair technique and the proper immobilization are used, the intrafraction three-dimensional change in the breast surface did not much influence the dose distribution. (C) 2008 Elsevier Inc.
  • Rumiko Kinoshita, Shinichi Shimizu, Hiroshi Taguchi, Norio Katoh, Masaharu Fujino, Rikiya Onimaru, Hidefumi Aoyama, Fumi Katoh, Tokuhiko Omatsu, Masayori Ishikawa, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 (3) 931 -934 2008年03月 [査読無し][通常論文]
     
    Purpose: To evaluate the three-dimensional intrafraction motion of the breast during tangential breast irradiation using a real-time tracking radiotherapy (RT) system with a high-sampling frequency. Methods and Materials: A total of 17 patients with breast cancer who had received breast conservation RT were included in this study. A 2.0-mm gold marker was placed on the skin near the nipple of the breast for RT. A fluoroscopic real-time tumor-tracking RT system was used to monitor the marker. The range of motion of each patient was calculated in three directions. Results: The mean standard deviation of the range of respiratory motion was 1.0 +/- 0.6 mm (median, 0.9; 95% confidence interval [CI] of the marker position, 0.4-2.6), 1.3 +/- 0.5 mm (median, 1.1; 95 % CI, 0.5-2.5), and 2.6 +/- 1.4 (median, 2.3; 95 % CI, 1.0-6.9) for the right-left, craniocaudal, and anteroposterior direction, respectively. No correlation was found between the range of motion and the body mass index or respiratory function. The mean +/- standard deviation of the absolute value of the baseline shift in the right-left, craniocaudal, and anteroposterior direction was 0.2 +/- 0.2 mm (range, 0.0-0.8 mm), 0.3 +/- 0.2 mm (range, 0.0-0.7 mm), and 0.8 +/- 0.7 mm (range, 0.1-1.8 mm), respectively. Conclusion: Both the range of motion and the baseline shift were within a few millimeters in each direction. As long as the conventional wedge-pair technique and the proper immobilization are used, the intrafraction three-dimensional change in the breast surface did not much influence the dose distribution. (C) 2008 Elsevier Inc.
  • Mikado Imura, Koichi Yamazaki, Kanako C. Kubota, Tomoo Itoh, Rikiya Onimaru, Yasushi Cho, Yasuhiro Hida, Kichizo Kaga, Yuya Onodera, Shigeaki Ogura, Hirotoshi Dosaka-Akita, Hiroki Shirato, Masaharu Nishimura INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 (2) 382 -384 2008年02月 [査読無し][通常論文]
     
    Purpose: Internal fiducial gold markers, safely inserted with bronchoscopy, have been used in real-time tumor-tracking radiotherapy for lung cancer. We investigated the histopathologic findings at several points after the insertion of the gold markers. Methods and Materials: Sixteen gold markers were inserted for preoperative marking in 7 patients who subsequently underwent partial resection of tumors by video-assisted thoracoscopic surgery within 7 days. Results: Fibrotic changes and hyperplasia of type 2 pneumocytes around the markers were seen 5 or 7 days after insertion, and fibrin exudation without fibrosis was detected 1 or 2 days after insertion. Conclusions: Because fibroblastic changes start approximately 5 days after gold marker insertion, real-time tumor-tracking radiotherapy should be started >5 days after gold marker insertion. (C) 2008 Elsevier Inc.
  • Yusuke Sakuhara, Fumi Kato, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Satoshi Terae, Hiroki Shirato JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 19 (2) 267 -271 2008年02月 [査読無し][通常論文]
     
    Kidney enlargement in autosomal-dominant polycystic kidney disease (ADPKD) may cause symptoms by compressing the alimentary tract, lungs, and heart. The clinical symptoms may be progressive, may markedly decrease quality of life, and may even be life-threatening. Although treatment of this disease is often difficult, transcatheter arterial embolization (TAE) with metallic coils has been reported as a renal contraction therapy that is less invasive than surgery. The present report describes a case of ADPKD successfully treated by TAE with absolute ethanol after a previous TAE procedure with metallic coils failed to contract the affected kidneys because of recanalization.
  • Rikiya Onimaru, Masaharu Fujino, Koichi Yamazaki, Yuya Onodera, Hiroshi Taguchi, Norio Katoh, Fumihiro Hommura, Satoshi Oizumi, Masaharu Nishimura, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 (2) 374 -381 2008年02月 [査読無し][通常論文]
     
    Purpose: To investigate the clinical outcomes of patients with pathologically proven, peripherally located, Stage I non-small-cell lung cancer who had undergone stereotactic body radiotherapy using real-time tumor tracking radiotherapy during the developmental period. Methods and Materials: A total of 41 patients (25 with Stage T1 and 16 with Stage T2) were admitted to the study between February 2000 and June 2005. A 5-mm planning target volume margin was added to the clinical target volume determined with computed tomography at the end of the expiratory phase. The gating window ranged from 2 to 3 rum. The dose fractionation schedule was 40 or 48 Gy in four fractions within 1 week. The dose was prescribed at the center of the planning target volume, giving more than an 80% dose at the planning target volume periphery. Results: For 28 patients treated with 48 Gy in four fractions, the overall actuarial survival rate at 3 years was 82% for those with Stage IA and 32% for those with Stage IB. For patients treated with 40 Gy in four fractions within 1 week, the overall actuarial survival rate at 3 years was 50% for those with Stage IA and 0% for those with Stage IB. A significant difference was found in local control between those with Stage IB who received 40 Gy vs. 48 Gy (p = 0.0015) but not in those with Stage IA (p = 0.5811). No serious radiation morbidity was observed with either dose schedule. Conclusion: The results of our study have shown that 48 Gy in four fractions within 1 week is a safe and effective treatment for peripherally located, Stage IA non-small-cell lung cancer. A steep dose-response curve between 40 and 48 Gy using a daily dose of 12 Gy delivered within 1 week was identified for Stage IB non-small-cell lung cancer in stereotactic body radiotherapy using real-time tumor tracking radiotherapy. (C) 2008 Elsevier Inc.
  • Mikado Imura, Koichi Yamazaki, Kanako C. Kubota, Tomoo Itoh, Rikiya Onimaru, Yasushi Cho, Yasuhiro Hida, Kichizo Kaga, Yuya Onodera, Shigeaki Ogura, Hirotoshi Dosaka-Akita, Hiroki Shirato, Masaharu Nishimura INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 (2) 382 -384 2008年02月 [査読無し][通常論文]
     
    Purpose: Internal fiducial gold markers, safely inserted with bronchoscopy, have been used in real-time tumor-tracking radiotherapy for lung cancer. We investigated the histopathologic findings at several points after the insertion of the gold markers. Methods and Materials: Sixteen gold markers were inserted for preoperative marking in 7 patients who subsequently underwent partial resection of tumors by video-assisted thoracoscopic surgery within 7 days. Results: Fibrotic changes and hyperplasia of type 2 pneumocytes around the markers were seen 5 or 7 days after insertion, and fibrin exudation without fibrosis was detected 1 or 2 days after insertion. Conclusions: Because fibroblastic changes start approximately 5 days after gold marker insertion, real-time tumor-tracking radiotherapy should be started >5 days after gold marker insertion. (C) 2008 Elsevier Inc.
  • Yusuke Sakuhara, Fumi Kato, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Satoshi Terae, Hiroki Shirato JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 19 (2) 267 -271 2008年02月 [査読無し][通常論文]
     
    Kidney enlargement in autosomal-dominant polycystic kidney disease (ADPKD) may cause symptoms by compressing the alimentary tract, lungs, and heart. The clinical symptoms may be progressive, may markedly decrease quality of life, and may even be life-threatening. Although treatment of this disease is often difficult, transcatheter arterial embolization (TAE) with metallic coils has been reported as a renal contraction therapy that is less invasive than surgery. The present report describes a case of ADPKD successfully treated by TAE with absolute ethanol after a previous TAE procedure with metallic coils failed to contract the affected kidneys because of recanalization.
  • Rikiya Onimaru, Masaharu Fujino, Koichi Yamazaki, Yuya Onodera, Hiroshi Taguchi, Norio Katoh, Fumihiro Hommura, Satoshi Oizumi, Masaharu Nishimura, Hiroki Shirato INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 70 (2) 374 -381 2008年02月 [査読無し][通常論文]
     
    Purpose: To investigate the clinical outcomes of patients with pathologically proven, peripherally located, Stage I non-small-cell lung cancer who had undergone stereotactic body radiotherapy using real-time tumor tracking radiotherapy during the developmental period. Methods and Materials: A total of 41 patients (25 with Stage T1 and 16 with Stage T2) were admitted to the study between February 2000 and June 2005. A 5-mm planning target volume margin was added to the clinical target volume determined with computed tomography at the end of the expiratory phase. The gating window ranged from 2 to 3 rum. The dose fractionation schedule was 40 or 48 Gy in four fractions within 1 week. The dose was prescribed at the center of the planning target volume, giving more than an 80% dose at the planning target volume periphery. Results: For 28 patients treated with 48 Gy in four fractions, the overall actuarial survival rate at 3 years was 82% for those with Stage IA and 32% for those with Stage IB. For patients treated with 40 Gy in four fractions within 1 week, the overall actuarial survival rate at 3 years was 50% for those with Stage IA and 0% for those with Stage IB. A significant difference was found in local control between those with Stage IB who received 40 Gy vs. 48 Gy (p = 0.0015) but not in those with Stage IA (p = 0.5811). No serious radiation morbidity was observed with either dose schedule. Conclusion: The results of our study have shown that 48 Gy in four fractions within 1 week is a safe and effective treatment for peripherally located, Stage IA non-small-cell lung cancer. A steep dose-response curve between 40 and 48 Gy using a daily dose of 12 Gy delivered within 1 week was identified for Stage IB non-small-cell lung cancer in stereotactic body radiotherapy using real-time tumor tracking radiotherapy. (C) 2008 Elsevier Inc.
  • F. Yin, M. Roach, H. Shirato, J. Balter Medical Physics 35 2866 -2867 2008年01月01日 [査読無し][通常論文]
     
    While technology for image guided radiotherapy (IGRT) has advanced dramatically over the past few years, the basic fact remains that the actual treated target remains poorly or not at all visible using most in‐room imaging technologies. As a result, target localization and tracking is typically performed via the use of surrogates of the tumor. These surrogates may be endogenous to the patient (e.g. skeletal anatomy, diaphragm, external surface indicators), or exogenous and introduced into the patient to aid in localization / tracking (e.g. implanted radiopaque or electromagnetic fiducial markers). The selection of a surrogate should take into account the dynamic relationship between reference information and tumor position / configuration, and immobilization techniques (especially for breathing) may further aid in the fidelity of a given anatomic surrogate. Implanted markers carry a number of special considerations, including selection of marker, implant location and technique, clinical implications and marker stability over the time course of treatment, reference identification method, and guidance technique. As the vast majority of implanted marker methods have been developed on an ad hoc basis, a systematic discussion of these methods and related considerations can significantly help to guide medical physicists. Educational Objectives: 1. To discuss the various types of tumor surrogates, both anatomical and implanted, used for radiation therapy targeting. 2. To discuss techniques for identifying or implanting surrogates. 3. To discuss in‐room localization or imaging techniques for different surrogates, including the relationship between immobilization and surrogate fidelity. 4. To discuss the application of different surrogates, clinical feasibility and efficacy, and limitations. 5. To discuss quality assurance procedures and programs. 6. To discuss current challenges and future directions. © 2008, American Association of Physicists in Medicine. All rights reserved.
  • Huanmei Wu, Qingya Zhao, Ross Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6913 2008年 [査読無し][通常論文]
     
    Tumor motion induced by patient breathing decreases the effectiveness of radiation treatment. Image guided radiation treatment (IGRT) is an advanced approach for cancer radiation treatment. The success of IGRT is largely dependent on the accurate localization of tumor in real-time. There are two major imaging approaches currently in use to localize a tumor: internal imaging and external imaging. Internal imaging determines the tumor locations by directly x-ray of the tumor area. It is accurate however radiation dose is a big concern. External imaging derives the internal tumor locations through an external mark on the patient surface. It is radiation dose free however the insufficient accuracy limits its wide application. Integrating the internal and external signals together is necessary for reliable radiation treatment and acceptable patient radiation exposure. Our work tries to identify the correlation patterns between internal/external signals and the influential factors so that the hybrid signal will give desire accuracy in dose delivery while limiting radiation exposure to the patients. Both theoretical simulation based on sinusoidal functions and statistical analysis on real patient data are performed. The sinusoidal simulation will identify the potential influence factors of different correlation conditions. The results have demonstrated the various correlation patterns with amplitude various, frequency changes (duration changes), phase shifts, and baseline drift. The results will aid the statistical analytical on real-patients to identify the dominant factors of the internal/external motion signals for a specific patients. The described work is very useful in advanced IGRT to update the internal/external correlation in real-time for better cancer patient care.
  • Neurol Med Chir (Tokyo) 48 (9) 397 -400 2008年 [査読無し][通常論文]
  • [Intramedullary spinal cord metastasis treated with radiation therapy: report of 3 cases]
    No Shinkei Geka. 36(4) 345 -349 2008年 [査読無し][通常論文]
  • Seiko Nishioka, Takeshi Nishioka, Masaki Kawahara, Shigeru Tanaka, Tadao Hiromura, Kazuo Tomita, Hiroki Shirato RADIOTHERAPY AND ONCOLOGY 86 (1) 69 -76 2008年01月 [査読無し][通常論文]
     
    Purpose: For optimal respiratory-gated radiotherapy, exhale fluctuation was assessed by monitoring internal fiducials in a synchronized internal/external marker detection system. Methods: Synchronized internal/external position data were collected during the entire course of treatments for 12 lung patients with 24 fiducials. Baseline was determined in the exhale phase during pre-treatment observation time, and a gating level of external waves was set in each treatment session in a simulation of respiratory-gated radiotherapy. Patients were treated under a real-time tumor-tracking (RTRT) system with an external (abdominal) respiratory motion detector. In the simulation, external gating windows were defined as those below the 30% amplitude level (i.e., imaginary beams would be triggered when part of the respiratory wave falls into this window). Exhale fluctuation (EF) was defined as the phenomenon in which the lowest point of the external wave crossed downward past the predetermined baseline. Gating efficiency (GE) was defined as the ratio between the amount of gate-ON time and the total treatment time. Results: EF occurred in 18.4% of total measurements. EF varied depending on the patient, fiducial sites, and treatment session. The mean incidence of EF for each patient varied from 2.9% to 37.5% (18.4 +/- 9.9). The EF magnitude was 0.2-12.2 mm in the left-right direction, 0.7-12.7 mm in the cranio-caudal direction, and 0.4-9.7 mm in the anterior-posterior direction. Total fiducial movement was 0.5-28.7 mm. GE was 36.1-69.2% (55.4 +/- 11.0). EF magnitude correlated with total fiducial movement. Conclusion: This study showed that EF is not a rare phenomenon and needs to be taken into consideration for individualized precise 4D radiotherapy. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Hiroaki MOTEGI, Satoshi KURODA, Nobuaki ISHII, Hidefumi AOYAMA, Satoshi TERAE, Hiroki SHIRATO, Yoshinobu IWASAKI Neurol Med Chir (Tokyo). 48 (9) 397 -400 2008年 [査読無し][通常論文]
  • [Intramedullary spinal cord metastasis treated with radiation therapy: report of 3 cases]
    No Shinkei Geka. 36(4) 345 -349 2008年 [査読無し][通常論文]
  • Seiko Nishioka, Takeshi Nishioka, Masaki Kawahara, Shigeru Tanaka, Tadao Hiromura, Kazuo Tomita, Hiroki Shirato RADIOTHERAPY AND ONCOLOGY 86 (1) 69 -76 2008年01月 [査読無し][通常論文]
     
    Purpose: For optimal respiratory-gated radiotherapy, exhale fluctuation was assessed by monitoring internal fiducials in a synchronized internal/external marker detection system. Methods: Synchronized internal/external position data were collected during the entire course of treatments for 12 lung patients with 24 fiducials. Baseline was determined in the exhale phase during pre-treatment observation time, and a gating level of external waves was set in each treatment session in a simulation of respiratory-gated radiotherapy. Patients were treated under a real-time tumor-tracking (RTRT) system with an external (abdominal) respiratory motion detector. In the simulation, external gating windows were defined as those below the 30% amplitude level (i.e., imaginary beams would be triggered when part of the respiratory wave falls into this window). Exhale fluctuation (EF) was defined as the phenomenon in which the lowest point of the external wave crossed downward past the predetermined baseline. Gating efficiency (GE) was defined as the ratio between the amount of gate-ON time and the total treatment time. Results: EF occurred in 18.4% of total measurements. EF varied depending on the patient, fiducial sites, and treatment session. The mean incidence of EF for each patient varied from 2.9% to 37.5% (18.4 +/- 9.9). The EF magnitude was 0.2-12.2 mm in the left-right direction, 0.7-12.7 mm in the cranio-caudal direction, and 0.4-9.7 mm in the anterior-posterior direction. Total fiducial movement was 0.5-28.7 mm. GE was 36.1-69.2% (55.4 +/- 11.0). EF magnitude correlated with total fiducial movement. Conclusion: This study showed that EF is not a rare phenomenon and needs to be taken into consideration for individualized precise 4D radiotherapy. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
  • Huanmei Wu, George Sandison, Li Zhao, Qingya Zhao, Hiroki Shirato, Steve Jiang AUSTRALASIAN PHYSICAL & ENGINEERING SCIENCES IN MEDICINE 30 (4) 341 -344 2007年12月 [査読無し][通常論文]
     
    Characterizing respiratory-induced tumour motion is an important step in the effective image-guided radiation treatment of moving tumours, especially for tumours in the lung and lower abdomen. This study characterized turnout motion based on a piecewise linear model representing tumour motion at defined stages of the breathing cycle. Lung tumour locations were categorized based on broncho-pulmonary segments. Association rules between tumour motion characteristics and their locations in the lung were discovered and parameterized through statistical analysis. Results show there is a correlation between tumour motion characteristics and turnout location in the lungs. Generally, tumours with small motion (amplitude < 10mm) are observed most frequently in the apex region of lung or when attached to a fixed structure, Such as the chest wall or aorta. Tumours with relatively large motion (amplitude > 20mm) are located close to the diaphragm or mid-level periphery of the lungs close to the chest wall.
  • Huanmei Wu, George Sandison, Li Zhao, Qingya Zhao, Hiroki Shirato, Steve Jiang AUSTRALASIAN PHYSICAL & ENGINEERING SCIENCES IN MEDICINE 30 (4) 341 -344 2007年12月 [査読無し][通常論文]
     
    Characterizing respiratory-induced tumour motion is an important step in the effective image-guided radiation treatment of moving tumours, especially for tumours in the lung and lower abdomen. This study characterized turnout motion based on a piecewise linear model representing tumour motion at defined stages of the breathing cycle. Lung tumour locations were categorized based on broncho-pulmonary segments. Association rules between tumour motion characteristics and their locations in the lung were discovered and parameterized through statistical analysis. Results show there is a correlation between tumour motion characteristics and turnout location in the lungs. Generally, tumours with small motion (amplitude < 10mm) are observed most frequently in the apex region of lung or when attached to a fixed structure, Such as the chest wall or aorta. Tumours with relatively large motion (amplitude > 20mm) are located close to the diaphragm or mid-level periphery of the lungs close to the chest wall.
  • Qing Ren, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco PHYSICS IN MEDICINE AND BIOLOGY 52 (22) 6651 -6661 2007年11月 [査読無し][通常論文]
     
    One potential application of image-guided radiotherapy is to track the target motion in real time, then deliver adaptive treatment to a dynamic target by dMLC tracking or respiratory gating. However, the existence of a finite time delay (or a system latency) between the image acquisition and the response of the treatment system to a change in tumour position implies that some kind of predictive ability should be included in the real-time dynamic target treatment. If diagnostic x-ray imaging is used for the tracking, the dose given over a whole image-guided radiotherapy course can be significant. Therefore, the x-ray beam used for motion tracking should be triggered at a relatively slow pulse frequency, and an interpolation between predictions can be used to provide a fast tracking rate. This study evaluates the performance of an autoregressive- moving average (ARMA) model based prediction algorithm for reducing tumour localization error due to system latency and slow imaging rate. For this study, we use 3D motion data from ten lung tumour cases where the peak-to-peak motion is greater than 8 mm. Some strongly irregular traces with variation in amplitude and phase were included. To evaluate the prediction accuracy, the standard deviations between predicted and actual motion position are computed for three system latencies (0.1, 0.2 and 0.4 s) at several imaging rates (1.25-10 Hz), and compared against the situation of no prediction. The simulation results indicate that the implementation of the prediction algorithm in real-time target tracking can improve the localization precision for all latencies and imaging rates evaluated. From a common initial setting of model parameters, the predictor can quickly provide an accurate prediction of the position after collecting 20 initial data points. In this retrospective analysis, we calculate the standard deviation of the predicted position from the twentieth position data to the end of the session at 0.1 s interval. For both regular and irregular lung tumour motions, with prediction the range of average errors is 0.4-2.5mm in the SI direction from shorter to longer latency, corresponding to a range of 0.8-4.3 mm without prediction; for the AP direction a range of 0.3-1.6 mm is obtained with prediction, corresponding to a range of 0.6-3.0 mm without prediction. For 0.2 s and 0.4 s system latency, with prediction the localization based on a relatively slowimaging rate (2.5 Hz) can achieve a better or similar precision compared with no prediction but on a fast imaging rate (10 Hz). This means that precise localization can be realized at a slow imaging rate. This is important for the application of kV x-ray imaging systems and EPID-based systems in image-guided radiotherapy. In conclusion, the adaptive predictor can successfully predict irregular respiratory motion, and the adaptive prediction of respiration motion can effectively improve the delivery precision of real-time motion compensation radiotherapy.
  • Yusuke Sakuhara, Tadashi Shimizu, Daisuke Abo, Yu Hasegawa, Fumi Kato, Yoshihisa Kodama, Hiroki Shirato CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 30 (6) 1201 -1205 2007年11月 [査読無し][通常論文]
     
    Purpose During radiofrequency ablation (RFA), there is a risk that the multitined expandable electrode will come into contact with one of the surgical staples used to treat local recurrence after surgical operations. Our objective was to evaluate whether a surgical staple would influence the RFA of egg white using a multitined expandable electrode. Methods Multitined expandable electrodes, LeVeen needles (expandable diameter 3.0 cm), were sunk into an egg white bath with (a) no surgical staple, (b) a surgical staple touching one of the tines, or (c) a surgical staple touching two of the tines simultaneously. By connecting the LeVeen needle and copper plate at the bottom of the bath, RFA was then performed on the egg whites as a substitute for human tissue. Ten egg white baths were ablated under each of conditions (a), (b), and (c), for a total of 30 sets of coagulated egg white. Results There was no significant difference in the time from the power-on to the roll-off (i.e., the completion and shutting off of the electric circuit) or in the maximum diameter of the thermal lesion between conditions (a) and (b) or (a) and (c). However, the minimum diameter of the thermal lesion was significantly smaller in (c) compared with (a) (p < 0.01). Conclusions Surgical staples have the capacity to interfere with the electromagnetic field and decrease the minimum diameter of the thermal lesion in the event that a staple touches two of the tines of a multitined expandable electrode during RFA. Although the difference might be small enough to be neglected under many clinical circumstances, we recommend that, if possible, the tines not be expanded near metallic material.
  • Hiroshi Yokouchi, Kenji Chamoto, Daiko Wakita, Koichi Yamazaki, Hiroki Shirato, Tsuguhide Takeshima, Hirotoshi Dosaka-Akita, Masaharu Nishimura, Zhang Yue, Hidemitsu Kitamura, Takashi Nishimura CLINICAL & EXPERIMENTAL METASTASIS 24 (7) 533 -540 2007年11月 [査読無し][通常論文]
     
    Mice bearing established Lewis lung carcinoma (LLC) expressing model tumor antigen, ovalbumin (OVA) (LLC-OVA) marginally responded to local radiotherapy, but none of the mice was cured. In contrast, treatment of the tumor-bearing mice with intratumoral injection of tumor-specific T helper type 1 (Th1) cells and tumor antigen (OVA) after radiotherapy dramatically prolonged the survival days and induced complete cure of the mice at high frequency (80%). Radiation therapy combined with Th1 cells or OVA alone showed no significant therapeutic activity against LLC-OVA. Such a strong therapeutic activity was not induced by intratumoral injection of Th1 cells plus OVA. Compared with other treatment, radiation therapy combined with Th1 cells and OVA was superior to induce the generation of OVA/H-2(b) tetramer (+) tumor-specific cytotoxic T lymphocyte (CTL) with a strong cytotoxicity against LLC-OVA in draining lymph node (DLN). Moreover, the combined therapy is demonstrated to inhibit the growth of tumor mass, which grew at contralateral side. These results indicated that radiotherapy combined with Th1 cell/vaccine therapy induced a systemic antitumor immunity. These findings suggested that combination therapy with radiotherapy and Th1 cell/vaccine therapy may become a practical strategy for cancer treatment.
  • Qing Ren, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco PHYSICS IN MEDICINE AND BIOLOGY 52 (22) 6651 -6661 2007年11月 [査読無し][通常論文]
     
    One potential application of image-guided radiotherapy is to track the target motion in real time, then deliver adaptive treatment to a dynamic target by dMLC tracking or respiratory gating. However, the existence of a finite time delay (or a system latency) between the image acquisition and the response of the treatment system to a change in tumour position implies that some kind of predictive ability should be included in the real-time dynamic target treatment. If diagnostic x-ray imaging is used for the tracking, the dose given over a whole image-guided radiotherapy course can be significant. Therefore, the x-ray beam used for motion tracking should be triggered at a relatively slow pulse frequency, and an interpolation between predictions can be used to provide a fast tracking rate. This study evaluates the performance of an autoregressive- moving average (ARMA) model based prediction algorithm for reducing tumour localization error due to system latency and slow imaging rate. For this study, we use 3D motion data from ten lung tumour cases where the peak-to-peak motion is greater than 8 mm. Some strongly irregular traces with variation in amplitude and phase were included. To evaluate the prediction accuracy, the standard deviations between predicted and actual motion position are computed for three system latencies (0.1, 0.2 and 0.4 s) at several imaging rates (1.25-10 Hz), and compared against the situation of no prediction. The simulation results indicate that the implementation of the prediction algorithm in real-time target tracking can improve the localization precision for all latencies and imaging rates evaluated. From a common initial setting of model parameters, the predictor can quickly provide an accurate prediction of the position after collecting 20 initial data points. In this retrospective analysis, we calculate the standard deviation of the predicted position from the twentieth position data to the end of the session at 0.1 s interval. For both regular and irregular lung tumour motions, with prediction the range of average errors is 0.4-2.5mm in the SI direction from shorter to longer latency, corresponding to a range of 0.8-4.3 mm without prediction; for the AP direction a range of 0.3-1.6 mm is obtained with prediction, corresponding to a range of 0.6-3.0 mm without prediction. For 0.2 s and 0.4 s system latency, with prediction the localization based on a relatively slowimaging rate (2.5 Hz) can achieve a better or similar precision compared with no prediction but on a fast imaging rate (10 Hz). This means that precise localization can be realized at a slow imaging rate. This is important for the application of kV x-ray imaging systems and EPID-based systems in image-guided radiotherapy. In conclusion, the adaptive predictor can successfully predict irregular respiratory motion, and the adaptive prediction of respiration motion can effectively improve the delivery precision of real-time motion compensation radiotherapy.
  • Yusuke Sakuhara, Tadashi Shimizu, Daisuke Abo, Yu Hasegawa, Fumi Kato, Yoshihisa Kodama, Hiroki Shirato CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 30 (6) 1201 -1205 2007年11月 [査読無し][通常論文]
     
    Purpose During radiofrequency ablation (RFA), there is a risk that the multitined expandable electrode will come into contact with one of the surgical staples used to treat local recurrence after surgical operations. Our objective was to evaluate whether a surgical staple would influence the RFA of egg white using a multitined expandable electrode. Methods Multitined expandable electrodes, LeVeen needles (expandable diameter 3.0 cm), were sunk into an egg white bath with (a) no surgical staple, (b) a surgical staple touching one of the tines, or (c) a surgical staple touching two of the tines simultaneously. By connecting the LeVeen needle and copper plate at the bottom of the bath, RFA was then performed on the egg whites as a substitute for human tissue. Ten egg white baths were ablated under each of conditions (a), (b), and (c), for a total of 30 sets of coagulated egg white. Results There was no significant difference in the time from the power-on to the roll-off (i.e., the completion and shutting off of the electric circuit) or in the maximum diameter of the thermal lesion between conditions (a) and (b) or (a) and (c). However, the minimum diameter of the thermal lesion was significantly smaller in (c) compared with (a) (p < 0.01). Conclusions Surgical staples have the capacity to interfere with the electromagnetic field and decrease the minimum diameter of the thermal lesion in the event that a staple touches two of the tines of a multitined expandable electrode during RFA. Although the difference might be small enough to be neglected under many clinical circumstances, we recommend that, if possible, the tines not be expanded near metallic material.