Feb. 2018, 一般社団法人科学技術と経済の会（JATES）, 技術経営・イノベーション賞 科学技術と経済の会会長賞　　　　　　　　　　　　　　　

Dec. 2017, SGL, SGH特別賞　　　　　　　　　　　　　　　
Japan

Jun. 2017, Japan Institute of Invention and Innovation, 恩賜発明賞　　　　　　　　　　　　　　　
Japan

Aug. 2015, MEXT, 産学官連携功労者文部科学大臣賞　　　　　　　　　　　　　　　
Japan

Feb. 2015, Hokkaido, 北海道科学技術賞　　　　　　　　　　　　　　　
Japan

Feb. 2012, Hokkaido Univ,, 北海道大学研究総長賞　　　　　　　　　　　　　　　
Japan

2007, Research Front Award 2007　　　　　　　　　　　　　　　
Japan

Multi-institutional prospective observational study of radiotherapy for metastatic bone tumor.
Hideyuki Harada, Naoto Shikama, Akifumi Notsu, Hiroki Shirato, Kazunari Yamada, Haruka Uezono, Yutaro Koide, Hikaru Kubota, Takuya Yamazaki, Kei Ito, Joichi Heianna, Yukinori Okada, Ayako Tonari, Norio Katoh, Hitoshi Wada, Yasuo Ejima, Kayo Yoshida, Takashi Kosugi, Shigeo Takahashi, Takafumi Komiyama, Nobue Uchida, Misako Miwa, Miho Watanabe, Hisayasu Nagakura, Hiroko Ikeda, Tetsuo Saito, Isao Asakawa, Takeo Takahashi, Naoyuki Shigematsu
Journal of radiation research, 20 Aug. 2024, [International Magazine]
English, Scientific journal, Purpose of this study is to evaluate patient characteristics, treatments and outcomes in bone metastasis radiotherapy practice. Patients for whom radiotherapy for bone metastasis was planned at 26 institutions in Japan between December 2020 and March 2021 were consecutively registered in this prospective, observational study. Study measures included patient characteristics, pain relief, skeletal-related events (SREs), overall survival and incidence of radiation-related adverse events. Pain was evaluated using a numerical rating scale (NRS) from 0 to 10. Irradiated dose was analyzed by the biologically effective dose (BED) assuming α/β = 10. Overall, 232 patients were registered; 224 patients and 302 lesions were fully analyzed. Eastern Cooperative Oncology Group Performance Status was 0/1/2/3/4 in 23%/38%/22%/13%/4%; 59% of patients had spinal metastases and 84% had painful lesions (NRS ≥ 2). BED was <20 Gy (in 27%), 20-30 Gy (24%), 30-40 Gy (36%) and ≥ 40 Gy (13%); 9% of patients were treated by stereotactic body radiotherapy. Grade 3 adverse events occurred in 4% and no grade 4-5 toxicity was reported. Pain relief was achieved in 52% at 2 months. BED is not related to pain relief. The cumulative incidence of SREs was 6.5% (95% confidence interval (CI) 3.1-9.9) at 6 months; no factors were significantly associated with SREs. With spinal lesions, 18% of patients were not ambulatory at baseline and 50% of evaluable patients in this group could walk at 2 months. The 6-month overall survival rate was 70.2% (95% CI 64.2-76.9%). In conclusion, we report real-world details of radiotherapy in bone metastasis.

A novel method for measurements of sleep/wake states, feeding and drinking behaviors using the tracking technique of 3D positions in freely moving mice
Hamada T, Sutherland K, Ishikawa M, Saito J, Miyamoto N, Honma S, Shirato H, Honma K-I ( * Correspondence)
Biochemical and Biophysical Research Communications, Jul. 2024, [Peer-reviewed]
English, Scientific journal

A Single-Institution Prospective Study To Evaluate the Safety and Efficacy of Real- Time Image-Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer.
Kentaro Nishioka, Takayuki Hashimoto, Takashi Mori, Yusuke Uchinami, Rumiko Kinoshita, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Yoichi M Ito, Seishin Takao, Masaya Tamura, Taeko Matsuura, Shinichi Shimizu, Hiroki Shirato, Hidefumi Aoyama
Advances in radiation oncology, 9, 5, 101464, 101464, May 2024, [International Magazine]
English, Scientific journal, PURPOSE: In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. METHODS AND MATERIALS: Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE. RESULTS: Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%). CONCLUSIONS: The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies.

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial.
Michael F Gensheimer, Harriet Gee, Hiroki Shirato, Hiroshi Taguchi, John M Snyder, Alexander L Chin, Lucas K Vitzthum, Peter G Maxim, Heather A Wakelee, Joel Neal, Millie Das, Daniel T Chang, Elizabeth Kidd, Steven L Hancock, David B Shultz, Kathleen C Horst, Quynh-Thu Le, Samantha Wong, Eleanor Brown, Ngan Nguyen, Rachel Liang, Billy W Loo Jr, Maximilian Diehn
JAMA oncology, 9, 11, 1525, 1534, 01 Nov. 2023, [International Magazine]
English, Scientific journal, IMPORTANCE: Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. OBJECTIVE: To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). INTERVENTION: Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. MAIN OUTCOME: Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. RESULTS: In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). CONCLUSIONS AND RELEVANCE: The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01463423.

Factors associated with quality of life in patients receiving palliative radiotherapy for bone metastases: a secondary cross-sectional analysis of data from a prospective multicenter observational study.
Tetsuo Saito, Naoto Shikama, Takeo Takahashi, Hideyuki Harada, Shuichi Ueno, Akifumi Notsu, Hiroki Shirato, Kazunari Yamada, Haruka Uezono, Yutaro Koide, Hikaru Kubota, Takuya Yamasaki, Kei Ito, Joichi Heianna, Yukinori Okada, Ayako Tonari, Norio Katoh, Hitoshi Wada, Yasuo Ejima, Kayo Yoshida, Takashi Kosugi, Shigeo Takahashi, Takafumi Komiyama, Nobue Uchida, Misako Miwa, Miho Watanabe, Hisayasu Nagakura, Hiroko Ikeda, Isao Asakawa, Naoyuki Shigematsu
The British journal of radiology, 20230351, 20230351, 03 Oct. 2023, [International Magazine]
English, Scientific journal, OBJECTIVE: To identify factors significantly associated with quality of life (QOL) and determine if these associations are strong enough to predict certain aspects of QOL without measuring them. METHODS: We conducted an exploratory secondary analysis of baseline data of 224 patients (enrolled between December 2020 and March 2021) from a previously published prospective observational study on radiotherapy for bone metastases at 26 centres. Using univariable linear regression, we assessed the association between patient/treatment factors and QOL scale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative (QLQ-C15-PAL) and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). RESULTS: Age and sex were not significantly associated with QOL. Worse performance status, higher pain scores, and opioid and single-fraction use were significantly associated with most QOL scales; these four factors were associated with worse global QOL, worse functioning status, and more severe symptoms. The coefficients of determination for most QOL scales were less than 0.2, indicating that most of the variability in QOL scores was not explained by any of the explanatory variables. CONCLUSION: Performance status, pain intensity, and opioid and single-fraction use were significantly associated with most QOL scales. However, the associations were not strong enough to estimate QOL. ADVANCES IN KNOWLEDGE: To date, the association between treatment factors and QOL in patients with bone metastases has not been fully studied. We identified the factors that were significantly associated with QOL and found that these associations were not strong enough to predict QOL.

Income and Employment of Patients at the Start of and During Follow-up After Palliative Radiation Therapy for Bone Metastasis
Hiroki Shirato, Hideyuki Harada, Yukako Iwasaki, Akifumi Notsu, Kazunari Yamada, Haruka Uezono, Yutaro Koide, Hitoshi Wada, Hikaru Kubota, Naoto Shikama, Takuya Yamazaki, Kei Ito, Joichi Heianna, Yukinori Okada, Ayako Tonari, Shigeo Takahashi, Takashi Kosugi, Yasuo Ejima, Norio Katoh, Kayo Yoshida, Takafumi Komiyama, Nobue Uchida, Misako Miwa, Miho Watanabe, Hisayasu Nagakura, Tetsuo Saito, Hiroko Ikeda, Isao Asakawa, Tateishi Seiichiro, Takeo Takahashi, Naoyuki Shigematsu
Advances in Radiation Oncology, 8, 4, 101205, 101205, Elsevier BV, Jul. 2023
Scientific journal

Injectable Fiducial Marker for Image-Guided Radiation Therapy Based on Gold Nanoparticles and a Body Temperature-Activated Gel-Forming System
Haoran Liu, Naoki Miyamoto, Mai Thanh Nguyen, Hiroki Shirato, Tetsu Yonezawa
ACS Applied Bio Materials, 08 Sep. 2022, [Peer-reviewed], [International Magazine]
Scientific journal

A real-time measurement system for gene expression rhythms from deep tissues of freely moving mice under light-dark conditions.
Nakaya M, Wakamatsu M, Motegi H, Ami Tanaka A, Sutherland K, Ishikawa M, Ozaki M, Shirato H, Hamada K, Hamada T* (* Correspondence).
Biochemistry and Biophysics Reports, 32, 101344, 101344, Sep. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Clock gene expression in most organs of the living body exhibits a diurnal rhythm synchronized with the external 24 h light-dark (LD) cycle via circadian pacemaker suprachiasmatic nucleus (SCN). Disturbances in clock gene expression due to desynchronization of clock gene expression of the external LD cycle are risk factors for developing various diseases. Measuring the in vivo clock genes expression rhythm for a long duration under LD conditions can greatly contribute to understand the pathogenic mechanism of the disease caused by the disturbance of the biological rhythm. However, it is presently difficult to continuously measure gene expression for a long duration under LD conditions. In present study, we succeeded in measuring Period1 (Per1) gene expression under LD conditions using ultraviolet (UV) light with filter cut the visible light range. In addition, we succeeded in measuring the kinetic change of liver Per1 gene expression during the process of desynchronization of behavioral rhythm from the LD cycle by chronic administration of methamphetamine (MAP). In the future, by using this system to measure clock gene expression rhythms of brain tissues such as SCN and peripheral tissues under LD conditions, it could contribute to understand the onset mechanism of diseases induced by the desynchronization mechanism of biological rhythm to the LD cycle.

A Consistent Protocol Reveals a Large Heterogeneity in the Biological Effectiveness of Proton and Carbon-Ion Beams for Various Sarcoma and Normal-Tissue-Derived Cell Lines.
Masashi Yagi, Yutaka Takahashi, Kazumasa Minami, Taeko Matsuura, Jin-Min Nam, Yasuhito Onodera, Takashi Akagi, Takuya Maeda, Tomoaki Okimoto, Hiroki Shirato, Kazuhiko Ogawa
Cancers, 14, 8, 15 Apr. 2022, [International Magazine]
English, Scientific journal, This study investigated variations in the relative biological effectiveness (RBE) values among various sarcoma and normal-tissue-derived cell lines (normal cell line) in proton beam and carbon-ion irradiations. We used a consistent protocol that specified the timing of irradiation after plating cells and detailed the colony formation assay. We examined the cell type dependence of RBE for proton beam and carbon-ion irradiations using four human sarcoma cell lines (MG63 osteosarcoma, HT1080 fibrosarcoma, SW872 liposarcoma, and SW1353 chondrosarcoma) and three normal cell lines (HDF human dermal fibroblast, hTERT-HME1 mammary gland, and NuLi-1 bronchus epithelium). The cells were irradiated with gamma rays, proton beams at the center of the spread-out Bragg peak, or carbon-ion beams at 54.4 keV/μm linear energy transfer. In all sarcoma and normal cell lines, the average RBE values in proton beam and carbon-ion irradiations were 1.08 ± 0.11 and 2.08 ± 0.36, which were consistent with the values of 1.1 and 2.13 used in current treatment planning systems, respectively. Up to 34% difference in the RBE of the proton beam was observed between MG63 and HT1080. Similarly, a 32% difference in the RBE of the carbon-ion beam was observed between SW872 and the other sarcoma cell lines. In proton beam irradiation, normal cell lines had less variation in RBE values (within 10%), whereas in carbon-ion irradiation, RBE values differed by up to 48% between hTERT-HME1 and NuLi-1. Our results suggest that specific dose evaluations for tumor and normal tissues are necessary for treatment planning in both proton and carbon-ion therapies.

Preparation of Biopex-Supported Gold Nanoparticles as Potential Fiducial Markers for Image-Guided Radiation Therapy.
Kai Ikeda, Haoran Liu, Naoki Miyamoto, Mai Thanh Nguyen, Hiroki Shirato, Tetsu Yonezawa
ACS applied bio materials, 5, 3, 1259, 1266, 21 Mar. 2022, [International Magazine]
English, Scientific journal, Image-guided radiation therapy (IGRT) has emerged as a promising technique for cancer treatment to improve radiation precision and accuracy, thereby reducing the treatment toxicity and optimizing therapeutic efficacy. In IGRT, fiducial markers are required to be inserted near the tumor to get the spatial information of the tumor. Currently used metal fiducial markers with large sizes would be highly invasive; therefore, it is critical to develop minimally invasive alternatives to these markers. In this work, an injectable marker based on Biopex-supported Au NPs with adequate radio-opacity for X-ray visualization was developed. Biopex can function as a substrate for the growth of Au NPs and avoid excessive reaction-induced aggregation and precipitation. The self-curing property of Biopex prevents the leakage and elimination of isolated Au NPs, enabling long-term X-ray observation and radiotherapy. The effect of Biopex amount, gold precursor concentration, and reaction time were evaluated. The visibility of samples prepared by the optimized formula was also examined. The developed Biopex-Au NPs could be injected through a 21 G needle and exhibit great visibility in the X-ray visualization test, showing great potential as a fiducial marker for image-guided radiation therapy.

Dosimetric advantages of daily adaptive strategy in IMPT for high-risk prostate cancer.
Hiroshi Tamura, Keiji Kobashi, Kentaro Nishioka, Takaaki Yoshimura, Takayuki Hashimoto, Shinichi Shimizu, Yoichi M Ito, Yoshikazu Maeda, Makoto Sasaki, Kazutaka Yamamoto, Hiroyasu Tamamura, Hidefumi Aoyama, Hiroki Shirato
Journal of applied clinical medical physics, 23, 4, e13531, 19 Jan. 2022, [International Magazine]
English, Scientific journal, PURPOSE: To evaluate the dosimetric advantages of daily adaptive radiotherapy (DART) in intensity-modulated proton therapy (IMPT) for high-risk prostate cancer by comparing estimated doses of the conventional non-adaptive radiotherapy (NART) that irradiates according to an original treatment plan through the entire treatment and the DART that uses an adaptive treatment plan generated by using daily CT images acquired before each treatment. METHODS: Twenty-three patients with prostate cancer were included. A treatment plan with 63 Gy (relative biological effectiveness (RBE)) in 21 fractions was generated using treatment planning computed tomography (CT) images assuming that all patients had high-risk prostate cancer for which the clinical target volume (CTV) needs to include prostate and the seminal vesicle (SV) in our treatment protocol. Twenty-one adaptive treatment plans for each patient (total 483 data sets) were generated using daily CT images, and dose distributions were calculated. Using a 3 mm set-up uncertainty in the robust optimization, the doses to the CTV, prostate, SV, rectum, and bladder were compared. RESULTS: Estimated accumulated doses of NART and DART in the 23 patients were 60.81 ± 3.47 Gy (RBE) and 63.24 ± 1.04 Gy (RBE) for CTV D99 (p < 0.01), 62.99 ± 1.28 Gy (RBE) and 63.43 ± 1.33 Gy (RBE) for the prostate D99 (p = 0.2529), and 59.07 ± 5.19 Gy (RBE) and 63.17 ± 1.04 Gy (RBE) for SV D99 (p < 0.001). No significant differences were observed between NART and DART in the estimated accumulated dose for the rectum and bladder. CONCLUSION: Compared with the NART, DART was shown to be a useful approach that can maintain the dose coverage to the target without increasing the dose to the organs at risk (OAR) using the 3 mm set-up uncertainty in the robust optimization in patients with high-risk prostate cancer.

Green and effective synthesis of gold nanoparticles as an injectable fiducial marker for real-time image gated proton therapy
Haoran Liu, Naoki Miyamoto, Mai Thanh Nguyen, Hiroki Shirato, Tetsu Yonezawa
Materials Advances, Royal Society of Chemistry ({RSC}), 2022
Scientific journal

Prediction of liver Dmean for proton beam therapy using deep learning and contour-based data augmentation
Sira Jampa-ngern, Keiji Kobashi, Shinichi Shimizu, Seishin Takao, Keiji Nakazato, Hiroki Shirato
Journal of Radiation Research, Oxford University Press (OUP), 06 Oct. 2021
Scientific journal, Abstract

The prediction of liver Dmean with 3-dimensional radiation treatment planning (3DRTP) is time consuming in the selection of proton beam therapy (PBT), and deep learning prediction generally requires large and tumor-specific databases. We developed a simple dose prediction tool (SDP) using deep learning and a novel contour-based data augmentation (CDA) approach and assessed its usability. We trained the SDP to predict the liver Dmean immediately. Five and two computed tomography (CT) data sets of actual patients with liver cancer were used for the training and validation. Data augmentation was performed by artificially embedding 199 contours of virtual clinical target volume (CTV) into CT images for each patient. The data sets of the CTVs and OARs are labeled with liver Dmean for six different treatment plans using two-dimensional calculations assuming all tissue densities as 1.0. The test of the validated model was performed using 10 unlabeled CT data sets of actual patients. Contouring only of the liver and CTV was required as input. The mean relative error (MRE), the mean percentage error (MPE) and regression coefficient between the planned and predicted Dmean was 0.1637, 6.6%, and 0.9455, respectively. The mean time required for the inference of liver Dmean of the six different treatment plans for a patient was 4.47±0.13 seconds. We conclude that the SDP is cost-effective and usable for gross estimation of liver Dmean in the clinic although the accuracy should be improved further if we need the accuracy of liver Dmean to be compatible with 3DRTP.

Prediction of target position from multiple fiducial markers by partial least squares regression in real-time tumor-tracking radiation therapy.
Kanako Ukon, Yohei Arai, Seishin Takao, Taeko Matsuura, Masayori Ishikawa, Hiroki Shirato, Shinichi Shimizu, Kikuo Umegaki, Naoki Miyamoto
Journal of radiation research, 62, 5, 926, 933, 13 Sep. 2021, [International Magazine]
English, Scientific journal, The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers' positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior-inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.

Radiological tumour classification across imaging modality and histology
Jia Wu, Chao Li, Michael Gensheimer, Sukhmani Padda, Fumi Kato, Hiroki Shirato, Yiran Wei, Carola-Bibiane Schönlieb, Stephen John Price, David Jaffray, John Heymach, Joel W. Neal, Billy W. Loo, Heather Wakelee, Maximilian Diehn, Ruijiang Li
Nature Machine Intelligence, 3, 9, 787, 798, Springer Science and Business Media LLC, Sep. 2021
Scientific journal

Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction.
Takahiro Yamada, Seishin Takao, Hidenori Koyano, Hideaki Nihongi, Yusuke Fujii, Shusuke Hirayama, Naoki Miyamoto, Taeko Matsuura, Kikuo Umegaki, Norio Katoh, Isao Yokota, Hiroki Shirato, Shinichi Shimizu
Journal of radiation research, 62, 4, 626, 633, 10 Jul. 2021, [International Magazine]
English, Scientific journal, In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5-D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%-2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: -0.5%-0.7%). The mean differences of D99, D5-D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.

Fundamental study on quality assurance (QA) procedures for a real-time tumor tracking radiotherapy (RTRT) system from the viewpoint of imaging devices.
Suguru Kimura, Naoki Miyamoto, Kenneth L Sutherland, Ryusuke Suzuki, Hiroki Shirato, Masayori Ishikawa
Journal of applied clinical medical physics, 22, 7, 165, 176, Jul. 2021, [International Magazine]
English, Scientific journal, PURPOSE: The real-time tumor tracking radiotherapy (RTRT) system requires periodic quality assurance (QA) and quality control. The goal of this study is to propose QA procedures from the viewpoint of imaging devices in the RTRT system. METHODS: Tracking by the RTRT system (equips two sets of colored image intensifiers (colored I.I.s) fluoroscopy units) for the moving gold-marker (diameter 2.0 mm) in a rotating phantom were performed under various X-ray conditions. To analyze the relationship between fluoroscopic image quality and precision of gold marker coordinate calculation, the standard deviation of the 3D coordinate (σ3D [mm]) of the gold marker, the mean of the pattern recognition score (PRS) and the standard deviation of the distance between rays (DBR) (σDBR [mm]) were evaluated. RESULTS: When tracking with speed of 10-60 mm/s, σDBR increased, though the mean PRS did not change significantly (p>0.05). On the contrary, the mean PRS increased depending on the integral noise equivalent quanta (∫NEQ) that is an indicator of image quality calculated from the modulation transfer function (MTF) as an indicator of spatial resolution and the noise power spectrum (NPS) as an indicator of noise characteristic. CONCLUSION: The indicators of NEQ, MTF, and NPS were useful for managing the tracking accuracy of the RTRT system. We propose observing the change of these indicators as additional QA procedures for each imaging device from the commissioning baseline.

Period1 gene expression in the olfactory bulb and liver of freely moving streptozotocin-treated diabetic mouse.
Harumi Kanou, Kouki Nagasawa, Yuki Ishii, Aya Chishima, Juri Hayashi, Sanae Haga, Kenneth Sutherland, Masayori Ishikawa, Michitaka Ozaki, Hiroki Shirato, Kazuko Hamada, Toshiyuki Hamada
Biochemical and biophysical research communications, 560, 14, 20, 30 Jun. 2021, [International Magazine]
English, Scientific journal, Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity. In the present study, to explore the role of clock genes in developing diabetes, we examined the effect of streptozotocin (STZ)-induced high glucose on Period1 (Per1) gene expression rhythm in the liver and the olfactory bub (OB) in the brain. We found a drastic increase of Per1 expression in both tissues after STZ injection while blood glucose content was low. After a rapid expression peak, Per1 expression showed no rhythm. Associated with an increase of glucose content, behavior became arrhythmic. Finally, we succeeded in detecting an increase of Per1 expression in mice hair follicles on day 1 after STZ administration, before the onset of symptoms. These results show that elevated Per1 expression by STZ plays an important role in the aggravation of diabetes.

Assessment of the confidence interval in the multivariable normal tissue complication probability model for predicting radiation-induced liver disease in primary liver cancer.
Anussara Prayongrat, Natchalee Srimaneekarn, Sira Sriswasdi, Yoichi M Ito, Norio Katoh, Masaya Tamura, Yasuhiro Dekura, Chie Toramatsu, Chonlakiet Khorprasert, Napapat Amornwichet, Petch Alisanant, Yuichi Hirata, Anthony Hayter, Hiroki Shirato, Shinichi Shimizu, Keiji Kobashi
Journal of radiation research, 62, 3, 483, 493, 12 May 2021, [International Magazine]
English, Scientific journal, We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.

Calibrated uncertainty estimation for interpretable proton computed tomography image correction using Bayesian deep learning.
Yusuke Nomura, Sodai Tanaka, Jeff Wang, Hiroki Shirato, Shinichi Shimizu, Lei Xing
Physics in medicine and biology, 66, 6, 065029, 065029, 16 Mar. 2021, [International Magazine]
English, Scientific journal, Integrated-type proton computed tomography (pCT) measures proton stopping power ratio (SPR) images for proton therapy treatment planning, but its image quality is degraded due to noise and scatter. Although several correction methods have been proposed, techniques that include estimation of uncertainty are limited. This study proposes a novel uncertainty-aware pCT image correction method using a Bayesian convolutional neural network (BCNN). A DenseNet-based BCNN was constructed to predict both a corrected SPR image and its uncertainty from a noisy SPR image. A total 432 noisy SPR images of 6 non-anthropomorphic and 3 head phantoms were collected with Monte Carlo simulations, while true noise-free images were calculated with known geometric and chemical components. Heteroscedastic loss and deep ensemble techniques were performed to estimate aleatoric and epistemic uncertainties by training 25 unique BCNN models. 200-epoch end-to-end training was performed for each model independently. Feasibility of the predicted uncertainty was demonstrated after applying two post-hoc calibrations and calculating spot-specific path length uncertainty distribution. For evaluation, accuracy of head SPR images and water-equivalent thickness (WET) corrected by the trained BCNN models was compared with a conventional method and non-Bayesian CNN model. BCNN-corrected SPR images represent noise-free images with high accuracy. Mean absolute error in test data was improved from 0.263 for uncorrected images to 0.0538 for BCNN-corrected images. Moreover, the calibrated uncertainty represents accurate confidence levels, and the BCNN-corrected calibrated WET was more accurate than non-Bayesian CNN with high statistical significance. Computation time for calculating one image and its uncertainties with 25 BCNN models is 0.7 s with a consumer grade GPU. Our model is able to predict accurate pCT images as well as two types of uncertainty. These uncertainties will be useful to identify potential cause of SPR errors and develop a spot-specific range margin criterion, toward elaboration of uncertainty-guided proton therapy.

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients.
Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Seishin Takao, Masaya Tamura, Nayuta Tsushima, Takayoshi Suzuki, Satoshi Kano, Takatsugu Mizumachi, Takashi Mori, Kentaro Nishioka, Motoyasu Shido, Norio Katoh, Hiroshi Taguchi, Noriyuki Fujima, Rikiya Onimaru, Isao Yokota, Keiji Kobashi, Shinichi Shimizu, Akihiro Homma, Hiroki Shirato, Hidefumi Aoyama
Journal of radiation research, 62, 2, 329, 337, 10 Mar. 2021, [International Magazine]
English, Scientific journal, Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.

Stability of d-luciferin for bioluminescence to detect gene expression in freely moving mice for long durations.
Kanako Nakajima, Kazuko Hamada, Ryoga Ito, Yukina Yoshida, Kenneth Sutherland, Masayori Ishikawa, Michitaka Ozaki, Hiroki Shirato, Toshiyuki Hamada
Luminescence : the journal of biological and chemical luminescence, 36, 1, 94, 98, Feb. 2021, [International Magazine]
English, Scientific journal, Circadian disturbance of clock gene expression is a risk factor for diseases such as obesity, cancer, and sleep disorders. To study these diseases, it is necessary to monitor and analyze the expression rhythm of clock genes in the whole body for a long duration. The bioluminescent reporter enzyme firefly luciferase and its substrate d-luciferin have been used to generate optical signals from tissues in vivo with high sensitivity. However, little information is known about the stability of d-luciferin to detect gene expression in living animals for a long duration. In the present study, we examined the stability of a luciferin solution over 21 days. l-Luciferin, which is synthesized using racemization of d-luciferin, was at high concentrations after 21 days. In addition, we showed that bioluminescence of Period1 (Per1) expression in the liver was significantly decreased compared with the day 1 solution, although locomotor activity rhythm was not affected. These results showed that d-luciferin should be applied to the mouse within, at most, 7 days to detect bioluminescence of Per1 gene expression rhythm in vivo.

The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma.
Yuji Nakamaru, Masanobu Suzuki, Satoshi Kano, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Akihiro Homma
Auris, nasus, larynx, 48, 1, 131, 137, Feb. 2021, [International Magazine]
English, Scientific journal, OBJECTIVE: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. METHODS: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. RESULTS: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). CONCLUSION: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC.

Multiparametric Analysis of Tumor Morphological and Functional MR Parameters Potentially Predicts Local Failure in Pharynx Squamous Cell Carcinoma Patients.
Noriyuki Fujima, Yukie Shimizu, Daisuke Yoshida, Satoshi Kano, Takatsugu Mizumachi, Akihiro Homma, Koichi Yasuda, Rikiya Onimaru, Osamu Sakai, Kohsuke Kudo, Hiroki Shirato
The journal of medical investigation : JMI, 68, 3.4, 354, 361, 2021, [Domestic magazines]
English, Scientific journal, Purpose : To predict local control / failure by a multiparametric approach using magnetic resonance (MR)-derived tumor morphological and functional parameters in pharynx squamous cell carcinoma (SCC) patients. Materials and Methods : Twenty-eight patients with oropharyngeal and hypopharyngeal SCCs were included in this study. Quantitative morphological parameters and intratumoral characteristics on T2-weighted images, tumor blood flow from pseudo-continuous arterial spin labeling, and tumor diffusion parameters of three diffusion models from multi-b-value diffusion-weighted imaging as well as patients' characteristics were analyzed. The patients were divided into local control / failure groups. Univariate and multiparametric analysis were performed for the patient group division. Results : The value of morphological parameter of 'sphericity' and intratumoral characteristic of 'homogeneity' was revealed respectively significant for the prediction of the local control status in univariate analysis. Higher diagnostic performance was obtained with the sensitivity of 0.8, specificity of 0.75, positive predictive value of 0.89, negative predictive value of 0.6 and accuracy of 0.79 by multiparametric diagnostic model compared to results in the univariate analysis. Conclusion : A multiparametric analysis with MR-derived quantitative parameters may be useful to predict local control in pharynx SCC patients. J. Med. Invest. 68 : 354-361, August, 2021.

Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?
Kentaro Nishioka, Kento Gotoh, Takayuki Hashimoto, Takashige Abe, Takahiro Osawa, Ryuji Matsumoto, Isao Yokota, Norio Katoh, Rumiko Kinoshita, Koichi Yasuda, Toshiaki Yakabe, Takaaki Yoshimura, Seishin Takao, Nobuo Shinohara, Hidefumi Aoyama, Shinichi Shimizu, Hiroki Shirato
BJR|Open, 3, 1, British Institute of Radiology, Jan. 2021
Scientific journal, The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer.

A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV.

The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years.

Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated.

Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.

Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.
Hideki Minatogawa, Koichi Yasuda, Yasuhiro Dekura, Seishin Takao, Taeko Matsuura, Takaaki Yoshimura, Ryusuke Suzuki, Isao Yokota, Noriyuki Fujima, Rikiya Onimaru, Shinichi Shimizu, Hidefumi Aoyama, Hiroki Shirato
Journal of applied clinical medical physics, 22, 1, 174, 183, Jan. 2021, [International Magazine]
English, Scientific journal, PURPOSE: To investigate potential advantages of adaptive intensity-modulated proton beam therapy (A-IMPT) by comparing it to adaptive intensity-modulated X-ray therapy (A-IMXT) for nasopharyngeal carcinomas (NPC). METHODS: Ten patients with NPC treated with A-IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A-IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A-IMXT with A-IMPT. RESULTS: The means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A-IMPT are lower than those of A-IMXT, with statistical significance. The means of, D0.03cc , and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A-IMPT are significantly lower than those of A-IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1). CONCLUSIONS: An adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.

Mouse period1 gene expression recording from olfactory bulb under free moving conditions with a portable optic fibre device.
Ryoga Ito, Kazuko Hamada, Shigeru Kasahara, Yoshihiro Kikuchi, Kanako Nakajima, Kenneth Sutherland, Hiroki Shirato, Michitaka Ozaki, Masayori Ishikawa, Toshiyuki Hamada
Luminescence : the journal of biological and chemical luminescence, 35, 8, 1248, 1253, Dec. 2020, [International Magazine]
English, Scientific journal, Because the disruption of circadian clock gene is a risk factor in many diseases such as obesity and cancer, it is important to monitor and analyzed the expression of the rhythm of the clock gene throughout the body over a long period of time. Although we previously reported on a new gene expression analysis system tracking a target position on the body surface of freely moving mice, the experimental apparatus required a large space. We have therefore developed an in vivo recording system using a portable photomultiplier tube (PMT) system attached to an optical fibre. Directly connecting the target area with the device, we could easily measure the photon counts in a very small space. However, little information is known about the characteristics of optical fibres when exposed to twisting/looping in association with a moving mouse and the effect of the surface of optical fibre. In the present study, we report on the characteristics of optical fibres to detect gene expression rhythm in freely moving mice. Using this portable optical device directly connected with a target area, we were able to measure the circadian rhythm of clock gene expression over a prolonged period in freely moving mice in a small space.

Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation
Ping-Hsiu Wu, Yasuhito Onodera, Amato J. Giaccia, Quynh-Thu Le, Shinichi Shimizu, Hiroki Shirato, Jin-Min Nam
Communications Biology, 3, 1, Springer Science and Business Media LLC, Dec. 2020
Scientific journal, Enhanced invasiveness, a critical determinant of metastasis and poor prognosis, has been observed in cancer cells that survive cancer therapy, including radiotherapy. Here, we show that invasiveness in radiation-surviving cancer cells is associated with alterations in lysosomal exocytosis caused by the enhanced activation of Arl8b, a small GTPase that regulates lysosomal trafficking. The binding of Arl8b with its effector, SKIP, is increased after radiation through regulation of BORC-subunits. Knockdown of Arl8b or BORC-subunits decreases lysosomal exocytosis and the invasiveness of radiation-surviving cells. Notably, high expression ofARL8Band BORC-subunit genes is significantly correlated with poor prognosis in breast cancer patients. Sp1, an ATM-regulated transcription factor, is found to increase BORC-subunit genes expression after radiation. In vivo experiments show that ablation of Arl8b decreases IR-induced invasive tumor growth and distant metastasis. These findings suggest that BORC-Arl8b-mediated lysosomal trafficking is a target for improving radiotherapy by inhibiting invasive tumor growth and metastasis.

Quantitative analysis of treatments using real-time image gated spot-scanning with synchrotron-based proton beam therapy system log data.
Takaaki Yoshimura, Shinichi Shimizu, Takayuki Hashimoto, Kentaro Nishioka, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Taeko Matsuura, Seishin Takao, Masaya Tamura, Sodai Tanaka, Yoichi M Ito, Yuto Matsuo, Hiroshi Tamura, Kenji Horita, Kikuo Umegaki, Hiroki Shirato
Journal of applied clinical medical physics, 21, 12, 10, 19, Dec. 2020, [International Magazine]
English, Scientific journal, A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.

Fast spot-scanning proton dose calculation method with uncertainty quantification using a three-dimensional convolutional neural network
Yusuke Nomura, Jeff Wang, Hiroki Shirato, Shinichi Shimizu, Lei Xing
Physics in Medicine & Biology, {IOP} Publishing, 26 Oct. 2020, [Peer-reviewed]
Scientific journal

Double recording system of Period1 gene expression rhythm in the olfactory bulb and liver in freely moving mouse.
Kazuko Hamada, Akari Oota, Ryoga Ito, Shigeru Kasahara, Kanako Nakajima, Yoshihiro Kikuchi, Kenneth Sutherland, Masayori Ishikawa, Hiroki Shirato, Michitaka Ozaki, Toshiyuki Hamada
Biochemical and biophysical research communications, 529, 4, 898, 903, 03 Sep. 2020, [International Magazine]
English, Scientific journal, Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity and cancer. To understand the mechanism of regulating clock gene expression rhythms in vivo, multiple real time recording systems are required. In the present study, we developed a double recording system of Period1 expression rhythm in peripheral tissue (liver) and the brain. In peripheral tissue, quantification of gene expression in a steadily moving target was achieved by using a photomultiplier tube (PMT) attached to a tissue contact optical sensor (TCS). Using this technique, we were able to analyze circadian rhythms of clock gene expression over a prolonged period in the liver and olfactory bub (OB) of the brain. The present double recording system has no effect on behavioral activity or rhythm. Our novel system thus successfully quantifies clock gene expression in deep areas of the body in freely moving mice for a period sufficient to analyze circadian dynamics. In addition, our double recording system can be widely applied to many areas of biomedical research, as well as applications beyond medicine.

The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters.
Koki Kasamatsu, Taeko Matsuura, Sodai Tanaka, Seishin Takao, Naoki Miyamoto, Jin-Min Nam, Hiroki Shirato, Shinichi Shimizu, Kikuo Umegaki
Medical physics, 47, 9, 4644, 4655, 11 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, PURPOSE: The purpose of this study is to evaluate the sub-lethal damage (SLD) repair effect in prolonged proton irradiation using the biophysical model with various cell-specific parameters of (α/β)x and T1/2 (repair half time). At present, most of the model-based studies on protons have focused on acute radiation, neglecting the reduction in biological effectiveness due to SLD repair during the delivery of radiation. Nevertheless, the dose-rate dependency of biological effectiveness may become more important as advanced treatment techniques, such as hypofractionation and respiratory gating, come into clinical practice, as these techniques sometimes require long treatment times. Also, while previous research using the biophysical model revealed a large repair effect with a high physical dose, the dependence of the repair effect on cell-specific parameters has not been evaluated systematically. METHODS: Biological dose (relative biological effectiveness (RBE) × physical dose) calculation with repair included was carried out using the linear energy transfer (LET)-dependent linear-quadratic (LQ) model combined with the theory of dual radiation action (TDRA). First, we extended the dose protraction factor in the LQ model for the arbitrary number of different LET proton irradiations delivered sequentially with arbitrary time lags, referring to the TDRA. Using the LQ model, the decrease in biological dose due to SLD repair was systematically evaluated for spread-out Bragg peak (SOBP) irradiation in a water phantom with the possible ranges of both (α/β)x and repair parameters ((α/β)x = 1-15 Gy, T1/2 = 0-90 min). Then, to consider more realistic irradiation conditions, clinical cases of prostate, liver, and lung tumors were examined with the cell-specific parameters for each tumor obtained from the literature. Biological D99% and biological dose homogeneity coefficient (HC) were calculated for the clinical target volumes (CTVs), assuming dose-rate structures with a total irradiation time of 0-60 min. RESULTS: The differences in the cell-specific parameters resulted in considerable variation in the repair effect. The biological dose reduction found at the center of the SOBP with 30 min of continuous irradiation varied from 1.13% to 14.4% with a T1/2 range of 1-90 min when (α/β)x is fixed as 10 Gy. It varied from 2.3% to 6.8% with an (α/β)x range of 1-15 Gy for a fixed value of T1/2 = 30 min. The decrease in biological D99% per 10 min was 2.6, 1.2, and 3.0% for the prostate, liver, and lung tumor cases, respectively. The value of the biological D99% reduction was neither in the order of (α/β)x nor prescribed dose, but both comparably contributed to the repair effect. The variation of HC was within the range of 0.5% for all cases; therefore, the dose distribution was not distorted. CONCLUSION: The reduction in biological dose caused by the SLD repair largely depends on the cell-specific parameters in addition to the physical dose. The parameters should be considered carefully in the evaluation of the repair effect in prolonged proton irradiation.

Microstructural Alterations in Bipolar and Major Depressive Disorders: A Diffusion Kurtosis Imaging Study.
Daisuke Sawamura, Hisashi Narita, Naoki Hashimoto, Shin Nakagawa, Hiroyuki Hamaguchi, Noriyuki Fujima, Kohsuke Kudo, Hiroki Shirato, Khin K Tha
Journal of magnetic resonance imaging : JMRI, 23 Apr. 2020, [Peer-reviewed], [International Magazine]
English, BACKGROUND: Identifying structural and functional abnormalities in bipolar (BD) and major depressive disorders (MDD) is important for understanding biological processes. HYPOTHESIS: Diffusion kurtosis imaging (DKI) may be able to detect the brain's microstructural alterations in BD and MDD and any differences between the two. STUDY TYPE: Prospective. SUBJECTS: In all, 16 BD patients, 19 MDD patients, and 20 age- and gender-matched healthy volunteers. FIELD STRENGTH/SEQUENCE: DKI at 3.0T. ASSESSMENT: The major DKI indices of the brain were compared voxel-by-voxel among the three groups. Significantly different voxels were tested for correlation with clinical variables (ie, Young Mania Rating Scale [YMRS], 17-item Hamilton Depression Rating Scale [17-HDRS], Montgomery-Åsberg Depression Rating Scale, total disease duration, duration of current episode, and the number of past manic/depressive episodes). The performance of the DKI indices in identifying microstructural alterations was estimated. STATISTICAL TESTS: One-way analysis of variance (ANOVA) was used for group comparison of DKI indices. The performance of these indices in detecting microstructural alterations was determined by receiver operating characteristic (ROC) analysis. Pearson's product-moment correlation analyses were used to test the correlations of these indices with clinical variables. RESULTS: DKI revealed widespread microstructural alterations across the brain in each disorder (P < 0.05). Some were significantly different between the two disorders. Mean kurtosis (MK) in the gray matter of the right inferior parietal lobe was able to distinguish BD and MDD with an accuracy of 0.906. A strong correlation was revealed between MK in that region and YMRS in BD patients (r = -0.641, corrected P = 0.042) or 17-HDRS in MDD patients (r = -0.613, corrected P = 0.030). There were also strong correlations between a few other DKI indices and disease duration (r = -0.676 or 0.626, corrected P < 0.05). DATA CONCLUSION: DKI detected microstructural brain alterations in BD and MDD. Its indices may be useful to distinguish the two disorders or to reflect disease severity and duration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Dynamic gating window technique for the reduction of dosimetric error in respiratory-gated spot-scanning particle therapy: An initial phantom study using patient tumor trajectory data.
Naoki Miyamoto, Kouhei Yokokawa, Seishin Takao, Taeko Matsuura, Sodai Tanaka, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki
Journal of applied clinical medical physics, 21, 4, 13, 21, 18 Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Spot-scanning particle therapy possesses advantages, such as high conformity to the target and efficient energy utilization compared with those of the passive scattering irradiation technique. However, this irradiation technique is sensitive to target motion. In the current clinical situation, some motion management techniques, such as respiratory-gated irradiation, which uses an external or internal surrogate, have been clinically applied. In surrogate-based gating, the size of the gating window is fixed during the treatment in the current treatment system. In this study, we propose a dynamic gating window technique, which optimizes the size of gating window for each spot by considering a possible dosimetric error. The effectiveness of the dynamic gating window technique was evaluated by simulating irradiation using a moving target in a water phantom. In dosimetric characteristics comparison, the dynamic gating window technique exhibited better performance in all evaluation volumes with different effective depths compared with that of the fixed gate approach. The variation of dosimetric characteristics according to the target depth was small in dynamic gate compared to fixed gate. These results suggest that the dynamic gating window technique can maintain an acceptable dose distribution regardless of the target depth. The overall gating efficiency of the dynamic gate was approximately equal or greater than that of the fixed gating window. In dynamic gate, as the target depth becomes shallower, the gating efficiency will be reduced, although dosimetric characteristics will be maintained regardless of the target depth. The results of this study suggest that the proposed gating technique may potentially improve the dose distribution. However, additional evaluations should be undertaken in the future to determine clinical applicability by assuming the specifications of the treatment system and clinical situation.

The updated outcomes of bladder-preserving trimodal therapy using a real-time tumor-tracking radiotherapy system for patients with muscle-invasive bladder cancer.
Haruka Miyata, Takahiro Osawa, Takashige Abe, Hiroshi Kikuchi, Ryuji Matsumoto, Satoru Maruyama, Kentaro Nishioka, Shinichi Shimizu, Takayuki Hashimoto, Hiroki Shirato, Nobuo Shinohara
Japanese journal of clinical oncology, 19 Jan. 2020, [Peer-reviewed], [International Magazine]
English, OBJECTIVE: Bladder-preserving trimodal therapy is recognized as a promising alternative treatment for muscle-invasive bladder cancer. We report the updated outcomes of muscle-invasive bladder cancer patients that were treated using our treatment protocol, which involves radiotherapy delivered with a real-time tumor-tracking radiotherapy system. METHODS: Thirty-eight patients who were diagnosed with T2-T4N0M0 bladder cancer between 1998 and 2016 and had clinically inoperable disease or refused to undergo surgery were enrolled. The treatment protocol included maximal transurethral resection followed by whole-bladder radiotherapy (40 Gy). Concurrent nedaplatin-based chemotherapy was administered to patients with adequate renal function. At the time of the first evaluation (via transurethral resection of the tumor bed), fiducial markers were endoscopically inserted into the bladder wall around the tumor. A boost of 25 Gy was administered using the real-time tumor-tracking radiotherapy system. The second evaluation (via transurethral resection of the tumor bed) was performed 6 months after the start of treatment. The Kaplan-Meier method and Cox hazards analysis were used to analyze overall survival and cancer-specific survival. RESULTS: The median duration of the follow-up period was 28 months (range: 3-161 months). The 5- and 10-year overall survival rates were 54.9 and 41.2%, respectively. Twenty-five (65.8%) and twenty (74.1%) patients had achieved complete responses to chemoradiation at the first and second evaluations, respectively. In univariate and multivariate analyses, performance status was found to be significantly associated with overall survival [P = 0.03, hazard ratio: 3.48, 95% confidence interval: 1.15-10.6] and cancer-specific survival [P = 0.02, hazard ratio: 4.57, 95% confidence interval: 1.32-16.9], and sex was shown to be significantly associated with cancer-specific survival [P = 0.03, hazard ratio: 3.07, 95% confidence interval: 1.09-8.30]. CONCLUSIONS: Our bladder-preserving trimodal therapy protocol, which involves the use of a real-time tumor-tracking radiotherapy system, produced an acceptable overall survival rate. This therapy is a reasonable alternative for patients that are medically unfit for or do not want to undergo cystectomy.

Modified fast adaptive scatter kernel superposition (mfASKS) correction and its dosimetric impact on CBCT-based proton therapy dose calculation
Yusuke Nomura, Qiong Xu, Hao Peng, Seishin Takao, Shinichi Shimizu, Lei Xing, Hiroki Shirato
MEDICAL PHYSICS, 47, 1, 190, 200, WILEY, Jan. 2020
English, Scientific journal, Purpose While cone beam computed tomography (CBCT) is able to provide patient anatomical information, its image quality is severely degraded due to scatter contamination, which degrades the accuracy of CBCT-based dose distribution estimation in proton therapy. In this work, we combined two existing scatter kernel correction methods: the point-spread function (PSF)-based scatter kernel derivation method and the fast adaptive scatter kernel superposition (fASKS) model, and evaluated the impact of the modified fASKS (mfASKS) correction on the accuracy of proton dose distribution estimation. To evaluate feasibility of the mfASKS approach using accurate scatter distributions, both Monte Carlo simulations and experiments were performed for an on-board CBCT machine integrated with a proton therapy machine. Methods We developed a strategy to modify central intensity, constant intensity, and amplitude of the scatter kernels derived from PSFs for the fASKS model. A parameter required for the fASKS model was derived by optimizing uniformity in the mfASKS-corrected reconstructed images. Subsequently, the mfASKS model was used to remove scatter in CBCT imaging. We quantitatively compared the Hounsfield Unit (HU) and proton stopping power ratio (SPR) images for five different phantoms. To assess improvement of dose calculation accuracy, a series of proton treatment plans were produced using the CBCT images with and without the mfASKS correction. Results The accuracies of both HU and SPR intensity quantifications are improved as a result of the mfASKS correction. Mean absolute water-equivalent path length difference to the true value decreases from 10.3 to 0.934 mm for the Gammex phantom (simulation). At the same time, mfASKS is able to offer more accurate dose distributions, especially at the distal fall-off region where noticeable dose overestimation is observed in the uncorrected scenario. Mean absolute relative error of proton range in the pelvic phantom improves from 5.03% to 2.57% (experiment). Conclusions mfASKS enables more accurate CBCT-based proton dose calculation. This technique has significant implications in image-guided radiotherapy and dose verifications in adaptive proton therapy.

Modified fast adaptive scatter kernel superposition (mfASKS) correction and its dosimetric impact on CBCT-based proton therapy dose calculation.
Yusuke Nomura, Qiong Xu, Hao Peng, Seishin Takao, Shinichi Shimizu, Lei Xing, Hiroki Shirato
Medical physics, 47, 1, 190, 200, Jan. 2020, [International Magazine]
English, Scientific journal, PURPOSE: While cone beam computed tomography (CBCT) is able to provide patient anatomical information, its image quality is severely degraded due to scatter contamination, which degrades the accuracy of CBCT-based dose distribution estimation in proton therapy. In this work, we combined two existing scatter kernel correction methods: the point-spread function (PSF)-based scatter kernel derivation method and the fast adaptive scatter kernel superposition (fASKS) model, and evaluated the impact of the modified fASKS (mfASKS) correction on the accuracy of proton dose distribution estimation. To evaluate feasibility of the mfASKS approach using accurate scatter distributions, both Monte Carlo simulations and experiments were performed for an on-board CBCT machine integrated with a proton therapy machine. METHODS: We developed a strategy to modify central intensity, constant intensity, and amplitude of the scatter kernels derived from PSFs for the fASKS model. A parameter required for the fASKS model was derived by optimizing uniformity in the mfASKS-corrected reconstructed images. Subsequently, the mfASKS model was used to remove scatter in CBCT imaging. We quantitatively compared the Hounsfield Unit (HU) and proton stopping power ratio (SPR) images for five different phantoms. To assess improvement of dose calculation accuracy, a series of proton treatment plans were produced using the CBCT images with and without the mfASKS correction. RESULTS: The accuracies of both HU and SPR intensity quantifications are improved as a result of the mfASKS correction. Mean absolute water-equivalent path length difference to the true value decreases from 10.3 to 0.934 mm for the Gammex phantom (simulation). At the same time, mfASKS is able to offer more accurate dose distributions, especially at the distal fall-off region where noticeable dose overestimation is observed in the uncorrected scenario. Mean absolute relative error of proton range in the pelvic phantom improves from 5.03% to 2.57% (experiment). CONCLUSIONS: mfASKS enables more accurate CBCT-based proton dose calculation. This technique has significant implications in image-guided radiotherapy and dose verifications in adaptive proton therapy.

Rab27b contributes to radioresistance and exerts a paracrine effect via epiregulin in glioblastoma
Soichiro Nishioka, Ping-Hsiu Wu, Toshiaki Yakabe, Amato J Giaccia, Quynh-Thu Le, Hidefumi Aoyama, Shinichi Shimizu, Hiroki Shirato, Yasuhito Onodera, Jin-Min Nam
Neuro-Oncology Advances, 2, 1, Oxford University Press (OUP), 01 Jan. 2020
Scientific journal,


Radiotherapy is the standard treatment for glioblastoma (GBM). However, radioresistance of GBM cells leads to recurrence and poor patient prognosis. Recent studies suggest that secretion factors have important roles in radioresistance of tumor cells. This study aims to determine whether Rab27b, a small GTPase involved in secretory vesicle trafficking, plays a role in radioresistance of GBM.





Microarray analysis, cell viability analysis, apoptosis assay, immunostaining, and in vivo experiments were performed to assess the effect of Rab27b on radioresistance of GBM. We further investigated paracrine effects mediated by Rab27b after X-ray irradiation using coculture systems of glioma cell lines.





Rab27b was specifically upregulated in irradiated U87MG cells. Furthermore, Rab27b knockdown decreased the proliferation of GBM cells after irradiation. Knockdown of Rab27b in U87MG cells combined with radiation treatment suppressed orthotopic tumor growth in the mouse brain and prolonged the survival of recipient mice. Interestingly, the co-upregulation of Rab27b and epiregulin (EREG), a member of the epidermal growth factor (EGF) family, correlated with radioresistance in glioma cell lines. Additionally, EREG, which was secreted from U87MG cells via Rab27b-mediated mechanism, activated EGF receptor and contributed to H4 cell proliferation in a paracrine manner.





Our results show that Rab27b mediates the radioresistance of highly malignant GBM cells. Rab27b promotes the proliferation of adjacent cells through EREG-mediated paracrine signaling after irradiation. Thus, the Rab27b-EREG pathway is a novel potential target to improve the efficacy of radiotherapy in GBM.

The urethral position may shift due to urethral catheter placement in the treatment planning for prostate radiation therapy.
Yasuhiro Dekura, Kentaro Nishioka, Takayuki Hashimoto, Naoki Miyamoto, Ryusuke Suzuki, Takaaki Yoshimura, Ryuji Matsumoto, Takahiro Osawa, Takashige Abe, Yoichi M Ito, Nobuo Shinohara, Hiroki Shirato, Shinichi Shimizu
Radiation oncology (London, England), 14, 1, 226, 226, 12 Dec. 2019, [Peer-reviewed], [International Magazine]
English, PURPOSE: To determine the best method to contour the planning organ at risk volume (PRV) for the urethra, this study aimed to investigate the displacement of a Foley catheter in the urethra with a soft and thin guide-wire. METHODS: For each patient, the study used two sets of computed tomography (CT) images for radiation treatment planning (RT-CT): (1) set with a Foley urethral catheter (4.0 mm diameter) plus a guide-wire (0.46 mm diameter) in the first RT-CT and (2) set with a guide-wire alone in the second CT recorded 2 min after the first RT-CT. Using three fiducial markers in the prostate for image fusion, the displacement between the catheter and the guide-wire in the prostatic urethra was calculated. In 155 consecutive patients treated between 2011 and 2017, 5531 slices of RT-CT were evaluated. RESULTS: Assuming that ≥3.0 mm of difference between the catheter and the guide-wire position was a significant displacement, the urethra with the catheter was displaced significantly from the urethra with the guide-wire alone in > 20% of the RT-CT slices in 23.2% (36/155) of the patients. The number of patients who showed ≥3.0 mm anterior displacement with the catheter in ≥20% RT-CT slices was significantly larger at the superior segment (38/155) than at the middle (14/155) and inferior segments (18/155) of the prostatic urethra (p < 0.0167). CONCLUSIONS: The urethral position with a Foley catheter is different from the urethral position with a thin and soft guide-wire in a significant proportion of the patients. This should be taken into account for the PRV of the urethra to ensure precise radiotherapy such as in urethra-sparing radiotherapy.

Combination of FDG-PET and FMISO-PET as a treatment strategy for patients undergoing early-stage NSCLC stereotactic radiotherapy.
Shiro Watanabe, Tetsuya Inoue, Shozo Okamoto, Keiichi Magota, Ayumi Takayanagi, Jun Sakakibara-Konishi, Norio Katoh, Kenji Hirata, Osamu Manabe, Takuya Toyonaga, Yuji Kuge, Hiroki Shirato, Nagara Tamaki, Tohru Shiga
EJNMMI research, 9, 1, 104, 104, 04 Dec. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: We investigated the prognostic predictive value of the combination of fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET in patients with non-small cell lung carcinoma (NSCLC) treated with stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: We prospectively examined patients with pathologically proven NSCLC; all underwent FDG and FMISO PET/CT scans before SBRT. PET images were acquired using a whole-body time-of-flight PET-CT scanner with respiratory gating. We classified them into recurrent and non-recurrent groups based on their clinical follow-ups and compared the groups' tumor diameters and PET parameters (i.e., maximum of the standardized uptake value (SUVmax), metabolic tumor volume, tumor-to-muscle ratio, and tumor-to-blood ratio). We performed univariate analysis to evaluate the impact of the PET variables on the patients' progression-free survival (PFS). We divided the patients by thresholds of FDG SUVmax and FMISO SUVmax obtained from receiver operating characteristic analysis for assessment of recurrence rate and PFS. RESULTS: Thirty-two NSCLC patients (19 male and 13 females; median age, 83 years) were enrolled. All received SBRT. At the study endpoint, 23 patients (71.9%) were non-recurrent and nine patients (28.1%) had recurrent disease. Significant between-group differences were observed in tumor diameter and all the PET parameters, demonstrating that those were significant predictors of the recurrence in all patients. In the 22 patients with tumors > 2 cm, tumor diameter and FDG SUVmax were not significant predictors. Thirty-two patients were divided into three patterns from the thresholds of FDG SUVmax (6.81) and FMISO SUVmax (1.89); A, low FDG and low FMISO (n = 14); B, high FDG and low FMISO (n = 8); C, high FDG and high FMISO (n = 10). No pattern A patient experienced tumor recurrence, whereas two pattern B patients (25%) and seven pattern C patients (70%) exhibited recurrence. A Kaplan-Meier analysis of all patients revealed a significant difference in PFS between patterns A and B (p = 0.013) and between patterns A and C (p < 0.001). In the tumors > 2 cm patients, significant differences in PFS were demonstrated between pattern A and C patients (p = 0.002). CONCLUSION: The combination of FDG- and FMISO-PET can identify patients with a baseline risk of recurrence and indicate whether additional therapy might be performed to improve survival.

OC-078: Development of Gated Proton Imaging System for Moving Target
S. Tanaka, N. Miyamoto, T. Nishio, T. Yoshimura, S. Takao, Y. Matsuo, S. Shimizu, H. Shirato, T. Matsuura
Radiotherapy and Oncology, 141, S32, S33, Elsevier BV, Dec. 2019
Scientific journal

Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.
Yoshimura T, Shimizu S, Hashimoto T, Nishioka K, Katoh N, Inoue T, Taguchi H, Yasuda K, Matsuura T, Takao S, Tamura M, Ito YM, Matsuo Y, Tamura H, Horita K, Umegaki K, Shirato H
Journal of applied clinical medical physics, 21, 2, 38, 49, Wiley, Dec. 2019, [Peer-reviewed]
Scientific journal

胸部食道扁平上皮癌に対する術前補助化学療法・根治切除術および根治的化学放射線療法についての後方視的検討
中積 宏之, 村中 徹人, 川本 泰之, 小松 嘉人, 結城 敏志, 中野 真太郎, 澤田 憲太郎, 坂本 直哉, 打浪 雄介, 田口 大志, 白土 博樹, 海老原 裕磨, 七戸 俊明, 平野 聡
北海道医学雑誌, 94, 2, 120, 121, 北海道医学会, Nov. 2019
Japanese

当科における局所進行外耳道扁平上皮癌の治療成績の検討
加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 対馬 那由多, 鈴木 崇祥, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
頭頸部癌, 45, 3, 300, 304, (一社)日本頭頸部癌学会, Oct. 2019
Japanese, 我々は、局所進行外耳道扁平上皮癌に対する治療成績、特にドセタキセル、シスプラチン、5-FUの併用(TPF)の化学療法同時併用放射線療法(CCRT)の治療成績と安全性、および腫瘍の進展範囲と予後との関係を検討した。対象は当科で根治治療を行った外耳道癌扁平上皮癌で、ピッツバーグ分類のT3-4の21症例とした。その結果、硬膜と顎関節への進展が頸部転移と相関を示し、顎関節への進展が局所再発と相関を示した。全症例の2年粗生存率(OS)は61.1%、2年局所制御率(LC)は52.1%であった。CCRT症例では、TPF併用の2年OSは85.7%、それ以外では25.0%、TPF併用の2年LCは57.1%、それ以外では25.0%であった。また、TPF併用CCRTにおけるG3以上の白血球減少は55%、好中球減少は45%であった。TPF併用のCCRTは局所進行外耳道扁平上皮癌に対して高い有効性と安全性を示した。(著者抄録)

Prediction of Hypoxia in Brain Tumors Using a Multivariate Model Built from MR Imaging and ¹⁸F-Fluorodeoxyglucose Accumulation Data.
Shimizu Y, Kudo K, Kameda H, Harada T, Fujima N, Toyonaga T, Tha KK, Shirato H
Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 19, 3, 227, 234, Oct. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, PURPOSE: The aim of this study was to generate a multivariate model using various MRI markers of blood flow and vascular permeability and accumulation of 18F-fluorodeoxyglucose (FDG) to predict the extent of hypoxia in an 18F-fluoromisonidazole (FMISO)-positive region. METHODS: Fifteen patients aged 27-74 years with brain tumors (glioma, n = 13; lymphoma, n = 1; germinoma, n = 1) were included. MRI scans were performed using a 3T scanner, and dynamic contrast-enhanced (DCE) perfusion and arterial spin labeling images were obtained. Ktrans and Vp maps were generated using the DCE images. FDG and FMISO positron emission tomography scans were also obtained. A model for predicting FMISO positivity was generated on a voxel-by-voxel basis by a multivariate logistic regression model using all the MRI parameters with and without FDG. Receiver-operating characteristic curve analysis was used to detect FMISO positivity with multivariate and univariate analysis of each parameter. Cross-validation was performed using the leave-one-out method. RESULTS: The area under the curve (AUC) was highest for the multivariate prediction model with FDG (0.892) followed by the multivariate model without FDG and univariate analysis with FDG and Ktrans (0.844 for all). In cross-validation, the multivariate model with FDG had the highest AUC (0.857 ± 0.08) followed by the multivariate model without FDG (0.834 ± 0.119). CONCLUSION: A multivariate prediction model created using blood flow, vascular permeability, and glycometabolism parameters can predict the extent of hypoxia in FMISO-positive areas in patients with brain tumors.

Particle therapy for prostate cancer: The past, present and future.
Ishikawa H, Tsuji H, Murayama S, Sugimoto M, Shinohara N, Maruyama S, Murakami M, Shirato H, Sakurai H
International journal of urology : official journal of the Japanese Urological Association, 26, 10, 971, 979, Oct. 2019, [Peer-reviewed]

脾臓への放射線照射が奏功した脾機能亢進症の1例　　　　　　　　　　　　　　　
岩崎 愛美, 安田 耕一, 遠藤 知之, 大東 寛幸, 清水 伸一, 鬼丸 力也, 豊嶋 崇徳, 白土 博樹
日本医学放射線学会秋季臨床大会抄録集, 55回, S518, S518, (公社)日本医学放射線学会, Sep. 2019
Japanese

The Potential Benefit of Adaptive Intensity Modulated Proton Therapy in Nasopharyngeal Carcinoma: Planning Comparison Study
H. Minatogawa, K. Yasuda, T. Matsuura, R. Onimaru, T. Yoshimura, S. Takao, Y. Matsuo, Y. Dekura, R. Suzuki, M. Tamura, N. Miyamoto, S. Shimizu, H. Shirato
International Journal of Radiation Oncology*Biology*Physics, 105, 1, E394, E394, Elsevier BV, Sep. 2019
Scientific journal

局所進行食道癌に対してspot scanning法による根治的化学陽子線療法を施行した一例　　　　　　　　　　　　　　　
宮崎 智彦, 打浪 雄介, 田口 大志, 加藤 徳雄, 清水 伸一, 白土 博樹, 中積 宏之, 中野 真太郎, 坂本 直哉, 高尾 聖心, 田村 昌也, 松浦 妙子
日本医学放射線学会秋季臨床大会抄録集, 55回, S520, S520, (公社)日本医学放射線学会, Sep. 2019
Japanese

Initial Clinical Outcomes of Real-Time-Image Gated Spot-Scanning Proton Beam Therapy for Hepatocellular Carcinomas
N. Katoh, Y. Uchinami, D. Abo, S. Takao, T. Inoue, H. Taguchi, R. Morita, T. Soyama, T. Hashimoto, R. Onimaru, A. Prayongrat, M. Tamura, T. Matsuura, S. Shimizu, H. Shirato
International Journal of Radiation Oncology*Biology*Physics, 105, 1, E222, E223, Elsevier BV, Sep. 2019
Scientific journal

Percutaneous insertion of hepatic fiducial true-spherical markers for real-time adaptive radiotherapy.
Morita R, Abo D, Sakuhara Y, Soyama T, Katoh N, Miyamoto N, Uchinami Y, Shimizu S, Shirato H, Kudo K
Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy, 29, 6, 1, 10, Sep. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Purpose: This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating.Material and methods: We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR. Complications related to marker placement were assessed.Results: The technical success rate for true-spherical gold marker implantation was 92.2% (107/116). Nine of 116 markers migrated (intra-procedurally in seven patients, delayed in two patients). Migration out of the liver (n = 4) or intrahepatic vessels (n = 5) occurred without complications; these markers were not retrieved. The clinical success rate was 100.0% (115/115). Abdominal pain occurred in 16 patients, fever and hemorrhage in seven patients each, and pneumothorax and nausea in one patient each. No major complications were encountered.Conclusions: Percutaneous transhepatic implantation of true-spherical gold markers for RAR is feasible and can be conducted with a high success rate and low complication rate.

Lambda-Carrageenan Enhances the Effects of Radiation Therapy in Cancer Treatment by Suppressing Cancer Cell Invasion and Metastasis through Racgap1 Inhibition
Ping-Hsiu Wu, Yasuhito Onodera, Frances C. Recuenco, Amato J. Giaccia, Quynh-Thu Le, Shinichi Shimizu, Hiroki Shirato, Jin-Min Nam
Cancers, 11, 8, 1192, 1192, MDPI AG, 16 Aug. 2019
Scientific journal, Radiotherapy is used extensively in cancer treatment, but radioresistance and the metastatic potential of cancer cells that survive radiation remain critical issues. There is a need for novel treatments to improve radiotherapy. Here, we evaluated the therapeutic benefit of λ-carrageenan (CGN) to enhance the efficacy of radiation treatment and investigated the underlying molecular mechanism. CGN treatment decreased viability in irradiated cancer cells and enhanced reactive oxygen species accumulation, apoptosis, and polyploid formation. Additionally, CGN suppressed radiation-induced chemoinvasion and invasive growth in 3D lrECM culture. We also screened target molecules using a gene expression microarray analysis and focused on Rac GTPase-activating protein 1 (RacGAP1). Protein expression of RacGAP1 was upregulated in several cancer cell lines after radiation, which was significantly suppressed by CGN treatment. Knockdown of RacGAP1 decreased cell viability and invasiveness after radiation. Overexpression of RacGAP1 partially rescued CGN cytotoxicity. In a mouse xenograft model, local irradiation followed by CGN treatment significantly decreased tumor growth and lung metastasis compared to either treatment alone. Taken together, these results suggest that CGN may enhance the effectiveness of radiation in cancer therapy by decreasing cancer cell viability and suppressing both radiation-induced invasive activity and distal metastasis through downregulating RacGAP1 expression.

Impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with intensity-modulated radiotherapy.
Uchinami Y, Suzuki R, Katoh N, Taguchi H, Yasuda K, Miyamoto N, Ito YM, Shimizu S, Shirato H
Journal of applied clinical medical physics, 20, 8, 78, 86, WILEY, Aug. 2019, [Peer-reviewed]
English, Scientific journal, Purpose Interplay effects may influence dose distributions to a moving target when using dynamic delivery techniques such as intensity-modulated radiotherapy (IMRT). The aim of this study was to evaluate the impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with IMRT. Methods Ten patients who had been treated with IMRT for stomach lymphomas were enrolled. The clinical target volume (CTV) was contoured as the whole stomach. Considering interfractional uncertainty, the internal target volume (ITV) margin was uniformly 1.5 cm to the CTV and then modified based on the 4DCT images in case of the large respiratory motion. The planning target volume (PTV) was created by adding 5 mm to the ITV. The impact of organ motion on the volumetric and dosimetric parameters was evaluated retrospectively (4D simulation). The organ motion was reproduced by shifting the isocenter on the radiation treatment planning system. Several simulation plans were created to test the influence of the beam-on timing in the respiration cycle on the dose distribution. The homogeneity index (HI), volume percentage of stomach covered by the prescribed dose (V-p), and D-99 of the CTV were evaluated. Results The organ motion was the largest in the superior-inferior direction (10.1 +/- 4.5 mm [average +/- SD]). Stomach volume in each respiratory phase compared to the mean volume varied approximately within a +/- 5% range in most of the patients. The PTV margin was sufficiently large to cover the CTV during the IMRT. There was a significant reduction in V-p and D-99 but not in HI in the 4D simulation in free-breathing and multiple fractions compared to the clinically-used plan (P < 0.05) suggesting that interplay effects deteriorate the dose distribution. The absolute difference of D-99 was less than 1% of the prescribed dose. Conclusions There were significant interplay effects affecting the dose distribution in stomach IMRT. The magnitude of the dose reduction was small when patients were treated on free-breathing and multiple fractions.

Quantitative evaluation of image recognition performance of fiducial markers in real-time tumor-tracking radiation therapy.　　　　　　　　　　　　　　　
Miyamoto N, Maeda K, Abo D, Morita R, Takao S, Matsuura T, Katoh N, Umegaki K, Shimizu S, Shirato H
Physica Medica, 65, 33, 36, Aug. 2019, [Peer-reviewed]
English, Scientific journal

Projection‐domain scatter correction for cone beam computed tomography using a residual convolutional neural network
Yusuke Nomura, Qiong Xu, Hiroki Shirato, Shinichi Shimizu, Lei Xing
Medical Physics, 05 Jun. 2019, [Peer-reviewed]
English, Scientific journal

The normal tissue complication probability model-based approach considering uncertainties for the selective use of radiation modality in primary liver cancer patients.
Prayongrat A, Kobashi K, Ito YM, Katoh N, Tamura M, Dekura Y, Toramatsu C, Khorprasert C, Amornwichet N, Alisanant P, Shirato H, Shimizu S
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 135, 100, 106, Jun. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, PURPOSE: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients. METHODS AND MATERIALS: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/β ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method. RESULTS: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision. CONCLUSIONS: Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.

Machine-Learning-Based Prediction of Treatment Outcomes Using MR Imaging-Derived Quantitative Tumor Information in Patients with Sinonasal Squamous Cell Carcinomas: A Preliminary Study.
Fujima N, Shimizu Y, Yoshida D, Kano S, Mizumachi T, Homma A, Yasuda K, Onimaru R, Sakai O, Kudo K, Shirato H
Cancers, 11, 6, Jun. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The purpose of this study was to determine the predictive power for treatment outcome of a machine-learning algorithm combining magnetic resonance imaging (MRI)-derived data in patients with sinonasal squamous cell carcinomas (SCCs). Thirty-six primary lesions in 36 patients were evaluated. Quantitative morphological parameters and intratumoral characteristics from T2-weighted images, tumor perfusion parameters from arterial spin labeling (ASL) and tumor diffusion parameters of five diffusion models from multi-b-value diffusion-weighted imaging (DWI) were obtained. Machine learning by a non-linear support vector machine (SVM) was used to construct the best diagnostic algorithm for the prediction of local control and failure. The diagnostic accuracy was evaluated using a 9-fold cross-validation scheme, dividing patients into training and validation sets. Classification criteria for the division of local control and failure in nine training sets could be constructed with a mean sensitivity of 0.98, specificity of 0.91, positive predictive value (PPV) of 0.94, negative predictive value (NPV) of 0.97, and accuracy of 0.96. The nine validation data sets showed a mean sensitivity of 1.0, specificity of 0.82, PPV of 0.86, NPV of 1.0, and accuracy of 0.92. In conclusion, a machine-learning algorithm using various MR imaging-derived data can be helpful for the prediction of treatment outcomes in patients with sinonasal SCCs.

強度変調X線治療および強度変調陽子線治療における皮膚炎と皮膚線量に関する検討　　　　　　　　　　　　　　　
安田 耕一, 湊川 英樹, 出倉 康裕, 対馬 那由多, 鈴木 崇祥, 加納 里志, 水町 貴諭, 鬼丸 力也, 清水 伸一, 本間 明宏, 白土 博樹
頭頸部癌, 45, 2, 134, 134, (一社)日本頭頸部癌学会, May 2019
Japanese

外耳道癌における強度変調陽子線治療と強度変調X線治療との線量分布の比較　　　　　　　　　　　　　　　
出倉 康裕, 安田 耕一, 湊川 英樹, 対馬 那由多, 鈴木 崇祥, 加納 里志, 水町 貴諭, 鬼丸 力也, 清水 伸一, 本間 明宏, 白土 博樹
頭頸部癌, 45, 2, 138, 138, (一社)日本頭頸部癌学会, May 2019
Japanese

Clinical experience of craniospinal intensity-modulated spot-scanning proton therapy using large fields for central nervous system medulloblastomas and germ cell tumors in children, adolescents, and young adults.
Hashimoto T, Shimizu S, Takao S, Terasaka S, Iguchi A, Kobayashi H, Mori T, Yoshimura T, Matsuo Y, Tamura M, Matsuura T, Ito YM, Onimaru R, Shirato H
Journal of radiation research, 60, 4, 527, 537, May 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13-20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-body-sparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044-0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s ± 2 min 24 s (minimum to maximum: 22 min 49 s - 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.

Assessment of Coronary Flow Velocity Reserve in the Left Main Trunk Using Phase-contrast MR Imaging at 3T: Comparison with 15O-labeled Water Positron Emission Tomography.
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, 10 Apr. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, 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.

頭頸部癌化学放射線療法におけるEPA高配合栄養機能食品(プロシュア)の有用性の検討
水町 貴諭, 加納 里志, 本間 明宏, 赤澤 美樹子, 長谷川 千春, 城石 陽子, 岡本 千秋, 熊谷 聡美, 西村 雅勝, 高崎 裕代, 武田 宏司, 安田 耕一, 湊川 英樹, 出倉 康裕, 鬼丸 力也, 白土 博樹, 福田 諭
癌と化学療法, 46, 4, 685, 689, (株)癌と化学療法社, Apr. 2019
Japanese, 頭頸部癌に対する化学放射線療法により生じる代表的な副作用には口腔粘膜炎と体重減少があげられる。今回われわれは、中咽頭癌、下咽頭癌症例にてシスプラチンと放射線療法を同時併用する化学放射線療法施行症例において、ω3系脂肪酸高配合栄養機能食品であるプロシュアの口腔粘膜炎と体重減少に対する有用性の検討を行った。放射線治療開始から終了までの期間プロシュアを投与し、最大体重減少率、口腔粘膜炎、化学放射線療法完遂率についてプロシュアの介入を行っていない過去の当科症例を対照群として比較検討を行った。プロシュア投与群は対照群と比べ体重減少率の改善(7.3% vs 10.3%、p<0.01)、口腔粘膜炎の改善を認めた(CTCAE v3.0 Grade 3以上;24% vs 58%、p<0.05)が、化学放射線療法完遂率は両群の差を認めなかった(77% vs 60%、NS)。プロシュアの投与が化学放射線療法施行中において、体重減少や口腔粘膜炎の改善に寄与する可能性が示唆された。(著者抄録)

[A Nutritional Supplement with a High Blend Ratio of ω-3 Fatty Acids(Prosure®) Reduces Severe Oral Mucositis and Body Weight Loss for Head and Neck Cancer Patients Treated with Chemoradiotherapy].
Mizumachi T, Kano S, Homma A, Akazawa M, Hasegawa C, Shiroishi Y, Okamoto C, Kumagai S, Nishimura M, Takasaki H, Takeda H, Yasuda K, Minatogawa H, Dekura Y, Onimaru R, Shirato H, Fukuda S
Gan to kagaku ryoho. Cancer & chemotherapy, 46, 4, 685, 689, Apr. 2019, [Peer-reviewed], [Domestic magazines]
Japanese, Scientific journal, BACKGROUND: Oral mucositis and body weight loss are the most critical conditions known to lead to the discontinuation of chemoradiotherapy for head and neck cancer. We investigated the effect of a nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)on body weight loss, oral mucositis, and the completion rate of chemoradiotherapy in patients with oropharyngeal and hypopharyngeal cancer. PATIENTS AND METHODS: The study group comprised patients with oropharyngeal and hypopharyngeal cancer who were treated with concomitant cisplatin and 70 Gy of radiotherapy. These patients received 2 packs of Prosure®per day during chemoradiotherapy. RESULTS: A total of 17 patients were included in this study. The reduction in body weight was significantly improved compared with that in the historical control group that did not receive Prosure®(7.3% vs 10.3%, p<0.01), and the rate of Grade 3-4 oral mucositis was significantly reduced for the patient groups that received Prosure®(CTCAE v3.0 GradeB3; 24% vs 58%, p<0.05). The completion rate of chemoradiotherapy was not significantly different between both groups(77% vs 60%, NS). CONCLUSIONS: A nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)had effects on oral mucositis and body weight loss in head and neck cancer patients treated with chemoradiotherapy.

Predicting metastasis in clinically negative axillary lymph nodes with minimum apparent diffusion coefficient value in luminal A-like breast cancer.
Kato F, Kudo K, Yamashita H, Baba M, Shimizu A, Oyama-Manabe N, Kinoshita R, Li R, Shirato H
Breast cancer (Tokyo, Japan), 26, 5, 628, 636, Apr. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: We investigated the usefulness of the minimum ADC value of primary breast lesions for predicting axillary lymph node (LN) status in luminal A-like breast cancers with clinically negative nodes in comparison with the mean ADC. METHODS: Forty-four luminal A-like breast cancers without axillary LN metastasis at preoperative clinical evaluation, surgically resected with sentinel LN biopsy, were retrospectively studied. Mean and minimum ADC values of each lesion were measured and statistically compared between LN positive (n = 12) and LN negative (n = 32) groups. An ROC curve was drawn to determine the best cutoff value to differentiate LN status. Correlations between mean and minimum ADC values and the number of metastatic axillary LNs were investigated. RESULTS: Mean and minimum ADC values of breast lesions with positive LN were significantly lower than those with negative LN (mean 839.9 ± 110.9 vs. 1022.2 ± 250.0 × 10- 6 mm2/s, p = 0.027, minimum 696.7 ± 128.0 vs. 925.0 ± 257.6 × 10- 6 mm2/s, p = 0.004). The sensitivity and NPV using the best cutoff value from ROC using both mean and minimum ADC were 100%. AUC of the minimum ADC (0.784) was higher than that of the mean ADC (0.719). Statistically significant negative correlations were observed between both mean and minimum ADCs and number of positive LNs, with stronger correlation to minimum ADC than mean ADC. CONCLUSIONS: The minimum ADC value of primary breast lesions predicts axillary LN metastasis in luminal A-like breast cancer with clinically negative nodes, with high sensitivity and high NPV.

A novel range-verification method using ionoacoustic wave generated from spherical gold markers for particle-beam therapy: a simulation study.
Takayanagi T, Uesaka T, Kitaoka M, Unlu MB, Umegaki K, Shirato H, Xing L, Matsuura T
Scientific reports, 9, 1, 4011, Mar. 2019, [Peer-reviewed]

The utility of MRI histogram and texture analysis for the prediction of histological diagnosis in head and neck malignancies
Fujima Noriyuki, Homma Akihiro, Harada Taisuke, Shimizu Yukie, Tha Khin Khin, Kano Satoshi, Mizumachi Takatsugu, Li Ruijiang, Kudo Kohsuke, Shirato Hiroki
CANCER IMAGING, 19, 04 Feb. 2019, [Peer-reviewed]

脳動静脈奇形SRS後に妊娠,分娩に至った1例　　　　　　　　　　　　　　　
森 崇, 鬼丸 力也, 白土 博樹, 細川 亜美, 森川 守, 水上 尚典, 中山 若樹, 西村 あや子
Japanese Journal of Radiology, 37, Suppl., 14, 14, (公社)日本医学放射線学会, Feb. 2019
Japanese

強度変調放射線治療中に皮下気腫をきたし,再検証を要した頭頸部癌患者の1例　　　　　　　　　　　　　　　
湊川 英樹, 安田 耕一, 白土 博樹, 土屋 和彦, 鈴木 隆介, 宮本 直樹, 坂下 智博, 本間 明宏, 福田 諭
Japanese Journal of Radiology, 37, Suppl., 4, 4, (公社)日本医学放射線学会, Feb. 2019
Japanese

特徴的な画像所見を呈した鞍上部immature teratomaの1例　　　　　　　　　　　　　　　
藤井 宝顕, 原田 太以佑, 清水 幸衣, 藤間 憲幸, Tha Khin Khin, 工藤 與亮, 寺坂 俊介, 長 祐子, 白土 博樹
Japanese Journal of Radiology, 37, Suppl., 4, 4, (公社)日本医学放射線学会, Feb. 2019
Japanese

くも膜下出血後にびまん性の白質障害を呈した1例　　　　　　　　　　　　　　　
古家 翔, 原田 太以佑, 清水 幸衣, 藤間 憲幸, Tha Khin Khin, 工藤 與亮, 月花 正幸, 中山 若樹, 白土 博樹
Japanese Journal of Radiology, 37, Suppl., 10, 10, (公社)日本医学放射線学会, Feb. 2019
Japanese

The utility of MRI histogram and texture analysis for the prediction of histological diagnosis in head and neck malignancies.
Fujima N, Homma A, Harada T, Shimizu Y, Tha KK, Kano S, Mizumachi T, Li R, Kudo K, Shirato H
Cancer imaging : the official publication of the International Cancer Imaging Society, 19, 1, 5, 5, Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: To assess the utility of histogram and texture analysis of magnetic resonance (MR) fat-suppressed T2-weighted imaging (Fs-T2WI) for the prediction of histological diagnosis of head and neck squamous cell carcinoma (SCC) and malignant lymphoma (ML). METHODS: The cases of 57 patients with SCC (45 well/moderately and 12 poorly differentiated SCC) and 10 patients with ML were retrospectively analyzed. Quantitative parameters with histogram features (relative mean signal, coefficient of variation, kurtosis and skewness) and gray-level co-occurrence matrix (GLCM) features (contrast, correlation, energy and homogeneity) were calculated using Fs-T2WI data with a manual tumor region of interest (ROI). RESULTS: The following significantly different values were obtained for the total SCC versus ML groups: relative mean signal (3.65 ± 0.86 vs. 2.61 ± 0.49), contrast (72.9 ± 16.2 vs. 49.3 ± 8.7) and homogeneity (2.22 ± 0.25 × 10- 1 vs. 2.53 ± 0.12 × 10- 1). In the comparison of the SCC histological grades, the relative mean signal and contrast were significantly lower in the poorly differentiated SCC (2.89 ± 0.63, 56.2 ± 12.9) compared to the well/moderately SCC (3.85 ± 0.81, 77.5 ± 13.9). The homogeneity in poorly differentiated SCC (2.56 ± 0.15 × 10- 1) was higher than that of the well/moderately SCC (2.1 ± 0.18 × 10- 1). CONCLUSIONS: Parameters obtained by histogram and texture analysis of Fs-T2WI may be useful for noninvasive prediction of histological type and grade in head and neck malignancy.

Treatment outcomes of local advanced external auditory canal squamous cell carcinomas
Satoshi Kano, Shinya Morita, Yuji Nakamaru, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Akira Nakazono, Atsushi Fukuda, Koichi Yasuda, Rikiya Onimaru, Hiroki Shirato, Akihiro Homma
Japanese Journal of Head and Neck Cancer, 45, 3, 300, 304, 2019, [Peer-reviewed]
Scientific journal, © 2019, Japan Society for Head and Neck Cancer. All rights reserved. We analyzed the treatment outcomes and safety of concomitant chemoradiotherapy (CCRT), especially with a combination of docetaxel, cisplatin and 5FU (TPF), for local advanced external auditory canal squamous cell carcinomas. In addition, we analyzed the correlation between tumor invasion site and prognosis. The study comprised 21 patients with the following criteria: (1) external auditory canal squamous cell carcinomas which were subject to radical treatment at Hokkaido University Hospital between 2007 and 2017, and (2) T3–4 classified according to the University of Pittsburg system. As a result, tumor invasion into the dura or temporomandibular joint was associated with neck lymph node metastasis, and tumor invasion into the temporomandibular joint was associated with local recurrence. The 2-year overall survival rate (OS) and 2-year local control rate (LC) were 61.1％ and 52.1％ in all patients, respectively. In patients treated with CCRT, the 2-year OS was 85.7％ in CCRT with TPF and 25.0％ in CCRT with others, and the 2-year LC was 57.1％ in CCRT with TPF and 25.0％ in CCRT with others. Grade 3︲4 leucopenia and neutropenia occurred in 55％ and 45％ of patients treated with CCRT with TPF, respectively. CCRT with TPF shows high efficacy and safety for local advanced external auditory canal squamous cell carcinomas.

3D Transformation Matrix Calculation and Pixel Intensity Normalization for the Dual Focus Tracking System　　　　　　　　　　　　　　　
Kenneth Sutherland, Toshiyuki Hamada, Masayori Ishikawa, Naoki Miyamoto, Masahiro Mizuta, Hiroyuki Date, Hiroki Shirato
Journal of Medical and Biological Engineering, 2019, [Peer-reviewed]
English, Scientific journal

くも膜下出血後にびまん性の白質障害を呈した一例
古家 翔, 原田 太以佑, 清水 幸衣, 藤間 憲幸, Tha Khin Khin, 工藤 與亮, 月花 正幸, 中山 若樹, 白土 博樹
核医学, 55, 1, 40, 40, (一社)日本核医学会, Dec. 2018
Japanese

Integrating quantitative morphological and intratumoural textural characteristics in FDG-PET for the prediction of prognosis in pharynx squamous cell carcinoma patients.
N Fujima, K Hirata, T Shiga, R Li, K Yasuda, R Onimaru, K Tsuchiya, S Kano, T Mizumachi, A Homma, K Kudo, H Shirato
Clinical radiology, 73, 12, 1059.e1-1059.e8, Dec. 2018, [Peer-reviewed], [International Magazine]
English, AIM: To assess potential prognostic factors in pharynx squamous cell carcinoma (SCC) patients by quantitative morphological and intratumoural characteristics obtained by 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: The cases of 54 patients with pharynx SCC who underwent chemoradiation therapy were analysed retrospectively. Using their FDG-PET data, the quantitative morphological and intratumoural characteristics of 14 parameters were calculated. The progression-free survival (PFS) and overall survival (OS) information was obtained from patient medical records. Univariate and multivariate analyses were performed to assess the 14 quantitative parameters as well as the T-stage, N-stage, and tumour location data for their relation to PFS and OS. When an independent predictor was suggested in the multivariate analysis, the parameter was further assessed using the Kaplan-Meier method. RESULTS: In the assessment of PFS, the univariate and multivariate analyses indicated the following as independent predictors: the texture parameter of homogeneity and the morphological parameter of sphericity. In the Kaplan-Meier analysis, the PFS rate was significantly improved in the patients who had both a higher value of homogeneity (p=0.01) and a higher value of sphericity (p=0.002). With the combined use of homogeneity and sphericity, the patients with different PFS rates could be divided more clearly. CONCLUSION: The quantitative parameters of homogeneity and sphericity obtained by FDG-PET can be useful for the prediction of the PFS of pharynx SCC patients, especially when used in combination.

Intensity-Modulated Proton Therapy with Dose Painting based on Hypoxia Imaging for Nasopharyngeal Cancer
K. Yasuda, S. Takao, Y. Matsuo, T. Yoshimura, M. Tamura, H. Minatogawa, Y. Dekura, T. Matsuura, R. Onimaru, T. Shiga, S. Shimizu, K. Umegaki, H. Shirato
International Journal of Radiation Oncology*Biology*Physics, 102, 3, e378, e378, Elsevier BV, Nov. 2018
Scientific journal

Uncertainties of Normal Tissue Complication Probability (NTCP) and NTCP Difference between Radiation Treatment Modalities for Radiation-Induced Liver Toxicity in Child-Pugh A Primary Liver Cancer Patients
A. Prayongrat, K. Kobashi, Y. Ito, N. Katoh, Y. Dekura, N. Amornwichet, S. Shimizu, H. Shirato
International Journal of Radiation Oncology*Biology*Physics, 102, 3, e65, e66, Elsevier BV, Nov. 2018
Scientific journal

Analysis of Beam Delivery Times and Dose Rates for the Treatment of Mobile Tumors Using Real Time Image Gated Spot-Scanning Proton Beam Therapy
S. Shimizu, T. Yoshimura, N. Katoh, T. Inoue, T. Hashimoto, K. Nishioka, S. Takao, T. Matsuura, N. Miyamoto, Y.M. Ito, K. Umegaki, H. Shirato
International Journal of Radiation Oncology*Biology*Physics, 102, 3, S182, S183, Elsevier BV, Nov. 2018
Scientific journal

Real-Time Tumor-Tracking Radiotherapy and General Stereotactic Body Radiotherapy for Adrenal Metastasis in Patients With Oligometastasis
Katoh N, Onishi H, Uchinami Y, Inoue T, Kuriyama K, Nishioka K, Shimizu S, Komiyama T, Miyamoto N, Shirato H
TECHNOLOGY IN CANCER RESEARCH & TREATMENT, 17, 1533033818809983, Nov. 2018, [Peer-reviewed]
English, Scientific journal

喉頭癌cT3の喉頭温存治療(CRT vs RADPLAT) 喉頭癌に対する超選択的動注と放射線同時併用療法
本間 明宏, 加納 里志, 水町 貴諭, 中薗 彬, 鈴木 崇祥, 坂下 智博, 福田 諭, 鬼丸 力也, 安田 耕一, 湊川 英樹, 出倉 康裕, 土屋 和彦, 白土 博樹
日本気管食道科学会会報, 69, 5, 319, 320, (NPO)日本気管食道科学会, Oct. 2018
Japanese

Final report of survival and late toxicities in the Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer (JCOG0702)
Onimaru R, Onishi H, Ogawa G, Hiraoka M, Ishikura S, Karasawa K, Matsuo Y, Kokubo M, Shioyama Y, Matsushita H, Ito Y, Shirato H
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 48, 12, 1076, 1082, Oct. 2018, [Peer-reviewed]
English, Scientific journal

Long-term Outcomes of Tri-modality Therapy using a real-time tumor-tracking radiotherapy system for Patients with Muscle-invasive Bladder Cancer
Miyata Haruka, Osawa Takahiro, Matsumoto Ryuji, Abe Takashige, Maruyama Satoru, Nishioka Kentaro, Shimizu Shinichi, Hashimoto Takayuki, Shirato Hiroki, Shinohara Nobuo
INTERNATIONAL JOURNAL OF UROLOGY, 25, 321, Oct. 2018, [Peer-reviewed]

Determination of the urethra position for accurate radiation therapy of prostate cancers
Dekura Yasuhiro, Nishioka Kentaro, Hashimoto Takayuki, Miyamoto Naoki, Suzuki Ryusuke, Matsumoto Ryuji, Osawa Takahiro, Abe Takashige, Maruyama Satoru, Shinohara Nobuo, Shirato Hiroki, Shimizu Shinichi
INTERNATIONAL JOURNAL OF UROLOGY, 25, 445, 445, WILEY, Oct. 2018, [Peer-reviewed]
English

Semi-quantitative analysis of pre-treatment morphological and intratumoral characteristics using F-18-fluorodeoxyglucose positron-emission tomography as predictors of treatment outcome in nasal and paranasal squamous cell carcinoma
Fujima Noriyuki, Hirata Kenji, Shiga Tohru, Yasuda Koichi, Onimaru Rikiya, Tsuchiya Kazuhiko, Kano Satoshi, Mizumachi Takatsugu, Homma Akihiro, Kudo Kohsuke, Shirato Hiroki
QUANTITATIVE IMAGING IN MEDICINE AND SURGERY, 8, 8, 788, 795, Sep. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background: To investigate the utility of quantitative morphological and intratumoral characteristics obtained by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) for the prediction of treatment outcome in patients with nasal or paranasal cavity squamous cell carcinoma (SCC). Methods: Twenty-four patients with nasal or paranasal cavity SCC who received curative non-surgical therapy (a combination of super-selective arterial cisplatin infusion and radiotherapy) were retrospectively analyzed. From pre-treatment FDG-PET data, a total of 13 parameters of quantitative morphological characteristics (tumor volume, surface area and sphericity), intratumoral characteristics (the maximum and mean standard uptake value, three intratumoral histogram and four textural parameters) and total lesion glycolysis (TLG) were respectively calculated. Information regarding the treatment outcome was determined from the histological diagnosis or clinical follow-up. Each of the 13 quantitative parameters as well as T- and N-stage was assessed for its relation to treatment outcome of local control or failure. Results: In univariate analysis, significant differences in surface area and sphericity between the local control and failure groups were observed. The receiver operating characteristic (ROC) curve analysis showed that sphericity had the highest accuracy of 0.88. In the multivariate analysis, sphericity was revealed as an independent predictor of the local control or failure. Conclusions: The quantitative parameters of sphericity are useful to predict the treatment outcome in patients with nasal or paranasal SCC.

Investigation of energy absorption by clustered gold nanoparticles
Jihun Kwon, Kenneth Sutherland, Anastasia Makarova, Taeko Matsuura, Takayuki Hashimoto, Hao Peng, Toshiyuki Toshito, Kikuo Umegaki, Hiroki Shirato, Shinichi Shimizu
Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms, 429, 34, 41, 15 Aug. 2018, [Peer-reviewed]
Scientific journal, © 2018 Elsevier B.V. The utilization of gold nanoparticles (GNPs) as a radiation sensitizer has received broad attention. Although GNPs form clusters in living cells, most previous simulation studies have assumed a homogeneous distribution of GNPs. In this study, a GNP cluster was constructed for simulations and the impact of cluster formation on dose enhancement was examined. Energy absorption by the GNPs was compared between clustered and homogeneous distributions for several different GNP concentrations and diameters under 100 keV X-ray irradiations. Our simulations showed that clusters more efficiently absorbed the secondary electrons and photons produced by GNPs themselves. Furthermore, the impact of cluster formation on dose enhancement was more significant for smaller GNPs and higher concentrations. Our results suggest that previous simulations assuming a homogeneous GNP distribution have overestimated the dose enhancement, especially for smaller GNPs and higher concentrations. These findings should guide the selection of GNP size and concentration for effectively optimizing dose enhancement in future studies.

Stereotactic body radiotherapy to treat small lung lesions clinically diagnosed as primary lung cancer by radiological examination: A prospective observational study
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, Elsevier Ireland Ltd, 01 Aug. 2018, [Peer-reviewed]
English, Scientific journal, 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.

An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.
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, Jul. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, PURPOSE: To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LETd ) is required. In this study, we have developed the analytical LETd calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. METHODS: In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LETd value for the lateral distribution of a pencil beam, the actual LETd increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LETd behavior, we have assumed that the LETs of primary and halo components can take different values (LETp and LEThalo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LETd distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LETd distributions and mean LETd (LETd,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. RESULTS: In the homogeneous phantom, the LETd profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LETd profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LETd,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/μm in homogeneous phantoms and 0.08 keV/μm in patient geometries under all tested conditions, respectively. CONCLUSIONS: We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LETd was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs.

Arf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe.
Onodera Y, Nam JM, Horikawa M, Shirato H, Sabe H
Nature communications, 9, 1, 2682, 2682, Jul. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Mitochondria dynamically alter their subcellular localization during cell movement, although the underlying mechanisms remain largely elusive. The small GTPase Arf6 and its signaling pathway involving AMAP1 promote cell invasion via integrin recycling. Here we show that the Arf6-AMAP1 pathway promote the anterograde trafficking of mitochondria. Blocking the Arf6-based pathway causes mitochondrial aggregation near the microtubule-organizing center, and subsequently induces detrimental reactive oxygen species (ROS) production, likely via a mitochondrial ROS-induced ROS release-like mechanism. The Arf6-based pathway promotes the localization of ILK to focal adhesions to block RhoT1-TRAK2 association, which controls mitochondrial retrograde trafficking. Blockade of the RhoT1-TRAK1 machinery, rather than RhoT1-TRAK2, impairs cell invasion, but not two-dimensional random cell migration. Weakly or non-invasive cells do not notably express TRAK proteins, whereas they clearly express their mRNAs. Our results identified a novel association between cell movement and mitochondrial dynamics, which is specific to invasion and is necessary for avoiding detrimental ROS production.

Effects of Surgery With Salvage Stereotactic Radiosurgery Versus Surgery With Whole-Brain Radiation Therapy in Patients With One to Four Brain Metastases (JCOG0504): A Phase III, Noninferiority, Randomized Controlled Trial.
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, 20 Jun. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Time has come for proton and carbon beam therapy
Hiroki Shirato
International Journal of Clinical Oncology, 23, 3, 421, 422, Springer Tokyo, 01 Jun. 2018, [Peer-reviewed]
English, Scientific journal

当科における局所進行外耳道扁平上皮癌の治療成績の検討　　　　　　　　　　　　　　　
加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
頭頸部癌, 44, 2, 181, 181, (一社)日本頭頸部癌学会, May 2018
Japanese

Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan
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, Blackwell Publishing Ltd, 01 May 2018, [Peer-reviewed]
English, Scientific journal, 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.

当科における局所進行外耳道扁平上皮癌の治療成績の検討　　　　　　　　　　　　　　　
加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
頭頸部癌, 44, 2, 181, 181, (一社)日本頭頸部癌学会, May 2018
Japanese

Toll-like receptor 3 signal augments radiation-induced tumor growth retardation in a murine model
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, Blackwell Publishing Ltd, 01 Apr. 2018, [Peer-reviewed]
English, Scientific journal, 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.

Comparison of the average surviving fraction model with the integral biologically effective dose model for an optimal irradiation scheme
Ryo Takagi, Yuriko Komiya, Kenneth L Sutherland, Hiroki Shirato, Hiroyuki Date, Masahiro Mizuta
Journal of Radiation Research, 59, suppl_1, i32, i39, Oxford University Press, 01 Mar. 2018, [Peer-reviewed]
English, Scientific journal, 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.

Prospective study to evaluate the safety of the world-first spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy system
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, 01 Mar. 2018, [Peer-reviewed]
International conference proceedings, © 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.

Selection of external beam radiotherapy approaches for precise and accurate cancer treatment
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, Oxford University Press, 01 Mar. 2018, [Peer-reviewed]
English, Scientific journal, 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.

Long-term outcomes of proton therapy for prostate cancer in Japan: a multi-institutional survey of the Japanese Radiation Oncology Study Group.
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, Mar. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Present developments in reaching an international consensus for a model-based approach to particle beam therapy.
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, 01 Mar. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Assessing the uncertainty in a normal tissue complication probability difference ('NTCP): Radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy
Keiji Kobashi, Anussara Prayongrat, Takuya Kimoto, Chie Toramatsu, Yasuhiro Dekura, Norio Katoh, Shinichi Shimizu, Yoichi M Ito, Hiroki Shirato
Journal of Radiation Research, 59, suppl_1, i50, i57, Oxford University Press, 01 Mar. 2018, [Peer-reviewed]
English, Scientific journal, 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.

30年後の再発が疑われる脊髄Germinomaの1例　　　　　　　　　　　　　　　
木野田 直也, 原田 太以佑, 吉田 篤司, 清水 幸衣, 藤間 憲幸, 工藤 興亮, Khin Khin Tha, 白土 博樹, 山口 秀, 小林 浩之, 寺坂 俊介, 岡田 宏美, 畑中 佳奈子
Japanese Journal of Radiology, 36, Suppl., 3, 3, (公社)日本医学放射線学会, Feb. 2018
Japanese

長期間経過を追えたCerebral Amyloid Angiopathyの1例　　　　　　　　　　　　　　　
常田 慧徳, 原田 太以佑, 吉田 篤司, 清水 幸衣, 藤間 憲幸, 工藤 與亮, 西村 洋昭, 佐々木 秀直, Khin Khin Tha, 白土 博樹
Japanese Journal of Radiology, 36, Suppl., 13, 13, (公社)日本医学放射線学会, Feb. 2018
Japanese

亜急性連合性脊髄変性症の1例　　　　　　　　　　　　　　　
長島 諒太, 原田 太以佑, 吉田 篤司, 清水 幸衣, 藤間 憲幸, 工藤 與亮, Khin Khin Tha, 白土 博樹, 西村 洋昭, 佐々木 秀直
Japanese Journal of Radiology, 36, Suppl., 16, 16, (公社)日本医学放射線学会, Feb. 2018
Japanese

同時期に異所性に発生した悪性腫瘍に対して、二部位同時にIMRTを施行した症例　　　　　　　　　　　　　　　
湊川 英樹, 安田 耕一, 白土 博樹, 土屋 和彦, 原田 八重, 水町 貴諭, 坂下 智博, 本間 明宏, 福田 諭, 石嶋 漢, 宮本 直樹, 高尾 聖心, 鈴木 隆介, 松浦 妙子, 牧永 綾乃, 田村 昌也
Japanese Journal of Radiology, 36, Suppl., 6, 6, (公社)日本医学放射線学会, Feb. 2018
Japanese

Utility of a Hybrid IVIM-DKI Model to Predict the Development of Distant Metastasis in Head and Neck Squamous Cell Carcinoma Patients.
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, 10 Jan. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, 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.

【悪性脊椎脊髄腫瘍に対する治療】 原発性悪性脊椎脊髄腫瘍に対する放射線治療
鬼丸 力也, 森 崇, 加藤 徳雄, 関 俊隆, 白土 博樹
脊椎脊髄ジャーナル, 30, 7, 673, 676, (株)三輪書店, Jul. 2017
Japanese

北海道大学病院の小児がん陽子線治療に対する取り組み
橋本孝之, 井口晶裕, 寺坂俊介, 杉山美奈子, 大島淳二郎, 山口秀, 小林浩之, 長祐子, 清水伸一, 鬼丸力也, 白土博樹
日本小児科学会雑誌, 121, 5, 914‐915, 915, (公社)日本小児科学会, 01 May 2017
Japanese

骨軟部腫瘍に対する陽子線治療
橋本孝之, 清水伸一, 白土博樹
北海道整形災害外科学会雑誌, 58, 2, 187‐192, 24 Mar. 2017
Japanese

Prediction of the treatment outcome using intravoxel incoherent motion and diffusional kurtosis imaging in nasal or sinonasal squamous cell carcinoma 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, SPRINGER, Mar. 2017, [Peer-reviewed]
English, Scientific journal, 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.

Long-term follow-up after proton beam therapy for pediatric tumors: a Japanese national survey
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, WILEY, Mar. 2017, [Peer-reviewed]
English, Scientific journal, 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 (5.03-1.2 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.

粒子線治療装置等が地域経済へ及ぼす影響
畔木智己, 橋本孝之, 清水伸一, 土屋和彦, 鬼丸力也, 白土博樹
Japanese Journal of Radiology, 35, Supplement, 4, 4, (公社)日本医学放射線学会, 25 Feb. 2017
Japanese

乳房温存術後接線照射後にFitz‐Hugh‐Curtis症候群様の肝周囲炎を来した1例
出倉康裕, 森崇, 西川由記子, 木下留美子, 橋本孝之, 白土博樹, 西岡健太郎, 清水伸一, 細田充主, 山下啓子
Japanese Journal of Radiology, 35, Supplement, 4, 4, (公社)日本医学放射線学会, 25 Feb. 2017
Japanese

放射線腸炎の指標としての便中αディフェンシンの可能性　　　　　　　　　　　　　　　
小野寺 俊輔, 中村 公則, 綾部 時芳, 白土 博樹
Japanese Journal of Radiology, 35, Suppl., 10, 10, (公社)日本医学放射線学会, Feb. 2017
Japanese

新たな放射線治療用病変識別マーカーの開発のための基礎的検討　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 曽山 武士, 森田 亮, 工藤 與亮, 白土 博樹, 高橋 文也
IVR: Interventional Radiology, 31, 4, 374, 374, (一社)日本インターベンショナルラジオロジー学会, Jan. 2017
Japanese

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells
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, DOVE MEDICAL PRESS LTD, 2017, [Peer-reviewed]
English, Scientific journal, 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 alpha 5-and alpha v-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.

前立腺癌の放射線治療時における尿量の変動の解析
後藤謙斗, 西岡健太郎, 松崎有華, 松浦妙子, 高尾聖心, 橋本孝之, 木下留美子, 西川由記子, 清水伸一, 白土博樹
日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集, 30th, 55, 2017
Japanese

高次医療連携システムによる医療情報の有効活用について 患者と医療者のためのがん治療の道標の可視化 患者中心のがん診断・治療ナビゲーションシステム開発　　　　　　　　　　　　　　　
白土 博樹, 安田 耕一, 熊木 康雄, 上杉 正人
医療情報学連合大会論文集, 36回, 1, 126, 127, (一社)日本医療情報学会, Nov. 2016
Japanese

自由行動マウスの複数組織における時計遺伝子発現のin vivo追跡定量化 (Best articles of the year)　　　　　　　　　　　　　　　
浜田俊幸, ケネスリーサザーランド, 石川正純, 宮本直樹, 本間さと, 白土博樹, 本間研一
The Hokkaido Journal of Medical Science, 91, 2, Nov. 2016, [Peer-reviewed]

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients
Tamura,Masaya, Sakurai,Hideyuki, Mizumoto,Masashi, Kamizawa,Satoshi, Murayama,Shigeyuki, Yamashita,Haruo, Takao,Seishin, Suzuki,Ryusuke, Shirato,Hiroki, Ito,M. Yoichi
J Radiat Res, 58, 3, 363, 371, OXFORD UNIV PRESS, Oct. 2016, [Peer-reviewed]
English, Scientific journal, 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)

Quantitative Analysis of F-18-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy
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, ELSEVIER SCIENCE INC, Sep. 2016, [Peer-reviewed]
English, Scientific journal, 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.

中咽頭扁平上皮癌に対する化学放射線療法施行症例の臨床的検討　　　　　　　　　　　　　　　
水町 貴諭, 坂下 智博, 加納 里志, 畠山 博充, 本間 明宏, 土屋 和彦, 安田 耕一, 鬼丸 力也, 白土 博樹, 福田 諭
頭頸部癌, 42, 2, 181, 181, (一社)日本頭頸部癌学会, May 2016
Japanese

下咽頭癌に対する化学放射線療法後の嚥下障害 欧米の報告との比較　　　　　　　　　　　　　　　
本間 明宏, 畠山 博充, 水町 貴諭, 加納 里志, 坂下 智博, 鬼丸 力也, 土屋 和彦, 安田 耕一, 白土 博樹, 福田 諭
頭頸部癌, 42, 2, 214, 214, (一社)日本頭頸部癌学会, May 2016
Japanese

最前線の研究治療 強度変調陽子線治療
清水伸一, 白土博樹
医学のあゆみ, 257, 1, 19‐24, 24, 医歯薬出版, 02 Apr. 2016
Japanese

椎体IMRTとその精度に関する研究
安田耕一, 清水伸一, 橋本孝之, SUTHERLAND Ken, 白土博樹, 土屋和彦, 加藤徳雄, 鬼丸力也, 木下留美子, 井上哲也, 西岡健太郎, 西川由記子, 森崇, 原田慶一, 原田八重, 鈴木隆介, 寅松千枝, 松浦妙子, 高尾聖心, 宮本直樹, 伊藤陽一
Japanese Journal of Radiology, 34, Supplement, 5, 5, (公社)日本医学放射線学会, 25 Feb. 2016
Japanese

照射中と4DCT撮像時の肺内マーカー移動の比較
原田慶一, 加藤徳雄, 井上哲也, 鬼丸力也, 清水伸一, 白土博樹, 鈴木隆介, 宮本直樹, 石川正純
Japanese Journal of Radiology, 34, Supplement, 10, 10, (公社)日本医学放射線学会, 25 Feb. 2016
Japanese

Clinical application and future vision of the real-time tumor-tracking radiotherapy
宮本直樹, 石川正純, 井上哲也, 加藤徳雄, 清水伸一, 鬼丸力也, 白土博樹
臨床放射線, 61, 2, 293‐302, 302, 金原出版(株), 10 Feb. 2016
Japanese

呼吸性移動の複雑さと対策:最新の動体追跡放射線治療
宮本直樹, 高尾聖心, 原田慶一, 石川正純, 鈴木隆介, 松浦妙子, 牧永彩乃, 井上哲也, 加藤徳雄, 清水伸一, 鬼丸力也, 白土博樹
日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集, 29th, 46, 2016
Japanese

食道癌術後/化学放射線療法後再発に対する化学放射線療法の成績
井上哲也, 原田慶一, 加藤徳雄, 清水伸一, 白土博樹, 中積宏之, 福島拓, 小松嘉人, 海老原裕磨, 七戸俊明
北海道医学雑誌, 90, 2, 153‐154, 154, 北海道医学会, 01 Nov. 2015
Japanese

S2-1 New Parading in Particle Beam Therapy　　　　　　　　　　　　　　　
Hiroki,Shirato, Hideyuki,Sakurai, Tetsuo,Akimoto, Shigeyuki,Murayama, Tomoaki,Okimoto, Yasuhiro,Kikuchi, Kazutaka,Yamamoto
日本放射線腫瘍学会第28回学術大会報文集, 126, 126, Nov. 2015, [Peer-reviewed]
Japanese, International conference proceedings

閉塞性黄疸患者における胆道ドレナージ術前後の肝硬度の変化　　　　　　　　　　　　　　　
久保 公利, 河上 洋, 桑谷 将城, 川久保 和道, 阿部 容子, 川畑 修平, 坂本 直哉, 作原 佑介, 白土 博樹, 工藤 悠輔, 西田 睦
日本消化器病学会雑誌, 112, 臨増大会, A855, A855, (一財)日本消化器病学会, Sep. 2015
Japanese

Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer with PTV<100cc using a continual reassessment method (JCOG0702).
Onimaru R, Shirato H, Shibata T, Hiraoka M, Ishikura S, Karasawa K, Matsuo Y, Kokubo M, Shioyama Y, Matsushita H, Ito Y, Onishi H
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 116, 2, 276, 280, Elsevier {BV}, Jul. 2015, [Peer-reviewed]
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) &lt; 100cc. 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 180days 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 60Gy in 4 fractions. It was difficult to fulfill the dose constraints at 60Gy in 4 fractions, and the maximum dose level assigned by CRM was changed to 55Gy in 4 fractions. The lower limit of 95% of the credible interval exceeded the adjacent level, and the RD was determined as 55Gy in 4 fractions. CONCLUSIONS: The RD of SBRT for peripheral T2N0M0 NSCLC with PTV&lt;100cc was determined to be 55Gy in 4 fractions.

Improvement of cerebral hypometabolism after resection of radiation-induced necrotic lesion in a patient with cerebral arteriovenous malformation.
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, Jun. 2015, [Peer-reviewed], [International Magazine]
English, 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.

4DCTを用いた肺内マーカー移動の解析
加藤徳雄, 原田慶一, 鈴木隆介, 井上哲也, 鬼丸力也, 清水伸一, 宮本直樹, 白土博樹
Jpn J Radiol, 33, Supplement, 5, 5, (公社)日本医学放射線学会, 25 Feb. 2015
Japanese

頭頸部における扁平上皮癌と悪性リンパ腫の腫瘍血流の違い　　　　　　　　　　　　　　　
亀田 浩之, 藤間 憲幸, 吉川 仁人, 吉田 篤司, 清水 幸衣, 吉田 大介, 塚原 亜希子, 工藤 與亮, Tha Khin Khin, 白土 博樹
Japanese Journal of Radiology, 33, Suppl., 1, 1, (公社)日本医学放射線学会, Feb. 2015
Japanese

発熱と骨病変が先行した小児白血病の1例　　　　　　　　　　　　　　　
藪崎 哲史, 宮本 憲幸, 白土 博樹, 真鍋 徳子, 藤間 憲幸, 菊池 穏香, 坂本 圭太, 三村 理恵, 加藤 芙美, 工藤 與亮, 佐藤 智信, 長 祐子, 井口 晶裕
Japanese Journal of Radiology, 33, Suppl., 2, 2, (公社)日本医学放射線学会, Feb. 2015
Japanese

孤発性筋萎縮性側索硬化症における上行性感覚路のDTI解析　　　　　　　　　　　　　　　
清水 幸衣, 藤間 憲幸, 塚原 亜希子, 工藤 與亮, 矢部 一郎, 廣谷 真, 佐々木 秀直, Tha KhinKhin, 白土 博樹
Japanese Journal of Radiology, 33, Suppl., 9, 9, (公社)日本医学放射線学会, Feb. 2015
Japanese

肝内門脈-静脈シャントによる高アンモニア血症に対して塞栓術が著効した1例　　　　　　　　　　　　　　　
高橋 文也, 作原 祐介, 薮崎 哲史, 阿保 大介, 曽山 武士, 工藤 與亮, 白土 博樹, 米澤 和彦
Japanese Journal of Radiology, 33, Suppl., 6, 6, (公社)日本医学放射線学会, Feb. 2015
Japanese

骨転移をきたした小脳膠芽腫の1例　　　　　　　　　　　　　　　
湊川 英樹, 森 崇, 鬼丸 力也, 小野寺 俊輔, 白土 博樹, 東海林 菊太郎, 吉田 道春, 小林 浩之, 寳金 清博, 菅野 宏美, 田中 伸哉
Japanese Journal of Radiology, 33, Suppl., 4, 4, (公社)日本医学放射線学会, Feb. 2015
Japanese

閉塞性黄疸患者における胆道ドレナージ後の肝硬度の変化　　　　　　　　　　　　　　　
久保 公利, 河上 洋, 桑谷 将城, 川久保 和道, 阿部 容子, 川畑 修平, 坂本 直哉, 作原 佑介, 白土 博樹, 西田 睦
超音波医学, 42, 1, 89, 89, (公社)日本超音波医学会, Jan. 2015
Japanese

International standardization of four dimensional radiotherapy system:— Enhancement of effects of irradiation and assurance of safety —
HIRATA Yuichi, SHIRATO Hiroki, MIYAMOTO Naoki, SHIMIZU Morihito, YOSHIDA Mitsuhiro, HIRAMOTO Kazuo, ICHIKAWA Yoshiaki, KANEKO Shuji, SASAGAWA Tsuyoshi, HIRAOKA Masahiro
Synthesiology English edition, 7, 4, 229, 238, National Institute of Advanced Industrial Science and Technology, 2015, [Peer-reviewed]
English, In radiation therapy for cancer, there are possibilities of position changes 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 effects. 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 aspect. 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.

局所進行食道癌に対する強度変調放射線治療を用いた放射線化学療法の経験
井上哲也, 加藤徳雄, 清水伸一, 白土博樹, 鈴木隆介, 佐々木尚英, 福島拓, 小松嘉人
北海道外科雑誌, 59, 2, 206, 206, 北海道外科学会, 20 Dec. 2014
Japanese

肝臓への放射線治療用病変識別マーカー留置　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 曽山 武士, 安井 太一, 寺江 聡, 加藤 徳雄, 白土 博樹
IVR: Interventional Radiology, 29, 4, 425, 425, (一社)日本インターベンショナルラジオロジー学会, Dec. 2014
Japanese

【放射線治療活用BOOK 2014】 (DIVISION-3)これからの放射線治療の展望 最新の動体追跡放射線治療装置　　　　　　　　　　　　　　　
宮本 直樹, 石川 正純, 松浦 妙子, 井上 哲也, 加藤 徳雄, 清水 伸一, 鬼丸 力也, 梅垣 菊男, 白土 博樹
Rad Fan, 12, 15, 75, 77, (株)メディカルアイ, Dec. 2014
Japanese, 動体追跡法は、日本が世界に先駆けて実現してきた治療法であり、多くの実績を有する。本稿では、最新の迎撃照射型動体追跡装置として、島津製作所からリリースされたX線治療用動体追跡装置「SyncTraX」、日立製作所からリリースされた動体追跡陽子線スポットスキャニングシステム「PROBEAT-RT」について、その特徴と利点を紹介する。(著者抄録)

Intramyocellular lipid is increased in the skeletal muscle of patients with dilated cardiomyopathy with lowered exercise capacity
Hirabayashi K, Kinugawa S, Yokota T, Takada S, Fukushima A, Suga T, Takahashi M, Ono T, Morita N, Omokawa M, Harada K, Oyama-Manabe N, Shirato H, Matsushima S, Okita K, Tsutsui H
Int J Cardiol, 176, 3, 1110, 1112, Oct. 2014, [Peer-reviewed]
English, Scientific journal

内分泌療法併用動態追跡放射線治療の治療成績　　　　　　　　　　　　　　　
丸山 覚, 篠原 信雄, 安部 崇重, 土屋 邦彦, 宮島 直人, 西岡 健太郎, 清水 伸一, 白土 博樹, 野々村 克也
泌尿器外科, 27, 8, 1349, 1351, 医学図書出版(株), Aug. 2014
Japanese, 【目的】高リスク前立腺癌に対する内分泌療法を併用した動態追跡強度変調放射線治療(RT-IMRT)の治療成績を検討する。【対象と方法】RT-IMRTを施行した204例を対象とした。治療法毎に群分けし、治療成績を比較検討した。【結果】内分泌療法を併用したのは19例(併用群)、併用しなかったのが40例(非併用群)であった。5年時の疾患特異生存率/全生存率/生化学的非再発率はそれぞれ、併用群で100%/100%/95%、非併用群で100%/100%/59%であり併用群の予後が有意に良い結果であった。【結語】内分泌療法併用RT-IMRTは今後期待される治療法と思われた。(著者抄録)

北海道大学病院陽子線治療センターの小児陽子線治療開始準備状況　　　　　　　　　　　　　　　
橋本 孝之, 清水 伸一, 鬼丸 力也, 大島 淳二郎, 長 祐子, 井口 晶裕, 山口 秀, 小林 浩之, 寺坂 俊介, 岡田 忠雄, 本田 昌平, 武冨 紹信, 岡村 麗香, 中村 宏治, 白土 博樹
日本小児血液・がん学会雑誌, 51, 2, 183, 183, (NPO)日本小児血液・がん学会, Jun. 2014
Japanese

デジタル/シミュレーターハイブリッドファントムの開発とUS-CT Fusion Imagingのバリデーション　　　　　　　　　　　　　　　
曽山 武士, 作原 祐介, 阿保 大介, Wang Jeff, 伊藤 陽一, 長谷川 悠, 工藤 與亮, 白土 博樹
IVR: Interventional Radiology, 29, Suppl., 200, 200, (一社)日本インターベンショナルラジオロジー学会, May 2014
Japanese

局所進行頭頸部癌に対する導入化学療法後のweekly CDDP併用化学放射線療法の安全性と有用性の検討　　　　　　　　　　　　　　　
水町 貴諭, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 清水 康, 秋田 弘俊, 土屋 和彦, 安田 耕一, 鬼丸 力也, 白土 博樹, 福田 諭
頭頸部癌, 40, 2, 177, 177, (一社)日本頭頸部癌学会, May 2014
Japanese

下咽頭癌に対するRADPLATとweekly CDDP併用化学放射線治療の比較検討　　　　　　　　　　　　　　　
古沢 純, 本間 明宏, 坂下 智博, 畠山 博充, 加納 里志, 水町 貴諭, 土屋 和彦, 吉田 大介, 安田 耕一, 白土 博樹, 福田 諭
頭頸部癌, 40, 2, 198, 198, (一社)日本頭頸部癌学会, May 2014
Japanese

中咽頭扁平上皮癌症例に対するWeekly CDDP併用化学放射線療法の臨床的検討
水町 貴諭, 本間 明宏, 坂下 智博, 加納 里志, 畠山 博充, 土屋 和彦, 安田 耕一, 鬼丸 力也, 白土 博樹, 福田 諭
頭頸部癌, 40, 1, 66, 70, (一社)日本頭頸部癌学会, Apr. 2014
Japanese, 当院にてCDDP 40mg/m2/週併用の化学放射線療法を行った中咽頭扁平上皮癌新鮮例22例に対して臨床的検討を行った。22例中13例がHPV陽性であった。放射線治療は本人希望にて50Gyで終了した1例以外は全例70Gy完遂できた。CDDPの平均投与量は179mg/m2であった。有害事象はGrade4以上は認めなかったが、Grade3の粘膜炎が16例(73%)、好中球減少、皮膚炎が各4例(18%)認めた。原発病変に対する一次治療効果は、HPV陰性の1例がPRであったが、21例はCRとなった。頸部に対しては22例全例CRとなった。HPV陽性例の3年粗生存率は92.3%であったのに対し陰性例は66.7%であった。統計学的有意差は得られなかったが、HPV陽性例の方が予後が良好な傾向にあった。HPV陽性例は導入化学療法を先行させた症例が多かったものの、本治療における治療成績は良好で十分な効果が期待できると思われた。HPV陰性例に対しては一次治療効果は良好であるものの再発や転移を来す症例が陽性例に比べ多く生じた。(著者抄録)

Naming rule for radiation therapy
安田耕一, 土屋和彦, 井上哲也, 西岡健太郎, 原田慶一, 西川由記子, 鬼丸力也, 清水伸一, 加藤徳雄, 木下留美子, 小野寺俊介, 白土博樹, 鈴木隆介, 藤田勝久, 辻真太郎, 山崎理衣
Jpn J Radiol, 32, Supplement, 7, 7, (公社)日本医学放射線学会, 25 Feb. 2014
Japanese

北海道大学病院における髄膜腫に対する強度変調放射線治療(IMRT)の初期成績
西川由記子, 原田慶一, 西岡健太郎, 安田耕一, 井上哲也, 土屋和彦, 小野寺俊輔, 木下留美子, 加藤徳雄, 清水伸一, 鬼丸力也, 白土博樹, 鈴木隆介, 石川正純
Jpn J Radiol, 32, Supplement, 5, 5, (公社)日本医学放射線学会, 25 Feb. 2014
Japanese

高精度放射線治療における呼吸性移動対策のコツとピットフォール RTRTによる呼吸性移動対策:有用性と今後の展望
宮本直樹, 石川正純, 井上哲也, 加藤徳雄, 清水伸一, 鬼丸力也, 白土博樹
Rad Fan, 12, 3, 70-73,20, 73, (株)メディカルアイ, 25 Feb. 2014
Japanese, RTRTは、X線透視装置と治療装置を組み合わせた治療システムにより、体内マーカーを利用した待ち伏せ照射をすることで、呼吸性移動対策を実現している。これまでの長きにわたり、臨床的な成績はもちろん、呼吸性移動に関する様々な知見が得られた。また、昨春に次世代型のRTRTシステムがリリースされ、今後のさらなる発展と普及が期待される。(著者抄録)

骨盤部CBCT画像での臓器輪郭描出に関する検討　　　　　　　　　　　　　　　
西岡 健太郎, 白土 博樹
Japanese Journal of Radiology, 32, Suppl., 7, 7, (公社)日本医学放射線学会, Feb. 2014
Japanese

右肝円索の4例　　　　　　　　　　　　　　　
藪崎 哲史, 阿保 大介, 安井 太一, 曽山 武士, 作原 祐介, 白土 博樹
Japanese Journal of Radiology, 32, Suppl., 2, 2, (公社)日本医学放射線学会, Feb. 2014
Japanese

腎血管筋脂肪腫に対するマイクロバルーン閉塞下エタノール塞栓術の有効性の検討　　　　　　　　　　　　　　　
児玉 芳尚, 櫻井 康雄, 作原 祐介, 阿保 大介, 曽山 武士, 寺江 聡, 白土 博樹
Japanese Journal of Radiology, 32, Suppl., 3, 3, (公社)日本医学放射線学会, Feb. 2014
Japanese

前立腺癌に対する動体追跡放射線療法における金マーカー埋め込み術　　　　　　　　　　　　　　　
土屋 邦彦, 篠原 信雄, 丸山 覚, 清水 伸一, 西岡 健太郎, 安部 崇重, 白土 博樹, 野々村 克也
泌尿器外科, 27, 2, 263, 263, 医学図書出版(株), Feb. 2014
Japanese

4次元放射線治療システムに関する国際標準化 ― 照射効果の向上と安全性の確保 ―
平田, 雄一, 宮本, 直樹, 清水, 森人, 吉田, 光宏, 平本, 和夫, 市川, 芳明, 金子, 周史, 篠川, 毅, 平岡, 真寛, 白土, 博樹
Synthesiology, 7, 4, 238, 246, National Institute of Advanced Industrial Science and Technology, 2014, [Peer-reviewed]
Japanese, Scientific journal, 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.

Influence of respiration on dose calculation in stereotactic body radiotherapy of the lung
Yamazaki R, Onimaru R, Katoh N, Inoue T, Nishioka T, Shirato H, Date H
Radiol Phys Technol, 7, 2, 284, 289, 2014, [Peer-reviewed]

Salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy
Sakashita T, Homma A, Hatakeyama H, Kano S, Mizumachi T, Furusawa J, Yoshida D, Fujima N, Onimaru R, Tsuchiya K, Yasuda K, Shirato H, Suzuki F, Fukuda S
Br J Oral Maxillofac Surg, 52, 4, 323, 8, 2014, [Peer-reviewed]

Prospective phase II study of image-guided local boost using a real-time tumor-tracking radiotherapy (RTRT) system for locally advanced bladder cancer
Nishioka K, Shimizu S, Shinohara N, Ito Y. M, Abe T, Maruyama S, Kinoshita R, Harada K, Nishikawa N, Miyamoto N, Onimaru R, Shirato H
Jpn J Clin Oncol, 44, 1, 28, 35, 2014, [Peer-reviewed]

Design, development of water tank-type lung phantom and dosimetric verification in institutions participating in a phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer: Japan Clinical Oncology Group trial
Nishio T, Shirato H, Ishikawa M, Miyabe Y, Kito S, Narita Y, Onimaru R, Ishikura S, Ito Y, Hiraoka M
J Radiat Res, 55, 3, 600, 7, 2014, [Peer-reviewed]

局所進行食道癌に対する通常照射と強度変調放射線治療を組み合わせた放射線化学療法
井上哲也, 加藤徳雄, 清水伸一, 白土博樹, 鈴木隆介, 佐々木尚英, 福島拓, 小松嘉人
北海道外科雑誌, 58, 2, 112, 216, 北海道外科学会, 20 Dec. 2013
Japanese

Detachable fibered coilを用いた肝動注reservoir留置前血流改変の経験　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 長谷川 悠, 曽山 武士, 工藤 京平, 寺江 聡, 白土 博樹
IVR: Interventional Radiology, 28, 4, 483, 483, (一社)日本インターベンショナルラジオロジー学会, Oct. 2013
Japanese

中心静脈ポートのカテーテル先端部分に形成されたフィブリンシース・血栓をウロキナーゼで溶解した1例　　　　　　　　　　　　　　　
曽山 武士, 長谷川 悠, 工藤 京平, 阿保 大介, 作原 祐介, 寺江 聡, 白土 博樹
IVR: Interventional Radiology, 28, 4, 484, 484, (一社)日本インターベンショナルラジオロジー学会, Oct. 2013
Japanese

小児生体肝移植術後に複合的IVRを施行した1例　　　　　　　　　　　　　　　
阿保 大介, 曽山 武士, 作原 祐介, 長谷川 悠, 寺江 聡, 白土 博樹, 渡辺 正明, 山下 健一郎, 鈴木 友己, 嶋村 剛
IVR: Interventional Radiology, 28, 4, 484, 484, (一社)日本インターベンショナルラジオロジー学会, Oct. 2013
Japanese

甲状頸動脈から分岐する気管支動脈からBAEを行った1例　　　　　　　　　　　　　　　
工藤 京平, 作原 祐介, 阿保 大介, 曽山 武士, 長谷川 悠, 寺江 聡, 白土 博樹
IVR: Interventional Radiology, 28, 4, 484, 485, (一社)日本インターベンショナルラジオロジー学会, Oct. 2013
Japanese

気管腫瘍からの出血に対しTAEを施行した1例　　　　　　　　　　　　　　　
長谷川 悠, 阿保 大介, 曽山 武士, 工藤 京平, 作原 祐介, 寺江 聡, 白土 博樹
IVR: Interventional Radiology, 28, 4, 485, 485, (一社)日本インターベンショナルラジオロジー学会, Oct. 2013
Japanese

医療情報誘導治療の最新 リアルタイム4次元放射線治療の―スーパー特区の成果―
白土博樹, 鬼丸力也, 清水伸一, 石川正純, 宮本直樹, SUTHERLAND Ken, 鈴木隆介, 寅松千枝
映像情報Medical, 45, 7, 619, 623, 産業開発機構, 01 Jul. 2013
Japanese

Impaired integrity of the brain parenchyma in non-geriatric patients with major depressive disorder revealed by diffusion tensor imaging.
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, 30 Jun. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Impaired integrity of the brain parenchyma in non-geriatric patients with major depressive disorder revealed by diffusion tensor imaging
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-NEUROIMAGING, 212, 3, 208, 215, ELSEVIER IRELAND LTD, Jun. 2013, [Peer-reviewed]
English, Scientific journal, 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Guidelines for respiratory motion management in radiation therapy
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, May 2013, [Peer-reviewed]
English, Scientific journal, 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.

化学放射線療法の現状と役割 動注化学療法による化学放射線療法 上顎洞癌を中心に　　　　　　　　　　　　　　　
本間 明宏, 畠山 博充, 加納 里志, 水町 貴諭, 坂下 智博, 吉田 大介, 鬼丸 力也, 土屋 和彦, 安田 耕一, 白土 博樹, 藤井 正人, 福田 諭
頭頸部癌, 39, 2, 134, 134, (一社)日本頭頸部癌学会, May 2013
Japanese

子宮体がんの画像診断 筋層浸潤・頸部浸潤の判定はどこまで可能か
三村理恵, 加藤扶美, 白土博樹
臨床婦人科産科, 67, 5, 458, 464, 医学書院, May 2013
Japanese

Regional control after concomitant chemoradiotherapy without planned neck dissection in node-positive head and neck squamous cell carcinomas
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, ELSEVIER SCI LTD, Apr. 2013, [Peer-reviewed]
English, Scientific journal, 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.

Accuracy and Reliability Assessment of CT and MR Perfusion Analysis Software Using a Digital Phantom
Kohsuke Kudo, Soren Christensen, Makoto Sasaki, Leif Ostergaard, Hiroki Shirato, Kuniaki Ogasawara, Max Wintermark, Steven Warach
RADIOLOGY, 267, 1, 201, 211, RADIOLOGICAL SOC NORTH AMERICA, Apr. 2013, [Peer-reviewed]
English, Scientific journal, 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

肝移植術後肝動脈狭窄に対するIVR　　　　　　　　　　　　　　　
阿保 大介, 作原 祐介, 児玉 芳尚, 清水 匡, 曽山 武士, 山下 健一郎, 嶋村 剛, 寺江 聡, 白土 博樹
IVR: Interventional Radiology, 28, Suppl., 77, 77, (一社)日本インターベンショナルラジオロジー学会, Apr. 2013
Japanese

マイクロバルーンカテーテル「LOGOS」を用いた腎血管筋脂肪腫(AML)に対する選択的動脈塞栓術の初期経験　　　　　　　　　　　　　　　
阿保 大介, 作原 祐介, 曽山 武士, 寺江 聡, 白土 博樹
IVR: Interventional Radiology, 28, Suppl., 119, 119, (一社)日本インターベンショナルラジオロジー学会, Apr. 2013
Japanese

豚動脈を用いたコイル併用n-butyl-2-cianoacrylate(NBCA)塞栓術の実現性の検討　　　　　　　　　　　　　　　
阿保 大介, 作原 祐介, 曽山 武士, 寺江 聡, 白土 博樹
IVR: Interventional Radiology, 28, Suppl., 161, 161, (一社)日本インターベンショナルラジオロジー学会, Apr. 2013
Japanese

前立腺癌に対する動体追跡放射線療法における金マーカー埋め込み術
土屋邦彦, 篠原信雄, 丸山覚, 清水伸一, 西岡健太郎, 安部崇重, 白土博樹, 野々村克也
日本泌尿器科学会雑誌, 104, 2, 288, 288, (一社)日本泌尿器科学会, 20 Mar. 2013
Japanese

動体追跡装置を用いた位置照合に基づく膀胱癌放射線治療時のマージンの解析
西岡健太郎, 清水伸一, 安部崇重, 丸山覚, 鬼丸力也, 木下留美子, 小野寺俊輔, 原田慶一, 篠原信雄, 白土博樹
日本医学放射線学会総会抄録集, 72nd, S397, S397, (公社)日本医学放射線学会, 28 Feb. 2013
Japanese

Dose comparison study between RapidArc and fixed-field IMRT for postoperative whole pelvic irradiation with cervical cancer
土屋和彦, 原田慶一, 西岡健太郎, 木下留美子, 清水伸一, 白土博樹
Jpn J Radiol, 31, Supplement 1, 11, 25 Feb. 2013
Japanese

Symptomatic outcomes in relation to tumor expansion after fractionated stereotactic radiation therapy for vestibular schwannomas: Single-institutional long-term experience
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, 01 Feb. 2013, [Peer-reviewed]
Scientific journal, 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.

Real-time virtual sonography(RVS)を用いた経皮的針生検　　　　　　　　　　　　　　　
藪崎 哲史, 作原 祐介, 曽山 武士, 長谷川 悠, 阿保 大介, 寺江 聡, 白土 博樹
Japanese Journal of Radiology, 31, Suppl.I, 8, 8, (公社)日本医学放射線学会, Feb. 2013
Japanese

豚動脈を用いたコイル併用n-butyl-2-cianoacrylate(NBCA)塞栓術の実現性の検討　　　　　　　　　　　　　　　
阿保 大介, 作原 祐介, 曽山 武士, 寺江 聡, 白土 博樹
日本医学放射線学会学術集会抄録集, 72回, S309, S309, (公社)日本医学放射線学会, Feb. 2013
Japanese

[F-18]fluoromisonidazole and a New PET System With Semiconductor Detectors and a Depth of Interaction System for Intensity Modulated Radiation Therapy for Nasopharyngeal Cancer
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, ELSEVIER SCIENCE INC, Jan. 2013, [Peer-reviewed]
English, Scientific journal, 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.

beta 1-integrin via NF-kappa B signaling is essential for acquisition of invasiveness in a model of radiation treated in situ breast cancer
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
BREAST CANCER RESEARCH, 15, 4, BIOMED CENTRAL LTD, 2013, [Peer-reviewed]
English, Scientific journal, 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, alpha 5 beta 1-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-kappa B) to the beta 1-integrin promoter region, associated with up-regulation of alpha 5 beta 1-integrins. Inhibition of NF-kappa B or beta 1-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 beta 1-integrin and NF-kappa B signaling.

[18F]fluoromisonidazole and a new PET system with semiconductor detectors and a depth of interaction system for intensity modulated radiation therapy for nasopharyngeal cancer
Yasuda K, Onimaru R, Okamoto S, Shiga T, Katoh N, Tsuchiya K, Suzuki R, Takeuchi W, Kuge Y, Tamaki N, Shirato H
Int J Radiat Oncol Biol Phys, 85, 1, 142, 7, 2013, [Peer-reviewed]

Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer
Homma A, Sakashita T, Yoshida D, Onimaru R, Tsuchiya K, Suzuki F, Yasuda K, Hatakeyama H, Furusawa J, Mizumachi T, Kano S, Inamura N, Taki S, Shirato H, Fukuda S
Br J Cancer, 109, 12, 2980, 6, 2013, [Peer-reviewed]

Safety, Stability, and Location of Implantation of Multiple Gold Markers Into the Soft Bladder Wall by Rigid Cystoscopy
Nishioka K, Shimizu S, Onimaru R, Kinoshita R, Kato N, Harada K, Abe T, Maruyama S, Shinohara N, Shirato H
International Journal of Radiation Oncology Biology Physics, 87, 2, S397, 2013, [Peer-reviewed]

Can 4DCT Imaging Predict Lung Motion During Stereotactic Body Radiation Therapy?
Harada K, Katoh N, Suzuki R, Inoue T, Omimaru R, Shimizu S, Miyamoto N, Ishikawa M, Shirato H
International Journal of Radiation Oncology Biology Physics, 87, 2, S67, 2013, [Peer-reviewed]

Baseline Shift of Intrafractional Lung Tumor Motion in Real-Time Tumor-Tracking Radiation Therapy
Takao S, Miyamoto N, Matsuura T, Shimizu S, Onimaru R, Katoh N, Inoue T, Shirato H
International Journal of Radiation Oncology Biology Physics, 87, 2, S67, 2013, [Peer-reviewed]

Association of Renal Volume with the Degree of Aortic Contrast Enhancement in Abdominal CT　　　　　　　　　　　　　　　
Muto NS, Kamishima T, Sasaki T, Terae S, Tha KK, Shirato H, Bae KT
Advances in Computed Tomography, 2, 55, 62, 2013, [Peer-reviewed]
English, Scientific journal

A Mathematical Study to Select Fractionation Regimen Based on Physical Dose Distribution and the Linear-Quadratic Model
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, ELSEVIER SCIENCE INC, Nov. 2012, [Peer-reviewed]
English, Scientific journal, 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.

Graphical representation of the effects on tumor and OAR for determining the appropriate fractionation regimen in radiation therapy planning
Masahiro Mizuta, Hiroyuki Date, Seishin Takao, Naoki Kishimoto, Kenneth L. Sutherland, Rikiya Onimaru, Hiroki Shirato
MEDICAL PHYSICS, 39, 11, 6791, 6795, AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS, Nov. 2012, [Peer-reviewed]
English, Scientific journal, 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]

マルチベンダに対応した放射線治療計画管理システムの開発　　　　　　　　　　　　　　　
辻 真太朗, 谷川原 綾子, 鈴木 隆介, 宮崎 智夫, 藤田 勝久, 石川 正純, 白土 博樹
医療情報学連合大会論文集, 32回, 1444, 1445, (一社)日本医療情報学会, Nov. 2012
Japanese

Combined modality therapy for laryngeal cancer with superselective intra-arterial cisplatin infusion and concomitant radiotherapy
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, SPRINGER JAPAN KK, Oct. 2012, [Peer-reviewed]
English, Scientific journal, 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.

Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for squamous cell carcinoma of the nasal vestibule: a report of two cases
Homma Akihiro, Suzuki Fumiyuki, Hatakeyama Hiromitsu, Sakashita Tomohiro, Yoshida Daisuke, Tsuchiya Kazuhiko, Onimaru Rikiya, Oridate Nobuhiko, Shirato Hiroki, Fukuda Satoshi
International Cancer Conference Journal, 1, 4, 215, 219, Springer, Oct. 2012
English, Squamous cell carcinoma of the nasal vestibule (SCC-NV) is rare among head and neck malignancies. It behaves differently from cancers arising in the nasal cavity and paranasal sinuses, and skin cancer of the external nose. Prognosis is more favorable than nasal cavity tumors and less favorable than skin cancers. We experienced two cases of SCC-NV who were treated with rapid superselective high-dose cisplatin infusion with concomitant radiotherapy (RADPLAT). A 56-year-old male and a 68-year-old female with SCC-NV, classified as T4aN0M0 according to UICC and T2 according to Wang classification, were given superselective intra-arterial infusions of cisplatin, with simultaneous intravenous infusions of thiosulfate to neutralizecisplatin toxicity, together with conventionalradiotherapy. In both cases, the internal maxillary artery and the facial artery were considered to be feeders of the tumor. No serious adverse events have been observed in either patient to date during follow-up of 7.3 and 5.3 years, respectively. Both patients are alive without disease and show excellent cosmetic results. RADPLAT is considered to be useful for the treatment of patients with SCC of the nasal vestibule.

放射線治療の過去と未来 放射線治療の30年前と30年後　　　　　　　　　　　　　　　
白土 博樹, 鬼丸 力也, 清水 伸一, 土屋 和彦
日本癌治療学会誌, 47, 3, 622, 622, (一社)日本癌治療学会, Oct. 2012
Japanese

Simulation for a Real-time Positioning System for Radiotherapy Based on Annihilation Gamma-rays’ Detection from a Radiopharmaceutical Concentrated Tumor
Kaneko JH, Takada E, Hara Y, Fujita F, Yamaguchi T, Kubo N, Ishikawa M, Shirato H
PROGRESS IN NUCLEAR SCIENCE AND TECHNOLOGY, 3, 124, 126, Atomic Energy Society of Japan, Oct. 2012, [Peer-reviewed]
English

一方向X線透視による低被曝・省スペース型動体追跡装置の開発
宮本直樹, 石川正純, SUTHERLAND Kenneth, 鈴木隆介, 松浦妙子, 高尾聖心, 寅松千枝, 二本木英明, 清水伸一, 梅垣菊男, 白土博樹
医学物理 Supplement, 32, 3, 281, 282, 13 Sep. 2012
Japanese

体内複数マーカを用いた高精度ゲーティング照射法の基礎検討
大友可奈子, 宮本直樹, SUTHERLAND Kenneth, 鈴木隆介, 松浦妙子, 鬼丸力也, 清水伸一, 梅垣菊男, 白土博樹, 石川正純
医学物理 Supplement, 32, 3, 155, 156, 13 Sep. 2012
Japanese

陽子線スキャニング照射における体内マーカーによる線量遮蔽のTCPを用いた評価
前田憲一郎, 松浦妙子, 高尾聖心, SUTHERLAND Kenneth, 寅松千枝, 二本木英明, 宮本直樹, 石川正純, 清水伸一, 梅垣菊男, 白土博樹
医学物理 Supplement, 32, 3, 101, 102, 13 Sep. 2012
Japanese

陽子線治療における最適な治療ワークフローの検討
高尾聖心, 松浦妙子, 寅松千枝, 二本木英明, 宮本直樹, 清水伸一, 木下留美子, 松田浩二, 木谷貴雄, 梅垣菊男, 白土博樹
医学物理 Supplement, 32, 3, 169, 170, 13 Sep. 2012
Japanese

Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study
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, AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS, Sep. 2012, [Peer-reviewed]
English, Scientific journal, 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]

Feasibility of a dual microcatheter-dual interlocking detachable coil technique in preoperative embolization in preparation for distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer
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, SPRINGER TOKYO, Jul. 2012, [Peer-reviewed]
English, Scientific journal, 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.

Hyperintense putaminal rim at 1.5 T: prevalence in normal subjects and distinguishing features from multiple system atrophy.
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, 18 Jun. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Rab5c promotes AMAP1-PRKD2 complex formation to enhance beta 1 integrin recycling in EGF-induced cancer invasion
Yasuhito Onodera, Jin-Min Nam, Ari Hashimoto, Jim C. Norman, Hiroki Shirato, Shigeru Hashimoto, Hisataka Sabe
JOURNAL OF CELL BIOLOGY, 197, 7, 983, 996, ROCKEFELLER UNIV PRESS, Jun. 2012, [Peer-reviewed]
English, Scientific journal, 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.

Adaptive external gating based on the updating method of internal/external correlation and gating window before each beam delivery
Qing Ren, Seiko Nishioka, Hiroki Shirato, Ross Berbeco
PHYSICS IN MEDICINE AND BIOLOGY, 57, 9, N145, N157, IOP PUBLISHING LTD, May 2012, [Peer-reviewed]
English, Scientific journal, 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.

Preoperative percutaneous transhepatic portal vein embolization with ethanol injection.
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, 4, Apr. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Prognostic Significance of Clusterin Expression in Advanced-Stage Cervical Cancer Treated With Curative Intended Radiotherapy
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, LIPPINCOTT WILLIAMS & WILKINS, Mar. 2012, [Peer-reviewed]
English, Scientific journal, 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.

A New Brain Positron Emission Tomography Scanner With Semiconductor Detectors for Target Volume Delineation and Radiotherapy Treatment Planning in Patients With Nasopharyngeal Carcinoma
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, ELSEVIER SCIENCE INC, Mar. 2012, [Peer-reviewed]
English, Scientific journal, 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.

Real-time 4-D radiotherapy for lung cancer
Hiroki Shirato, Rikiya Onimaru, Masayori Ishikawa, Jun-ichi Kaneko, Tsuguhide Takeshima, Kenta Mochizuki, Shinichi Shimizu, Kikuo Umegaki
CANCER SCIENCE, 103, 1, 1, 6, WILEY-BLACKWELL, Jan. 2012, [Peer-reviewed]
English, 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)

Usefulness of portography and contrast-enhanced computed tomography to predict the embolized area in percutaneous transhepatic portal vein embolization with absolute ethanol under temporary balloon occlusion
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, SPRINGER, Jan. 2012, [Peer-reviewed]
English, Scientific journal, 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.

A Pitfall of C-11 Methionine PET Cerebral Venous Infarction Mimicked a Glioma
Yae Harada, Kenji Hirata, Hiroyuki Kobayashi, Reiko Usui, Tohru Shiga, Satoshi Terae, Hiroki Shirato, Nagara Tamaki
CLINICAL NUCLEAR MEDICINE, 37, 1, 110, 111, LIPPINCOTT WILLIAMS & WILKINS, Jan. 2012, [Peer-reviewed]
English, 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.

Clinical outcomes of stereotactic body radiotherapy for patients with lung tumors in the state of oligo-recurrence.
Inoue T, Katoh N, Onimaru R, Shirato H
Pulmonary medicine, 2012, 369820, 2012, [Peer-reviewed]

Symptomatic Outcomes in Relation to Tumor Expansion After Fractionated Stereotactic Radiation Therapy for Vestibular Schwannomas: Single-Institutional Long-Term Experience
Aoyama H, Onodera S, Takeichi N, Onimaru R, Terasaka S, Sawamura Y, Shirato H
Int J Radiat Oncol Biol Phys, 85, 2, 329, 334, 2012, [Peer-reviewed]
English, Scientific journal

Clinical outcomes of stereotactic body radiotherapy for patients with lung tumors in the state of oligo-recurrence
Inoue T, Katoh N, Onimaru R, Shirato H
Pulm Med, 2012, 369820, 2012, [Peer-reviewed]

Improvement of tracking accuracy and stability by recursive image processing in real-time tumor-tracking radiotherapy system
Miyamoto Naoki, Sutherland Kenneth, Suzuki Ryusuke, Matsuura Taeko, Toramatsu Chie, Takao Seishin, Nihongi Hideaki, Kinoshita Rumiko, Shimizu Shinichi, Onimaru Rikiya, Umegaki Kikuo, Shirato Hiroki, Ishikawa Masayori
MEDICAL IMAGING 2012: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING, 8316, 83160, SPIE, 2012, [Peer-reviewed]
International conference proceedings

The Role of Spot Scanning Proton Therapy in the Treatment of Large Abdominal Tumors: A Comparative Planning Study of Hepatocellular Carcinoma
Toramatsu C, Katoh N, Shimizu S, Nihongi H, Matsuura T, Takao S, Miyamoto N, Kinoshita R, Umegaki K, Shirato H
International Journal of Radiation Oncology Biology Physics, 84, 3, S327, S328, 2012, [Peer-reviewed]

Stereotactic Body Radiation Therapy (SBRT) Using Real-time Tracking Radiation Therapy (RTRT) System for Patients With Lung Cancer Aged 80+
Onimaru R, Katoh N, Inoue T, Shimizu S, Shinagawa N, Sakakibara-Konishi J, Oizumi S, Shirato H
International Journal of Radiation Oncology Biology Physics, 84, 3, S575, 2012, [Peer-reviewed]

Real-time Tumor-tracking Radiation Therapy for Lymphoma of the Stomach
Katoh N, Suzuki R, Shimizu S, Inoue T, Yasuda K, Onimaru R, Kimura R, Kato M, Ishikawa M, Shirato H
International Journal of Radiation Oncology Biology Physics, 84, 3, S722, 2012, [Peer-reviewed]

Interfractional Setup Error and Intrafractional Bladder Motion During Radiation Therapy for Bladder Tumors
Nishioka K, Shimizu S, Onimaru R, Kinoshita R, Harada K, Nishikawa N, Abe T, Maruyama S, Shinohara N, Shirato H
International Journal of Radiation Oncology Biology Physics, 84, 3, S769, 2012, [Peer-reviewed]

Simulation for a Real-time Positioning System for Radiotherapy Based on Annihilation　　　　　　　　　　　　　　　
Junichi H. Kaneko, Eiji Takada, Yu Hara, Fumiyuki Fujita, Toru Yamaguchi, Naoki Kubo, Masayori Ishikawa, Hiroki Shirato
Progress in Nuclear Science and Technology, 3, 104, 108, 2012, [Peer-reviewed]
English, Scientific journal, （全体概要）

腫瘍に対する放射線治療の際に呼吸等によって腫瘍が移動し、治療用放射線が正常組織に照射されることがある。それを防ぐために少数の放射線検出器で腫瘍の移動を測定し、特定の位置に腫瘍があるときのみ治療用放射線を照射するシステムについて検討し、可能性を示した。

（担当部分概要）pp.124-126

可能性検討全般に参加した。

（著者：Junichi H. Kaneko, Eiji Takada, Yu Hara, Fumiyuki Fujita, Toru Yamaguchi, Naoki Kubo, Masayori Ishikawa, Hiroki Shirato）

食道癌IMRT(強度変調放射線治療)の初期経験
原田慶一, 井上哲也, 安田耕一, 加藤徳雄, 清水伸一, 白土博樹, BENGUA Gerard, 石川正純, 中積宏之, 結城敏志, 小松嘉人
北海道外科雑誌, 56, 2, 176-177, 177, 北海道外科学会, 20 Dec. 2011
Japanese

STEREOTACTIC BODY RADIOTHERAPY (SBRT) FOR OPERABLE STAGE I NON SMALL-CELL LUNG CANCER: CAN SBRT BE COMPARABLE TO SURGERY?
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, ELSEVIER SCIENCE INC, Dec. 2011, [Peer-reviewed]
English, Scientific journal, 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.

ACCURATE ANALYSIS OF THE CHANGE IN VOLUME, LOCATION, AND SHAPE OF METASTATIC CERVICAL LYMPH NODES DURING RADIOTHERAPY
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, ELSEVIER SCIENCE INC, Nov. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Phase I study of concurrent real-time tumor-tracking thoracic radiation therapy with paclitaxel and carboplatin in locally advanced non-small cell lung cancer
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, ELSEVIER IRELAND LTD, Nov. 2011, [Peer-reviewed]
English, Scientific journal, 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.

USE OF IMPLANTED MARKERS AND INTERPORTAL ADJUSTMENT WITH REAL-TIME TRACKING RADIOTHERAPY SYSTEM TO REDUCE INTRAFRACTION PROSTATE MOTION
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, ELSEVIER SCIENCE INC, Nov. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Identification and further differentiation of subendocardial and transmural myocardial infarction by fast strain-encoded (SENC) magnetic resonance imaging at 3.0 Tesla.
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, 11, Nov. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Power Doppler signal calibration using capillary phantom for pannus vascularity in rheumatoid finger joint: a pilot study
T. Kamishima, M. Nishida, T. Horie, A. Narita, A. Sagawa, M. Henmi, H. Shirato, S. Terae
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 29, 6, 1057, 1057, CLINICAL & EXPER RHEUMATOLOGY, Nov. 2011, [Peer-reviewed]
English

Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome
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, NATURE PUBLISHING GROUP, Sep. 2011, [Peer-reviewed]
English, Scientific journal, 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

Concomitant Weekly Cisplatin and Radiotherapy for Head and Neck Cancer
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, OXFORD UNIV PRESS, Aug. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Optimization of fluoroscopy parameters using pattern matching prediction in the real-time tumor-tracking radiotherapy system
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, IOP PUBLISHING LTD, Aug. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Rapid estimation of split renal function in kidney donors using software developed for computed tomographic renal volumetry
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, ELSEVIER IRELAND LTD, Jul. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Efficacy of therapy for advanced hepatocellular carcinoma: Intra-arterial 5-fluorouracil and subcutaneous interferon with image-guided radiation
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, WILEY-BLACKWELL, Jul. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Superselective arterial cisplatin infusion with concomitant radiation therapy for base of tongue cancer
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, ELSEVIER SCIENCE BV, Jul. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Improved Detection of Heat Stroke-Induced Brain Injury by High B-Value Diffusion-Weighted Imaging
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, LIPPINCOTT WILLIAMS & WILKINS, Jul. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Monitoring anti-interleukin 6 receptor antibody treatment for rheumatoid arthritis by quantitative magnetic resonance imaging of the hand and power Doppler ultrasonography of the finger
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, SPRINGER, Jun. 2011, [Peer-reviewed]
English, Scientific journal, 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.

膵頭十二指腸切除術後膵液瘻に対する非観血的内瘻化　　　　　　　　　　　　　　　
阿保 大介, 長谷川 悠, 作原 祐介, 森田 亮, 曽山 武士, 白土 博樹, 寺江 聡, 清水 匡, 田中 栄一, 平野 聡, 近藤 哲
IVR: Interventional Radiology, 26, 2, 235, 235, (一社)日本インターベンショナルラジオロジー学会, May 2011
Japanese

Renal cortical volume measured using automatic contouring software for computed tomography and its relationship with BMI, age and renal function
Natalia Sayuri Muto, Tamotsu Kamishima, Ardene A. Harris, Fumi Kato, Yuya Onodera, Satoshi Terae, Hiroki Shirato
EUROPEAN JOURNAL OF RADIOLOGY, 78, 1, 151, 156, ELSEVIER IRELAND LTD, Apr. 2011, [Peer-reviewed]
English, Scientific journal, 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.

RELATIONSHIP BETWEEN DISEASED LUNG TISSUES ON COMPUTED TOMOGRAPHY AND MOTION OF FIDUCIAL MARKER NEAR LUNG CANCER
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, ELSEVIER SCIENCE INC, Apr. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Long-term Outcomes of Fractionated Stereotactic Radiotherapy for Intracranial Skull Base Benign Meningiomas in Single Institution
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, OXFORD UNIV PRESS, Apr. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Dynamic gating window for compensation of baseline shift in respiratory-gated radiation therapy
Eric W. Pepin, Huanmei Wu, Hiroki Shirato
MEDICAL PHYSICS, 38, 4, 1912, 1918, AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS, Apr. 2011, [Peer-reviewed]
English, Scientific journal, 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]

Susceptibility of T-max to tracer delay on perfusion analysis: quantitative evaluation of various deconvolution algorithms using digital phantoms
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, NATURE PUBLISHING GROUP, Mar. 2011, [Peer-reviewed]
English, Scientific journal, 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

乳房温存術後の全乳房照射における接線照射と強度変調放射線治療との比較
土屋和彦, 木下留美子, 清水伸一, 森崇, 原田慶一, 白土博樹
日本医学放射線学会総会抄録集, 70th, S371, 28 Feb. 2011
Japanese

画像誘導局所Boostを併用した局所進行膀胱癌に対する根治的放射線治療
西岡健太郎, 清水伸一, 大坂康博, 西川昇, 喜多村圭, 白土博樹, 篠原信雄, 佐澤陽
日本医学放射線学会総会抄録集, 70th, S219-S220, 28 Feb. 2011
Japanese

Prenatal diagnosis of short-rib polydactyly syndrome type 3 (Verma-Naumoff type) by three-dimensional helical computed tomography
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, WILEY-BLACKWELL PUBLISHING, INC, Feb. 2011, [Peer-reviewed]
English, Scientific journal, 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.

A feasibility study of a molecular-based patient setup verification method using a parallel-plane PET system
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, IOP PUBLISHING LTD, Feb. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Single-slice epicardial fat area measurement: do we need to measure the total epicardial fat volume?
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, 2, Feb. 2011, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, 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.

聴神経鞘腫の定位放射線治療 一過性腫瘍増大と症状変化の関連　　　　　　　　　　　　　　　
青山 英史, 小野寺 俊輔, 白土 博樹
日本医学放射線学会学術集会抄録集, 70回, S298, S298, (公社)日本医学放射線学会, Feb. 2011
English

Single-slice epicardial fat area measurement: do we need to measure the total epicardial fat volume?
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, 109, SPRINGER, Feb. 2011, [Peer-reviewed]
English, Scientific journal, 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.
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.
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).
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.

Simplified approach to MR image quantification of the rheumatoid wrist: a pilot study
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, SPRINGER, Jan. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Radiotherapy for Glottic T1N0 Carcinoma with Slight Hypofractionation and Standard Overall Treatment Time: Importance of Overall Treatment Time
Rikiya Onimaru, Masakazu Hasegawa, Kouichi Yasuda, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda, Hiroki Shirato
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 41, 1, 103, 109, OXFORD UNIV PRESS, Jan. 2011, [Peer-reviewed]
English, Scientific journal, 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.

Radiation-induced Cancer Cell Repopulation: A Possible Mechanism Implied by Experiments Using Transplantable Mouse-derived Sarcoma Cell Line
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, JAPAN SOC CELL BIOLOGY, 2011, [Peer-reviewed]
English, Scientific journal, 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.

Comparison of H-1 MR Spectroscopy, 3-point DIXON, and Multi-echo Gradient Echo for Measuring Hepatic Fat Fraction
Kinya Ishizaka, Noriko Oyama, Suzuko Mito, Hiroyuki Sugimori, Mitsuhiro Nakanishi, Tomoyuki Okuaki, Hiroki Shirato, Satoshi Terae
MAGNETIC RESONANCE IN MEDICAL SCIENCES, 10, 1, 41, 48, JPN SOC MAGNETIC RESONANCE IN MEDICINE, 2011, [Peer-reviewed]
English, Scientific journal, Purpose: We evaluated and compared the reproducibility, diagnostic accuracy, and sequence dependency of the fat fraction (FF) determined by 3-point Dixon (DIXON) and multi-echo gradient-echo (MEGE) methods to those of the FF determined by magnetic resonance spectroscopy (MRS).
Methods: Our study included 98 volunteers, ten of whom underwent scanning twice to evaluate sequence reproducibility. We compared the FFs determined by the DIXON and MEGE methods to that by MRS as the gold standard, calculated sensitivity and specificity for each image analysis method at a threshold value of 6.25% of spectroscopic value, and used Pearson's correlation coefficient and Bland-Altman analysis to compare agreement among the repeated measurements and FF values with the 3 methods, in 98 volunteers.
Results: There was no significant difference in repeated scans in any sequence with Wilcoxon's t-test. Each correlation coefficient (r) exceeded 0.930 for the repeated measurements of all 3 sequences. Sensitivity of DIXON was 82% and specificity, 96%; sensitivity of MEGE was 70% and specificity, 99%. The FFs determined by DIXON and MEGE correlated well with that by MRS (r = 0.920) but showed significant difference (paired t-test, P < 0.001). The mean difference between the FF determined by DIXON and that by MEGE were 0.93 and 1.16, respectively. The slope of the regression lines as determined by DIXON was 0.655 (P < 0.001) and that by MEGE was 0.527 (P < 0.001). When the FF by MRS was less than 6.25%, the FF values by DIXON and MEGE were significantly higher; when the spectroscopic value was greater than 6.25%, their values were significantly lower.
Conclusion: We demonstrated the high reproducibility of each FF measurement using MRS, DIXON, and MEGE. Compared to MRS, both DIXON and MEGE showed high sensitivity and specificity for determining FF. The FFs by DIXON and MEGE showed sequence dependency because DIXON had proportional and additional errors, and MEGE had a proportional error.

Dynamic MR Findings of Ductal Carcinoma in Situ within a Fibroadenoma
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, JPN SOC MAGNETIC RESONANCE IN MEDICINE, 2011, [Peer-reviewed]
English, Scientific journal, 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.

Detection of patient setup errors with a portal image - DRR registration software application
Kenneth Sutherland, Masayori Ishikawa, Gerard Bengua, Yoichi M. Ito, Yoshiko Miyamoto, Hiroki Shirato
JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, 12, 3, 2, 15, MULTIMED INC, 2011, [Peer-reviewed]
English, Scientific journal, The purpose of this study was to evaluate a custom portal image - digitally reconstructed radiograph (DRR) registration software application. The software works by transforming the portal image into the coordinate space of the DRR image using three control points placed on each image by the user, and displaying the fused image. In order to test statistically that the software actually improves setup error estimation, an intra-and interobserver phantom study was performed. Portal images of anthropomorphic thoracic and pelvis phantoms with virtually placed irradiation fields at known setup errors were prepared. A group of five doctors was first asked to estimate the setup errors by examining the portal and DRR image side-by-side, not using the software. A second group of four technicians then estimated the same set of images using the registration software. These two groups of human subjects were then compared with an auto-registration feature of the software, which is based on the mutual information between the portal and DRR images. For the thoracic case, the average distance between the actual setup error and the estimated error was 4.3 +/- 3.0 mm for doctors using the side-by-side method, 2.1 +/- 2.4 mm for technicians using the registration method, and 0.8 +/- 0.4 mm for the automatic algorithm. For the pelvis case, the average distance between the actual setup error and estimated error was 2.0 +/- 0.5 mm for the doctors using the side-by-side method, 2.5 +/- 0.4 mm for technicians using the registration method, and 2.0 +/- 1.0 mm for the automatic algorithm. The ability of humans to estimate offset values improved statistically using our software for the chest phantom that we tested. Setup error estimation was further improved using our automatic error estimation algorithm. Estimations were not statistically different for the pelvis case. Consistency improved using the software for both the chest and pelvis phantoms. We also tested the automatic algorithm with a database of over 5,000 clinical cases from our hospital. The algorithm performed well for head and breast but performed poorly for pelvis cases, probably due to lack of contrast in the megavoltage portal image. The software incorporates an original algorithm to fuse portal and DRR images, which we describe in detail. The offset optimization algorithm used in the automatic mode of operation is also unique, and may be useful if the contrast of the portal images can be improved.

Use of implanted markers and interportal adjustment with real-time tracking radiotherapy system to reduce intrafraction prostate motion.
Shimizu S, Osaka Y, Shinohara N, Sazawa A, Nishioka K, Suzuki R, Onimaru R, Shirato H
Int J Radiat Oncol Biol Phys, 81, 4, e393, 9, 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Relationship between diseased lung tissues on computed tomography and motion of fiducial marker near lung cancer.
Onodera Y, Nishioka N, Yasuda K, Fujima N, Torres M, Kamishima T, Ooyama N, Onimaru R, Terae S, Ooizumi S, Nishimura M, Shirato H
Int J Radiat Oncol Biol Phys, 79, 5, 1408, 13, 2011, [Peer-reviewed]

Radiotherapy for glottic T1N0 carcinoma with slight hypofractionation and standard overall treatment time: importance of overall treatment time.
Onimaru R, Hasegawa M, Yasuda K, Homma A, Oridate N, Fukuda S, Shirato H
Jpn J Clin Oncol, 41, 1, 103, 9, 2011, [Peer-reviewed]

Phase I study of concurrent real-time tumor-tracking thoracic radiation therapy with paclitaxel and carboplatin in locally advanced non-small cell lung cancer.
Sakakibara-Konishi J, Oizumi S, Kinoshita I, Shinagawa N, Kikuchi J, Kato M, Inoue T, Katoh N, Onimaru R, Shirato H, Dosaka-Akita H, Nishimura M
Lung Cancer, 74, 2, 248, 52, 2011, [Peer-reviewed]

Optimization of fluoroscopy parameters using pattern matching prediction in the real-time tumor-tracking radiotherapy system.
Miyamoto N, Ishikawa M, Bengua G, Sutherland K, Suzuki R, Kimura S, Shimizu S, Onimaru R, Shirato H
Phys Med Biol, 56, 15, 4803, 13, 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

Concomitant weekly cisplatin and radiotherapy for head and neck cancer.
Homma A, Inamura N, Oridate N, Suzuki S, Hatakeyama H, Mizumachi T, Kano S, Sakashita T, Onimaru R, Yasuda K, Shirato H, Fukuda S
Jpn J Clin Oncol, 41, 8, 980, 6, 2011, [Peer-reviewed]

Accurate analysis of the change in volume, location, and shape of metastatic cervical lymph nodes during radiotherapy.
Takao S, Tadano S, Taguchi H, Yasuda K, Onimaru R, Ishikawa M, Bengua G, Suzuki R, Shirato H
Int J Radiat Oncol Biol Phys, 81, 3, 871, 9, 2011, [Peer-reviewed]

Organ-conserving Definitive Radiotherapy For Locally Advanced Bladder Carcinoma With Image-guided Local Boost
Nishioka K, Shimizu S, Osaka Y, Kitamura K, Onimaru R, Sazawa A, Harabayashi T, Shinohara N, Shirato H
International Journal of Radiation Oncology Biology Physics, 81, 2, S449, 2011, [Peer-reviewed]

Diffusion tensor imaging characteristics of normal human cervical spinal cord at 3T
Tha KK, Terae S, Ishizaka K, Okuaki T, Hirotani M, Fujima N, Tsukahara A, Shirato H
日本磁気共鳴医学会雑誌, 31, 1, 70, 70, 2011, [Invited]
Japanese

Contrast-Enhanced Whole-Body Joint MRI in Patients With Unclassified Arthritis Who Develop Early Rheumatoid Arthritis Within 2 Years: Feasibility Study and Correlation With MRI Findings of the Hands
Tamotsu Kamishima, Yuichiro Fujieda, Tatsuya Atsumi, Rie Mimura, Takao Koike, Satoshi Terae, Hiroki Shirato
AMERICAN JOURNAL OF ROENTGENOLOGY, 195, 4, W287, W292, AMER ROENTGEN RAY SOC, Oct. 2010, [Peer-reviewed]
English, Scientific journal, 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.

乳房温存療法後局所再発症例の検討
木下留美子, 清水伸一, 土屋和彦, 加藤徳雄, 田口大志, 高橋将人, 高橋弘昌, 白土博樹
日本医学放射線学会秋季臨床大会抄録集, 46th, S506, 25 Aug. 2010
Japanese

Stage C前立腺癌の治療成績—動体追跡強度変調放射線療法と前立腺全摘除術の比較—
丸山覚, 篠原信雄, 安部崇重, 佐澤陽, 原林透, 清水伸一, 白土博樹, 野々村克也
泌尿器外科, 23, 8, 1105-1107, 15 Aug. 2010
Japanese

RADIATION PNEUMONITIS AFTER HYPOFRACTIONATED RADIOTHERAPY: EVALUATION OF THE LQ(L) MODEL AND DIFFERENT DOSE PARAMETERS
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, ELSEVIER SCIENCE INC, Aug. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Clinical Outcomes of Stereotactic Brain and/or Body Radiotherapy for Patients with Oligometastatic Lesions
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, OXFORD UNIV PRESS, Aug. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Image-guided adaptive gating of lung cancer radiotherapy: a computer simulation study
Michalis Aristophanous, Joerg Rottmann, Sang-June Park, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco
PHYSICS IN MEDICINE AND BIOLOGY, 55, 15, 4321, 4333, IOP PUBLISHING LTD, Aug. 2010, [Peer-reviewed]
English, Scientific journal, 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.

生物学的効果を考慮した治療計画—Dose Volume Histogram解析による考察—
関原和正, 石川正純, SUTHERLAND Kenneth, BENGUA Gerard, 宮本直樹, 鈴木隆介, 清水伸一, 白土博樹
Jpn J Radiol, 28, Supplement 1, 15, 15, (公社)日本医学放射線学会, 25 Jul. 2010
Japanese

口唇癌の放射線治療のretrospective study
香泉和寿, 安田耕一, 長谷川雅一, 鬼丸力也, 清水伸一, 木下留美子, 井上哲也, 加藤徳雄, 小野寺俊輔, 田口大志, 溝口史樹, 青山英史, 白土博樹, 西岡健, 武島嗣英
Jpn J Radiol, 28, Supplement 1, 7, 7, (公社)日本医学放射線学会, 25 Jul. 2010
Japanese

PET‐CTを用いた放射線治療計画
藤野賢治, 小野寺俊輔, 清水伸一, 白土博樹, 真鍋治, 伊藤和夫, 細川正夫
Jpn J Radiol, 28, Supplement 1, 8, 25 Jul. 2010
Japanese

The impact of 18F-fluoromisonidazole PET for H&N cancer and the applying for IMRT
YASUDA KOICHI, HASEGAWA MASAICHI, ONIMARU RIKIYA, KINOSHITA RUMIKO, KATO NORIO, TAGUCHI HIROSHI, SHIMIZU SHIN'ICHI, INOUE TETSUYA, ONODERA SHUNSUKE, MIZOGUCHI FUMIKI, AOYAMA HIDEFUMI, SHIRATO HIROKI, SHIGA SATORU, OKAMOTO SHOZO, TAMAKI NAGARA, ISHIKAWA MASAZUMI, SUTHERLAND KENNETH, BENGUA GERARD, MIYAMOTO NAOKI, SUZUKI TAKASUKE
Jpn J Radiol, 28, Supplement 1, 14, 14, (公社)日本医学放射線学会, 25 Jul. 2010
Japanese

Splenic volume measurements on computed tomography utilizing automatically contouring software and its relationship with age, gender, and anthropometric parameters
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, ELSEVIER IRELAND LTD, Jul. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Cesium Implant for Tongue Carcinoma with a Thickness of 1.5 cm or More: Cases Successfully Treated with a Modified Manchester System
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, YONSEI UNIV COLLEGE MEDICINE, Jul. 2010, [Peer-reviewed]
English, Scientific journal, 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.

放射線がん治療における免疫系の役割と治療への応用　　　　　　　　　　　　　　　
武島 嗣英, 茶本 健司, 北村 秀光, 西村 孝司, 青山 英史, 白土 博樹
Japanese Journal of Radiology, 28, Suppl.I, 8, 8, (公社)日本医学放射線学会, Jul. 2010
Japanese

放射線がん治療における免疫系の役割と治療への応用　　　　　　　　　　　　　　　
武島 嗣英, 茶本 健司, 北村 秀光, 西村 孝司, 青山 英史, 白土 博樹
Japanese Journal of Radiology, 28, Suppl.I, 8, 8, (公社)日本医学放射線学会, Jul. 2010
Japanese

Remote Desktopアプリケーションを用いた遠隔放射線治療計画システム(第一報)　　　　　　　　　　　　　　　
鈴木 恵士郎, 島 勝美, 西尾 正道, 青山 英史, 白土 博樹, 影井 兼司, 八重樫 祐司, 平澤 之規, 宮坂 和男, 宮本 英樹
Japanese Journal of Radiology, 28, Suppl.I, 8, 8, (公社)日本医学放射線学会, Jul. 2010
Japanese

Inferior phrenic artery-pulmonary vasculature shuntの塞栓によりTACEを施行し得たHCCの1例　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 長谷川 悠, 加茂 武実, 清水 匡, 白土 博樹
Japanese Journal of Radiology, 28, Suppl.I, 6, 6, (公社)日本医学放射線学会, Jul. 2010
Japanese

EVALUATION OF THE EFFECTIVENESS OF THE STEREOTACTIC BODY FRAME IN REDUCING RESPIRATORY INTRAFRACTIONAL ORGAN MOTION USING THE REAL-TIME TUMOR-TRACKING RADIOTHERAPY SYSTEM
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, ELSEVIER SCIENCE INC, Jun. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Integrin beta 1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix
Seiichiro Ishihara, Hisashi Haga, Motoaki Yasuda, Takeomi Mizutani, Kazushige Kawabata, Hiroki Shirato, Takeshi Nishioka
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 396, 3, 651, 655, ACADEMIC PRESS INC ELSEVIER SCIENCE, Jun. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Site-specific volumetric analysis of lung tumour motion
Eric W. Pepin, Huanmei Wu, George A. Sandison, Mark Langer, Hiroki Shirato
PHYSICS IN MEDICINE AND BIOLOGY, 55, 12, 3325, 3337, IOP PUBLISHING LTD, Jun. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Semi-quantitative analysis of rheumatoid finger joint synovitis using power Doppler ultrasonography: when to perform follow-up study after treatment consisting mainly of antitumor necrosis factor alpha agent
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, SPRINGER, May 2010, [Peer-reviewed]
English, Scientific journal, 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.

64-Slice MDCT imaging of endocardial cushion defect associated with other cardiac and extracardiac abnormalities
Noriko Oyama, Daisuke Goto, Tsukasa Sasaki, Hiroyuki Tsutsui, Nagara Tamaki, Satoshi Terae, Hiroki Shirato
JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY, 4, 3, 218, 220, ELSEVIER SCIENCE INC, May 2010, [Peer-reviewed]
English, Scientific journal, 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.

Extramedullary plasmacytoma involving perirenal space accompanied by extramedullary hematopoiesis and amyloid deposition
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, 4, May 2010, [Peer-reviewed]
English, Scientific journal, 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.

膵頭十二指腸切除後に発症した上腸間膜動脈仮性瘤に対してcovered stent留置にて止血し得た1例
三浦 巧, 平野 聡, 川村 武史, 斉藤 博紀, 中山 智英, 松井 あや, 加藤 健太郎, 川崎 亮輔, 松本 譲, 土川 貴裕, 七戸 俊明, 田中 栄一, 近藤 哲, 阿保 大介, 作原 祐介, 白土 博樹
日本臨床外科学会雑誌, 71, 5, 1375, 1375, 日本臨床外科学会, May 2010
Japanese

化学放射線治療後の頸部郭清の必要性について　　　　　　　　　　　　　　　
本間 明宏, 折舘 伸彦, 鈴木 章之, 鈴木 清護, 原 敏浩, 加納 里志, 水町 貴諭, 古沢 純, 稲村 直哉, 福田 諭, 吉田 大介, 鬼丸 力也, 安田 耕一, 白土 博樹
頭頸部癌, 36, 2, 191, 191, (一社)日本頭頸部癌学会, May 2010
Japanese

頭頸部癌に対するweekly cisplatinと放射線同時併用療法の検討　　　　　　　　　　　　　　　
稲村 直哉, 本間 明宏, 折舘 伸彦, 鈴木 清護, 鈴木 章之, 原 敏浩, 真栄田 裕行, 加納 里志, 水町 貴諭, 福田 諭, 鬼丸 力也, 長谷川 雅一, 安田 耕一, 白土 博樹
頭頸部癌, 36, 2, 206, 206, (一社)日本頭頸部癌学会, May 2010
Japanese

Local Radiation Therapy Inhibits Tumor Growth through the Generation of Tumor-Specific CTL: Its Potentiation by Combination with Th1 Cell Therapy
Tsuguhide Takeshima, Kenji Chamoto, Daiko Wakita, Takayuki Ohkuri, Yuji Togashi, Hiroki Shirato, Hidemitsu Kitamura, Takashi Nishimura
CANCER RESEARCH, 70, 7, 2697, 2706, AMER ASSOC CANCER RESEARCH, Apr. 2010, [Peer-reviewed]
English, Scientific journal, 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.

診断X線領域における極微小光ファイバ線量計の基礎特性評価　　　　　　　　　　　　　　　
江口 菜弥帆, 石川 正純, 作原 祐介, 阿保 大介, 太田 真緒, Sutherland Kenneth, 白土 博樹
日本放射線技術学会総会学術大会予稿集, 66回, 153, 154, (公社)日本放射線技術学会, Feb. 2010
Japanese

Detection of Normal Spinal Veins by Using Susceptibility-Weighted Imaging
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, JOHN WILEY & SONS INC, Jan. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Differences in CT Perfusion Maps Generated by Different Commercial Software: Quantitative Analysis by Using Identical Source Data of Acute Stroke Patients
Kohsuke Kudo, Makoto Sasaki, Kei Yamada, Suketaka Momoshima, Hidetsuna Utsunomiya, Hiroki Shirato, Kuniaki Ogasawara
RADIOLOGY, 254, 1, 200, 209, RADIOLOGICAL SOC NORTH AMERICA, Jan. 2010, [Peer-reviewed]
English, Scientific journal, 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

High Dose Three-Dimensional Conformal Boost Using the Real-Time Tumor Tracking Radiotherapy System in Cervical Cancer Patients Unable to Receive Intracavitary Brachytherapy
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, YONSEI UNIV COLLEGE MEDICINE, Jan. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Metastases in Mediastinal and Hilar Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Quantitative Assessment With Diffusion-Weighted Magnetic Resonance Imaging and Apparent Diffusion Coefficient
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, LIPPINCOTT WILLIAMS & WILKINS, Jan. 2010, [Peer-reviewed]
English, Scientific journal, 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.

Susceptibility-weighted imaging of cerebral fat embolism.
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, 1, Jan. 2010, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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
Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato
JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, 11, 2, 158, 167, MULTIMED INC, 2010, [Peer-reviewed]
English, Scientific journal, Image-guided patient setup for respiratory-gated radiotherapy often relies on a pair of respiratory-gated orthogonal radiographs, acquired one after the other. This study quantifies the error due to changes in the internal/external correlation which may affect asynchronous (non-simultaneous) imaging. The dataset from eight patients includes internal and external coordinates acquired at 30Hz during multi-fraction SBRT treatments using the Mitsubishi RTRT system coupled with an external surrogate gating device. We performed a computational simulation of the position of an implanted fiducial marker in an asynchronous orthogonal image set. A comparison is made to the reference position, the actual 3D fiducial location at the initial time point, as would be obtainable by simultaneous orthogonal setup imaging at that time point. The time interval between the two simulated radiographic acquisitions was set to a minimum of 30, 60 or 90 seconds, based on our clinical experience. The setup position is derived from a combination of both the initial (AP) and the final (LR) simulated 2D images in the following way: LR(setup) = LR(initial), SI(setup) = SI(initial) + (SI(final) = SI(initial))/2, AP(setup) = AP(final). The 3D error is then the magnitude of the vector from the initial (reference) 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, 60 or 90 seconds later, at an amplitude within 0.5 mm from the first. A correlation between the time interval and the 3D error was also sought. The mean 3D error is found to be roughly equivalent for time intervals (t(interval)) of 30, 60 and 90 seconds between the orthogonal simulated images (0.8 mm, 0.8 mm, 0.6 mm, respectively). The 3D error is less than 1, 2 and 3 mm for 77%, 89% and 98% of the data points, respectively. The actual time between simulated images turned out to be very close to t(interval), with 90% of the second simulated image acquisitions being completed within 38, 68 and 95 seconds of the first simulated image for t(interval) of 30, 60 and 90 seconds, respectively. No correlation was found between the length of the time interval and the 3D error. When acquiring respiratory-gated radiographs for patient setup, only small errors should be expected if those images are not taken simultaneously.

A parameter study of pencil beam proton dose distributions for the treatment of ocular melanoma utilizing spot scanning
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, 1, Jan. 2010, [Peer-reviewed]
English, Scientific journal, 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.

An Internationally Compatible, Japanese Neurocognitive Function Test Battery for the Assessment of Radiation-induced Brain Injury
S. Onodera, H. Aoyama, N. Hashimoto, A. Toyomaki, N. Nishikawa, K. K. Tha, K. Ogisu, S. Terae, H. Shirato
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 78, 3, S293, S293, ELSEVIER SCIENCE INC, 2010, [Peer-reviewed]
English

Radiation pneumonitis after hypofractionated radiotherapy: evaluation of the LQ(L) model and different dose parameters.
Borst G. R, Ishikawa M, Nijkamp J, Hauptmann M, Shirato H, Bengua G, Onimaru R, de Josien Bois A, Lebesque J. V, Sonke J. J
Int J Radiat Oncol Biol Phys, 77, 5, 1596, 603, 2010, [Peer-reviewed]

Clinical outcomes of stereotactic brain and/or body radiotherapy for patients with oligometastatic lesions.
Inoue T, Katoh N, Aoyama H, Onimaru R, Taguchi H, Onodera S, Yamaguchi S, Shirato H
Jpn J Clin Oncol, 40, 8, 788, 94, 2010, [Peer-reviewed]

MultiTransmitを用いた3.0T乳腺MRI　　　　　　　　　　　　　　　
加藤扶美, 石坂欣也, 小原真, 大山徳子, 水戸寿々子, 寺江聡, 白土博樹
映像情報Medical, 42, 94, 99, 2010

臨床的に原発性肺癌と診断された病理組織診断のつかない小型肺腫瘍に対する体幹部定位放射線治療
井上哲也, 清水伸一, 鬼丸力也, 白土博樹, 武田篤也, 大西洋, 永田靖, 木村智樹, 唐澤克之, 有本卓郎, 晴山雅人, 菊地英毅
肺癌, 49, 7, 1057, 20 Dec. 2009
Japanese

乳房温存手術後接線照射における被照射腋窩リンパ節領域の検討
田口大志, 清水伸一, 木下留美子, 白土博樹, 高橋弘昌, 高橋將人, 細田充主, 藤堂省
北海道外科雑誌, 54, 2, 188, 20 Dec. 2009
Japanese

STEREOTACTIC RADIOTHERAPY FOR INTRACRANIAL NONACOUSTIC SCHWANNOMAS INCLUDING FACIAL NERVE SCHWANNOMA
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, ELSEVIER SCIENCE INC, Dec. 2009, [Peer-reviewed]
English, Scientific journal, 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.

尿路性器癌に対する放射線療法 放射線療法による合併症を減らすための最新の工夫
篠原信雄, 丸山覚, 安部崇重, 佐澤陽, 清水伸一, 白土博樹
Urol View, 7, 6, 15-20, 01 Dec. 2009
Japanese

CLINICAL OUTCOMES OF STEREOTACTIC BODY RADIOTHERAPY FOR SMALL LUNG LESIONS CLINICALLY DIAGNOSED AS PRIMARY LUNG CANCER ON RADIOLOGIC EXAMINATION
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, ELSEVIER SCIENCE INC, Nov. 2009, [Peer-reviewed]
English, Scientific journal, 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.

Outcome of MR-guided percutaneous cryoablation for hepatocellular carcinoma
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, SPRINGER TOKYO, Nov. 2009, [Peer-reviewed]
English, Scientific journal, 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.

導入化学療法と低線量放射線治療でジャーミノーマの治療は可能か　　　　　　　　　　　　　　　
澤村 豊, 鴨嶋 雄大, 白土 博樹, 青山 英史
小児がん, 46, プログラム・総会号, 353, 353, (NPO)日本小児がん学会, Nov. 2009
Japanese

放射線治療の現在 I.臨床 動体追跡放射線治療10年の経験
加藤徳雄, 鬼丸力也, 田口大志, 清水伸一, 白土博樹
映像情報Medical, 41, 12, 1222-1227,1207, 1261, 産業開発機構, 01 Nov. 2009
Japanese

Superselective High-Dose Cisplatin Infusion With Concomitant Radiotherapy in Patients With Advanced Cancer of the Nasal Cavity and Paranasal Sinuses A Single Institution Experience
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, WILEY, Oct. 2009, [Peer-reviewed]
English, Scientific journal, 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.

SURVEY OF STEREOTACTIC BODY RADIATION THERAPY IN JAPAN BY THE JAPAN 3-D CONFORMAL EXTERNAL BEAM RADIOTHERAPY GROUP
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, ELSEVIER SCIENCE INC, Oct. 2009, [Peer-reviewed]
English, Scientific journal, 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.

Can hybrid FDG-PET/CT detect subclinical lymph node metastasis of esophageal cancer appropriately and contribute to radiation treatment planning? A comparison of image-based and pathological findings
Shinichi Shimizu, Masao Hosokawa, Kazuo Itoh, Masahiro Fujita, Hiroaki Takahashi, Hiroki Shirato
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 14, 5, 421, 425, SPRINGER TOKYO, Oct. 2009, [Peer-reviewed]
English, Scientific journal, 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.

Intravenous pyogenic granuloma of the finger
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, SPRINGER, Oct. 2009, [Peer-reviewed]
English, Scientific journal, 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.

強度変調放射線治療(IMRT)の中長期成績 北海道大学病院での頭頸部癌に対する強度変調放射線治療の成績
鬼丸 力也, 長谷川 雅一, 安田 耕一, 木下 留美子, 白土 博樹, 本間 明宏, 折舘 伸彦, 福田 諭
頭頸部癌, 35, 3, 245, 249, (一社)日本頭頸部癌学会, Oct. 2009
Japanese, 2002年5月から2007年12月までに北大病院放射線科にて強度変調放射線治療(Intensity modulated radiation therapy,IMRT)を行った37例を検討した。上咽頭13例、中咽頭19例、下咽頭3例、上顎1例、口腔1例であった。死亡は4例で認められた。治療終了後4ヵ月で中咽頭癌(後壁T3N0)が咽頭膿瘍後の誤嚥性肺炎で死亡したが、他の3名は他癌死であった。原発・頸部リンパ節残存・再発は、上咽頭癌で原発巣再発1例、中咽頭癌では原発巣再発が3例、頸部リンパ節転移・残存が2名、下咽頭癌では1例で頸部リンパ節残存があった。重篤な晩期反応は、中咽頭後壁の1名で咽頭膿瘍の発生による死亡があり、1例の上咽頭癌症例(CDDP併用)で聴力低下と偶角閉塞がみられた。(著者抄録)

Volume-rendering and endocardial views of partially unroofed coronary sinus with 64-slice multidetector CT
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, 5, Sep. 2009, [Peer-reviewed]
English, Scientific journal, 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.

動体追跡装置におけるコントラスト‐ノイズ比の測定方法の検討
木村傑, 宮本直樹, 石川正純, SUTHERLAND Kenneth, BENGUA Gerard, 鈴木隆介, 清水伸一, 青山英史, 鬼丸力也, 白土博樹
医学物理 Supplement, 29, 3, 148-149, Sep. 2009
Japanese

動体追跡放射線治療におけるX線透視条件の最適化
宮本直樹, SUTHERLAND Kenneth, 石川正純, 鈴木隆介, BENGUA Gerard, 木村傑, 清水伸一, 青山英史, 鬼丸力也, 白土博樹
医学物理 Supplement, 29, 3, 150-151, Sep. 2009
Japanese

臨床的に原発性肺癌と診断された病理診断のつかない小型肺腫瘍に対する定位放射線治療
井上哲也, 清水伸一, 武田篤也, 大西洋, 永田靖, 木村智樹, 唐澤克之, 晴山雅人, 有本卓郎, 白土博樹
日本放射線腫よう学会誌, 21, Supplement 1, 75, 19 Aug. 2009
Japanese

動体追跡装置を用いた肺定位照射時の投与線量解析—動体追跡データに基づくDVH解析—
石川正純, サザランド ケネス, ベングア ジェラード, 鈴木隆介, 宮本直樹, 加藤徳雄, 清水伸一, 鬼丸力也, 青山英史, 白土博樹
日本放射線腫よう学会誌, 21, Supplement 1, 158, 19 Aug. 2009
Japanese

Synchronous monitoring of external/internal respiratory motion: validity of respiration-gated radiotherapy for liver tumors
Takeshi Nishioka, Seiko Nishioka, Masaki Kawahara, Shigeru Tanaka, Hiroki Shirato, Ken Nishi, Tadao Hiromura
JAPANESE JOURNAL OF RADIOLOGY, 27, 7, 285, 289, SPRINGER, Aug. 2009, [Peer-reviewed]
English, Scientific journal, 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.

新しい治療 画像誘導放射線治療(image‐guided radiotherapy:IGRT)
白土博樹, 青山英史, 鬼丸力也, 清水伸一, 石川正純, 西岡健
治療学, 43, 7, 781-783, 783, ライフサイエンス出版(株), 10 Jul. 2009
Japanese

Value of fluorodeoxyglucose positron emission tomography before radiotherapy for head and neck cancer: does the standardized uptake value predict treatment outcome?
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, SPRINGER, Jul. 2009, [Peer-reviewed]
English, Scientific journal, 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.

機能温存をめざした頭頸部癌治療update 強度変調放射線治療(intensity modulated radiotherapy;IMRT)
鬼丸力也, 木下留美子, 長谷川雅一, 安田耕一, 白土博樹
ENTONI, 103, 14, 20, (株)全日本病院出版会, 15 Jun. 2009
Japanese, 頭頸部癌に対する放射線治療は形態・機能温存を目的とした治療であるが、晩期反応に苦しむ患者さんも多かった。従来の放射線治療の欠点を解消すべく発展してきた強度変調放射線治療(intensity modulated radiotherapy;IMRT)は腫瘍には十分な線量を、リスク臓器には少ない線量を照射することを可能にした。IMRTを行う際には、CTで標的体積を設定する必要があるが、その際には正確な病期診断が必要である。また、治療計画の最適化や検証などの作業が必要であり、人手と時間を要する治療である。IMRTにより視神経などのリスク臓器のそばまで浸潤した腫瘍を従来の放射線治療よりも合併症を少なく治療できると期待されている一方、リスク臓器と指定しなかった臓器には高線量が照射される可能性があり注意が必要である。(著者抄録)

Radiation pneumonitis in patients treated for malignant pulmonary lesions with hypofractionated radiation therapy
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, ELSEVIER IRELAND LTD, Jun. 2009, [Peer-reviewed]
English, Scientific journal, 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

Alveolar hydatid disease of the adrenal gland: Computed tomography and magnetic resonance imaging findings
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, 5, Jun. 2009, [Peer-reviewed]
English, Scientific journal, 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.

Prediction of three-dimensional tumor shrinkage and deformation from radiotherapy using Linear-Quadratic model and mechanical analogy　　　　　　　　　　　　　　　
Takao, S, Tadano, S, Taguchi, H, Shirato, H
Proceedings of the 8th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, Jun. 2009, [Peer-reviewed]
English, International conference proceedings

Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells
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, WILEY-BLACKWELL PUBLISHING, INC, May 2009, [Peer-reviewed]
English, Scientific journal, 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).

Power Doppler ultrasound of rheumatoid synovitis: quantification of vascular signal and analysis of interobserver variability
Tamotsu Kamishima, Kazuhide Tanimura, Mihoko Henmi, Akihiro Narita, Fumihiko Sakamoto, Satoshi Terae, Hiroki Shirato
SKELETAL RADIOLOGY, 38, 5, 467, 472, SPRINGER, May 2009, [Peer-reviewed]
English, Scientific journal, 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.

Reduction of Bed Rest Time after Transfemoral Noncardiac Angiography from 4 Hours to 2 Hours: A Randomized Trial and a One-arm Study
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, ELSEVIER SCIENCE INC, May 2009, [Peer-reviewed]
English, Scientific journal, 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.

Sonazoid-enhanced sonography for guiding radiofrequency ablation for hepatocellular carcinoma: Better tumor visualization by Kupffer-phase imaging and vascular-phase imaging after reinjection
Noriyuki Miyamoto, Kazuhide Hiramatsu, Kazuhiko Tsuchiya, Yukihiko Sato, Satoshi Terae, Hiroki Shirato
Japanese Journal of Radiology, 27, 4, 185, 193, 4, May 2009, [Peer-reviewed]
English, Scientific journal, 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.

病理診断のついていない小型肺腫瘍に対する定位放射線治療
井上 哲也, 鬼丸 力也, 清水 伸一, 青山 英史, 白土 博樹
臨床放射線, 54, 5, 625, 630, 金原出版(株), May 2009
Japanese

Sonazoid-enhanced sonography for guiding radiofrequency ablation for hepatocellular carcinoma: better tumor visualization by Kupffer-phase imaging and vascular-phase imaging after reinjection
Noriyuki Miyamoto, Kazuhide Hiramatsu, Kazuhiko Tsuchiya, Yukihiko Sato, Satoshi Terae, Hiroki Shirato
JAPANESE JOURNAL OF RADIOLOGY, 27, 4, 185, 193, SPRINGER, May 2009, [Peer-reviewed]
English, Scientific journal, 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).
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.
Conventional sonography identified 30 (57%) of 52 HCCs, whereas Sonazoid-enhanced sonography detected 50 (96%) of 52 HCCs (P < 0.01, McNemar's chi(2) test). Complete ablation was achieved at a single session in 48 of 50 tumors.
Sonazoid-enhanced sonography is a useful technique for guiding RF ablation of HCCs, even when treating local progression of a previously treated HCC.

化学放射線療法後の救済手術 問題点とその対策 喉頭下咽頭癌に対する化学放射線療法後の救済手術　　　　　　　　　　　　　　　
鈴木 章之, 本間 明宏, 折舘 伸彦, 鈴木 清護, 水町 貴諭, 加納 里志, 瀧 重成, 稲村 直哉, 鬼丸 力也, 長谷川 雅一, 白土 博樹, 古田 康, 福田 諭
頭頸部癌, 35, 2, 61, 61, (一社)日本頭頸部癌学会, May 2009
Japanese

Alternative approach in the treatment of adrenal metastasis with a real-time tracking radiotherapy in patients with hormone refractory prostate cancer
Ataru Sazawa, Nobuo Shinohara, Toru Harabayashi, Takashige Abe, Hiroki Shirato, Katsuya Nonomura
INTERNATIONAL JOURNAL OF UROLOGY, 16, 4, 410, 412, WILEY-BLACKWELL PUBLISHING, INC, Apr. 2009, [Peer-reviewed]
English, Scientific journal, 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.

転移性脳腫瘍への放射線治療後の認知機能の推移　　　　　　　　　　　　　　　
青山 英史, 加藤 徳雄, 白土 博樹
Japanese Journal of Radiology, 27, Suppl., 12, 12, (公社)日本医学放射線学会, Apr. 2009
Japanese

脊髄AVMにおける磁化率強調画像(SWI)の有用性の検討　　　　　　　　　　　　　　　
藤間 憲幸, 工藤 興亮, Tha Khin Khin, 塚原 亜希子, 寺江 聡, 白土 博樹
Japanese Journal of Radiology, 27, Suppl., 4, 4, (公社)日本医学放射線学会, Apr. 2009
Japanese

多発性嚢胞腎に対する動脈塞栓術の治療成績　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 長谷川 悠, 藤田 希実, 白土 博樹, 清水 匡
IVR: Interventional Radiology, 24, 2, 187, 187, (一社)日本インターベンショナルラジオロジー学会, Apr. 2009
Japanese

EPIR-Lipiodol懸濁液を用いた肝TAI or TACEによるHCC局所制御率　　　　　　　　　　　　　　　
阿保 大介, 藤田 希実, 長谷川 悠, 作原 祐介, 白土 博樹, 清水 匡
IVR: Interventional Radiology, 24, 2, 187, 187, (一社)日本インターベンショナルラジオロジー学会, Apr. 2009
Japanese

EPIR-Lipiodol懸濁液を用いた肝TAI or TACEによるHCCの合併症　　　　　　　　　　　　　　　
藤田 希実, 阿保 大介, 長谷川 悠, 作原 祐介, 白土 博樹, 清水 匡
IVR: Interventional Radiology, 24, 2, 187, 187, (一社)日本インターベンショナルラジオロジー学会, Apr. 2009
Japanese

対向型PET装置を用いた分子イメージング動体追跡装置の開発〜¹⁸F点線源を用いた追跡精度の検証〜
棚邊哲史, 石川正純, 山口哲, 武島嗣英, 鈴木隆介, 宮本直樹, 加藤徳雄, 清水伸一, 鬼丸力也, 白土博樹
医学物理 Supplement, 29, 2, 101-102, Apr. 2009
Japanese

体内臓器同期照射を目的とした次世代動体追跡装置の開発〜透視画像の歪みと位置計算誤差〜
宮本直樹, SUTHERLAND Kenneth, 石川正純, 鈴木隆介, BENGUA Gerard, 木村傑, 清水伸一, 青山英史, 鬼丸力也, 白土博樹
医学物理 Supplement, 29, 2, 192-193, Apr. 2009
Japanese

体内臓器同期照射を目的とした次世代動体追跡装置の開発〜デジタル画像機器としての定量的評価〜
木村傑, 石川正純, SUTHERLAND Kenneth, 宮本直樹, BENGUA Gerard, 鈴木隆介, 清水伸一, 青山英史, 鬼丸力也, 白土博樹
医学物理 Supplement, 29, 2, 196-197, Apr. 2009
Japanese

体内臓器同期照射を目的とした次世代動体追跡装置の開発〜複数マーカ追跡への挑戦〜
石川正純, SUTHERLAND Kenneth, 宮本直樹, BENGUA Gerard, 清水伸一, 青山英史, 鬼丸力也, 木村傑, 白土博樹
医学物理 Supplement, 29, 2, 194-195, Apr. 2009
Japanese

Difference in CT Perfusion Maps among Commercially Available Software: Quantitative Analysis Using Identical Source Data of Acute Stroke Patients
Kudo Kohsuke, Sasaki Makoto, Yamada Kei, Momoshima Suketaka, Kuroiwa Taizo, Utsunomiya Hidetsuna, Shirato Hiroki, Ogasawara Kuniaki
STROKE, 40, 4, E114, Apr. 2009, [Peer-reviewed]

限局性前立腺癌のQOL評価を含む治療成績〜動体追跡強度変調放射線療法と前立腺全摘除術の比較〜
丸山覚, 篠原信雄, 安部崇重, 原林透, 佐澤陽, 清水伸一, 白土博樹, 野々村克也
泌尿器外科, 22, 349, 15 Mar. 2009
Japanese

上咽頭癌における半導体PET画像を用いた放射線治療計画
加藤徳雄, 志賀哲, 長谷川雅一, 鬼丸力也, 安田耕一, 清水伸一, ベングア ジェラード, 石川正純, 玉木長良, 白土博樹
日本医学放射線学会総会抄録集, 68th, S307-S308, S308, (公社)日本医学放射線学会, 28 Feb. 2009
Japanese

A New PET Scanner with Semiconductor Detectors Enables Better Identification of Intratumoral Inhomogeneity
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, SOC NUCLEAR MEDICINE INC, Jan. 2009, [Peer-reviewed]
English, Scientific journal, 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.

Novel Function of Transcription Factor ATF5: Blockade of p53-dependent Apoptosis Induced by Ionizing Irradiation
Takeshi Nishioka, Yusuke Miyai, Hisashi Haga, Kazushige Kawabata, Hiroki Shirato, Akihiro Homma, Kenichiro Shibata, Motoaki Yasuda
CELL STRUCTURE AND FUNCTION, 34, 1, 17, 22, JAPAN SOC CELL BIOLOGY, 2009, [Peer-reviewed]
English, Scientific journal, 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.

Increased Motility and Invasiveness in Tumor Cells That Survive 10 Gy Irradiation
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, JAPAN SOC CELL BIOLOGY, 2009, [Peer-reviewed]
English, Scientific journal, 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.

A web-based remote radiation treatment planning system using the remote desktop function of a computer operating system: a preliminary report
Keishiro Suzuki, Yukinori Hirasawa, Yuji Yaegashi, Hideki Miyamoto, Hiroki Shirato
JOURNAL OF TELEMEDICINE AND TELECARE, 15, 8, 414, 418, ROYAL SOC MEDICINE PRESS LTD, 2009, [Peer-reviewed]
English, Scientific journal, 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.

A new PET scanner with semiconductor detector reveals intratumoral inhomogeneous cell activity with high spatial and energy resolution　　　　　　　　　　　　　　　
Shiga T, Kubo N, Morimoto Y, Katoh N, Katoh C, Ueno Y, Hirata K, Usui R, Kobayashi K, Takeuchi W, Shirato H, Tamaki N
Molecular Imaging for Integrated Medical Therapy and Drug Development, 42, 51, 2009
English, International conference proceedings

Gating based on internal/external signals with dynamic correlation updates
Huanmei Wu, Qingya Zhao, Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang
PHYSICS IN MEDICINE AND BIOLOGY, 53, 24, 7137, 7150, IOP PUBLISHING LTD, Dec. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Surgical complications of salvage total laryngectomy following concurrent chemoradiotherapy
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, SPRINGER TOKYO, Dec. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Late recurrence and salvage therapy of CNS germinomas
Yuuta Kamoshima, Yutaka Sawamura, Jun Ikeda, Hiroki Shirato, Hidefumi Aoyama
JOURNAL OF NEURO-ONCOLOGY, 90, 2, 205, 211, SPRINGER, Nov. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Splenic Peliosis Mimicking a Solid Tumor: Findings in Multimodalities
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, LIPPINCOTT WILLIAMS & WILKINS, Nov. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Double microcatheter+IDC使用によるpinpointでの血流遮断術　　　　　　　　　　　　　　　
阿保 大介, 長谷川 悠, 作原 祐介, 白土 博樹, 清水 匡
IVR: Interventional Radiology, 23, 4, 403, 404, (一社)日本インターベンショナルラジオロジー学会, Oct. 2008
Japanese

Inferior phrenic artery-pulmonary vasculature shuntの塞栓によりTACEを施行し得たHCCの1例　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 長谷川 悠, 加茂 武実, 清水 匡, 白土 博樹
IVR: Interventional Radiology, 23, 4, 405, 405, (一社)日本インターベンショナルラジオロジー学会, Oct. 2008
Japanese

75歳以上の高齢者に対する子宮頚癌の放射線治療
木下留美子, 田口大志, 加藤徳雄, 清水伸一, 溝口史樹, 米坂祥朗, 北原利博, 白土博樹
日本放射線腫よう学会誌, 20, Supplement 1, 146, 22 Sep. 2008
Japanese

Evaluation of the vascular supply to regions of the pancreas on CT during arteriography
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, SPRINGER, Sep. 2008, [Peer-reviewed]
English, Scientific journal, 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.

De novo formation of cavernoma after radiosurgery for adult cerebral arteriovenous malformation - Case report
Hiroaki Motegi, Satoshi Kuroda, Nobuaki Ishii, Hidefumi Aoyama, Satoshi Terae, Hiroki Shirato, Yoshinobu Iwasaki
NEUROLOGIA MEDICO-CHIRURGICA, 48, 9, 397, 400, JAPAN NEUROSURGICAL SOC, Sep. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Low-dose craniospinal irradiation and ifosfamide, cisplatin and etoposide for non-metastatic embryonal tumors in the central nervous system
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, OXFORD UNIV PRESS, Jul. 2008, [Peer-reviewed]
English, Scientific journal, 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.

CT/MRIにて確定診断に至らなかった結節に対する造影超音波(CEUS)の位置づけ　　　　　　　　　　　　　　　
西田 睦, 増田 香織, 佐藤 恵美, 溝口 恵美, 小野寺 祐也, 尾松 徳彦, 神島 保, 加藤 扶美, 加賀 早苗, 井上 真美子, 横山 しのぶ, 鈴木 春樹, 清水 力, 松野 一彦, 玉木 長良, 白土 博樹
超音波医学, 35, 4, 463, 463, (公社)日本超音波医学会, Jul. 2008
Japanese

UAE後にsloughing fibroidを生じた1例　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 長谷川 悠, 清水 匡, 白土 博樹, 木村 広幸
IVR: Interventional Radiology, 23, 3, 313, 313, (一社)日本インターベンショナルラジオロジー学会, Jul. 2008
Japanese

肝移植後膵液瘻による合併症に対し複合的IVRが奏功した1例　　　　　　　　　　　　　　　
長谷川 悠, 阿保 大介, 佐原 祐介, 白土 博樹, 清水 匡, 嶋村 剛, 古川 博之, 桑谷 将城, 河上 洋
IVR: Interventional Radiology, 23, 3, 316, 316, (一社)日本インターベンショナルラジオロジー学会, Jul. 2008
Japanese

Real-time tumor-tracking radiotherapy for adrenal tumors
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, ELSEVIER IRELAND LTD, Jun. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Frontiers of Three-dimensional Conformal Radiation Therapy: Image-guided Radiation Therapy and Four-dimensional Radiation Therapy
KINOSHITA RUMIKO, ONODERA YUYA, SHIRATO HIROKI, SHIMIZU SHIN'ICHI, ONIMARU RIKIYA, AOYAMA HIDEFUMI
画像診断, 28, 6, 560-566, 566, (株)学研メディカル秀潤社, 25 Apr. 2008
Japanese

全身造影MRIによる関節リウマチの画像診断　　　　　　　　　　　　　　　
神島 保, 白土 博樹, 保田 晋介, 堀田 哲也, 渥美 達也, 小池 隆夫
Radiation Medicine, 26, Suppl.I, 11, 11, (公社)日本医学放射線学会, Apr. 2008
Japanese

Intramedullary spinal cord metastasis treated with radiation therapy: Report of 3 cases
Shogo Endo, Kazutoshi Hida, Shunsuke Yano, Masaki Ito, Shigeru Yamaguchi, Daina Kashiwazaki, Rumiko Kinoshita, Hiroki Shirato, Yoshinobu Iwasaki
NEUROLOGICAL SURGERY, 36, 4, 345, 349, IGAKU-SHOIN LTD, Apr. 2008, [Peer-reviewed]
Japanese, Scientific journal, 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.

64列および4列のCT angiographyでの肝移植ドナーにおける肝動脈描出能の比較検討　　　　　　　　　　　　　　　
藤間 憲幸, 小野寺 祐也, 白土 博樹
Radiation Medicine, 26, Suppl.I, 13, 13, (公社)日本医学放射線学会, Apr. 2008
Japanese

[非小細胞肺癌]画像誘導放射線治療と強度変調放射線治療
白土博樹, 鬼丸力也, 石川正純, 田口大志, 加藤徳雄, 清水伸一
MOOK肺癌の臨床, 2008-2009, 319-326, 31 Mar. 2008
Japanese

Three-dimensional intrafractional motion of breast during tangential breast irradiation monitored with high-sampling frequency using a real-time tumor-tracking radiotherapy system
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, ELSEVIER SCIENCE INC, Mar. 2008, [Peer-reviewed]
English, Scientific journal, 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.

病理診断のついていない小型肺癌に対する定位放射線治療の安全性及び有用性の検討
井上哲也, 鬼丸力也, 清水伸一, 武田篤也, 有本卓郎, 平岡眞寛, 山田章吾, 白土博樹
日本医学放射線学会総会抄録集, 67th, S193-S194, 28 Feb. 2008
Japanese

動態追跡照射時の肺腫瘍の動きに関連する因子の検討
小野寺祐也, 西岡典子, 安田耕一, 藤間憲幸, 鬼丸力也, 清水伸一, 白土博樹
日本医学放射線学会総会抄録集, 67th, S193, 28 Feb. 2008
Japanese

Histopathologic consideration of fiducial gold markers inserted for real-time tumor-tracking radiotherapy against lung cancer
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, ELSEVIER SCIENCE INC, Feb. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Steep dose-response relationship for stage I non-small-cell lung cancer using hypofractionated high-dose irradiation by real-time tumor-tracking radiotherapy
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, ELSEVIER SCIENCE INC, Feb. 2008, [Peer-reviewed]
English, Scientific journal, 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.

Transcatheter arterial embolization with absolute ethanol injection for enlarged polycystic kidneys after failed metallic coil embolization
Yusuke Sakuhara, Fumi Kato, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Satoshi Terae, Hiroki Shirato
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY, 19, 2, 267, 271, ELSEVIER SCIENCE INC, Feb. 2008, [Peer-reviewed]
English, Scientific journal, 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.

CT during arteriographyによる膵の血流分布領域の検討　　　　　　　　　　　　　　　
作原 祐介, 児玉 芳尚, 阿保 大介, 長谷川 悠, 清水 匡, 白土 博樹
日本医学放射線学会学術集会抄録集, 67回, S361, S361, (公社)日本医学放射線学会, Feb. 2008
Japanese

Exhale fluctuation in respiratory-gated radiotherapy of the lung: A pitfall of respiratory gating shown in a synchronized internal/external marker recording study
Seiko Nishioka, Takeshi Nishioka, Masaki Kawahara, Shigeru Tanaka, Tadao Hiromura, Kazuo Tomita, Hiroki Shirato
RADIOTHERAPY AND ONCOLOGY, 86, 1, 69, 76, ELSEVIER IRELAND LTD, Jan. 2008, [Peer-reviewed]
English, Scientific journal, 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.

PP-126 ハイリスク前立腺癌に対する動体追跡放射線療法(前立腺腫瘍/放射線治療2,一般演題ポスター,第96回日本泌尿器科学会総会)
三浦 克紀, 篠原 信雄, 大坂 康博, 土屋 邦彦, 安部 崇重, 佐澤 陽, 原林 透, 白土 博樹, 野々村 克也
日本泌尿器科学会雑誌, 99, 2, 409, 409, 一般社団法人 日本泌尿器科学会, 2008
Japanese

Correlation identification between internal/external motion signals
Huanmei Wu, Qingya Zhao, Ross Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang
MEDICAL IMAGING 2008: PHYSICS OF MEDICAL IMAGING, PTS 1-3, 6913, SPIE-INT SOC OPTICAL ENGINEERING, 2008, [Peer-reviewed]
English, International conference proceedings, 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.

Outcome of stereotactic body radiotherapy for small lung lesions highly suggestive of primary non-small cell lung cancer on clinical/radiological examination
Inoue T, Shimizu S, Takeda A, Onishi H, Nagata Y, Kimura T, Karasawa K, Arimoto T, Hareyama M, Shirato H
International Journal of Radiation Oncology Biology Physics, 72, 1, S432, 2008, [Peer-reviewed]

Correlation between parameters describing tumour motion and its location in the lungs
Huanmei Wu, George Sandison, Li Zhao, Qingya Zhao, Hiroki Shirato, Steve Jiang
AUSTRALASIAN PHYSICAL & ENGINEERING SCIENCES IN MEDICINE, 30, 4, 341, 344, AUSTRALASIAN COLL PHYSICAL SCIENTISTS & ENGINEERS MEDICINE, Dec. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Combination tumor immunotherapy with radiotherapy and Th1 cell therapy against murine lung carcinoma
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, SPRINGER, Nov. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Influence of surgical staples on Radiofrequency ablation using multitined expandable electrodes
Yusuke Sakuhara, Tadashi Shimizu, Daisuke Abo, Yu Hasegawa, Fumi Kato, Yoshihisa Kodama, Hiroki Shirato
CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY, 30, 6, 1201, 1205, SPRINGER, Nov. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Adaptive prediction of respiratory motion for motion compensation radiotherapy
Qing Ren, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco
PHYSICS IN MEDICINE AND BIOLOGY, 52, 22, 6651, 6661, IOP PUBLISHING LTD, Nov. 2007, [Peer-reviewed]
English, Scientific journal, 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.

64列および4列のCT angiographyでの肝移植ドナーにおける肝動脈描出能の比較検討
藤間 憲幸, 小野寺 祐也, 白土 博樹
核医学, 44, 4, 389, 390, (一社)日本核医学会, Nov. 2007
Japanese

HHTに合併した中枢神経AVFの検討
笹森徹, 中山若樹, 黒田敏, 飛騨一利, 岩崎喜信, 浅野剛, 吉田大介, 白土博樹
J Neuroendovascular Ther, 1, 2, 257, 01 Nov. 2007
Japanese

Intercepting radiotherapy using a real-time tumor-tracking radiotherapy system for highly selected patients with hepatocellular carcinoma unresectable with other modalities
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, ELSEVIER SCIENCE INC, Oct. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma
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, SPRINGER TOKYO, Oct. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Matrixmetalloproteinases: Up-regulated in subclones that survived 10-Gy irradiation
Takeshi Nishioka, Motoaki Yasuda, Kaori Tsutsumi, Hisashi Haga, Hiroki Shirato
Radiation Medicine - Medical Imaging and Radiation Oncology, 25, 8, 430, 431, 8, Oct. 2007, [Peer-reviewed]
English

Internal-external correlation investigations of respiratory induced motion of lung tumors
Dan Ionascu, Steve B. Jiang, Seiko Nishioka, Hiroki Shirato, Ross I. Berbeco
MEDICAL PHYSICS, 34, 10, 3893, 3903, AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS, Oct. 2007, [Peer-reviewed]
English, Scientific journal, 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.

The management of imaging dose during image-guided radiotherapy: Report of the AAPM Task Group 75
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, AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS, Oct. 2007, [Peer-reviewed]
English, 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.

Polycystic kidney diseaseに対するエタノールによる動脈塞栓術の経験　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 長谷川 悠, 藤間 憲幸, 白土 博樹, 清水 匡
IVR: Interventional Radiology, 22, 4, 503, 503, (一社)日本インターベンショナルラジオロジー学会, Oct. 2007
Japanese

Enlarged polycystic liverに対する動脈塞栓術の経験　　　　　　　　　　　　　　　
藤間 憲幸, 長谷川 悠, 作原 祐介, 阿保 大介, 白土 博樹, 清水 匡, 嶋村 剛
IVR: Interventional Radiology, 22, 4, 503, 503, (一社)日本インターベンショナルラジオロジー学会, Oct. 2007
Japanese

肝移植術時に作成された門脈下大静脈短絡路(PCシャント)をcoil塞栓できた1例　　　　　　　　　　　　　　　
阿保 大介, 作原 祐介, 長谷川 悠, 藤間 憲幸, 白土 博樹, 清水 匡, 嶋村 剛, 古川 博之
IVR: Interventional Radiology, 22, 4, 503, 503, (一社)日本インターベンショナルラジオロジー学会, Oct. 2007
Japanese

肝移植後膵液瘻による合併症に対しIVRにて複合的に対処した1例　　　　　　　　　　　　　　　
長谷川 悠, 阿保 大介, 作原 祐介, 藤間 憲幸, 白土 博樹, 清水 匡, 嶋村 剛, 古川 博之
IVR: Interventional Radiology, 22, 4, 505, 505, (一社)日本インターベンショナルラジオロジー学会, Oct. 2007
Japanese

胆嚢・胆管癌・膵癌根治術後出血に対し動脈塞栓術を施行した症例の検討　　　　　　　　　　　　　　　
阿保 大介, 作原 祐介, 長谷川 悠, 藤間 憲幸, 白土 博樹, 清水 匡
IVR: Interventional Radiology, 22, 4, 505, 505, (一社)日本インターベンショナルラジオロジー学会, Oct. 2007
Japanese

頭頸部癌に対する超選択的抗癌剤動注化学療法　　　　　　　　　　　　　　　
吉田 大介, 浅野 剛, 白土 博樹, 本間 明宏, 鈴木 章之, 福田 諭
IVR: Interventional Radiology, 22, 4, 502, 502, (一社)日本インターベンショナルラジオロジー学会, Oct. 2007
Japanese

Statistical analysis and correlation discovery of tumor respiratory motion
Huanmei Wu, Gregory C. Sharp, Qingya Zhao, Hiroki Shirato, Steve B. Jiang
PHYSICS IN MEDICINE AND BIOLOGY, 52, 16, 4761, 4774, IOP PUBLISHING LTD, Aug. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone
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, ELSEVIER SCIENCE INC, Aug. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Hypofractionated stereotactic radiotherapy (HypoFXSRT) for stage I non-small cell lung cancer: Updated results of 257 patients in a Japanese multi-institutional study
Hiroshi Onishi, Hiroki Shirato, Yasushi Nagata, Masahiro Hiraoka, Masaharu Fujino, Kotaro Gomi, Yuzuru Niibe, Katsuyuki Karasawa, Kazushige Hayakawa, Yoshihiro Takai, Tomoki Kimura, Atsuya Takeda, Atsushi Ouchi, Masato Hareyama, Masaki Kokubo, Ryusuke Hara, Jun Itami, Kazunari Yamada, Tsutomu Araki
JOURNAL OF THORACIC ONCOLOGY, 2, 7, S94, S100, LIPPINCOTT WILLIAMS & WILKINS, Jul. 2007, [Peer-reviewed]
English, Scientific journal, Introduction: Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study.
Methods: This is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18 to 75 Gy at the isocenter was administered in one to 22 fractions. The median calculated biological effective dose (BED) was 111 Gy (range, 57-180 Gy) based on alpha/beta = 10.
Results: During follow-up (median, 38 months), pulmonary complications of above grade 2 arose in 14 patients (5.4%). Local progression occurred in 36 patients (14.0%), and the local recurrence rate was 8.4% for a BED of 100 Gy or more compared with 42.9% for less than 100 Gy (p < 0.001). The 5-year overall survival rate of medically operable patients was 70.8% among those treated with a BED of 100 Gy or more compared with 30.2% among those treated with less than 100 Gy (p < 0.05).
Conclusions: Although this is a retrospective study, HypoFXSRT with a BED of less than 180 Gy was almost safe for stage I NSCLC, and the local control and overall survival rates in 5 years with a BED of 100 Gy or more were superior to the reported results for conventional radiotherapy. For all treatment methods and schedules, the local control and survival rates were better with a BED of 100 Gy or more compared with less than 100 Gy. HypoFXSRT is feasible for curative treatment of patients with stage I NSCLC.

Accuracy of tumor motion compensation algorithm from a robotic respiratory tracking system: A simulation study
Yvette Seppenwoolde, Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Ben Heijmen
MEDICAL PHYSICS, 34, 7, 2774, 2784, AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS, Jul. 2007, [Peer-reviewed]
English, Scientific journal, 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.

Experience of high-dose-rate brachytherapy for head and neck cancer treated by a customized intraoral mold technique
Kenichi Obinata, Keiichi Ohmori, Hiroki Shirato, Motoyasu Nakamura
Radiation Medicine - Medical Imaging and Radiation Oncology, 25, 4, 181, 186, 4, May 2007, [Peer-reviewed]
English, Scientific journal, 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.

腎・副腎腫瘍に対する動体追跡照射;臨床的検討について
芹澤慈子, 加藤徳雄, 白土博樹, 鬼丸力也, 大坂康博, 鈴木恵士郎, 渡辺明, 澤田明徳, 清水匡, 宮坂和男, 清水伸一
Radiat Med, 25, 18, 25 Apr. 2007
Japanese

腎・副腎腫瘍に対する動体追跡照射;技術的検討について
加藤徳雄, 芹澤慈子, 白土博樹, 鬼丸力也, 大坂康博, 鈴木恵士郎, 渡辺佳明, 阿保大介, 清水匡, 宮坂和男, 清水伸一
Radiat Med, 25, 17, 25 Apr. 2007
Japanese

頭頚部癌のDOC併用放射線療法;副作用軽減を目的としたステロイド使用について
小野寺俊輔, 木下留美子, 藤野賢治, 加藤徳雄, 田口大志, 鬼丸力也, 大阪康博, 清水伸一, 鈴木恵士郎, 西岡健, 白土博樹
Radiat Med, 25, 15, 25 Apr. 2007
Japanese

動体追跡装置を用いた照射中の乳腺表面の動きの検討
木下留美子, 清水伸一, 加藤徳雄, 藤野賢治, 鬼丸力也, 白土博樹
日本医学放射線学会学術集会抄録集, 66th, S212, 28 Feb. 2007
Japanese

Organ motion in image-guided radiotherapy: lessons from real-time tumor-tracking radiotherapy
Hiroki Shirato, Shinichi Shimizu, Kei Kitamura, Rikiya Onimaru
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 12, 1, 8, 16, SPRINGER TOKYO, Feb. 2007, [Peer-reviewed]
English, 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.

当院における乳幼児生体肝移植後の門脈狭窄に対するPTA症例の検討　　　　　　　　　　　　　　　
作原 祐介, 阿保 大介, 長谷川 悠, 児玉 芳尚, 清水 匡, 白土 博樹
日本医学放射線学会学術集会抄録集, 66回, S316, S317, (公社)日本医学放射線学会, Feb. 2007
Japanese

喉頭癌に対する化学放射線同時併用療法後salvage手術の合併症　　　　　　　　　　　　　　　
古田康, 本間明宏, 折舘伸彦, 鈴木章之, 畠山博充, 瀧重成, 坂下智博, 西岡健, 鈴木恵士郎, 白土博樹, 関堂充, 山本有平, 福田
頭頸部癌, 33, 356-360, Jan. 2007, [Peer-reviewed]
Japanese, Scientific journal

A novel approach to advanced carcinoma of the tongue: Cases successfully treated with combination of superselective intra-arterial chemotherapy and external/high-dose-rate interstitial radiotherapy
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, OXFORD UNIV PRESS, Dec. 2006, [Peer-reviewed]
English, Scientific journal, 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.

"Watch-and-see" policy for the clinically positive neck in head and neck cancer treated with chemoradiotherapy
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, 6, Dec. 2006, [Peer-reviewed]
English, Scientific journal, 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.

Dosimetric verification in participating institutions in a stereotactic body radiotherapy trial for stage I non-small cell lung cancer: Japan clinical oncology group trial (JCOG0403)
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, IOP PUBLISHING LTD, Nov. 2006, [Peer-reviewed]
English, Scientific journal, 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.

Residual motion of lung tumors in end-of-inhale respiratory gated radiotherapy based on external surrogates
Ross I. Berbeco, Seiko Nishioka, Hiroki Shirato, Steve B. Jiang
MEDICAL PHYSICS, 33, 11, 4149, 4156, AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS, Nov. 2006, [Peer-reviewed]
English, Scientific journal, 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.

副腎領域における腹臥位と仰臥位でのマーカー移動と迎撃照射の有効性の検討
加藤徳雄, 白土博樹, 鬼丸力也, 大坂康博, 清水伸一, 阿保大介, 作原祐介, 宮坂和男
日本放射線腫よう学会誌, 18, Supplement 1, 152, 25 Oct. 2006
Japanese

鼻副鼻腔癌に対する超選択的動注療法+照射の同時併用療法
本間 明宏, 古田 康, 鈴木 章之, 浅野 剛, 吉田 大介, 西岡 健, 鈴木 恵士郎, 白土 博樹, 福田 諭
耳鼻と臨床, 52, Suppl.3, S213, S219, 耳鼻と臨床会, Sep. 2006
Japanese, 鼻副鼻腔癌37例に対して根治治療として超選択的動注療法+照射の同時併用療法(以下RADPLAT)を行った。観察期間は平均で2年6ヵ月とまだ短いが、粗生存率では、全症例では73%で、T4b症例では66%、T3+T4aでは76%であった。原発巣の制御率(progression free rate)は、全体で84%、T4b症例では74%、T3+T4aでは90%であった。合併症としては視力障害、流涙、閉塞性の副鼻腔炎、骨壊死などが見られた。RADPLATの合併症は手術と比較してそれほど重篤とはいえず、RADPLATは鼻副鼻腔癌治療の一つの選択肢となり得るのではないかと考えられた。(著者抄録)

頭頸部癌におけるchemoradiationの有用性と限界 超選択的動注によるchemoradiationの有用性と限界　　　　　　　　　　　　　　　
本間 明宏, 古田 康, 鈴木 章之, 古沢 純, 折舘 伸彦, 浅野 剛, 吉田 大介, 西岡 健, 鈴木 恵士郎, 白土 博樹, 福田 諭
日本癌治療学会誌, 41, 2, 323, 323, (一社)日本癌治療学会, Sep. 2006
Japanese

Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases - A randomized controlled trial
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, AMER MEDICAL ASSOC, Jun. 2006, [Peer-reviewed]
English, Scientific journal, 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.

Hypofractionated radiotherapy boost for dose escalation as a treatment option for high-grade spinal cord astrocytic tumor
N Katoh, H Shirato, H Aoyama, R Onimaru, K Suzuki, K Hida, K Miyasaka, Y Iwasaki
JOURNAL OF NEURO-ONCOLOGY, 78, 1, 63, 69, SPRINGER, May 2006, [Peer-reviewed]
English, Scientific journal, 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.

超選択的動注療法+照射の同時併用療法のリンパ節転移への効果　　　　　　　　　　　　　　　
本間 明宏, 古田 康, 鈴木 章之, 浅野 剛, 古沢 純, 折舘 伸彦, 樋口 栄作, 永橋 立望, 鈴木 恵士郎, 西岡 健, 白土 博樹, 福田 諭
頭頸部癌, 32, 2, 177, 177, (一社)日本頭頸部癌学会, May 2006
Japanese

Uncertainty in treatment of head-and-neck tumors by use of intraoral mouthpiece and embedded fiducials
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, ELSEVIER SCIENCE INC, Apr. 2006, [Peer-reviewed]
English, Scientific journal, 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.

Spinal cord gliomas: A multi-institutional retrospective analysis
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, ELSEVIER SCIENCE INC, Mar. 2006, [Peer-reviewed]
English, Scientific journal, 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.

Speed and amplitude of lung tumor motion precisely detected in four-dimensional setup and in real-time tumor-tracking radiotherapy
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, ELSEVIER SCIENCE INC, Mar. 2006, [Peer-reviewed]
English, Scientific journal, 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.

副腎領域における動体追跡放射線治療
加藤徳雄, 白土博樹, 鬼丸力也, 清水伸一, 大坂康博, 阿保大介, 作原祐介, 沢田明宏, 清水匡, 宮坂和男
日本医学放射線学会学術集会抄録集, 65th, S214, 25 Feb. 2006
Japanese

Characteristics of patients who developed radiation pneumonitis requiring steroid therapy after stereotactic irradiation for lung tumors
M Fujino, H Shirato, H Onishi, H Kawamura, K Takayama, M Koto, R Onimaru, Y Nagata, M Hiraoka
CANCER JOURNAL, 12, 1, 41, 46, JONES AND BARTLETT PUBLISHERS, Jan. 2006, [Peer-reviewed]
English, Scientific journal, BACKGROUND To find possible risk factors for symptomatic radiation pneumonitis (RP) after stereotactic irradiation (STI) for peripheral non-small cell lung cancer (NSCLC), pre-treatment pulmonary function test and dose volume statistics in patients who developed RIP requiring steroid intake were retrospectively compared with statistics of those who did not develop RP.
MATERIALS AND METHODS From 1996 to 2002, 156 patients with Stage I NSCLC received STI at 5 hospitals in Japan. Of those patients, 12 were medicated with steroids for RP after treatment (RP group). For comparison, 31 patients were randomly selected from the remaining 144 patients who received STI but did not receive steroids (control group).
RESULTS There were no statistical differences in age, sex, tumor size, performance status, forced expiratory volume in 1 sec(FEV1.0%), or percent vital capacity (%VC) between patients medicated with steroids for RP and those who did not have RIP and received no steroids. V-20 (%) was 7 to 18% (median 8%) in patients medicated with steroids for RP and 2 to 16% (median 7%) in those who did not have RP No difference was observed in V-20, the biologically effectively dose (BED) at the periphery of the planning target volume, or the dose per fraction between the two groups.
CONCLUSIONS Pre-treatment pulmonary function test (%VC, FEV1.0%), and dose volume statistics (V-20, total dose. BED, dose per fraction, peripheral dose) were not predictive of RP requiring steroid intake after STI for stage I NSCLC.

CS3-6 局所浸潤性膀胱癌に対するネダプラチン併用動体追跡放射線療法(総合企画3「浸潤性膀胱癌に対する膀胱温存治療」,第94回日本泌尿器科学会総会)
白土 博樹, 大坂 康博, 宮坂 和男, 佐澤 陽, 原林 透, 篠原 信雄, 野々村 克也
日本泌尿器科学会雑誌, 97, 2, 116, 116, 一般社団法人 日本泌尿器科学会, 2006
Japanese

Real-time and precise monitoring of the breast motion during irradiation using real-time tumor-tracking radiotherapy (RTRT) system
Kinoshita R, Shimizu S, Katoh N, Onimaru R, Shirato H, Miyasaka
International Journal of Radiation Oncology Biology Physics, 66, 3, S608, 2006, [Peer-reviewed]

Can FDG-PET detect subclinical lymph node metastatis of esophageal cancer and contribute to the radiation treatment planning? Compared with images and pathological findings
Shimizu S, Hosokawa M, Itoh K, Takahashi H, Fujita M, Shirato H
International Journal of Radiation Oncology Biology Physics, 66, 3, S279, 2006, [Peer-reviewed]

Insertion and fixation of fiducial markers for setup and tracking of lung tumors in radiotherapy
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, ELSEVIER SCIENCE INC, Dec. 2005, [Peer-reviewed]
English, Scientific journal, 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.

放射線治療効果の向上を目指した新手法開発とその臨床応用 動体追跡照射装置を用いた放射線治療
鬼丸 力也, 白土 博樹, 藤野 賢治, 田口 大志, 加藤 徳雄, 大坂 康博, 清水 伸一, 青山 英史, 鈴木 恵士郎
日本放射線影響学会大会講演要旨集, 48回, 75, 75, (一社)日本放射線影響学会, Nov. 2005
English

当科における頭頸部高線量率放射線治療　　　　　　　　　　　　　　　
大森 桂一, 西岡 健, 土屋 和彦, 青山 英史, 木下 留美, 西岡 井子, 鈴木 恵士郎, 白土 博樹
日本放射線腫瘍学会誌, 17, Suppl.1, 126, 126, (公社)日本放射線腫瘍学会, Oct. 2005
Japanese

The effect of tumor location and respiratory function on tumor movement estimated by real-time tracking radiotherapy (RTRT) system
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, ELSEVIER SCIENCE INC, Sep. 2005, [Peer-reviewed]
English, Scientific journal, 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.

[Stereotactic irradiation (Linac) for brain tumors].
Shirato H, Aoyama H, Suzuki K, Miyasaka K
Nihon rinsho. Japanese journal of clinical medicine, 63 Suppl 9, 419, 424, Sep. 2005, [Peer-reviewed], [Domestic magazines]
Japanese, Scientific journal

【脳腫瘍の診断と治療 最新の研究動向】脳腫瘍の治療 放射線療法 定位放射線照射療法(リニアック)
白土 博樹, 青山 英史, 鈴木 恵士郎, 宮坂 和男
日本臨床, 63, 増刊9 脳腫瘍の診断と治療, 419, 424, (株)日本臨床社, Sep. 2005
Japanese

口腔癌の最新治療 舌癌に対する超選択的動注療法と高線量率組織内照射の併用療法　　　　　　　　　　　　　　　
本間 明宏, 古田 康, 鈴木 章之, 浅野 剛, 吉田 大介, 西岡 健, 鈴木 恵士郎, 白土 博樹, 福田 諭
日本癌治療学会誌, 40, 2, 236, 236, (一社)日本癌治療学会, Sep. 2005
Japanese

Residual motion of lung tumours in gated radiotherapy with external respiratory surrogates
RI Berbeco, S Nishioka, H Shirato, GTY Chen, SB Jiang
PHYSICS IN MEDICINE AND BIOLOGY, 50, 16, 3655, 3667, IOP PUBLISHING LTD, Aug. 2005, [Peer-reviewed]
English, Scientific journal, 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.

聴神経腫瘍に対する定位分割照射の治療成績　　　　　　　　　　　　　　　
坂本 徹, 白土 博樹, 澤村 豊, 鈴木 恵士郎, 青山 英史, 加藤 徳雄
定位的放射線治療, 9, 37, 44, 日本定位放射線治療学会, Aug. 2005
Japanese, 定位分割照射を行った聴神経腫瘍165例(男62例・女103例,中央値54歳)の成績を報告した.平均腫瘍径は照射前17.0mm,平均観察期間42ヵ月後13.9mmであった.2〜7年の累積腫瘍制御率は91.8%で,腫瘍増大を9例に認め,うち3例に手術,2例に追加照射を行った.累積腫瘍縮小率は3年で54%,7年で61.6%であった.腫瘍径25mm以上の31例では7年の累積腫瘍制御率90.5%,縮小率78.1%であった.腫瘍の性状別にみると,cystic typeは腫瘍制御率100%,縮小率88.6%で,solid typeは各々86.8%,56.6%と,縮小率に有意差を認めた.聴力検査の結果は,照射前が平均48.7dBで,照射1年後に10dB,5年で20.1dBの低下を認め,7年の累積聴力温存率は71.5%,保存率は56.3%であった.腫瘍縮小群は非縮小群に比較して聴力温存率が高い傾向であった.合併障害は三叉神経障害,めまいが9%,顔面神経麻痺が3%にみられたがいずれも一過性で,照射後にシャント手術を必要としたのは18例であった

Comparison of imaging modalities for the accurate delineation of arteriovenous malformation, with reference to stereotactic radiosurgery
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, ELSEVIER SCIENCE INC, Jul. 2005, [Peer-reviewed]
English, Scientific journal, 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.

北海道大学病院における超選択的動注療法+放射線の同時併用療法の治療成績　　　　　　　　　　　　　　　
本間 明宏, 古田 康, 鈴木 章之, 浅野 剛, 永橋 立望, 折舘 伸彦, 古沢 純, 畠山 博充, 鈴木 恵士郎, 西岡 健, 白土 博樹, 福田 諭
頭頸部癌, 31, 2, 242, 242, (一社)日本頭頸部癌学会, May 2005
Japanese

ドセタキセル・放射線同時併用療法におけるp53過剰発現と392セリン残基リン酸化の予後因子としての検討　　　　　　　　　　　　　　　
樋口 榮作, 折舘 伸彦, 本間 明宏, 永橋 立望, 古田 康, 鈴木 章之, 西岡 健, 鈴木 恵士郎, 滝沢 昌彦, 白土 博樹, 福田 諭
頭頸部癌, 31, 2, 227, 227, (一社)日本頭頸部癌学会, May 2005
Japanese

化学放射線同時併用療法後の喉頭全摘術における合併症の検討　　　　　　　　　　　　　　　
古田 康, 本間 明宏, 折舘 伸彦, 樋口 栄作, 鈴木 章之, 西岡 健, 青山 英史, 鈴木 恵士郎, 白土 博樹, 福田 諭
頭頸部癌, 31, 2, 220, 220, (一社)日本頭頸部癌学会, May 2005
Japanese

[Highly quality-controlled radiation therapy].
Shirato H
Gan to kagaku ryoho. Cancer & chemotherapy, 32, 448, 452, 4, Apr. 2005, [Peer-reviewed]

Long-term results of ethmoid squamous cell or undifferentiated carcinoma treated with radiotherapy with or without surgery
D Uchida, H Shirato, R Onimaru, H Endou, H Aoyama, K Tsuchiya, T Nishioka, A Homma, Y Furuta, S Fukuda, K Miyasaka
CANCER JOURNAL, 11, 2, 152, 156, JONES AND BARTLETT PUBLISHERS, Mar. 2005, [Peer-reviewed]
English, Scientific journal, PURPOSE Ethmoidal malignant tumors, for which intensity-modulated radiotherapy is expected to improve outcome, consist of heterogeneous pathological types. Reports about their outcome are influenced by the inclusion of favorable histology, such as adenocarcinoma and adenoid cystic carcinoma. We investigated the long-term treatment outcome of squamous cell carcinoma and undifferentiated carcinoma of the ethmoid sinus.
MATERIALS AND METHODS Between August 1976 and April 2002, 25 patients (20 squamous cell carcinomas and five undifferentiated carcinomas) received radical radiotherapy or preoperative radiotherapy in our institution. One (4%) had stage T2 disease, seven (28%) had stage T3, three (12%) had stage T4a, and 14 (56%) had stage T4b. Surgery was performed in 13 patients. Radiation dose varied from 50.4 Gy in 16 fractions (50.4 Gy/16 Fr) to 65 Gy in 26 fractions with or without stereotactic boost irradiation. Eleven patients received chemotherapy consisting mainly of platinum-based compounds.
RESULTS The 3- and 5-year overall survival rates for all 25 patients were 34% (95% confidence interval [CI]: 14%-54%) and 24% (CI: 6%-42%), respectively. The 3- or 5-year local progression-free rates for all patients were 48.9% and 36.7%, respectively. Visual acuity of a single eye was impaired in three patients and was lost in five patients as a result of tumor progression, but no patient had visual impairment or loss due to radiotherapy.
CONCLUSION Ethmoid squamous cell carcinoma or undifferentiated carcinoma was diagnosed at advanced T stages and was treated with radiotherapy; these patients had a poorer outcome than patients with adenocarcinoma or adenoid cystic carcinoma. Prospective trials using advanced technology should be carefully compared with historical controls because pathological types can considerably influence the treatment results.

頭頸部腫瘍における放射線治療前FDG-PETの検討 SUVの意義について　　　　　　　　　　　　　　　
鈴木 恵士郎, 西岡 健, 青山 英史, 土屋 和彦, 白土 博樹, 宮坂 和男, 加藤 千恵次, 志賀 哲, 中駄 邦博, 玉木 長良
日本医学放射線学会学術集会抄録集, 64回, S298, S299, (公社)日本医学放射線学会, Feb. 2005
Japanese

Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for advanced head and neck cancer
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, JOHN WILEY & SONS INC, Jan. 2005, [Peer-reviewed]
English, Scientific journal, 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.

Tracking errors in a prototype real-time tumour tracking system
GC Sharp, SB Jiang, S Shimizu, H Shirato
PHYSICS IN MEDICINE AND BIOLOGY, 49, 23, 5347, 5356, IOP PUBLISHING LTD, Dec. 2004, [Peer-reviewed]
English, Scientific journal, 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%.

A finite state model for respiratory motion analysis in image guided radiation therapy
HM Wu, GC Sharp, B Salzberg, D Kaeli, H Shirato, SB Jiang
PHYSICS IN MEDICINE AND BIOLOGY, 49, 23, 5357, 5372, IOP PUBLISHING LTD, Dec. 2004, [Peer-reviewed]
English, Scientific journal, 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.

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck
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, ELSEVIER SCIENCE INC, Nov. 2004, [Peer-reviewed]
English, Scientific journal, 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.

Stereotactic irradiation for intracranial arteriovenous malformation using stereotactic radiosurgery or hypofractionated stereotactic radiotherapy
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, ELSEVIER SCIENCE INC, Nov. 2004, [Peer-reviewed]
English, Scientific journal, 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.

High dose three-dimensional conformal boost (3DCB) using an orthogonal diagnostic X-ray set-up for patients with gynecological malignancy: a new application of real-time tumor-tracking system
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, ELSEVIER SCI IRELAND LTD, Nov. 2004, [Peer-reviewed]
English, Scientific journal, 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.

画像診断技術の進歩と放射線治療 脳動静脈奇形の定位照射を例として　　　　　　　　　　　　　　　
青山 英史, 加藤 徳雄, 土屋 和彦, 藤野 賢治, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 64, 8, 577, 577, (公社)日本医学放射線学会, Nov. 2004
Japanese

Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma - Clinical outcomes in 245 subjects in a Japanese multinstitutional study
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, WILEY-BLACKWELL, Oct. 2004, [Peer-reviewed]
English, Scientific journal, 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.

Three-dimensional conformal setup (3D-CSU) of patients using the coordinate system provided by three internal fiducial markers and two orthogonal diagnostic X-ray systems in the treatment room
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, ELSEVIER SCIENCE INC, Oct. 2004, [Peer-reviewed]
English, Scientific journal, 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.

肺癌放射線治療におけるFDG-PETでの標的体積の抽出法の観察者間差　　　　　　　　　　　　　　　
藤野 賢治, 加藤 徳雄, 白土 博樹, 青山 英史, 渡辺 良晴, 熊谷 まなみ, 西岡 健, 宮坂 和男
日本放射線腫瘍学会誌, 16, Suppl.1, 108, 108, (公社)日本放射線腫瘍学会, Oct. 2004
Japanese

Impact of margin for target volume in low-dose involved field radiotherapy after induction chemotherapy for intracranial germinoma
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, ELSEVIER SCIENCE INC, Sep. 2004, [Peer-reviewed]
English, Scientific journal, 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.

Feasibility of synchronization of real-time tumor-tracking radiotherapy and intensity-modulated radiotherapy from viewpoint of excessive dose from fluoroscopy
H Shirato, M Oita, K Fujita, Y Watanabe, K Miyasaka
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 60, 1, 335, 341, ELSEVIER SCIENCE INC, Sep. 2004, [Peer-reviewed]
English, Scientific journal, 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.

Randomized phase II trial of concomitant chemoradiotherapy using weekly carboplatin or daily low-dose cisplatin for squamous cell carcinoma of the head and neck
A Homma, H Shirato, Y Furuta, T Nishioka, N Oridate, K Tsuchiya, T Nagahashi, H Aoyama, Y Inuyama, S Fukuda
CANCER JOURNAL, 10, 5, 326, 332, JONES AND BARTLETT PUBLISHERS, Sep. 2004, [Peer-reviewed]
English, Scientific journal, Purpose
This randomized, phase II study aimed to compare concomitant chemoradiotherapy using weekly carboplatin or daily low-dose cisplatin as a treatment for squamous cell carcinoma of the head and neck.
Patients and Methods
One hundred nineteen patients with moderate- to advanced-stage disease were eligible for the study. Fifty-three patients had stage II disease, 28 had stage III, and the remaining 38 had stage IV disease. Primary tumor sites included the larynx (N = 63), oropharynx (N = 30), hypopharynx (N = 23), and oral cavity (N = 3). Each patient received either a weekly carboplatin dose (100 mg/m(2)) in one arm or daily cisplatin (4 mg/m(2)) in the other arm for the initial 4 weeks of radiotherapy. The radiotherapy dose of 65 Gy was given in 26 fractions over 45 days, dependent on a good tumor response at 40 Gy. Forty-nine (81.7%) of 60 patients treated with carboplatin and 41 (69.5%) of 59 patients treated with cisplatin received the full dose of radiotherapy. Surgical resection was optionally used for the remaining patients.
Results
The median follow-up time was 63 months. The local control rate at 5 years was 56.2% for the carboplatin-treated arm and 35.5% for the cisplatin-treated arm, respectively. The 5-year overall survival rate did not significantly differ between treatments: 71.4% for carboplatin and 66.0% for cisplatin. Hematologic toxicity was more frequent in the carboplatin-treated arm. No difference was observed in surgical complications or in radiation-related adverse effects.
Dicussion
These findings suggest that weekly carboplatin treatment is preferable to daily low-dose cisplatin. This could be because the total dose of cisplatin was too low to be effective.

頭頸部癌治療における最近の進歩と今後の臨床展開 治療の個別化に向けて 鼻副鼻腔進行癌に対する超選択的動注療法+放射線同時併用療法　　　　　　　　　　　　　　　
本間 明宏, 古田 康, 永橋 立望, 白土 博樹, 福田 諭
日本癌治療学会誌, 39, 2, 271, 271, (一社)日本癌治療学会, Sep. 2004
Japanese

放射線治療に期待されるもの 4次元放射線治療
白土博樹, 鬼丸力也, 清水伸一, 宮坂和男
日本癌学会総会記事, 63rd, 416, 25 Aug. 2004
Japanese

Application of real-time tumor-tracking and gated radiotherapy system for unresectable pancreatic cancer
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, YONSEI UNIV COLLEGE MEDICINE, Aug. 2004, [Peer-reviewed]
English, Scientific journal, 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.

化学療法併用放射線療法後に喉頭全摘術後の瘻孔発生率は高まるか? 過去10年間の喉頭全摘症例の検討　　　　　　　　　　　　　　　
古田 康, 本間 明宏, 永橋 立望, 樋口 栄作, 鈴木 章之, 折舘 伸彦, 福田 諭, 西岡 健, 青山 英史, 白土 博樹
頭頸部腫瘍, 30, 2, 270, 270, (一社)日本頭頸部癌学会, May 2004
Japanese

頬粘膜腫瘍の放射線治療成績　　　　　　　　　　　　　　　
大森 桂一, 中村 博行, 山崎 裕, 小野 貢伸, 青山 英史, 土屋 和彦, 西岡 健, 白土 博樹, 本間 明宏, 古田 康, 中村 太保
頭頸部腫瘍, 30, 2, 195, 195, (一社)日本頭頸部癌学会, May 2004
Japanese

頭頸部癌に対するDocetaxelと放射線同時併用療法の有用性の検討　　　　　　　　　　　　　　　
樋口 榮作, 本間 明宏, 永橋 立望, 折舘 伸彦, 古田 康, 鈴木 章之, 西岡 健, 土屋 和彦, 青山 英史, 滝沢 昌彦, 白土 博樹, 福田 諭
頭頸部腫瘍, 30, 2, 194, 194, (一社)日本頭頸部癌学会, May 2004
Japanese

Integration of functional brain information into stereotactic irradiation treatment planning using magnetoencephalography and magnetic resonance axonography
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, ELSEVIER SCIENCE INC, Mar. 2004, [Peer-reviewed]
English, Scientific journal, 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.

肺腫ようの呼吸性移動距離に対する呼吸機能と腫よう存在部位による影響—動体追跡照射装置での検討—
鬼丸力也, 藤野賢治, 清水伸一, 白土博樹, 宮坂和男
日本医学放射線学会雑誌, 64, 2, S154, 25 Feb. 2004
Japanese

Prediction of respiratory tumour motion for real-time image-guided radiotherapy
GC Sharp, SB Jiang, S Shimizu, H Shirato
PHYSICS IN MEDICINE AND BIOLOGY, 49, 3, 425, 440, IOP PUBLISHING LTD, Feb. 2004, [Peer-reviewed]
English, Scientific journal, 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.

Intrafractional tumor motion: Lung and liver
H Shirato, Y Seppenwoolde, K Kitamura, R Onimura, S Shimizu
SEMINARS IN RADIATION ONCOLOGY, 14, 1, 10, 18, W B SAUNDERS CO, Jan. 2004, [Peer-reviewed]
English, Scientific journal

Integrated radiotherapy imaging system (IRIS): design considerations of tumour tracking with linac gantry-mounted diagnostic x-ray systems with flat-panel detectors
RI Berbeco, SB Jiang, GC Sharp, GTY Chen, H Mostafavi, H Shirato
PHYSICS IN MEDICINE AND BIOLOGY, 49, 2, 243, 255, IOP PUBLISHING LTD, Jan. 2004, [Peer-reviewed]
English, Scientific journal, 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.

Real-time monitoring of a digestive-tract marker to reduce adverse effects of moving organs at risk (OAR) in radiotherapy for thoracic and abdominal tumors
T Hashimoto, M Kato, H Shirato, S Shimizu, Y Ahn, N Kurauchi, T Morikawa, K Yamazaki, Y Akine, K Miyasaka
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 60, 1, S414, S414, ELSEVIER SCIENCE INC, 2004, [Peer-reviewed]
English

CP9-7 Real-time tumor-tracking radiotherapy(総合企画9「前立腺癌に対する新しい放射線治療」)
白土 博樹, 篠原 信雄, 原林 透, 喜多村 圭, 大坂 康博, 野々村 克也, 宮坂 和男
日本泌尿器科学会雑誌, 95, 2, 168, 168, 一般社団法人 日本泌尿器科学会, 2004
Japanese

Clinical significance of 3D reconstruction of arteriovenous malformation using digital subtraction angiography and its modification with CT information in stereotactic radiosurgery
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, ELSEVIER SCIENCE INC, Dec. 2003, [Peer-reviewed]
English, Scientific journal, 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.

定位放射線照射における投与線量の解釈 アンケート調査結果報告 JASTRO H13,H14年度研究課題報告
直居 豊, 赤松 将之, 伊藤 佳菜, 渡辺 太志, 笹井 啓資, 青山 英史, 白土 博樹, 永田 靖, 平岡 真寛, 藤川 章
日本放射線腫瘍学会誌, 15, 4, 297, 306, (公社)日本放射線腫瘍学会, Dec. 2003
Japanese, アンケート方式により直線加速器を用いた定位放射線照射の投与線量について各施設での表現方法の違いによる差異を調査し,投与線量の表現を統一し,物理学的な実際の投与線景を標準化した.全国129施設に郵送し52施設から回答が得られ,一例として転移性脳腫瘍症例を送ってもらえたのは49施設であった.施設ごとのハード,ソフトの違いで共通のパラメータを設定することは容易でないが,定位放射線治療を行っている殆どの施設でD100内の中心線量は算出可能で,ICRU50,62に従いD100の中心線量を線量指示点とすることは可能と考えられた

少量白金製剤併用放射線化学療法と超選択的動注療法
本間 明宏, 古田 康, 永橋 立望, 八木 克憲, 鈴木 章之, 牛越 聡, 浅野 剛, 白土 博樹, 西岡 健, 犬山 征夫, 福田 諭
耳鼻と臨床, 49, Suppl.3, S167, S174, 耳鼻と臨床会, Nov. 2003
Japanese, 局所切除可能な頭頸部原発扁平上皮癌患者119例に対して放射線とCDDP或いはCBDCAとの同時併用の無作為化比較試験を行ったところ,予後の結果からは有効性に大差はない可能性が認められたが,CBDCAがより有効であると思われた.手術不能又は手術拒否の進行癌症例29例では,超選択的動注と照射の同時併用で原発巣は72.4%であった

Management of vestibular schwannoma by fractionated stereotactic radiotherapy and associated cerebrospinal fluid malabsorption
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, AMER ASSOC NEUROLOGICAL SURGEONS, Oct. 2003, [Peer-reviewed]
English, Scientific journal, 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.

定位放射線照射における投与線量の解釈　　　　　　　　　　　　　　　
直居 豊, 伊藤 佳菜, 渡辺 太志, 笹井 啓資, 青山 英史, 白土 博樹, 永田 靖, 平岡 真寛, 藤川 章
日本放射線腫瘍学会誌, 15, Suppl.1, 68, 68, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

前立腺癌への動体追跡装置を用いた強度変調放射線治療75 Gy/30 fの初期経験　　　　　　　　　　　　　　　
大坂 康博, 喜多村 圭, 青山 英史, 土屋 和彦, 西岡 健, 白土 博樹, 宮坂 和男
日本放射線腫瘍学会誌, 15, Suppl.1, 86, 86, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

JROSG99-1第III相試験中間報告 1〜4個脳転移に対する定位単独と定位+全脳照射の比較　　　　　　　　　　　　　　　
青山 英史, 白土 博樹, 中川 恵一, 多湖 正夫
日本放射線腫瘍学会誌, 15, Suppl.1, 87, 87, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

金マーカー埋入義歯を用いた透視セットアップ照射　　　　　　　　　　　　　　　
大森 桂一, 土屋 和彦, 笈田 将皇, 渡辺 良晴, 青山 英史, 西岡 健, 白土 博樹
日本放射線腫瘍学会誌, 15, Suppl.1, 121, 121, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

長径2.5cm以上の聴神経鞘腫に対する定位放射線治療　　　　　　　　　　　　　　　
坂井 亙, 白土 博樹, 青山 英史, 坂本 徹, 宮坂 和男
日本放射線腫瘍学会誌, 15, Suppl.1, 148, 148, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

動体追跡システムを用いたIMRTの基礎的検討(1) 移動による線量分布への影響　　　　　　　　　　　　　　　
笈田 将皇, 渡辺 良晴, 白土 博樹, 青山 英史, 土屋 和彦, 清水 祐介, 藤田 勝久
日本放射線腫瘍学会誌, 15, Suppl.1, 154, 154, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

動体追跡システムを用いたIMRTの基礎的検討(2) 移動によるIMRTの線量分布への影響　　　　　　　　　　　　　　　
渡辺 良晴, 笈田 将皇, 白土 博樹, 青山 英史, 土屋 和彦, 清水 祐介, 藤田 勝久
日本放射線腫瘍学会誌, 15, Suppl.1, 155, 155, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

動体追跡照射における消化管,胸腹腔への金マーカー挿入術の開発　　　　　　　　　　　　　　　
橋本 孝之, 白土 博樹, 清水 伸一, 大坂 康博, 鬼丸 力也, 藤野 賢治, 宮坂 和男
日本放射線腫瘍学会誌, 15, Suppl.1, 77, 77, (公社)日本放射線腫瘍学会, Oct. 2003
Japanese

Effect of treatment time on outcome of radiotherapy for oral tongue carcinoma
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, ELSEVIER SCIENCE INC, Sep. 2003, [Peer-reviewed]
English, Scientific journal, 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.

小児大脳PNET(primitive neuroectodermal tumor)に対するICE(IFX/CDDP/VP-16)化学療法を用いた集学的治療　　　　　　　　　　　　　　　
池田 潤, 小林 浩之, 石井 伸明, 澤村 豊, 岩崎 喜信, 青山 英史, 白土 博樹
日本癌治療学会誌, 38, 2, 510, 510, (一社)日本癌治療学会, Sep. 2003
Japanese

画像診断の進歩と放射線治療 治療計画と効果判定にどのように役立っているか 放射線脳壊死と腫瘍再発の鑑別におけるL-[methyl-11C]-methionine PET(Met-PET)
加藤 徳雄, 中駄 邦博, 青山 英史, 竹井 俊樹, 白土 博樹, 玉木 長良, 宮坂 和男
断層映像研究会雑誌, 30, 2〜3, 73, 73, 断層映像研究会, Sep. 2003
Japanese

頭頸部癌放射線・化学療法施行例における頸部リンパ節転移への対応　　　　　　　　　　　　　　　
本間 明宏, 古田 康, 永橋 立望, 白土 博樹, 西岡 健, 八木 克憲, 犬山 征夫, 福田 諭
日本癌治療学会誌, 38, 2, 352, 352, (一社)日本癌治療学会, Sep. 2003
Japanese

動体追跡照射データに対する関数データ解析法の適用
山谷 学, 島村 徹平, 小宮 由里子, 清水 伸一, 白土 博樹, 水田 正弘
日本統計学会講演報告集, 71, 0, 302, 303, 01 Sep. 2003
Japanese

Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull
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, ELSEVIER SCIENCE INC, Jul. 2003, [Peer-reviewed]
English, Scientific journal, 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.

Focal fractionated radiotherapy for intramedullary spinal arteriovenous malformations: 10-year experience
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, AMER ASSOC NEUROLOGICAL SURGEONS, Jul. 2003, [Peer-reviewed]
English, Scientific journal, 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.

Visualization of the corticospinal tract pathway using magnetic resonance axonography and magnetoencephalography for stereotactic irradiation planning of arteriovenous malformations
H Aoyama, K Kamada, H Shirato, F Takeuchi, S Kuriki, Y Iwasaki, K Miyasaka
RADIOTHERAPY AND ONCOLOGY, 68, 1, 27, 32, ELSEVIER SCI IRELAND LTD, Jul. 2003, [Peer-reviewed]
English, Scientific journal, 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.

Reduction in acute morbidity using hypofractionated intensity-modulated radiation therapy assisted with a fluoroscopic real-time tumor-tracking system for prostate cancer: Preliminary results of a phase I/II study
K Kitamura, H Shirato, N Shinohara, T Harabayashi, R Onimaru, K Fujita, S Shimizu, K Nonomura, T Koyanagi, K Miyasaka
CANCER JOURNAL, 9, 4, 268, 276, JONES AND BARTLETT PUBLISHERS, Jul. 2003, [Peer-reviewed]
English, Scientific journal, PURPOSE - The positioning of the prostate is improved with the use of the fluoroscopic real-time tumor-tracking radiation therapy system for prostate cancer. The acute radiation reaction and preliminary tumor response of prostate cancer to hypofractionated intensity-modulated radiation therapy assisted with real-time tumor tracking radiation therapy were investigated in this study.
METHODS - Patients were classified into prognostic risk groups on the basis of the presence of the pretreatment prostate-specific antigen, clinical stage, and histologic differentiation. Neoadjuvant hormonal therapy was administered to patients in the high-risk group for 6 months before radiation therapy commenced. The intensity-modulated radiation therapy employed a segmental multileaf collimator, which generated a field made up of two or more shaped subfields using forward planning. Real-time tumor-tracking radiation therapy was used for the precise positioning of the prostate to minimize geometric uncertainties, while the dose was escalated in increments of 5 Gy from 65 Gy using a daily dose of 2.5 Gy (65 Gy/2.5 Gy), following the dose-escalation rules. Acute and late gastrointestinal and genitourinary morbidities due to radiation therapy were scored according to the toxicity criteria of Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer.
RESULTS - Thirty-one patients were enrolled in this study between 1998 and 2001. Eighteen patients were classified as being members of the high-risk group. Total dose was escalated, with 65 Gy/2.5 Gy being administered to 12 patients and 70 Gy/2.5 Gy to 19 patients. The median follow-up period was 37 months (range, 30-43 months), and 19 months (range, 10-27 months), for the 65-Gy and 70-Gy arms, respectively. Patients experienced no acute toxicity and grade 1 late gastrointestinal toxicity (8.3%) in the 65-Gy/2.5-Gy arm. Patients in the 70-Gy/2.5-Gy arm experienced grade 1 acute gastrointestinal toxicity (5.3%) and grade 1 and 2 acute genitourinary toxicities (15.8%). No patients experienced dose-limiting toxicity (defined as a grade 3 or higher acute toxicity) or a grade 2 or higher late complication in this study period. One and two prostate-specific antigen relapses were observed in the 65-Gy and 70-Gy arms, respectively.
CONCLUSION - Up to 70 Gy/2.5 Gy, equivalent to 80 Gy with a daily dose of 2.0 Gy, assuming alp ratio of 1.5, intensity-modulated radiation therapy assisted with real-time tumor-tracking radiation therapy was administered safely with a reasonable biochemical control rate. A further dose-escalation study using this system is justifiable.

【脊髄・脊椎腫瘍の治療戦略】脊髄・脊椎腫瘍への放射線治療戦略　　　　　　　　　　　　　　　
白土 博樹, 鬼丸 力也, 青山 英史, 宮坂 和男, 関 俊隆, 飛騨 一利, 岩崎 喜信
脊椎脊髄ジャーナル, 16, 6, 681, 687, (株)三輪書店, Jun. 2003
Japanese

Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers
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, ELSEVIER SCIENCE INC, May 2003, [Peer-reviewed]
English, Scientific journal, 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.

Tumor location, cirrhosis, and surgical history contribute to tumor movement in the liver, as measured during stereotactic irradiation using a real-time tumor-tracking radiotherapy system
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, ELSEVIER SCIENCE INC, May 2003, [Peer-reviewed]
English, Scientific journal, 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.

Feasibility of insertion/implantation of 2.0-mm-diameter gold internal fiducial markers for precise setup and real-time tumor tracking in radiotherapy
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, ELSEVIER SCIENCE INC, May 2003, [Peer-reviewed]
English, Scientific journal, 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.

【脳腫瘍のキーワード】Linac surgery　　　　　　　　　　　　　　　
青山 英史, 白土 博樹
Clinical Neuroscience, 21, 5, 570, 571, (株)中外医学社, May 2003
Japanese

頭頸部がんに対する急速動注療法 頭頸部進行癌に対する超選択的動注療法と放射線の同時併用療法
本間 明宏, 古田 康, 牛越 聡, 鈴木 章之, 永橋 立望, 畠山 博充, 浅野 剛, 西岡 健, 白土 博樹, 福田 諭
頭頸部腫瘍, 29, 2, 265, 265, (一社)日本頭頸部癌学会, May 2003
Japanese, Superselective arterial infusion for patients with advanced head and neck cancer has increasingly been applied in Japan. We analyzed our experiences and evaluated the efficacy and safety of this treatment. Patients and Methods: Forty-four patients, who were considered contraindicated for surgery or rejected radical surgery, received superselective intra-arterial infusion therapy of cisplatin (100-120mg/m²/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity, and conventional concomitant extrabeam radiotherapy (65Gy/26f/6.5weeks). Results: During the median follow-up period of 17 months, 2-year progression-free survival rate of primary lesion was 66.9%, and that of patients with T4b diseases 57%. The 2-year overall survival rate was 52.4%. Although acute toxic effects were considered acceptable, severe toxic events occurred in some cases, namely, cranial nerve palsy, MRSA pneumonia, sepsis, and osteoradionecrosis. Conclusions: We confirmed the high effectiveness of superselective arterial infusion and concomitant radiotherapy, which can concentrate the attack of decadose cisplatin on locoregional disease. Moreover, even patients with unresectable disease can be cured. We must clarify the treatment results and late side effects, and establish the indications for this treatment.

Synchronized moving aperture radiation therapy (SMART): average tumour trajectory for lung patients
T Neicu, H Shirato, Y Seppenwoolde, SB Jiang
PHYSICS IN MEDICINE AND BIOLOGY, 48, 5, 587, 598, IOP PUBLISHING LTD, Mar. 2003, [Peer-reviewed]
English, Scientific journal, 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.

肝腫ように対する動体追跡システムを用いた体幹部定位放射線治療の初期経験
大坂康博, 喜多村圭, 鬼丸力也, 清水伸一, 児玉芳尚, 清水匡, 白土博樹, 宮坂和男
日本医学放射線学会雑誌, 63, 2, S125, 25 Feb. 2003
Japanese

Clinical study of a spacer to help prevent osteoradionecrosis resulting from brachytherapy for tongue cancer
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, MOSBY, INC, Feb. 2003, [Peer-reviewed]
English, Scientific journal, 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.

External beam radiation monotherapy for localized or locally advanced prostate cancer
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, OXFORD UNIV PRESS, Feb. 2003, [Peer-reviewed]
English, Scientific journal, 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.

放射線脳壊死と脳腫瘍の鑑別におけるL-[methyl-11C]-methionine PET(MET)　　　　　　　　　　　　　　　
加藤 徳雄, 中駄 邦博, 青山 英史, 竹井 俊樹, 白土 博樹, 玉木 長良, 宮坂 和男
日本医学放射線学会雑誌, 63, 2, S238, S238, (公社)日本医学放射線学会, Feb. 2003
Japanese

Is whole-brain irradiation necessary for primary central nervous system lymphoma? Patterns of recurrence after partial-brain irradiation
Y Shibamoto, N Hayabuchi, J Hiratsuka, S Tokumaru, H Shirato, M Sougawa, N Oya, Y Uematsu, M Hiraoka
CANCER, 97, 1, 128, 133, JOHN WILEY & SONS INC, Jan. 2003, [Peer-reviewed]
English, Scientific journal, 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.

Effect of irradiation on enzymes of the capillary bed in rat ventricles
M Gao, H Shirato, K Miyasaka, T Koyama
OXYGEN TRANSPORT TO TISSUE XXIV, 530, 527, 533, KLUWER ACADEMIC/PLENUM PUBL, 2003, [Peer-reviewed]
English, Scientific journal, The effect of localized irradiation on the enzyme activity in rat cardiac capillaries was examined in experiments in which the arteriolar and venular portions of the capillary bed were distinguished by the double-staining method. This method shows that the endothelial cells of the former contain alkaline phosphatase (AP) and those of the latter, dipeptidylpeptidase IV (DPP). At both 1 week and 3 weeks after irradiation with 20 Gy, staining for AP was reduced but staining for DPP was unchanged. The loss of enzyme from the arteriolar portions may be a consequence of the greater radiosensitivity of tissues exposed to high oxygen tension, or it may indicate that AP is less stable than DPP when exposed to irradiation.

頭部疾患の定位放射線照射と画像診断 良性腫瘍(聴神経鞘腫を中心に)　　　　　　　　　　　　　　　
青山 英史, 白土 博樹
臨床画像, 19, 1, 110, 115, (株)メジカルビュー社, Jan. 2003
Japanese

Long-term follow-up results with audiological assessment after fractionated stereotactic radiotherapy for vestibular schwannomas
Y Sawamura, H Shirato, T Sakamoto, H Aoyama, S Fukuda, K Miyasaka
ACOUSTIC NEUROMA, 10, 127, 128, SPRINGER-VERLAG TOKYO, 2003, [Peer-reviewed]
English, International conference proceedings, We investigated the appropriate management of patients with vestibular schwannoma treated with fractionated stereotactic radiotherapy (fSRT).

SUPERSELECTIVE ARTERIAL INFUSION AND CONCOMITANT RADIOTHERAPY FOR ADVANCED HEAD AND NECK CANCER
HOMMA Akihiro, FURUTA Yasushi, USHIKOSHI Satoshi, SUZUKI Fumiyuki, NAGAHASHI Tatsumi, HATAKEYAMA Hiromitsu, ASANO Takeshi, NISHIOKA Takeshi, SHIRATO Hiroki, FUKUDA Satoshi
Toukeibu Gan, 29, 3, 450, 456, Japan Society for Head and Neck Cancer, 2003
Japanese, Superselective arterial infusion for patients with advanced head and neck cancer has increasingly been applied in Japan. We analyzed our experiences and evaluated the efficacy and safety of this treatment. Patients and Methods: Forty-four patients, who were considered contraindicated for surgery or rejected radical surgery, received superselective intra-arterial infusion therapy of cisplatin (100-120mg/m²/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity, and conventional concomitant extrabeam radiotherapy (65Gy/26f/6.5weeks). Results: During the median follow-up period of 17 months, 2-year progression-free survival rate of primary lesion was 66.9%, and that of patients with T4b diseases 57%. The 2-year overall survival rate was 52.4%. Although acute toxic effects were considered acceptable, severe toxic events occurred in some cases, namely, cranial nerve palsy, MRSA pneumonia, sepsis, and osteoradionecrosis. Conclusions: We confirmed the high effectiveness of superselective arterial infusion and concomitant radiotherapy, which can concentrate the attack of decadose cisplatin on locoregional disease. Moreover, even patients with unresectable disease can be cured. We must clarify the treatment results and late side effects, and establish the indications for this treatment.

Calculation of rotational setup error using the real-time tracking radiation therapy (RTRT) system and its application to the treatment of spinal schwannoma
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, ELSEVIER SCIENCE INC, Nov. 2002, [Peer-reviewed]
English, Scientific journal, 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.

Three-dimensional conformal radiotherapy for astrocytic tumors involving the eloquent area in children and young adults
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, KLUWER ACADEMIC PUBL, Nov. 2002, [Peer-reviewed]
English, Scientific journal, 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.

【良性疾患の放射線治療】脳動静脈奇形　　　　　　　　　　　　　　　
張 大鎮, 青山 英史, 白土 博樹
臨床放射線, 47, 別冊, 84, 95, 金原出版(株), Nov. 2002
Japanese, 脳動静脈奇形の放射線治療における照射ターゲットの設定には,定位的血管造影の撮影とCT,MRI,MRA画像の重ね合わせで各々の特長を生かす.標的体積と照射の線量分布を一致させる方法として強度変調照射或いは多中心を用いたconformalityの向上により複雑な形態に対して照射野を一致することが可能となった.適切な線量の選択,大きなサイズ,重要部位の治療における少分割照射の可能性についても解説した

画像診断と放射線治療の統合化に向けて 腫ようイメージングの進歩 腫ようの三次元的動態の可視化と同期
喜多村圭, SEPPENWOOLDE Y, 鬼丸力也, 清水伸一, 笹木工, 白土博樹, 宮坂和男
映像情報Medical, 34, 14, 1330-1335, 1320,1301, 産業開発機構, 01 Nov. 2002
Japanese

Small-volume image-guided radiotherapy using hypofractionated, coplanar, and noncoplanar multiple fields for patients with inoperable stage I nonsmall cell lung carcinomas
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, WILEY-BLACKWELL, Oct. 2002, [Peer-reviewed]
English, Scientific journal, 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.

Real-time tumor-tracking radiation therapy for lung carcinoma by the aid of insertion of a gold marker using bronchofiberscopy
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, JOHN WILEY & SONS INC, Oct. 2002, [Peer-reviewed]
English, Scientific journal, 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.

脳腫瘍に対する放射線治療戦略 全脳画像の治療計画への利用　　　　　　　　　　　　　　　
白土 博樹, 青山 英史, 石井 伸明, 池田 潤, 澤村 豊, 鎌田 恭輔, 宮坂 和男, 岩埼 喜信
日本癌治療学会誌, 37, 2, 221, 221, (一社)日本癌治療学会, Sep. 2002
Japanese

新たに診断されたCNS胚細胞腫に対する減容量放射線照射を行う前の導入補助化学療法の長期追跡結果(Long-Term Follow-up Results of Induction Chemotherapy Followed by Reduced-Volume Irradiation for Newly Diagnosed CNS Germinoma)　　　　　　　　　　　　　　　
澤村 豊, 白土 博樹, 池田 潤, 青山 英史
日本癌治療学会誌, 37, 2, 222, 222, (一社)日本癌治療学会, Sep. 2002
English

頭頸部癌リンパ節転移陽性例に対する放射線化学療法の検討　　　　　　　　　　　　　　　
本間 明宏, 古田 康, 永橋 立望, 白土 博樹, 西岡 健, 八木 克憲, 影井 兼司, 犬山 征夫, 福田 諭
日本癌治療学会誌, 37, 2, 383, 383, (一社)日本癌治療学会, Sep. 2002
Japanese

Three-dimensional intrafractional movement of prostate measured during real-time tumor-tracking radiotherapy in supine and prone treatment positions
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, ELSEVIER SCIENCE INC, Aug. 2002, [Peer-reviewed]
English, Scientific journal, 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.

Precise and real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy
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, ELSEVIER SCIENCE INC, Jul. 2002, [Peer-reviewed]
English, Scientific journal, 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.

Image fusion between (18)FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas
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, ELSEVIER SCIENCE INC, Jul. 2002, [Peer-reviewed]
English, Scientific journal, 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.

T2N0声門癌の治療方針 放射線化学同時併用療法
永橋 立望, 福田 諭, 本間 明宏, 犬山 征夫, 白土 博樹
耳鼻と臨床, 48, Suppl.1, S41, S45, 耳鼻と臨床会, Jul. 2002
Japanese, CBDCA(carboplatin)ないしCDDP(cisplatin)の放射線化学同時併用療法を行った声門癌T2N0患者33例を対象として,その結果について検討した.治療方法はCBDCA 100mg/m2を週1回ないしCDDP 4mg/m2を週4回,照射日に一致して点滴静注し,照射は2.5Gy/fr週4回行い40Gyで評価し,NCでは手術,PR,CRでは65Gyまで続行するか否かを決定した.T2N0声門癌全症例での5年累積粗生存率は88.1%であった.同時併用療法にては,好中球減少,血小板減少,皮膚の剥離にてgrade 3の副反応が出現したが,死亡例は認めなかった.同時併用療法群をhistorical controlの放射線療法群15例と比較したところ,累積粗生存率にて有意差を認めたが,累積喉頭温存率では有意差を認めなかった

Stereotactic irradiation using linear accelerator
H Shirato, H Aoyama, K Hida, Y Sawamura, K Miyasaka, Y Iwasaki
NEUROLOGICAL SURGERY, 30, 6, 579, 591, IGAKU-SHOIN LTD, Jun. 2002, [Peer-reviewed]
Japanese

直線加速器を用いた定位放射線照射
白土 博樹, 青山 英史, 飛騨 一利, 澤村 豊, 宮坂 和男, 岩崎 喜信
Neurological Surgery, 30, 6, 579, 591, (株)医学書院, Jun. 2002
Japanese

頭頸部癌切除可能例に対するCDDP+RT vs CBDCA+RTの無作為化比較試験の検討　　　　　　　　　　　　　　　
本間 明宏, 福田 諭, 永橋 立望, 古田 康, 八木 克憲, 犬山 征夫, 白土 博樹, 西岡 健, 影井 兼司
頭頸部腫瘍, 28, 2, 380, 380, (一社)日本頭頸部癌学会, May 2002
Japanese

超選択的動注化学療法を施行した中・下咽頭癌症例における治療後の嚥下状態の検討　　　　　　　　　　　　　　　
鈴木 章之, 本間 明宏, 古田 康, 折館 伸彦, 永橋 立望, 畠山 博充, 福田 諭, 牛越 聡, 浅野 剛, 西岡 健, 白土 博樹
頭頸部腫瘍, 28, 2, 376, 376, (一社)日本頭頸部癌学会, May 2002
Japanese

A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma
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, JOHN WILEY & SONS INC, Apr. 2002, [Peer-reviewed]
English, Scientific journal, 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.

Efficacy of intense screening and treatment for synchronous second primary cancers in patients with esophageal cancer
K Kagei, M Hosokawa, H Shirato, T Kusumi, Y Shimizu, A Watanabe, M Ueda
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 32, 4, 120, 127, OXFORD UNIV PRESS, Apr. 2002, [Peer-reviewed]
English, Scientific journal, 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.

Registration accuracy and possible migration of internal fiducial gold marker implanted in prostate and liver treated with real-time tumor-tracking radiation therapy (RTRT)
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, ELSEVIER SCI IRELAND LTD, Mar. 2002, [Peer-reviewed]
English, Scientific journal, 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.

Anisotrophic diffusion-weighted MRIを用いた錐体路情報の定位照射治療計画への統合　　　　　　　　　　　　　　　
青山 英史, 鎌田 恭輔, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 62, 3, S116, S116, (公社)日本医学放射線学会, Mar. 2002
Japanese

Induction chemotherapy followed by low-dose involved-field radiotherapy for intracranial germ cell tumors
H Aoyama, H Shirato, J Ikeda, K Fujieda, K Miyasaka, Y Sawamura
JOURNAL OF CLINICAL ONCOLOGY, 20, 3, 857, 865, LIPPINCOTT WILLIAMS & WILKINS, Feb. 2002, [Peer-reviewed]
English, Scientific journal, 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.

動体追跡照射装置を用いた前立腺癌のConformal Set-up　　　　　　　　　　　　　　　
上垣 慎二, 白土 博樹, 喜多村 圭, 鬼丸 力也, 青山 英史, 米坂 祥朗, 井上 明大, 小前 隆, 土屋 和彦, 西岡 健
日本医学放射線学会雑誌, 62, 1, 47, 47, (公社)日本医学放射線学会, Jan. 2002
Japanese

動体追跡照射中における肺腫瘍の三次元的運動の解析　　　　　　　　　　　　　　　
喜多村 圭, 白土 博樹, 鬼丸 力也, 土屋 和彦, 西岡 井子, 西岡 健, 青山 英史, 宮坂 和男, Seppenwoolde Yvette
日本医学放射線学会雑誌, 62, 1, 46, 46, (公社)日本医学放射線学会, Jan. 2002
Japanese

頭蓋内原発胚細胞腫瘍に対する放射線治療の問題点 長期生存例における放射線誘発二次腫瘍と脳血管障害の発生について　　　　　　　　　　　　　　　
池田 潤, 澤村 豊, 石井 伸明, 岩崎 喜信, 青山 英史, 白土 博樹
小児がん, 38, 3, 374, 374, (NPO)日本小児がん学会, Dec. 2001
Japanese

肺定位照射における吸気・呼気・自由呼吸時と呼気時のみのCTでのDVH parameterの検討
鬼丸力也, 白土博樹, 喜多村圭, 清水伸一, 西岡健, 青山英史, 土屋和彦, 西岡井子, 宮坂和男
日本放射線腫よう学会誌, 13, Supplement 1, 114, 114, (公社)日本放射線腫瘍学会, Nov. 2001
Japanese

放射線医学の新展開 到達点と将来展望 放射線治療 定位放射線治療
清水伸一, 白土博樹, 喜多村圭
現代医療, 33, 10, 2585-2590, 2567, 現代医療社, 10 Oct. 2001
Japanese

Cisplatin抵抗性頭蓋内胚細胞腫瘍に対するgemcitabine/taxotere併用化学療法　　　　　　　　　　　　　　　
池田 潤, 石井 伸明, 澤村 豊, 岩崎 喜信, 青山 英史, 白土 博樹
日本癌治療学会誌, 36, 2, 590, 590, (一社)日本癌治療学会, Oct. 2001
Japanese

頭頸部腫瘍に対するCDDP+RT vs CBDCA+RTの無作為化比較試験　　　　　　　　　　　　　　　
本間 明宏, 福田 諭, 八木 克憲, 古田 康, 犬山 征夫, 白土 博樹, 西岡 健, 影井 兼司
日本癌治療学会誌, 36, 2, 594, 594, (一社)日本癌治療学会, Oct. 2001
Japanese

W11-1 気管支鏡による金マーカー挿入動体追跡放射線治療 (放射線治療の進歩)
原田 敏之, 小倉 滋明, 白土 博樹, 品川 尚文, 福元 伸一, 若林 修, 大泉 聡史, 本村 文宏, 山崎 浩一, 秋田 弘俊, 西村 正治, 鬼丸 力也, 清水 伸一, 喜多村 圭, 宮坂 和男
肺癌, 41, 5, 424, 424, 日本肺癌学会, 30 Sep. 2001
Japanese

小児後頭蓋窩悪性腫瘍に対する化学放射線療法
池田 潤, 石井 伸明, 澤村 豊, 岩崎 喜信, 青山 英史, 白土 博樹
小児の脳神経, 26, 4, 267, 267, (一社)日本小児神経外科学会, Aug. 2001
Japanese

頭蓋内原発胚芽腫に対する集学的治療 特にHCG-β陽性群のあつかいについて
石井 伸明, 池田 潤, 澤村 豊, 岩崎 喜信, 青山 英史, 白土 博樹
小児の脳神経, 26, 4, 316, 316, (一社)日本小児神経外科学会, Aug. 2001
Japanese

脊髄動静脈奇形・脊髄神経鞘腫に対する定位照射での画像レジストレーションと位置精度
鬼丸力也, 白土博樹, 喜多村圭, 清水伸一, 青山英史, 影井兼司, 土屋和彦, 西岡健, 宮坂和男
日本医学放射線学会雑誌, 61, 6, 319, 319, (公社)日本医学放射線学会, 25 May 2001
Japanese

頭頸部進行癌に対するシスプラチンの超選択的動注療法　　　　　　　　　　　　　　　
本間 明宏, 畠山 博充, 永橋 立望, 折舘 伸彦, 八木 克憲, 古田 康, 福田 諭, 犬山 征夫, 浅野 剛, 牛越 聡, 西岡 健, 白土 博樹, 宮坂 和男
頭頸部腫瘍, 27, 2, 356, 356, (一社)日本頭頸部癌学会, May 2001
Japanese

C-9 気管支鏡を用いた金マーカー挿入による動体追跡放射線治療
原田 敏之, 小倉 滋明, 品川 尚文, 白間 信行, 福元 伸一, 横内 浩, 若林 修, 大泉 聡史, 小島 哲弥, 山崎 浩一, 秋田 弘俊, 清水 伸一, 喜多村 圭, 白土 博樹
気管支学 : 日本気管支研究会雑誌, 23, 3, 244, 244, 日本呼吸器内視鏡学会, 25 Apr. 2001
Japanese

原発性・転移性肝腫ように対する動体追跡放射線治療の経験
喜多村圭, 白土博樹, 清水伸一, 橋本井子, 土屋和彦, 鬼丸力也, 青山英史, 影井兼司, 宮坂和男
日本医学放射線学会雑誌, 61, 4, 190, 190, (公社)日本医学放射線学会, 25 Mar. 2001
Japanese

動体追跡照射装置による照射中の肺癌の動態解析
清水伸一, 白土博樹, 喜多村圭, 青山英史, 鬼丸力也, 土屋和彦, 橋本井子, 宮坂和男, VAN HERK M
日本医学放射線学会雑誌, 61, 4, 191, 191, (公社)日本医学放射線学会, 25 Mar. 2001
Japanese

放射線治療におけるVirtualとRealのRegistration技術に関する考察
白土博樹, 鬼丸力也, 清水伸一, 橋本井子, 土屋和彦, 喜多村圭, 青山英史, 宮坂和男, 伊福部達
日本医学放射線学会雑誌, 61, 4, 192, 192, (公社)日本医学放射線学会, 25 Mar. 2001
Japanese

Stage B期の前立腺癌に対する局所放射線治療
喜多村圭, 白土博樹, 清水伸一, 橋本井子, 土屋和彦, 鬼丸力也, 青山英史, 影井兼司, 宮坂和男
日本医学放射線学会雑誌, 61, 4, 193, 193, (公社)日本医学放射線学会, 25 Mar. 2001
Japanese

線量率可変式全身照射用装置の使用経験　　　　　　　　　　　　　　　
井上 明大, 影井 兼司, 橋本 井子, 西岡 健, 喜多村 圭, 青山 英史, 鬼丸 力也, 土屋 和彦, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 61, 4, 190, 190, (公社)日本医学放射線学会, Mar. 2001
Japanese

頭頸部腫瘍の治療計画におけるFDGPETの利用　　　　　　　　　　　　　　　
西岡 健, 山崎 彰, 土屋 和彦, 青山 英史, 白土 博樹, 志賀 徹, 加藤 貴志, 塚本 江利子, 玉木 長良
日本医学放射線学会雑誌, 61, 4, 189, 189, (公社)日本医学放射線学会, Mar. 2001
Japanese

前立腺癌に対するIntensity modulated radiotherapy(IMRT) 動体追跡・内分泌療法併用によるprospective studyの初期成績
喜多村圭, 白土博樹, 清水伸一, 鬼丸力也, 西岡井子, 西岡健, 影井兼司, 土屋和彦, 宮坂和男
日本医学放射線学会雑誌, 61, 2, S128-S129, S129, (公社)日本医学放射線学会, 20 Feb. 2001
Japanese

FDGPETを用いた頭頸部癌の放射線治療計画　　　　　　　　　　　　　　　
西岡 健, 白土 博樹, 土屋 和彦, 山崎 彰, 志賀 哲, 塚本 江利子, 青山 英史, 宮坂 和男
日本医学放射線学会雑誌, 61, 2, S138, S138, (公社)日本医学放射線学会, Feb. 2001
Japanese

Pretreatment apoptotic scores do not predict response to radiation therapy in oropharyngeal squamous cell carcinoma
K Tsuchiya, H Shirato, T Nishioka, A Yamazaki, S Hashimoto, K Kagei, K Oomori, M Yasuda, M Shindo, K Miyasaka
ORAL ONCOLOGY, 37, 2, 159, 163, PERGAMON-ELSEVIER SCIENCE LTD, Feb. 2001, [Peer-reviewed]
English, Scientific journal, The prognostic value of tumor apoptosis was studied in patients with oropharyngeal squamous cell carcinoma treated with radical radiotherapy. Forty-eight patients with oropharyngeal squamous cell carcinoma who received radical radiotherapy between 1990 and 1995 were enrolled in the study. The radiation treatment for all patients involved the administration of 65 Gy in 26 fractions over a 6.5-week period. The apoptotic index (AI; the apoptotic cell count per 1000 tumor cells) was distributed from 0 to 10 with a median at 2 and a mode of 1. There was a significant linear correlation between the AI and mitotic index (MI) (r = 0.393, 95% confidence interval: 0.129-0.605). The cause-specific 5-year survival for patients with AI greater than the median was 46% and for the counterpart was 41%. There was no difference in cause-specific survival between AI/MI greater than the median (50%) and AI/MI smaller than the median (36%). The number of patients was too small to draw definite conclusions, but the AI and the AI/MI before treatment were not shown to have a prognostic value for oropharyngeal squamous cell carcinoma in our study. The primary sites and treatment methods may influence the prognostic value of AI even for the same histological types. (C) 2001 Elsevier Science Ltd. All rights reserved.

[Gated Radiotherapy]
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, 1, 17, 27, 1, 2001, [Peer-reviewed]
Japanese, Recent external radiotherapy requires precise localization of the target because advance in diagnostic imaging has made it possible to visualize a tiny tumor which would be curable with focused high dose irradiation. However, tumors in respiratory and bowel organs have been difficult to be given the high dose because of 1 to 3 cm movement during delivery of irradiation. Respiratory-gating techniques have been used with medical linear accelerators and particle therapy machines. Real-time tumortracking radiotherapy has been realized using fluoroscopic x-rays, internal gold-markers, and pattern recognition technology. Advantage and disadvantage of each gating technique have been realized. Active breath control method would be a cost-effective way of precise treatment without gating. More work is required to find the relationship between abdominal wall and internal movement of the tumor in many respiratorygating radiotherapy and between the internal markers and target volume in real-time tracking radiotherapy.

Computer-controlled, image-guided, new conformal radiotherapy for advanced head and neck cancer - Results of AcMAR (Accelerated Multiple-arc Radiotherapy) study in Kitami Red-cross General Hospital
T Arimoto, A Yamazaki, T Matsuzawa, W Ichimura, K Nishioka, H Shirato
CARS 2001: COMPUTER ASSISTED RADIOLOGY AND SURGERY, 1230, 471, 476, ELSEVIER SCIENCE BV, 2001, [Peer-reviewed]
English, International conference proceedings, A new form of conformal radiotherapy combined with accelerated hyperfractionation, AcMAR, was applied to 101 patients with advanced head and neck tumors. Analysi of the clinical results with mean follow-up period of 27 months revealed encoraging tumor control with improved patients' tolerance to acute mucositis. Late ulceration, however, was observed in some patients who were treated with higher single dose per fraction.

頭蓋内原発胚芽腫に対する集学的治療　　　　　　　　　　　　　　　
池田 潤, 石井 伸明, 澤村 豊, 岩崎 喜信, 青山 英史, 白土 博樹
小児がん, 37, 3, 370, 370, (NPO)日本小児がん学会, Nov. 2000
Japanese

Early detection of bone marrow involvement in extramedullary plasmacytoma by whole-body F-18FDG positron emission tomography
T Kato, E Tsukamoto, T Nishioka, A Yamazaki, H Shirato, S Kobayashi, M Asaka, M Imamura, N Tamaki
CLINICAL NUCLEAR MEDICINE, 25, 11, 870, 873, LIPPINCOTT WILLIAMS & WILKINS, Nov. 2000, [Peer-reviewed]
English, Scientific journal, The utility of positron emission tomography (PET) with the glucose analog 2-deoxy-2-[F-18] fluoro-D-glucose (F-18 FDG) in plasmacytoma has not been well evaluated. The authors report a case of extramedullary plasmacytoma (EMP) in which whole-body F-18 FDG PET was useful in the early detection of bone marrow involvement. A 34-year-old woman had EMP without histologic or radiologic evidence of bone lesions. However, the early phase of bone marrow involvement was considered because of spotty accumulation shown by F-18 FDG PET. A follow-up F-18 FDG PET study after radiotherapy showed intense multifocal accumulation in the bone marrow, which was confirmed on bone marrow aspiration as abnormal proliferation of plasma cells. Whole-body F-18 FDG PET has the potential to detect the early phase of bone marrow involvement in patients with EMP.

下咽頭癌における放射線・化学同時併用療法
永橋 立望, 福田 諭, 本間 明宏, 八木 克憲, 古田 康, 犬山 征夫, 西岡 健, 白土 博樹
頭頸部腫瘍, 26, 3, 476, 482, (一社)日本頭頸部癌学会, Nov. 2000
Japanese

視床部星細胞腫に対する放射線治療　　　　　　　　　　　　　　　
池田 潤, 澤村 豊, 石井 伸明, 青山 英史, 白土 博樹
日本脳神経外科学会総会抄録集, 59回, 235, 235, (一社)日本脳神経外科学会, Oct. 2000
Japanese

頭蓋内原発胚細胞腫瘍患者の長期生存例における放射線誘発脳血管障害の発生　　　　　　　　　　　　　　　
池田 潤, 澤村 豊, 石井 伸明, 青山 英史, 白土 博樹
日本脳神経外科学会総会抄録集, 59回, 91, 91, (一社)日本脳神経外科学会, Oct. 2000
Japanese

D-19 臨床病期I期非小細胞肺癌に対する定位放射線照射療法の臨床成績に関する検討
福元 伸一, 秋田 弘俊, 横内 浩, 原田 敏之, 若林 修, 小島 哲弥, 本村 文宏, 大泉 聡史, 山崎 浩一, 小倉 滋明, 白土 博樹, 清水 伸一, 立石 宇貴秀, 宮坂 和男
肺癌, 40, 5, 406, 406, 日本肺癌学会, 30 Sep. 2000
Japanese

W1-4 気管支鏡によるマーカー挿入動体追跡放射線治療の有用性の検討
原田 敏之, 小倉 滋明, 小西 純, 白間 信行, 福元 伸一, 横内 浩, 若林 修, 大泉 聡史, 小島 哲弥, 本村 文宏, 山崎 浩一, 秋田 弘俊, 清水 伸一, 白土 博樹, 宮坂 和男
肺癌, 40, 5, 363, 363, 日本肺癌学会, 30 Sep. 2000
Japanese

臨床病期I期非小細胞肺癌に対する定位放射線照射療法の臨床成績の検討
福元伸一, 秋田弘俊, 横内浩, 原田敏之, 若林修, 小島哲弥, 白土博樹, 清水伸一, 宮坂和男
日本癌治療学会誌, 35, 2, 520, 20 Sep. 2000
Japanese

前立腺癌への局所放射線治療の効果と副作用
喜多村圭, 鈴木恵士郎, 白土博樹, 西岡健, 影井兼司, 青山英史, 清水伸一, 篠原信雄, 出村孝義
泌尿器外科, 13, 8, 1133, 1133, 医学図書出版(株), 15 Aug. 2000
Japanese

体幹部定位放線照射における4次元治療計画と動体追跡放射線照射
白土博樹, 清水伸一, 清水匡, 喜多村圭, 青山英史, 西岡健, 影井兼司, 橋本井子, 宮坂和男
定位的放射線治療, 4, 131-136, 136, 日本定位放射線治療学会, 25 Jul. 2000
Japanese, 体幹部病巣の定位放射線照射の為に,病巣をリアルタイムに追跡して,計画部位に位置した瞬間のみ照射可能な装置を開発し,臨床経験を得た.腫瘍ないしその近傍に1〜2mmの金マーカーを刺入した上で,CTプランを行う.腫瘍と金マーカーの位置関係を直線加速器の動体追跡照射装置に伝送する.治療室に備えられた2組のX線透視装置を用いて,この金マーカーの三次元位置座標を計算し,isocenterに対応した座標を用いて患者セットアップを行う.その後,治療用X線の照射中,30回/秒の割合で透視し,リアルタイムに金マーカー位置を計算し,計画位置に金マーカーが透視した場合のみ,治療用X線が照射される.ファントム実験では,静的なものに対して1mm以下の精度で座標を計測できた.動くファントムを用いた実験では,秒速40mmまで追跡可能であった

頭頸部早期悪性リンパ腫に対するBiweekly CHOPと放射線治療　　　　　　　　　　　　　　　
西岡 健, 山崎 彰, 橋本 井子, 喜多村 圭, 土屋 和彦, 青山 英史, 清水 伸一, 影井 兼司, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 8, 466, 466, (公社)日本医学放射線学会, Jul. 2000
Japanese

Astrocytoma及びOligodendrogliomaへの放射線照射の治療経験　　　　　　　　　　　　　　　
小前 隆, 青山 英史, 西岡 健, 橋本 井子, 山崎 彰, 清水 伸一, 喜多村 圭, 土屋 和彦, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 8, 465, 465, (公社)日本医学放射線学会, Jul. 2000
Japanese

下咽頭癌のCT simulationにおける頸部リンパ節転移領域の解析　　　　　　　　　　　　　　　
山崎 彰, 西岡 健, 橋本 井子, 喜多村 圭, 土屋 和彦, 青山 英史, 清水 伸一, 影井 兼司, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 8, 466, 466, (公社)日本医学放射線学会, Jul. 2000
Japanese

【前立腺癌の診断と治療】 前立腺癌の治療 集学的治療 内分泌療法併用動体追跡放射線治療　　　　　　　　　　　　　　　
喜多村 圭, 白土 博樹, 清水 伸一, 出村 孝義, 篠原 信雄, 原林 透, 宮坂 和男
日本臨床, 58, 増刊 前立腺癌の診断と治療, 326, 329, (株)日本臨床社, Jul. 2000
Japanese

下咽頭・頸部食道癌 治療成績・QOL向上の工夫 北大における下咽頭癌の治療成績 放射線・化学同時併用療法を中心として
永橋 立望, 福田 諭, 本間 明宏, 八木 克憲, 古田 康, 犬山 征夫, 西岡 健, 白土 博樹
頭頸部腫瘍, 26, 2, 204, 204, (一社)日本頭頸部癌学会, May 2000
Japanese

II-51 気管支鏡によるマーカー挿入動体追跡放射線治療の試み
小倉 滋明, 横内 浩, 福元 伸一, 原田 敏之, 若林 修, 小島 哲弥, 大泉 聡史, 岡本 佳裕, 尾島 裕和, 山崎 浩一, 秋田 弘俊, 川上 義和, 清水 伸一, 白土 博樹, 宮坂 和男, 斉藤 達也
気管支学 : 日本気管支研究会雑誌, 22, 3, 212, 212, 日本呼吸器内視鏡学会, 25 Apr. 2000
Japanese

上咽頭腫ようの局所残存および再発病変に対する3次元小容積照射
西岡健, 山崎彰, 橋本井子, 喜多村圭, 土屋和彦, 清水伸一, 青山英史, 白土博樹, 宮坂和男
日本医学放射線学会雑誌, 60, 2, S239, 20 Feb. 2000
Japanese

前立腺癌へのintensity modulated radiotherapy(IMRT)におけるreal‐time tumor‐tracking systemの有用性
喜多村圭, 白土博樹, 清水伸一, 土屋和彦, 山崎彰, 青山英史, 橋本井子, 西岡健, 宮坂和男
日本医学放射線学会雑誌, 60, 2, S235-S236, S236, (公社)日本医学放射線学会, 20 Feb. 2000
Japanese

Glioblastoma細胞の放射線感受性におけるp53遺伝子の役割 温度感受性p53変異細胞株を用いた検討
土屋和彦, 多田光宏, 白土博樹, 西岡健, 橋本井子, 青山英史, 喜多村圭, 清水伸一, 宮坂和男
日本医学放射線学会雑誌, 60, 2, S148-S149, S149, (公社)日本医学放射線学会, 20 Feb. 2000
Japanese

前立腺癌に対する局所放射線治療の長期成績と副作用の検討　　　　　　　　　　　　　　　
喜多村 圭, 清水 伸一, 森 孝之, 土屋 和彦, 山崎 彰, 青山 英史, 橋本 井子, 西岡 健, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 3, 110, 110, (公社)日本医学放射線学会, Feb. 2000
Japanese

MRI治療計画装置を用いた頭蓋部病変三次元治療計画 複数観察者間の標的体積の検討　　　　　　　　　　　　　　　
青山 英史, 土屋 和彦, 橋本 井子, 西岡 健, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 2, S218, S218, (公社)日本医学放射線学会, Feb. 2000
Japanese

上咽頭腫瘍の局所残存及び再発病変に対する三次元小容積照射　　　　　　　　　　　　　　　
西岡 健, 山崎 彰, 橋本 井子, 喜多村 圭, 土屋 和彦, 清水 伸一, 青山 英史, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 2, S239, S239, (公社)日本医学放射線学会, Feb. 2000
Japanese

動体追跡放射線照射装置を用いた前立腺癌・膀胱癌への高精度conformal radiotherapyの経験　　　　　　　　　　　　　　　
喜多村 圭, 清水 伸一, 森 孝之, 土屋 和彦, 山崎 彰, 青山 英史, 橋本 井子, 西岡 健, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 3, 110, 110, (公社)日本医学放射線学会, Feb. 2000
Japanese

Pilocytic astrocytomaへの三次元conformal放射線治療の経験　　　　　　　　　　　　　　　
森 孝之, 青山 英史, 清水 伸一, 喜多村 圭, 土屋 和彦, 山崎 彰, 橋本 井子, 西岡 健, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 60, 3, 108, 108, (公社)日本医学放射線学会, Feb. 2000
Japanese

Prevention of vaginal shortening following radical hysterectomy
Ritsu Yamamoto, Kazuhira Okamoto, Yasuhiko Ebina, Hiroki Shirato, Noriaki Sakuragi, Seiichiro Fujimoto
BJOG: An International Journal of Obstetrics and Gynaecology, 107, 7, 841, 845, 2000, [Peer-reviewed]
English, Scientific journal, We describe a surgical procedure and post-operative management for the prevention of vaginal shortening following radical hysterectomy. A total of 452 patients who underwent hysterectomies were examined prospectively depending on the operation method. This study showed that our procedure was effective in the prevention of vaginal shortening following radical hysterectomy. Preservation of the ovaries appeared to be important in preventing vaginal shortening, and post-operative hormone replacement therapy was not as effective as the preservation of the ovaries. The effect of external irradiation on vaginal shortening was not conspicuous in the case that the ovaries were preserved. © 2017 Wiley. All rights reserved.

Reconstruction of medical treatment and radiotherapy. The latest radiotherapy. Real-tome tumor-tracking irradiation method and stereotactic radioirradiation.
SHIRATO HIROKI, NISHIOKA TAKESHI, KAGEI KENJI, HASHIMOTO SEIKO, AOYAMA HIDEFUMI, KITAMURA KEI, SHIMIZU SHIN'ICHI, KUNIEDA TATSUYA, GOTO MASAHARU
月刊新医療, 26, 12, 61-63, 63, (株)エムイー振興協会, 01 Dec. 1999
Japanese

定位放射線照射,三次元原体照射による治療が有効であったpilocytic,fibrillary astrocytomaの4例　　　　　　　　　　　　　　　
森 孝之, 青山 英史, 白土 博樹, 西岡 健, 橋本 井子, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 295, 295, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

下咽頭癌の化学療法 放射線同時併用療法
福田 諭, 永橋 立望, 本間 明宏, 犬山 征夫, 白土 博樹
耳鼻と臨床, 45, Suppl.3, 706, 709, 耳鼻と臨床会, Nov. 1999
Japanese, 1990年11月より頭頸部癌患者に対しCBDCAと放射線同時併用療法を行い,評価可能147例(男125例,女22例,年齢:34歳-82歳)のうち下咽頭癌患者22例について検討を加えた.治療方法はCBDCA 100mg/m2を週1回照射日に一致して点滴静注し,照射は60Co 2.5Gy/fr週4回行い40Gyで評価し,手術かfull doseまで続行するかを決定した.下咽頭全症例での5年disease free survivalは34.1%,stage II(2例)で100%,stage III(3例)で33%,stage IV(16例)で25%,救済手術を行わないCBDCA+放射線のみでの無再発生存は3例.症例数は少ないものの進行例の予後は他の報告どおり決して良くない

血管造影装置を配備した密封小線源治療施設における血管内小線源治療システムの開発と基礎的研究　　　　　　　　　　　　　　　
橋本 井子, 西岡 健, 土屋 和彦, 清水 伸一, 喜多村 圭, 山崎 彰, 青山 英史, 清水 匡, 白土 博樹, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 311, 311, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

肺腫瘍45病変に対する定位的放射線治療の臨床成績　　　　　　　　　　　　　　　
清水 伸一, 白土 博樹, 喜多村 圭, 青山 英史, 橋本 井子, 西岡 健, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 206, 206, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

頭蓋内,頭蓋底病変におけるMRI-planningの有用性 CT,MRIで定義されたGTVの複数観察者比較検討　　　　　　　　　　　　　　　
青山 英史, 土屋 和彦, 橋本 井子, 西岡 健, 山崎 彰, 喜多村 圭, 清水 伸一, 白土 博樹, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 240, 240, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

前立腺癌に対する局所放射線治療後の晩期直腸出血に関する検討　　　　　　　　　　　　　　　
喜多村 圭, 鈴木 恵士郎, 土屋 和彦, 山崎 彰, 清水 伸一, 青山 英史, 橋本 井子, 西岡 健, 白土 博樹, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 149, 149, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

Glioblastoma細胞の放射線感受性におけるp53遺伝子の役割 温度感受性p53変異細胞株を用いた検討　　　　　　　　　　　　　　　
土屋 和彦, 多田 光宏, 白土 博樹, 西岡 健, 橋本 井子, 青山 英史, 喜多村 圭, 清水 伸一, 山崎 彰, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 169, 169, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

動体追跡照射装置の開発と初期臨床効果　　　　　　　　　　　　　　　
白土 博樹, 清水 伸一, 喜多村 圭, 清水 匡, 青山 英史, 山崎 彰, 橋本 井子, 西岡 健, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 207, 207, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

頭頸部癌の至適臨床的標的体積決定のためのリンパ節転移分布の解析 下咽頭癌　　　　　　　　　　　　　　　
山崎 彰, 西岡 健, 白土 博樹, 橋本 井子, 喜多村 圭, 青山 英史, 清水 伸一, 土屋 和彦, 宮坂 和男
日本放射線腫瘍学会誌, 11, Suppl.1, 190, 190, (公社)日本放射線腫瘍学会, Nov. 1999
Japanese

【脳のイメージングupdate 解剖から治療まで】放射線治療 脳の定位放射線照射　　　　　　　　　　　　　　　
白土 博樹, 青山 英史
臨床放射線, 44, 11, 1478, 1488, 金原出版(株), Oct. 1999
Japanese

S2-5 末梢性小型肺癌への画像誘導定位放射線照射(肺末梢小型肺癌の治療成績向上をめざして,第40回日本肺癌学会総会号)
白土 博樹, 秋田 弘俊, 清水 伸一, 小倉 滋明, 喜多村 圭, 川上 義和, 宮坂 和男
肺癌, 39, 5, 525, 525, 日本肺癌学会, 25 Sep. 1999
Japanese

【Radiotherapy Today '99 放射線治療の最新動向】ライナックによる定位放射線照射の現状と展望
青山 英史, 白土 博樹
INNERVISION, 14, 10, 89, 92, (株)インナービジョン, Sep. 1999
Japanese

放射線治療計画用MRシステムの開発　　　　　　　　　　　　　　　
渡辺 良晴, 白土 博樹, 浅田 和佳, 前田 常雄, 影井 兼司, 西岡 健, 青山 英史, 橋本 井子, 清水 伸一, 南雲 淳也, 藤田 勝久, 古家 輝夫, 山口 恵, 宮坂 和男
メディックス, 31, 12, 17, (株)日立製作所ヘルスケアビジネスユニット, Sep. 1999
Japanese

【放射線治療の新潮流】MRI画像の放射線治療計画への応用
青山 英史, 渡辺 良晴, 古屋 輝夫, 橋本 井子, 影井 兼司, 西岡 健, 白土 博樹, 宮坂 和男
映像情報Medical, 31, 16, 895, 898, 産業開発機構(株), Aug. 1999
Japanese

【放射線治療の新潮流】 2軸X線透視装置を用いた三次元的患者セットアップシステムの開発
清水 伸一, 白土 博樹, 青山 英史, 宮坂 和男, 国枝 達也
映像情報Medical, 31, 16, 879, 884, 産業開発機構(株), Aug. 1999
Japanese

【放射線治療の新潮流】 次世代の放射線治療 動体追跡放射線治療　　　　　　　　　　　　　　　
白土 博樹, 清水 伸一, 喜多村 圭
映像情報Medical, 31, 16, 876, 878, 産業開発機構(株), Aug. 1999
Japanese

【MRIの到達点】北大における治療計画用MRIの概要と臨床応用　　　　　　　　　　　　　　　
青山 英史, 宮坂 和男, 白土 博樹, 渡辺 良晴, 古屋 輝夫, 影井 兼司
新医療, 26, 6, 109, 112, (株)エムイー振興協会, Jun. 1999
Japanese

脳動静脈奇形に対する定位照射後の出血に関わる因子の検討　　　　　　　　　　　　　　　
青山 英史, 白土 博樹, 西岡 健, 影井 兼司, 橋本 井子, 宮坂 和男
日本医学放射線学会雑誌, 59, 6, 278, 278, (公社)日本医学放射線学会, May 1999
Japanese

当科における中咽頭扁平上皮癌の頸部リンパ節転移の治療　　　　　　　　　　　　　　　
本間 明宏, 八木 克憲, 永橋 立望, 古田 康, 福田 諭, 犬山 征夫, 白土 博樹, 西岡 健, 影井 兼司
頭頸部腫瘍, 25, 2, 314, 314, (一社)日本頭頸部癌学会, May 1999
Japanese

MR治療計画システムの開発　　　　　　　　　　　　　　　
影井 兼司, 西岡 健, 橋本 井子, 青山 英史, 清水 伸一, 土屋 和彦, 橋 徳子, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 59, 6, 282, 282, (公社)日本医学放射線学会, May 1999
Japanese

Stereotactic Irradiation-from Three-dimensional to Four-dimensional Stereotaxy.
SHIRATO HIROKI, AOYAMA HIDEFUMI, SHIMIZU SHIN'ICHI
癌の臨床, 45, 4, 293-294, 01 Apr. 1999
Japanese

RADICAL RADIOTHERAPY FOR OROPHARYNGEAL CARCINOMAS
KAGEI Kenji, SHIMIZU Shinichi, HASHIMOTO Seiko, NISHIOKA Takeshi, SHIRATO Hiroki, HONMA Akihiro, KANEKO Masanori, OHMORI Keiichi, MIYASAKA Kazuo
Japanese jornal of Head and Neck Cancer, 25, 1, 30, 35, 25 Mar. 1999
Japanese

脳転移に対する定位放射線照射　　　　　　　　　　　　　　　
白土 博樹, 長谷川 正俊, 直居 豊, 林 靖之, 池田 裕子, 青山 英史, 柴山 千秋
日本放射線腫瘍学会誌, 10, Suppl.2, 34, 37, (公社)日本放射線腫瘍学会, Mar. 1999
Japanese, 定位放射線照射の転移性脳腫瘍への適応基準は,思ったほど施設間差がなく,同治療法が的確に普及しつつあることを示唆した.一方,線量分布の急峻さから,辺縁線量の指示は大きくばらついていた.アンケートに現れなかった要素に違いがあり,実際の線量はあまり違っていない可能性もある

脳少分割定位照射の合併症に関する検討　　　　　　　　　　　　　　　
青山 英史, 白土 博樹, 西岡 健, 影井 兼司, 橋本 井子, 宮坂 和男
日本医学放射線学会雑誌, 59, 2, S234, S234, (公社)日本医学放射線学会, Feb. 1999
Japanese

血管造影装置を配備した密封小線源治療施設における血管内小線源治療システムの開発　　　　　　　　　　　　　　　
西岡 健, 清水 匡, 土屋 和彦, 清水 伸一, 山崎 彰, 青山 英史, 橋本 井子, 影井 兼司, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 59, 2, S191, S191, (公社)日本医学放射線学会, Feb. 1999
Japanese

放射線治療計画専用MRIの開発及びその臨床応用　　　　　　　　　　　　　　　
影井 兼司, 土屋 和彦, 清水 伸一, 山崎 彰, 青山 英史, 橋本 井子, 西岡 健, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 59, 2, S188, S188, (公社)日本医学放射線学会, Feb. 1999
Japanese

2軸X線透視装置を用いた三次元的患者セットアップシステムの開発
清水 伸一, 白土 博樹, 西岡 健, 影井 兼司, 橋本 井子, 青山 英史, 山崎 彰, 土屋 和彦, 宮坂 和男, 国枝 達也
日本医学放射線学会雑誌, 59, 2, S189, S189, (公社)日本医学放射線学会, Feb. 1999
Japanese

Spinal cord compressionに対する放射線治療開始時期と効果 緊急照射に対する遠隔放射線治療支援システムTHERAPISの利用　　　　　　　　　　　　　　　
橋本 井子, 白土 博樹, 西岡 健, 影井 兼司, 清水 伸一, 山崎 彰, 青山 英史, 土屋 和彦, 瀬川 広志, 小笠原 弘
日本医学放射線学会雑誌, 59, 2, S67, S68, (公社)日本医学放射線学会, Feb. 1999
Japanese

Role of radiotherapy for mucoepidermoid carcinoma of salivary gland
Y Hosokawa, H Shirato, K Kagei, S Hashimoto, T Nishioka, K Tei, M Ono, K Ohmori, M Kaneko, K Miyasaka, M Nakamura
ORAL ONCOLOGY, 35, 1, 105, 111, PERGAMON-ELSEVIER SCIENCE LTD, Jan. 1999, [Peer-reviewed]
English, Scientific journal, This report analyzes 61 patients with mucoepidermoid carcinomas of the salivary gland treated by surgery alone or by surgery plus radiotherapy. Local control for all 61 patients at 5 and 10 years was achieved for 88.8 and 79.7% of the cases. Although the rate of positive surgical margin was higher in patients treated with surgery and radiotherapy (radiotherapy group) than in patients treated by surgery alone (surgery group), the local control rates of the two groups showed no statistically significant differences. There was no local recurrence in seven patients receiving post-operative radiotherapy above 55 Gy while there were three local relapses among 17 patients receiving 55 Gy or lower doses (P < 0.05). The 5- and 10-year actual survival rates were 73.4 and 63.3%, respectively. Histopathologic subtype of mucoepidermoid carcinomas correlated with regional lymph node involvement and survival. There were no differences in the local control and survival rates of patients with major salivary gland tumors and patients with minor salivary gland tumors. Radiotherapy using 55 Gy or more combined with operation achieved local control and survival rates comparable with complete resection of tumors even if a positive surgical margin was more frequent in the radiotherapy group. (C) 1998 Elsevier Science Ltd. All rights reserved.

中咽頭腫瘍の予後因子の検討　　　　　　　　　　　　　　　
土屋 和彦, 西岡 健, 影井 兼司, 橋本 井子, 清水 伸一, 山崎 彰, 青山 英史, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 58, 14, 855, 855, (公社)日本医学放射線学会, Dec. 1998
Japanese

子宮頸癌の術後放射線治療　　　　　　　　　　　　　　　
山崎 彰, 西岡 健, 影井 兼司, 橋本 井子, 清水 伸一, 土屋 和彦, 青山 英史, 白土 博樹, 宮坂 和男
日本医学放射線学会雑誌, 58, 14, 859, 859, (公社)日本医学放射線学会, Dec. 1998
Japanese

【頭頸部癌 私の治療方針と成績】 声帯癌T3症例の保存的治療 北海道大学病院の場合
犬山 征夫, 福田 諭, 古田 康, 本間 明宏, 白土 博樹
耳鼻咽喉科・頭頸部外科, 70, 12, 799, 804, (株)医学書院, Nov. 1998
Japanese, 1)原発部位別の5年粗生存率は,喉頭癌75.6%,口腔癌69.7%,中咽頭癌と下咽頭癌は32.9%,34.1%であった. 2)喉頭癌のII期について,照射+CBDCA群と照射単独群の5年粗生存率は86.4%,66.7%,また,5年cause-specific survivalは97%,69%で共に有意差が認められた. 3)喉頭癌のT2症例での5年生存率でも,併用群91.2%,照射単独群70.7%で有意差が認められた. 4)声門上癌T2の喉頭温存を伴った5年生存率は,併用群66.5%,対照群36%で有意差が認められた. 5)喉頭癌T3症例の喉頭温存を伴った5年粗生存率,cause-specific survivalは,おのおの51.4%,61.5%と良好であった

舌腫瘍の超音波所見　　　　　　　　　　　　　　　
土屋 和彦, 橋本 井子, 青山 英史, 朱 強, 唐 少珊, 白土 博樹, 北原 利博, 影井 兼司, 清水 匡, 宮坂 和男
超音波医学, 25, 9, 967, 967, (公社)日本超音波医学会, Sep. 1998
Japanese

頭蓋内胚細胞腫に対する照射前化学療法と限局照射野を用いた低線量放射線治療　　　　　　　　　　　　　　　
白土 博樹, 喜多村 圭, 青山 英史, 宮坂 和男, 澤村 豊, 池田 潤
小児がん, 35, 3, 439, 439, (NPO)日本小児がん学会, Sep. 1998
Japanese

中咽頭がんの治療 頭頚部外科医と放射線治療医との対話 中咽頭癌に対する根治的放射線治療
影井兼司, 清水伸一, 橋本井子, 西岡健, 白土博樹, 金子正範, 大森圭一, 本間明宏, 宮坂和男
頭頚部腫よう, 24, 2, 148, May 1998
Japanese

The Experience of Teleradiology in Radiotherapy Planning
小笠原 弘, 白土 博樹, 橋本 井子, 瀬川 広志
Japanese Journal of Radiological Technology, 54, 9, 1121, 1121, Japanese Society of Radiological Technology, 1998
Japanese

Small volume Multiple non-coplanar Arc Radiotherapy (SMART) for tumors of the lung, head & neck and the abdominopelvic region.
T Arimoto, H Usubuchi, T Matsuzawa, A Yonesaka, S Shimizu, H Shirato, K Miyasaka
CAR '98 - COMPUTER ASSISTED RADIOLOGY AND SURGERY, 1165, 257, 261, ELSEVIER SCIENCE BV, 1998, [Peer-reviewed]
English, International conference proceedings

A telecommunications helped radiotherapy planning and information system (THERAPIS)
S Hashimoto, H Shirato, K Inamura, J Mizuno, Y Watanabe, H Ogawawara, M Hosokawa, K Miyasaka
CAR '98 - COMPUTER ASSISTED RADIOLOGY AND SURGERY, 1165, 276, 281, ELSEVIER SCIENCE BV, 1998, [Peer-reviewed]
English, International conference proceedings

放射線治療の最前線 定位的放射線照射の現況
青山 英史, 白土 博樹
映像情報Medical, 29, 16, 946, 950, 産業開発機構(株), Aug. 1997
Japanese

Three-dimensional movement of lung and liver tumors during noncoplaner external radiotherapy analyzed by high speed computed tomography (CT) and magnetic resonance imaging (MRI).
Shimizu S, Shirato H, Kagei K, Kitahara T, Hashimoto S, Miyasaka
International Journal of Radiation Oncology Biology Physics, 39, 2, 347, 1997, [Peer-reviewed]

SUPERFICIAL ESOPHAGEAL CANCER - MULTICENTER ANALYSIS OF RESULTS OF DEFINITIVE RADIATION-THERAPY IN JAPAN
T OKAWA, M TANAKA, M KITAOKAWA, M NISHIO, Y KIKUCHI, H SHIRATO, S YAMADA, H ASAKAWA, H NIIBE, T DOKIYA, Y TANAKA, Y HISHIKAWA, S HIROTA, Y IMAJO, Y HIROKAWA, N HAYABUCHI, N MIYAJI
RADIOLOGY, 196, 1, 271, 274, RADIOLOGICAL SOC NORTH AMER, Jul. 1995, [Peer-reviewed]
English, Scientific journal, PURPOSE: To assess the effectiveness of definitive radiation therapy in patients with superficial esophageal cancer.
MATERIALS AND METHODS: Method of irradiation, local control rate, survival rate, and complications were assessed in 105 patients (89 men, 16 women; age range, 50-88 years) with superficial esophageal cancer treated with definitive radiation therapy at 15 hospitals in 1981-1990.
RESULTS: All lesions were confirmed to be squamous cell carcinoma. The overall 5-year survival rate was 38.7%; the 5-year disease-specific survival rate was 71.0%. The 2-year local control rate was 83.0%. Late complications occurred in 16 patients. The prevalence of complications was relatively high in the group treated with intraluminal radiation therapy.
CONCLUSION: Local control and survival rates in patients treated with radiation therapy were excellent especially in the group treated with external and intraluminal radiation therapy; however, the optimal dose and optimal combination of external and intraluminal radiation therapy should be further assessed.

Recent topics in chemotherapy for head and neck cancer
Y Inuyama, S Fukuda, T Kamata, H Shirato, M Fujii, J Kanzaki, M Horiuchi
CANCER CHEMOTHERAPY: CHALLENGES FOR THE FUTURE, VOL 10, 1110, 109, 119, ELSEVIER SCIENCE PUBL B V, 1995, [Peer-reviewed]
English, International conference proceedings

RADIOTHERAPY DEDICATED CT SYSTEM - RT-CT SYSTEM - THE HOKKAIDO-UNIVERSITY EXPERIENCE
T KAMADA, H TSUJII, G IRIE, J MIZOE, T ARIMOTO, H SHIRATO, A TAKAMURA
PROCEEDINGS OF THE XVI INTERNATIONAL CANCER CONGRESS - FREE PAPERS AND POSTERS, TOMES 1-4, 2713, 2717, MONDUZZI EDITORE, 1994, [Peer-reviewed]
English, International conference proceedings

Prof.　　　　　　　　　　　　　　　
SHIRATO Hiroki
[Peer-reviewed]

がん治療における緩和的放射線治療の評価と普及啓発のための研究 放射線治療を含むがん治療の経済毒性と両立支援に関する研究
青山英史, 白土博樹, 西岡健太郎, 岩崎由加子, 高橋健夫, 原田英幸, 立石清一郎, 内海暢子, 浅川勇雄, がん治療における緩和的放射線治療の評価と普及啓発のための研究 令和3年度 総括・分担研究報告書(Web), 2022

中小企業等における治療と仕事の両立支援の取り組み促進のための研究「治療と仕事の両立支援」に資する大学病院モデルの構築
白土博樹, 西岡健太郎, 岩崎由加子, 渋谷麻実, 本多和典, 梶本祐介, 五十嵐中, 五十嵐中, 中小企業等における治療と仕事の両立支援の取り組み促進のための研究 令和3年度 総括・分担研究報告書(Web), 2022

SLD repair impact on prolonged proton irradiation with various cell specific parameters
KASAMATSU Koki, MATSUURA Taeko, MATSUURA Taeko, TAKAO Seishin, TAKAO Seishin, TANAKA Sodai, TANAKA Sodai, MIYAMOTO Naoki, MIYAMOTO Naoki, NAM Jin-Min, SHIRATO Hiroki, SHIRATO Hiroki, UMEGAKI Kikuo, UMEGAKI Kikuo, 日本医学物理学会学術大会報文集, 119th, 2020

局所進行食道癌に対してspot scanning法による根治的化学陽子線療法を施行した一例　　　　　　　　　　　　　　　
宮崎 智彦, 打浪 雄介, 田口 大志, 加藤 徳雄, 清水 伸一, 白土 博樹, 中積 宏之, 中野 真太郎, 坂本 直哉, 高尾 聖心, 田村 昌也, 松浦 妙子, 日本医学放射線学会秋季臨床大会抄録集, 55回, S520, S520, Sep. 2019
(公社)日本医学放射線学会, Japanese

Bladder-preserving therapy using a real-time tumor-tracking radiotherapy system for muscle-invasive bladder cancer.
Haruka Miyata, Takahiro Osawa, Jun Frumido, Hiroshi Kikuchi, Ryuji Matsumoto, Takashige Abe, Satoru Maruyama, Kentaro Nishioka, Shinichi Shimizu, Takayuki Hashimoto, Hiroki Shirato, Nobuo Shinohara, JOURNAL OF CLINICAL ONCOLOGY, 37, 7, Mar. 2019
AMER SOC CLINICAL ONCOLOGY, English, Summary international conference

A retrospective analysis of neoadjuvant chemotherapy followed by surgery or definitive chemoradiotherapy in patients with advanced esophageal squamous cell carcinoma.
Hiroshi Nakatsumi, Yoshito Komatsu, Shintaro Nakano, Kentaro Sawada, Tetsuhito Muranaka, Yasuyuki Kawamoto, Satoshi Yuki, Yusuke Uchinami, Hiroshi Taguchi, Hiroki Shirato, Yuma Ebihara, Toshiaki Shichinohe, Satoshi Hirano, Naoya Sakamoto, JOURNAL OF CLINICAL ONCOLOGY, 37, 4, Feb. 2019
AMER SOC CLINICAL ONCOLOGY, English, Summary international conference

Automatic metastatic bone tumor classification with DCNN-based features using treatment-planning CT
Haruna Watanabe, Ren Togo, Takahiro Ogawa, Miki Haseyama, Koichi Yasuda, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato, Proceedings of SPIE - The International Society for Optical Engineering, 11050, 01 Jan. 2019
© 2019 SPIE. In this paper, we propose a method to classify metastatic bone tumors using treatment-planning computed tomography images. The proposed method utilizes pre-trained deep convolutional neural network (DCNN) models as feature extractors and enables the metastatic bone tumor classification by using the obtained features. Performance of several state-of-the-art DCNN-based features was compared and evaluated in our experiment.

放射線治療用微粒子マーカの実現可能性の検証
森田亮, 阿保大介, 曽山武士, 工藤與亮, 白土博樹, 作原祐介, IVR, 33, 3, 314, 25 Nov. 2018
Japanese

Big Data Analysis of Treatment Process Time for the Real-Time-Image Gated-Spot-Scanning Proton-Beam Therapy (RGPT) System
T. Yoshimura, S. Shimizu, T. Hashimoto, N. Katoh, T. Inoue, K. Nishioka, T. Matsuura, S. Takao, M. Tamura, H. Tamura, K. Horita, K. Umegaki, H. Shirato, International Journal of Radiation Oncology*Biology*Physics, 102, 3, e501, e502, Nov. 2018, [Peer-reviewed]
Elsevier BV, Summary international conference

深層学習に基づく画像特徴量を利用した放射線治療用CT画像における転移性骨腫瘍の検出に関する検討
渡邊はるな, 藤後廉, 小川貴弘, 長谷山美紀, 安田耕一, THA Khin Khin, 工藤與亮, 白土博樹, 電気・情報関係学会北海道支部連合大会講演論文集(CD-ROM), 2018, ROMBUNNO.87, 27 Oct. 2018
Japanese

前立腺癌治療の新たな展開:ハイリスク前立腺癌に対する拡大手術、粒子線治療、ネオアジュバント治療 ハイリスク前立腺がんに対する強度変調放射線治療・陽子線治療 現状と可能性　　　　　　　　　　　　　　　
清水 伸一, 橋本 孝之, 西岡 健太郎, 安部 崇重, 大澤 崇宏, 松本 隆児, 松浦 妙子, 宮本 直樹, 高尾 聖心, 鈴木 隆介, 梅垣 菊男, 篠原 信雄, 白土 博樹, 日本癌治療学会学術集会抄録集, 56回, SY5, 2, Oct. 2018
(一社)日本癌治療学会, English

全脳全脊髄強度変調陽子線照射が骨髄抑制軽減に有用であったAYA世代胚細胞腫瘍の2例
橋本孝之, 井口晶裕, 寺坂俊介, 杉山未奈子, 山口秀, 小林浩之, 長祐子, 鬼丸力也, 清水伸一, 白土博樹, 日本小児科学会雑誌, 122, 7, 1240, 1240, 01 Jul. 2018
(公社)日本小児科学会, Japanese

Improvement of the repeatability of parallel transmission at 7T using interleaved acquisition in the calibration scan.
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, Jul. 2018, [International Magazine]
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., English

全脳全脊髄強度変調陽子線照射(IMPT)が骨髄抑制軽減に有用であったAYA世代胚細胞腫瘍の2例　　　　　　　　　　　　　　　
橋本 孝之, 寺坂 俊介, 井口 晶裕, 山口 秀, 小林 浩之, 杉山 未奈子, 長 祐子, 森 崇, 高尾 聖心, 松浦 妙子, 鬼丸 力也, 清水 伸一, 白土 博樹, 日本小児血液・がん学会雑誌, 55, 1, 76, 76, Jun. 2018
(一社)日本小児血液・がん学会, Japanese

聴神経鞘腫に対する定位放射線治療後に腫瘍内出血を来した2例
打浪雄介, 鬼丸力也, 白土博樹, 森崇, 山口秀, 寺坂俊介, 小林浩之, 藤原圭志, 本間明宏, Japanese Journal of Radiology, 36, Supplement, 8, 8, 25 Feb. 2018
(公社)日本医学放射線学会, Japanese

ヘリウム・陽子線ハイブリッド治療に関する考察(コンセプト)
白土博樹, 清水伸一, 鬼丸力也, 高尾聖心, 松浦妙子, 梅垣菊雄, Japanese Journal of Radiology, 36, Supplement, 7, 7, 25 Feb. 2018
(公社)日本医学放射線学会, Japanese

A note on classification of brain metastases from MR images based on machine learning
菅田健斗, 小川貴弘, 長谷山美紀, THA Khin Khin, THA Khin Khin, 工藤與亮, 工藤與亮, 白土博樹, 白土博樹, 電子情報通信学会技術研究報告, 117, 431, 311, 314, 15 Feb. 2018
電子情報通信学会, Japanese

乳癌眼窩尖部転移により視力低下をきたし、放射線治療により著明な改善を認めた1例　　　　　　　　　　　　　　　
湊川 英樹, 安田 耕一, 打浪 雄介, 白土 博樹, 土屋 和彦, 加藤 徳雄, 木下 留美子, 石田 直子, 山下 啓子, 石嶋 漢, Japanese Journal of Radiology, 36, Suppl., 11, 11, Feb. 2018
(公社)日本医学放射線学会, Japanese

A note on classification of brain metastases from MR images based on machine learning
菅田 健斗, 小川 貴弘, 長谷山 美紀, タ キンキン, 工藤 與亮, 白土 博樹, 映像情報メディア学会技術報告 = ITE technical report, 42, 4, 311, 314, Feb. 2018
映像情報メディア学会, Japanese

Heterogeneity of longitudinal and circumferential contraction in relation to late gadolinium enhancement in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction.
Keita Sakamoto, Noriko Oyama-Manabe, Osamu Manabe, Tadao Aikawa, Yasuka Kikuchi, Harue Sasai-Masuko, Masanao Naya, Kohsuke Kudo, Fumi Kato, Nagara Tamaki, Hiroki Shirato, Japanese journal of radiology, 36, 2, 103, 112, Feb. 2018, [Domestic magazines]
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 (LSregional, LSglobal, CSregional, CSglobal), and their regional heterogeneities were evaluated using coefficients of variation (LSCoV, CSCoV) in relation to LGE. Receiver operating characteristic curve analysis was performed to identify patients with a total left ventricular myocardial LGE ≥ 15%. RESULTS: LSglobal in HCM patients was significantly decreased compared to that in controls (- 14.4 ± 2.4% vs - 17.2 ± 2.0%; p = 0.0004), while CSglobal was not (p = 1.0). Negative LGE segments demonstrated decreased LSregional in HCM patients compared to in controls (p < 0.0001), while CSregional was not decreased. CSCoV 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 LSCoV was low (0.49). CONCLUSION: The heterogeneity in CSregional has a high diagnostic value for detection of HCM patients with extensive LGE., English

Pulmonary tumor thrombotic microangiopathy(PTTM)の1例-生前~死後CT,そして解剖との対比-
吉野裕紀, 菊池穏香, 菊池穏香, 常田慧徳, 加藤扶美, 加藤扶美, 工藤與亮, 工藤與亮, 仲川心平, 田中敏, 白土博樹, 白土博樹, 日本医学放射線学会秋季臨床大会抄録集, 54th, 2018

全脳全脊髄照射におけるスポットスキャニング陽子線治療とIMRTによる誘発二次発がん率の比較
鈴木俊介, 田村昌也, 鈴木隆介, 高尾聖心, 橋本孝之, 清水伸一, 白土博樹, 日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集, 31st (CD-ROM), 2018

リンパ脈管筋腫症(LAM)を合併した乳癌に対し乳房温存術後に術後照射を施行した2例
木下留美子, 長江伸樹, 西岡健太郎, 橋本孝之, 清水伸一, 白土博樹, 加藤扶美, 石田直子, 山下啓子, 清水薫子, 鈴木雅, 今野哲, 北海道外科雑誌, 63, 2, 2018

Prostate position deviation analysis using real-time-image gated spot-scanning proton therapy (RGPT) system for prostate cancer
TAMURA Hiroshi, TAMURA Hiroshi, SHIMIZU Shinichi, NISHIOKA Kentaro, HASHIMOTO Takayuki, YOSHIMURA Takaaki, MATSUO Yuto, MATSUURA Taeko, MATSUURA Taeko, TAKAO Seishin, UMEGAKI Kikuo, UMEGAKI Kikuo, SHIRATO Hiroki, 医学物理 Supplement, 38, 1, 2018

放射線治療における数値指標の医学物理的利用
清水伸一, 小橋啓司, 伊藤陽一, PRAYONGRAT Anussara, 加藤徳雄, 安田耕一, 出倉康裕, 木元拓也, 白土博樹, 日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集, 31st (CD-ROM), 39, 2018
Japanese

Simple modification of arm position improves B1+ and signal homogeneity in the thoracolumbar spine at 3T.
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, Jan. 2018, [International Magazine]
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., English

Noninvasive electrical conductivity measurement by MRI: a test of its validity and the electrical conductivity characteristics of glioma.
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, Jan. 2018, [International Magazine]
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., English

Characteristics of immunoglobulin G4-related aortitis/periaortitis and periarteritis on fluorodeoxyglucose positron emission tomography/computed tomography co-registered with contrast-enhanced computed tomography.
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, Dec. 2017, [International Magazine]
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., English

Benefits of Craniospinal Intensity-modulated Proton Beam Therapy in Reducing the Myelosuppression for Adolescent Germ Cell Tumors: Two Case Reports
Takayuki Hashimoto, Syunsuke Terasaka, Akihiro Iguchi, Shigeru Yamaguchi, Hiroyuki Kobayashi, Minako Sugiyama, Yuko Cho, Takashi Mori, Seishin Takao, Taeko Matsuura, Rikiya Onimaru, Shinichi Shimizu, Hiroki Shirato, PEDIATRIC BLOOD & CANCER, 64, S87, S88, Nov. 2017
WILEY, English, Summary international conference

An Organ Motion and Acute Toxicity Study of Image-Guided Spot-Scanning Proton Beam Therapy With An Internal Fiducial Marker for Pancreatic Cancers.
Y. Uchinami, N. Katoh, D. Abo, K. Harada, Y. Nishikawa, T. Inoue, T. Hashimoto, R. Onimaru, N. Miyamoto, Y. Sakuhara, S. Shimizu, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 99, 2, E194, E194, Oct. 2017
ELSEVIER SCIENCE INC, English, Summary international conference

Long-Term Outcomes of Proton Therapy for Prostate Cancer in Japan: Retrospective Analysis of a Multi-institutional Survey
H. Iwata, H. Ishikawa, M. Takagi, T. Okimoto, S. Murayama, T. Akimoto, H. Wada, T. Arimura, Y. Sato, M. Araya, J. E. Mizoe, H. Shirato, H. Sakurai, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 99, 2, E241, E242, Oct. 2017
ELSEVIER SCIENCE INC, English, Summary international conference

Analysis of Threshold Doses for Radiation Induced Liver Parenchymal Changes on MRI after Real TimeeImage Gated Spot-Scanning Proton Beam Therapy of Hepatocellular Carcinomas
N. Katoh, Y. Uchinami, S. Takao, K. Yasuda, K. Harada, T. Inoue, T. Matsuura, T. Hashimoto, S. Shimizu, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 99, 2, E159, E160, Oct. 2017
ELSEVIER SCIENCE INC, English, Summary international conference

Can F-18-fluoromisonidazole PET/CT Predict the Clinical Outcome for Stage I Non-small Cell Lung Cancer Treated By Stereotactic Body Radiation Therapy?
T. Inoue, S. Watanabe, K. Harada, K. Yasuda, N. Katoh, S. Okamoto, T. Shiga, Y. Kuge, N. Tamaki, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 99, 2, E466, E466, Oct. 2017
ELSEVIER SCIENCE INC, English, Summary international conference

Kasabach-Merritt症候群を合併した血管腫に対する陽子線治療の有用性について　　　　　　　　　　　　　　　
渡邊 敏史, 井口 晶裕, 長 祐子, 杉山 未奈子, 廣瀬 文, 森 崇, 高尾 聖心, 橋本 孝之, 鬼丸 力也, 清水 伸一, 白土 博樹, 日本小児血液・がん学会雑誌, 54, 4, 347, 347, Oct. 2017
(一社)日本小児血液・がん学会, Japanese

Identifying Relations Between Imaging Phenotypes and Molecular Subtypes of Breast Cancer: Model Discovery and External Validation
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, Oct. 2017
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., WILEY, English

Educational outcomes of a medical physicist program over the past 10 years in Japan
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, Sep. 2017
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., OXFORD UNIV PRESS, English

Volume of high-risk intratumoral subregions at multi-parametric MR imaging predicts overall survival and complements molecular analysis of glioblastoma
Yi Cui, Shangjie Ren, Khin Khin Tha, Jia Wu, Hiroki Shirato, Ruijiang Li, EUROPEAN RADIOLOGY, 27, 9, 3583, 3592, Sep. 2017
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., SPRINGER, English

Local relapse of nasopharyngeal cancer and Voxel-based analysis of FMISO uptake using PET with semiconductor detectors
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, Sep. 2017
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., BIOMED CENTRAL LTD, English

北海道大学の死因究明教育研究センターでのオートプシーイメージング部門および放射線診断医の役割
菊池穏香, 吉野裕紀, 工藤與亮, 工藤與亮, 加藤扶美, 加藤扶美, 南須原康行, 南須原康行, 南須原康行, 品川尚文, 清水康, 田中敏, 兵頭秀樹, 的場光太郎, 的場光太郎, 三上八郎, 田中伸哉, 田中伸哉, 白土博樹, 白土博樹, 日本医学放射線学会秋季臨床大会抄録集, 53rd, S506, 18 Aug. 2017
Japanese

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells
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, 14 Jul. 2017
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., Dove Medical Press Ltd., English

肝腫瘍に対する動態追跡照射のための経皮的マーカ留置
森田 亮, 曽山 武士, 阿保 大介, 作原 祐介, 工藤 與亮, 加藤 徳雄, 白土 博樹, IVR: Interventional Radiology, 32, 2, 161, 161, Jul. 2017
(一社)日本インターベンショナルラジオロジー学会, Japanese

A simulation study on the dosimetric benefit of real-time motion compensation in spot-scanning proton therapy for prostate
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, Jul. 2017
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., OXFORD UNIV PRESS, English

甲状腺癌分化癌の骨転移に対するIMRTを含めた外照射の治療成績
安田耕一, 加藤徳雄, 岡本祥三, 木下留美子, 志賀哲, 水町貴諭, 畠山博充, 本間明宏, 田口純, 清水康, 森崇, 土屋和彦, 白土博樹, 頭けい部癌, 43, 2, 221, 221, 10 May 2017
日本頭頸部癌学会, Japanese

Non-invasive prediction of the tumor growth rate using advanced diffusion models in head and neck squamous cell carcinoma patients
Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Taisuke Harada, Yukie Shimizu, Khin Khin Tha, Kohsuke Kudo, Hiroki Shirato, ONCOTARGET, 8, 20, 33631, 33643, May 2017
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., IMPACT JOURNALS LLC, English

Residual tumour detection in post-treatment granulation tissue by using advanced diffusion models in head and neck squamous cell carcinoma patients
Noriyuki Fujima, Daisuke Yoshida, Tomohiro Sakashita, Akihiro Homma, Kohsuke Kudo, Hiroki Shirato, EUROPEAN JOURNAL OF RADIOLOGY, 90, 14, 19, May 2017
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., ELSEVIER IRELAND LTD, English

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients
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, May 2017
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., OXFORD UNIV PRESS, English

肝腫瘍に対する動態追跡照射のための経皮的マーカ留置(Percutaneous hepatic fiducial marker implantation for Real-time Tumor-tracking Radiotherapy(RTRT))　　　　　　　　　　　　　　　
森田 亮, 作原 祐介, 曽山 武士, 阿保 大介, 加藤 徳雄, 工藤 與亮, 白土 博樹, IVR: Interventional Radiology, 32, Suppl., 173, 173, Apr. 2017
(一社)日本インターベンショナルラジオロジー学会, English

Commissioning of Eclipse Treatment Planning System for Spot-scanning Nozzle in Hokkaido University Proton Therapy Center
YOSHIMURA Takaaki, YOSHIMURA Takaaki, MATSUO Yuto, MATSUURA Taeko, MATSUURA Taeko, TAKAO Seishin, FUJII Takaaki, HIRAYAMA Shusuke, UMEGAKI Kikuo, SHIMIZU Shinichi, SHIRATO Hiroki, 医学物理 Supplement, 37, 1, 176, 01 Apr. 2017
English

Automatic Estimation of Volumetric Breast Density Using Artificial Neural Network-Based Calibration of Full-Field Digital Mammography: Feasibility on Japanese Women With and Without Breast Cancer
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, Apr. 2017
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., SPRINGER, English

Long-term follow-up after proton beam therapy for pediatric tumors: a Japanese national survey
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, 01 Mar. 2017
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., Blackwell Publishing Ltd, English

Analysis of inter- and intra fractional partial bladder wall movement using implanted fiducial markers
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, Mar. 2017
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., BIOMED CENTRAL LTD, English

Tufted angiomaに対し放射線治療を行った1例
長江伸樹, 森崇, 木下留美子, 鬼丸力也, 白土博樹, 西村真智子, 畑中佳奈子, 木村鉄宣, Japanese Journal of Radiology, 35, Supplement, 4, 25 Feb. 2017
Japanese

頭蓋底腫瘍術後に強度変調放射線治療を行った2例
森崇, 宮本直樹, 鈴木隆介, 鬼丸力也, 白土博樹, Japanese Journal of Radiology, 35, Supplement, 4, 25 Feb. 2017
Japanese

下咽頭癌に対する強度変調放射線治療(IMRT)と強度変調陽子線治療(IMPT)の治療計画の比較
土屋和彦, 安田耕一, 原田八重, 鬼丸力也, 白土博樹, Japanese Journal of Radiology, 35, Supplement, 10, 10, 25 Feb. 2017
(公社)日本医学放射線学会, Japanese

画像診断に苦慮したHHV8-unrelated primary effusion lymphoma-like lymphomaの1例　　　　　　　　　　　　　　　
中川 純一, 加藤 扶美, 三村 理恵, 藪崎 哲史, 坂本 圭太, 真鍋 徳子, 工藤 與亮, 菅野 宏美, 松野 吉宏, 豊嶋 崇徳, 金谷 穣, 渡利 英道, 櫻木 範明, 白土 博樹, Japanese Journal of Radiology, 35, Suppl., 3, 3, Feb. 2017
(公社)日本医学放射線学会, Japanese

Phase I study of stereotactic body radiation therapy for peripheral T2NOM0 non-small cell lung cancer (JCOG0702): Results for the group with PTV >= 100 cc
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, Feb. 2017
Purpose: A dose escalation study to determine the recommended dose (RD) with stereotactic body radiation therapy (SBRT) for peripheral T2NOMO 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 MID. 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. (c) 2016 Elsevier Ireland Ltd. All rights reserved., ELSEVIER IRELAND LTD, English

Advanced diffusion models in head and neck squamous cell carcinoma patients: Goodness of fit, relationships among diffusion parameters and comparison with dynamic contrast-enhanced perfusion
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, Feb. 2017
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., ELSEVIER SCIENCE INC, English

Impact of Real-Time Image Gating on Spot Scanning Proton Therapy for Lung Tumors: A Simulation Study
Takahiro Kanehira, Taeko Matsuura, Seishin Takao, Yuka Matsuzaki, Yusuke Fujii, Takaaki Fujii, Yoichi M. Ito, Naoki Miyamoto, Tetsuya Inoue, Norio Katoh, Shinichi Shimizu, Kikuo Umegaki, Hiroki Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 97, 1, 173, 181, Jan. 2017
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. (C) 2016 Elsevier Inc. All rights reserved., ELSEVIER SCIENCE INC, English

Breath-holding during the Calibration Scan Improves the Reproducibility of Parallel Transmission at 7T for Human Brain
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
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., JPN SOC MAGNETIC RESONANCE IN MEDICINE, English

Clinical outcomes of stage I and IIA non-small cell lung cancer patients treated with stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system
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, Jan. 2017
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., BIOMED CENTRAL LTD, English

Mean kurtosis alterations of cerebral white matter in patients with schizophrenia revealed by diffusion kurtosis imaging.
Hisashi Narita, Khin K Tha, Naoki Hashimoto, Hiroyuki Hamaguchi, Shin Nakagawa, Hiroki Shirato, Ichiro Kusumi, Progress in neuro-psychopharmacology & biological psychiatry, 71, 169, 75, 03 Nov. 2016, [International Magazine]
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., English

Development of Patient-centered Navigation System of Cancer Diagnosis and Treatment
白土博樹, 安田耕一, 熊木康雄, 上杉正人, 医療情報学, 36, Supplement 1, 126‐127, 01 Nov. 2016
Japanese

気管内挿管下全身麻酔管理で陽子線治療を実施した小児がんの2症例(Proton beam therapy for pediatric cancer with endotracheal intubation under the general anesthesia: A report of two cases)
橋本 孝之, 敦賀 健吉, 小林 浩之, 井口 晶裕, 本多 昌平, 杉山 未奈子, 安田 耕一, 宮城 久之, 山口 秀, 藤田 憲明, 大島 淳二郎, 長 祐子, 鬼丸 力也, 清水 伸一, 寺坂 俊介, 森本 裕二, 白土 博樹, 日本小児血液・がん学会雑誌, 53, 4, 366, 366, Nov. 2016
(NPO)日本小児血液・がん学会, English

The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy
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, Nov. 2016
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., SPRINGER, English

Glucose Metabolism and Its Complicated Relationship with Tumor Growth and Perfusion in Head and Neck Squamous Cell Carcinoma
Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Kenji Hirata, Tohru Shiga, Kohsuke Kudo, Hiroki Shirato, PLOS ONE, 11, 11, Nov. 2016
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., PUBLIC LIBRARY SCIENCE, English

A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-beta-D-Ribo-Pentofuranosyl)Cytosine, Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak (SOBP) of Proton Beam
Kenichiro Maeda, Hironobu Yasui, Tohru Yamamori, Taeko Matsuura, Seishin Takao, Motofumi Suzuki, Akira Matsuda, Osamu Inanami, Hiroki Shirato, PLOS ONE, 11, 11, Nov. 2016
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., PUBLIC LIBRARY SCIENCE, English

Feasibility Study of Using Dual-Energy Cone Beam Computed Tomography (DE-CBCT) in Proton Therapy Treatment Planning
H. Peng, T. Kanehira, S. Takao, T. Matsuura, K. Umegaki, H. Shirato, L. Xing, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, E697, E697, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

From Simulation Studies to Clinical Measurements: Challenges, Limitations, and Future Outlook in Proton Acoustic Range Verification
S. Yousefi, M. Ahmad, L. Xiang, Y. Chen, M. Zhang, S. Tang, W. Zou, K. Umegaki, H. Shirato, L. Xing, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, E620, E621, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

A Retrospective Multi-institutional Study of Proton Beam Therapy for Head and Neck Cancer With Non-Squamous Cell Histologies
T. Akimoto, S. Zenda, N. Nakamura, Y. Demizu, T. Okimoto, S. Murayama, M. Mizumoto, H. Sakurai, T. Nakamura, Y. Kikuchi, K. Yamamoto, H. Shirato, T. Onoe, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, E337, E337, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

Enabling Conventional Cone Beam Computed Tomography With the Capability of Dual Energy Imaging Using a Simple Add-on Beam Modifier
R. Vinke, S. Takao, K. Umegaki, H. Shirato, H. Peng, L. Xing, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, E636, E636, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

Analysis of Durations and Dose Rates for Treatment of Moving Liver Tumors Using Real-Time Image Gated Spot Scanning Proton Beam Therapy
S. Shimizu, N. Katoh, T. Hashimoto, K. Nishioka, T. Yoshimura, S. Takao, T. Matsuura, N. Miyamoto, K. Umegaki, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, S211, S212, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

Autonomous Quality Assurance for Spot-Scanning Proton Therapy and SRS/SBRT Using Radioluminescent Phantoms, Optical Imaging, and Machine Vision
C. H. Jenkins, Y. Yang, S. J. Yu, H. Yu, Y. Matsuzaki, T. Yoshimura, Y. Fujii, K. Umegaki, H. Shirato, L. Xing, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, S170, S171, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

Gold Nanoparticles With RGD Peptide in Radiation Therapy Suppress the Invasion Activity of Breast Cancer Cells
P. H. Wu, Y. Onodera, Y. Ichikawa, Y. Watanabe, W. Qian, T. Hashimoto, H. Shirato, J. M. Nam, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, E574, E574, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

Stereotactic Body Radiation Therapy Using a Real-time Tumor-Tracking Radiation Therapy System for Hepatocellular Carcinomas
Y. Uchinami, N. Katoh, D. Abo, K. Harada, T. Inoue, H. Taguchi, R. Onimaru, S. Shimizu, Y. Sakuhara, K. Ogawa, T. Kamiyama, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, E155, E155, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

Radiation Dose to Internal Mammary Lymph Node in Standard Tangential Breast Irradiation
R. Kinoshita, S. Shimizu, Y. Nishikawa, K. Nishioka, T. Hashimoto, R. Suzuki, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 96, 2, E17, E18, Oct. 2016
ELSEVIER SCIENCE INC, English, Summary international conference

非小細胞肺癌FMISO PET/CTにおける呼吸性移動距離と低酸素過小評価の検討　　　　　　　　　　　　　　　
渡邊 史郎, 平田 健司, 岡本 祥三, 志賀 哲, 井上 哲也, 孫田 惠一, 西嶋 剣一, 豊永 拓哉, 久下 裕司, 白土 博樹, 玉木 長良, 核医学, 53, Suppl., S317, S317, Oct. 2016
(一社)日本核医学会, Japanese

Effectiveness of superselective intra-arterial chemoradiotherapy targeting retropharyngeal lymph node metastasis
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, Oct. 2016
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., SPRINGER, English

Spatial distributions of dose enhancement around a gold nanoparticle at several depths of proton Bragg peak
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, Oct. 2016
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., ELSEVIER SCIENCE BV, English

Utility of noncontrast-enhanced time-resolved four-dimensional MR angiography with a vessel-selective technique for intracranial arteriovenous malformations
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, Oct. 2016
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., WILEY-BLACKWELL, English

NTCP modeling analysis of acute hematologic toxicity in whole pelvic radiation therapy for gynecologic malignancies - A dosimetric comparison of IMRT and spot-scanning proton therapy (SSPT)
Takaaki Yoshimura, Rumiko Kinoshita, Shunsuke Onodera, Chie Toramatsu, Ryusuke Suzuki, Yoichi M. Ito, Seishin Takao, Taeko Matsuura, Yuka Matsuzaki, Kikuo Umegaki, Hiroki Shirato, Shinichi Shimizu, PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS, 32, 9, 1095, 1102, Sep. 2016
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. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license., ELSEVIER SCI LTD, English

Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort study (vol 16, 65, 2016)
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, Sep. 2016
© 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., BIOMED CENTRAL LTD, English, Others

Effect of respiratory and cardiac gating on the major diffusion-imaging metrics.
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, Aug. 2016, [International Magazine]
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., English

A Retrospective Study of G-Tube Use in Japanese Patients Treated with Concurrent Chemoradiotherapy for Hypopharyngeal Cancer
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, Aug. 2016
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., PUBLIC LIBRARY SCIENCE, English

Oligo-recurrence predicts favorable prognosis of brain-only oligometastases in patients with non-small cell lung cancer treated with stereotactic radiosurgery or stereotactic radiotherapy: a multi-institutional study of 61 subjects
Yuzuru Niibe, Tetsuo Nishimura, Tetsuya Inoue, Katsuyuki Karasawa, Yoshiyuki Shioyama, Keiichi Jingu, Hiroki Shirato, BMC CANCER, 16, Aug. 2016
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., BIOMED CENTRAL LTD, English

Comparison of conventional ultrasonography and ultrasonography-computed tomography fusion imaging for target identification using digital/real hybrid phantoms: a preliminary study
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, Jul. 2016
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., SPRINGER JAPAN KK, English

Proton beam therapy for pediatric malignancies: a retrospective observational multicenter study in Japan
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, Jul. 2016
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., WILEY-BLACKWELL, English

Optimization and evaluation of multiple gating beam delivery in a synchrotron-based proton beam scanning system using a real-time imaging technique
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, Jul. 2016
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., ELSEVIER SCI LTD, English

Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort studya prospective cohort study
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, Jul. 2016
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., BIOMED CENTRAL LTD, English

Enabling Conventional Cone Beam CT with the Capability of Dual Energy Imaging Using a Simple Add-On Beam Modifier
R. Vinke, S. Takao, K. Umegaki, H. Shirato, H. Peng, L. Xing, MEDICAL PHYSICS, 43, 6, 3457, 3457, Jun. 2016
WILEY, English, Summary international conference

An Evaluation Method of Lifetime Attributable Risk for Comparing Between Proton Beam Therapy and Intensity Modulated X-Ray Therapy for Pediatric Cancer Patients by Averaging Four Dose-Response Models for Carcinoma Induction
M. Tamura, Y. Ito, H. Sakurai, M. Mizumoto, S. Kamizawa, S. Murayama, H. Yamashita, S. Takao, R. Suzuki, H. Shirato, MEDICAL PHYSICS, 43, 6, 3508, 3508, Jun. 2016
WILEY, English, Summary international conference

Simulation Study of Real-Time-Image Gating On Spot Scanning Proton Therapy for Lung Tumors
T. Kanehira, T. Matsuura, S. Takao, Y. Matsuzaki, Y. Fujii, T. Fujii, N. Miyamoto, T. Inoue, N. Katoh, S. Shimizu, K. Umegaki, H. Shirato, MEDICAL PHYSICS, 43, 6, Jun. 2016
WILEY, English, Summary international conference

Dose Enhancement by Gold Nanoparticles Around the Bragg Peak of Proton Beams
J. Kwon, K. Sutherland, T. Hashimoto, H. Peng, L. Xing, H. Shirato, H. Date, MEDICAL PHYSICS, 43, 6, 3787, +, Jun. 2016
WILEY, English, Summary international conference

Feasibility Study of Using a Dual-Energy Cone Beam CT (DECBCT) in Proton Therapy Treatment Planning
H. Peng, T. Kanehira, S. Takao, T. Matsuura, K. Umegaki, H. Shirato, L. Xing, MEDICAL PHYSICS, 43, 6, 3457, 3458, Jun. 2016
WILEY, English, Summary international conference

Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface
S. Takao, T. Matsuura, Y. Matsuzaki, Y. Fujii, T. Fujii, N. Katoh, S. Shimizu, K. Umegaki, H. Shirato, MEDICAL PHYSICS, 43, 6, 3505, 3505, Jun. 2016
WILEY, English, Summary international conference

Software Development for 4D-CBCT Research of Real-Time-Image Gated Spot Scanning Proton Therapy
T. Fujii, T. Matsuura, S. Takao, N. Miyamoto, Y. Matsuzaki, Y. Fujii, K. Umegaki, S. Shimizu, H. Shirato, MEDICAL PHYSICS, 43, 6, 3389, 3389, Jun. 2016
WILEY, English, Summary international conference

No Increase in Biological Effectiveness Through Collimator Scattered Low Energy Protons
T. Matsuura, S. Takao, Y. Matsuzaki, Y. Fujii, T. Fujii, K. Maeda, H. Ueda, H. Koyano, K. Umegaki, H. Shirato, MEDICAL PHYSICS, 43, 6, 3492, 3492, Jun. 2016
WILEY, English, Summary international conference

3T乳腺MRIにおける拡散尖度画像を用いた浸潤性乳癌の評価 バイオマーカーおよび腋窩リンパ節転移との比較　　　　　　　　　　　　　　　
加藤 扶美, 工藤 與亮, 藤原 太郎, Wang Jeff, 杉森 博行, 山下 啓子, 細田 充主, 真鍋 徳子, 三村 理恵, 白土 博樹, 日本乳癌学会総会プログラム抄録集, 24回, 250, 250, Jun. 2016
(一社)日本乳癌学会, Japanese

Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro
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, Jun. 2016
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., OXFORD UNIV PRESS, English

In vivo imaging of clock gene expression in multiple tissues of freely moving mice
Toshiyuki Hamada, Kenneth Sutherland, Masayori Ishikawa, Naoki Miyamoto, Sato Honma, Hiroki Shirato, Ken-ichi Honma, NATURE COMMUNICATIONS, 7, Jun. 2016
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., NATURE PUBLISHING GROUP, English

上咽頭癌再発例におけるFMISO‐PETと放射線治療に関する解析
安田耕一, 西川由記子, 岡本祥三, 伊藤陽一, 土屋和彦, 志賀哲, 鬼丸力也, 久下裕司, 玉木長良, 白土博樹, 頭けい部癌, 42, 2, 158, 158, 08 May 2016
日本頭頸部癌学会, Japanese

分子イメージングを用いた放射線治療
安田耕一, 安田耕一, 岡本祥三, 西川由記子, 伊藤陽一, 志賀哲, 井上哲也, 森崇, 豊永拓哉, 鬼丸力也, 渡邊史郎, 土屋和彦, 竹内渉, 加藤徳雄, 加藤徳雄, 久下裕司, 玉木長良, 白土博樹, 白土博樹, JSMI Report, 9, 2, 83, 83, 25 Apr. 2016
日本分子イメージング学会, Japanese

Comparison between borderline ovarian tumors and carcinomas using semi-automated histogram analysis of diffusion-weighted imaging: focusing on solid components.
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, Mar. 2016, [Domestic magazines]
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., English