Cost-effectiveness analysis for multi adverse events of proton beam therapy for pediatric medulloblastoma in Japan
Takaaki Yoshimura, Yasuhiro Morii, Honoka Tamori, Ryuki Kita, Takayuki Hashimoto, Hidefumi Aoyama, Katsuhiko Ogasawara
Journal of Radiation Research, Oxford University Press (OUP), 19 Nov. 2024
Scientific journal, Abstract

Medulloblastomas are one of the most common malignant cancers of the central nervous system in children. Proton beam therapy (PBT) is expected to provide equivalent tumor control to photon therapy while reducing the various adverse events caused by irradiation. Few studies have considered the cost-effectiveness of PBT for pediatric medulloblastoma, considering the multiple adverse effects and reflecting on the latest treatment advancements. A cost-utility analysis of PBT for pediatric medulloblastoma was conducted in a Japanese setting and compared to conventional photon therapy. The analysis was conducted from the public healthcare payer’s perspective, and direct costs for the treatment of radiation therapy and radiation-induced adverse events were included. A Markov model was used, and the health states of secondary cancer, hypothyroidism and hearing loss were defined as adverse events. The time horizon was the lifetime. Incremental cost-effectiveness ratio (ICER) was used as a measurement of cost-effectiveness, with quality-adjusted life years (QALYs) used as an outcome. The costs were estimated from the national fee schedule, and the utility and transition probabilities were estimated from published literature. PBT incurred an additional 1387116 Japanese yen (JPY) and 1.56 QALYs to the comparator. The ICER was JPY 887053/QALY, indicating that PBT was cost-effective, based on the reference value of JPY 5 million/QALY used in the Japanese cost-effectiveness analysis. Deterministic sensitivity analysis showed that the ICER ranged from JPY 284782/QALY to JPY 1918603/QALY as a result of deterministic sensitivity analysis, and probabilistic sensitivity analysis showed that PBT was cost-effective, with a probability of 91.7%.

Decision regret after curative treatment and its association with the decision-making process and quality of life for prostate cancer patients.
Miho Sato, Takahiro Osawa, Kentaro Nishioka, Tomohiko Miyazaki, Shuhei Takahashi, Takashi Mori, Takayuki Hashimoto, Haruka Miyata, Ryuji Matsumoto, Takashige Abe, Kazuki Ohashi, Sachiyo Murai, Yoichi M Ito, Nobuo Shinohara
International journal of urology : official journal of the Japanese Urological Association, 09 Oct. 2024, [International Magazine]
English, Scientific journal, OBJECTIVES: To determine how the treatment decision-making process and posttreatment health-related quality of life (HRQOL) are related to regret about treatment choice for prostate cancer patients in Japan. METHODS: We invited a total of 614 patients who were treated with radiation therapy (RT), radical prostatectomy (RP), or active surveillance/watchful waiting (AS/WW) from April 2007 to March 2021. Posttreatment regret was evaluated by the Decision Regret Scale. HRQOL was evaluated by the Expanded Prostate Cancer Index Composite and the 12-item Short Form Survey. The decision-making process was assessed by patient evaluation of the decision-making process. We compared the decision regret scale scores across treatment types, HRQOL, and decision-making processes. RESULTS: Data from 371 patients were analyzed (RT: 202, RP: 149, AS/WW: 20). The median length of time since treatment was 64 (IQR: 43-93) months. The decision regret scale scores were not significantly different among the treatment groups but were significantly greater (strong regret) in patients with poor urinary summary scores, bowel summary scores, and hormonal summary scores. The decision regret scale scores were significantly lower (less regret) for patients who reported being adequately informed at the time of the treatment decision and who had adequately communicated their questions and concerns to physicians than for patients who reported less adequate communication. This result was also observed among patients who reported low HRQOL scores. CONCLUSIONS: These findings underline the important influence of posttreatment HRQOL and decision-making as an interactive process between physicians and their patients on posttreatment regret in prostate cancer patients.

A simulation study of MR-guided proton therapy system using iron-yoked superconducting open MRI: a conceptual study.
Yusuke Fujii, Hideaki Ueda, Taisuke Takayanagi, Kentaro Nishioka, Takashi Mori, Takayuki Hashimoto, Hidefumi Aoyama, Kikuo Umegaki, Taeko Matsuura
Journal of radiation research, 04 Oct. 2024, [International Magazine]
English, Scientific journal, Radiotherapy platforms integrated with magnetic resonance imaging (MRI) have been significantly successful and widely used in X-ray therapy over the previous decade. MRI provides greater soft-tissue contrast than conventional X-ray techniques, which enables more precise radiotherapy with on-couch adaptive treatment planning and direct tracking of moving tumors. The integration of MRI into a proton beam irradiation system (PBS) is still in the research stage. However, this could be beneficial as proton therapy is more sensitive to anatomical changes and organ motion. In this simulation study, we considered the integration of PBS into the 0.3-T superconducting open MRI system. Our proposed design involves proton beams traversing a hole at the center of the iron yoke, which allows for a reduced fringe field in the irradiation nozzle while maintaining a large proton scan field of the current PBS. The shape of the bipolar MRI magnets was derived to achieve a large MRI field-of-view. To monitor the beam position and size accurately while maintaining a small beam size, the beam monitor installation was redesigned from the current system. The feasibility of this system was then demonstrated by the treatment plan quality, which showed that the magnetic field did not deteriorate the plan quality from that without the magnetic field for both a rectangular target and a prostate case. Although numerous challenges remain before the proposed simulation model can be implemented in a clinical setting, the presented conceptual design could assist in the initial design for the realization of the MR-guided proton therapy.

Geometric target margin strategy of proton craniospinal irradiation for pediatric medulloblastoma.
Takaaki Yoshimura, Keigo Kondo, Takayuki Hashimoto, Kentaro Nishioka, Takashi Mori, Takahiro Kanehira, Taeko Matsuura, Seishin Takao, Hiroshi Tamura, Takuya Matsumoto, Kenneth Sutherland, Hidefumi Aoyama
Journal of radiation research, 15 Sep. 2024, [International Magazine]
English, Scientific journal, In proton craniospinal irradiation (CSI) for skeletally immature pediatric patients, a treatment plan should be developed to ensure that the dose is uniformly delivered to all vertebrae, considering the effects on bone growth balance. The technical (t) clinical target volume (CTV) is conventionally set by manually expanding the CTV from the entire intracranial space and thecal sac, based on the physician's experience. However, there are differences in contouring methods among physicians. Therefore, we aimed to propose a new geometric target margin strategy. Nine pediatric patients with medulloblastoma who underwent proton CSI were enrolled. We measured the following water equivalent lengths for each vertebra in each patient: body surface to the dorsal spinal canal, vertebral limbus, ventral spinal canal and spinous processes. A simulated tCTV (stCTV) was created by assigning geometric margins to the spinal canal using the measurement results such that the vertebral limb and dose distribution coincided with a margin assigned to account for the uncertainty of the proton beam range. The stCTV with a growth factor (correlation between body surface area and age) and tCTV were compared and evaluated. The median values of each index for cervical, thoracic and lumber spine were: the Hausdorff distance, 9.14, 9.84 and 9.77 mm; mean distance-to-agreement, 3.26, 2.65 and 2.64 mm; Dice coefficient, 0.84, 0.81 and 0.82 and Jaccard coefficient, 0.50, 0.60 and 0.62, respectively. The geometric target margin setting method used in this study was useful for creating an stCTV to ensure consistent and uniform planning.

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.

A new predictive parameter for dose‐volume metrics in intensity‐modulated radiation therapy planning for prostate cancer: Initial phantom study
Yuki Saito, Ryusuke Suzuki, Naoki Miyamoto, Kenneth Lee Sutherland, Takahiro Kanehira, Masaya Tamura, Takashi Mori, Kentaro Nishioka, Takayuki Hashimoto, Hidefumi Aoyama
Journal of Applied Clinical Medical Physics, Apr. 2024, [Peer-reviewed]
Scientific journal

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.
Takaaki Yoshimura, Ryota Yamada, Rumiko Kinoshita, Taeko Matsuura, Takahiro Kanehira, Hiroshi Tamura, Kentaro Nishioka, Koichi Yasuda, Hiroshi Taguchi, Norio Katoh, Keiji Kobashi, Takayuki Hashimoto, Hidefumi Aoyama
Journal of radiation research, 17 Mar. 2024, [International Magazine]
English, Scientific journal, This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

北大病院放射線治療科関連施設における乳癌の放射線治療に関するアンケート結果リンパ節領域に対する照射について
木下 留美子, 田口 大志, 高橋 周平, 宮崎 智彦, 森 崇, 西岡 健太郎, 橋本 孝之, 青山 英史
北海道外科雑誌, 68, 2, 163, 164, 北海道外科学会, Dec. 2023
Japanese

【臨床脳腫瘍学-最新の診断・治療と病態-】脳腫瘍の治療 脳腫瘍の放射線療法・他 放射線療法 概論
青山 英史, 西岡 健太郎, 橋本 孝之
日本臨床, 81, 増刊9 臨床脳腫瘍学, 362, 366, (株)日本臨床社, Dec. 2023
Japanese

Slow-growing WNT medulloblastoma with atypical magnetic resonance imaging findings: illustrative case.
Makoto Mizushima, Michinari Okamoto, Shigeru Yamaguchi, Sogo Oki, Hiroaki Motegi, Minako Sugiyama, Atsushi Manabe, Ai Shimizu, Kentaro Nishioka, Takayuki Hashimoto, Junko Hirato, Yonehiro Kanemura, Miki Fujimura
Journal of neurosurgery. Case lessons, 6, 7, 14 Aug. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Medulloblastomas, with four molecular subgroups, are generally rapid-growing tumors with significant contrast enhancement and well-defined margins. However, each subgroup's clinical features, including disease time course and imaging characteristics, are not well defined. OBSERVATIONS: The authors describe the case of a 15-year-old female who presented with a 7-month history of impaired left-hand movement and was found to have a lesion on the dorsal side of the fourth ventricle. T2-weighted magnetic resonance imaging (MRI) at the patient's first presentation showed diffuse hyperintense signal without apparent mass, and gadolinium-enhanced T1-weighted imaging showed very slight contrast enhancement. In 1 month, her symptoms progressed, and follow-up MRI revealed an increase in the size of the lesion, showing greater diffusion restriction and contrast enhancement. She underwent gross-total resection, and pathology was consistent with classic medulloblastoma. Genetic analysis of the tumor confirmed the wingless (WNT) molecular subgroup. Adjuvant chemotherapy and proton beam therapy were performed. At the 18-month follow-up, MRI showed no recurrence of disease. LESSONS: Slow-growing medulloblastoma is very rare and not known to be associated with a specific molecular subgroup. Here, the authors report a case of slow-growing WNT medulloblastoma, indicating that slow growth may be a feature of this subgroup.

PO-2122 Effect of early fractional lymphocyte loss on lymphopenia probability models for NSCLC
T. Kanehira, H. Taguchi, N. Katoh, Y. Uchinami, T. Yoshimura, M. Tamura, R. Suzuki, T. Hashimoto, H. Aoyama
Radiotherapy and Oncology, 182, S1909, S1911, Elsevier BV, May 2023
Scientific journal

Brain metastases in Japanese NSCLC patients: prognostic assessment and the use of osimertinib and immune checkpoint inhibitors-retrospective study.
Hajime Higaki, Kentaro Nishioka, Manami Otsuka, Noboru Nishikawa, Motoyasu Shido, Hideki Minatogawa, Yukiko Nishikawa, Rikiya Takashina, Takayuki Hashimoto, Norio Katoh, Hiroshi Taguchi, Rumiko Kinoshita, Koichi Yasuda, Takashi Mori, Yusuke Uchinami, Fuki Koizumi, Yoshihiro Fujita, Shuhei Takahashi, Takahiro Hattori, Noriaki Nishiyama, Hidefumi Aoyama
Radiation oncology (London, England), 18, 1, 25, 25, 07 Feb. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed. METHODS: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results. RESULTS: The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months). CONCLUSIONS: We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions.

尿管癌への放射線治療後に転移による直腸狭窄を来した1例　　　　　　　　　　　　　　　
服部 敬寛, 西岡 健太郎, 橋本 孝之, 大塚 愛美, 木下 留美子, 青山 英史, 安部 崇重, 大澤 崇宏, 松本 隆児, 菊地 央, 篠原 信雄, 高桑 恵美
Japanese Journal of Radiology, 41, Suppl., 4, 4, (公社)日本医学放射線学会, Feb. 2023
Japanese

Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.
Rumiko Kinoshita, Takashi Mitamura, Fumi Kato, Takahiro Hattori, Hajime Higaki, Shuhei Takahashi, Yoshihiro Fujita, Manami Otsuka, Fuki Koizumi, Yusuke Uchinami, Takashi Mori, Kentaro Nishioka, Takayuki Hashimoto, Yoichi M Ito, Hidemichi Watari, Hidefumi Aoyama
Journal of radiation research, 64, 2, 463, 470, 03 Jan. 2023, [International Magazine]
English, Scientific journal, Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.

Prostatic urinary tract visualization with super-resolution deep learning models.
Takaaki Yoshimura, Kentaro Nishioka, Takayuki Hashimoto, Takashi Mori, Shoki Kogame, Kazuya Seki, Hiroyuki Sugimori, Hiroko Yamashina, Yusuke Nomura, Fumi Kato, Kohsuke Kudo, Shinichi Shimizu, Hidefumi Aoyama
PloS one, 18, 1, e0280076, 2023, [International Magazine]
English, Scientific journal, In urethra-sparing radiation therapy, prostatic urinary tract visualization is important in decreasing the urinary side effect. A methodology has been developed to visualize the prostatic urinary tract using post-urination magnetic resonance imaging (PU-MRI) without a urethral catheter. This study investigated whether the combination of PU-MRI and super-resolution (SR) deep learning models improves the visibility of the prostatic urinary tract. We enrolled 30 patients who had previously undergone real-time-image-gated spot scanning proton therapy by insertion of fiducial markers. PU-MRI was performed using a non-contrast high-resolution two-dimensional T2-weighted turbo spin-echo imaging sequence. Four different SR deep learning models were used: the enhanced deep SR network (EDSR), widely activated SR network (WDSR), SR generative adversarial network (SRGAN), and residual dense network (RDN). The complex wavelet structural similarity index measure (CW-SSIM) was used to quantitatively assess the performance of the proposed SR images compared to PU-MRI. Two radiation oncologists used a 1-to-5 scale to subjectively evaluate the visibility of the prostatic urinary tract. Cohen's weighted kappa (k) was used as a measure of agreement of inter-operator reliability. The mean CW-SSIM in EDSR, WDSR, SRGAN, and RDN was 99.86%, 99.89%, 99.30%, and 99.67%, respectively. The mean prostatic urinary tract visibility scores of the radiation oncologists were 3.70 and 3.53 for PU-MRI (k = 0.93), 3.67 and 2.70 for EDSR (k = 0.89), 3.70 and 2.73 for WDSR (k = 0.88), 3.67 and 2.73 for SRGAN (k = 0.88), and 4.37 and 3.73 for RDN (k = 0.93), respectively. The results suggest that SR images using RDN are similar to the original images, and the SR deep learning models subjectively improve the visibility of the prostatic urinary tract.

強度変調回転照射法(VMAT)で術後照射を行った2例
木下 留美子, 檜垣 朔, 藤田 祥博, 森 崇, 西岡 健太郎, 橋本 孝之, 青山 英史, 押野 智博, 高橋 将人, 加藤 扶美, 金平 孝博
北海道外科雑誌, 67, 2, 162, 163, 北海道外科学会, Dec. 2022
Japanese

Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset.
Shigeru Yamaguchi, Michinari Okamoto, Yukitomo Ishi, Ryosuke Sawaya, Hiroaki Motegi, Minako Sugiyama, Taisuke Harada, Noriyuki Fujima, Takashi Mori, Takayuki Hashimoto, Emi Takakuwa, Atsushi Manabe, Kohsuke Kudo, Hidefumi Aoyama, Miki Fujimura
Journal of neurosurgery. Pediatrics, 1, 8, 09 Sep. 2022, [International Magazine]
English, Scientific journal, OBJECTIVE: In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. METHODS: The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. RESULTS: Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. CONCLUSIONS: End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.

In reply to "Comment on "Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study"".
Takayuki Hashimoto
Japanese journal of radiology, 40, 5, 544, 545, May 2022, [Peer-reviewed], [Domestic magazines]
English

北海道大学病院放射線治療科関連施設における子宮頸癌に対する根治放射線治療に関するアンケート結果について　　　　　　　　　　　　　　　
木下 留美子, 打浪 雄介, 高橋 周平, 小泉 富基, 森 崇, 西岡 健太郎, 田口 大志, 橋本 孝之, 高邑 明夫, 西岡 井子, 北原 利博, 土屋 和彦, 井上 哲也, 有本 卓郎, 出倉 康裕, 米坂 祥朗, 鈴木 恵士郎, 川島 和之, 小野寺 俊輔, 喜多村 圭, 長谷川 雅一, 鬼丸 力也, 富田 雅義, 池田 潤, 西山 典明, 青山 英史
北海道放射線医学雑誌, 2, 13, 18, (NPO)メディカルイメージラボ, Mar. 2022
Japanese, 子宮頸癌に対する根治的放射線治療において子宮内から照射を行う腔内照射は必要不可欠な要素である。腔内照射の設備の維持・更新および子宮頸癌根治照射人数等について北海道大学病院放射線治療科関連病院にアンケートを行った。道内の施設の子宮頸癌根治照射人数は年間10人以下の施設が大半で、腔内照射設備を保有している施設の年間の腔内照射人数は5-9人が4施設、10人以上が2施設であった。腔内照射設備を保有している6施設の内4施設で設備の維持・更新が採算面で難しいという理由で腔内照射の休止を検討している事が明らかとなった。北海道内の子宮頸癌に対する根治照射を継続して行うためには、腔内照射設備を持つ施設への適切な紹介システムの構築と腔内照射が可能な施設の地域性を考慮した適切な集約化が必要と考えられた。(著者抄録)

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.

Impact of a spatially dependent dose delivery time structure on the biological effectiveness of scanning proton therapy.
Koki Kasamatsu, Sodai Tanaka, Koichi Miyazaki, Seishin Takao, Naoki Miyamoto, Shusuke Hirayama, Kentaro Nishioka, Takayuki Hashimoto, Hidefumi Aoyama, Kikuo Umegaki, Taeko Matsuura
Medical physics, 49, 1, 702, 713, Jan. 2022, [International Magazine]
English, Scientific journal, PURPOSE: In the scanning beam delivery of protons, different portions of the target are irradiated with different linear energy transfer protons with various time intervals and irradiation times. This research aimed to evaluate the spatially dependent biological effectiveness of protracted irradiation in scanning proton therapy. METHODS: One and two parallel opposed fields plans were created in water phantom with the prescribed dose of 2 Gy. Three scenarios (instantaneous, continuous, and layered scans) were used with the corresponding beam delivery models. The biological dose (physical dose × relative biological effectiveness) was calculated using the linear quadratic model and the theory of dual radiation action to quantitatively evaluate the dose delivery time effect. In addition, simulations using clinical plans (postoperative seminoma and prostate tumor cases) were conducted to assess the impact of the effects on the dose volume histogram parameters and homogeneity coefficient (HC) in targets. RESULTS: In a single-field plan of water phantom, when the treatment time was 19 min, the layered-scan scenario showed a decrease of <0.2% (almost 3.3%) in the biological dose from the plan on the distal (proximal) side because of the high (low) dose rate. This is in contrast to the continuous scenario, where the biological dose was almost uniformly decreased over the target by approximately 3.3%. The simulation with clinical geometry showed that the decrease rates in D99% were 0.9% and 1.5% for every 10 min of treatment time prolongation for postoperative seminoma and prostate tumor cases, respectively, whereas the increase rates in HC were 0.7% and 0.2%. CONCLUSIONS: In protracted irradiation in scanning proton therapy, the spatially dependent dose delivery time structure in scanning beam delivery can be an important factor for accurate evaluation of biological effectiveness.

Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study.
Takayuki Hashimoto, Yusuke Demizu, Haruko Numajiri, Tomonori Isobe, Shigekazu Fukuda, Masaru Wakatsuki, Haruo Yamashita, Shigeyuki Murayama, Shigeyuki Takamatsu, Hiroyuki Katoh, Kazutoshi Murata, Ryosuke Kohno, Takeshi Arimura, Taeko Matsuura, Yoichi M Ito
Japanese journal of radiology, 40, 5, 525, 533, 15 Nov. 2021, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, PURPOSE: To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). MATERIALS AND METHODS: From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. RESULTS: Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). CONCLUSION: Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.

A treatment planning study of urethra-sparing intensity-modulated proton therapy for localized prostate cancer
Takaaki Yoshimura, Kentaro Nishioka, Takayuki Hashimoto, Kazuya Seki, Shouki Kogame, Sodai Tanaka, Takahiro Kanehira, Masaya Tamura, Seishin Takao, Taeko Matsuura, Keiji Kobashi, Fumi Kato, Hidefumi Aoyama, Shinichi Shimizu
Physics and Imaging in Radiation Oncology, 20, 23, 29, Elsevier BV, Oct. 2021, [International Magazine]
English, Scientific journal, BACKGROUND AND PURPOSE: Urethra-sparing radiation therapy for localized prostate cancer can reduce the risk of radiation-induced genitourinary toxicity by intentionally underdosing the periurethral transitional zone. We aimed to compare the clinical impact of a urethra-sparing intensity-modulated proton therapy (US-IMPT) plan with that of conventional clinical plans without urethral dose reduction. MATERIALS AND METHODS: This study included 13 patients who had undergone proton beam therapy. The prescribed dose was 63 GyE in 21 fractions for 99% of the clinical target volume. To compare the clinical impact of the US-IMPT plan with that of the conventional clinical plan, tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with a generalized equivalent uniform dose-based Lyman-Kutcher model using dose volume histograms. The endpoints of these model parameters for the rectum, bladder, and urethra were fistula, contraction, and urethral stricture, respectively. RESULTS: The mean NTCP value for the urethra in US-IMPT was significantly lower than that in the conventional clinical plan (0.6% vs. 1.2%, p < 0.05). There were no statistically significant differences between the conventional and US-IMPT plans regarding the mean minimum dose for the urethra with a 3-mm margin, TCP value, and NTCP value for the rectum and bladder. Additionally, the target dose coverage of all plans in the robustness analysis was within the clinically acceptable range. CONCLUSIONS: Compared with the conventional clinically applied plans, US-IMPT plans have potential clinical advantages and may reduce the risk of genitourinary toxicities, while maintaining the same TCP and NTCP in the rectum and bladder.

Cost-effectiveness analysis using lifetime attributable risk of proton beam therapy for pediatric medulloblastoma in Japan.
Takaaki Yoshimura, Honoka Tamori, Yasuhiro Morii, Takayuki Hashimoto, Shinichi Shimizu, Katsuhiko Ogasawara
Journal of radiation research, 29 Sep. 2021, [International Magazine]
English, Scientific journal, Compared to conventional X-ray therapy, proton beam therapy (PBT) has more clinical and physical advantages such as irradiation dose reduction to normal tissues for pediatric medulloblastoma. However, PBT is expensive. We aimed to compare the cost-effectiveness of PBT for pediatric medulloblastoma with that of conventional X-ray therapy, while focusing on radiation-induced secondary cancers, which are rare, serious and negatively affect a patient's quality of life (QOL). Based on a systematic review, a decision tree model was used for the cost-effectiveness analysis. This analysis was performed from the perspective of health care payers; the cost was estimated from medical fees. The target population was pediatric patients with medulloblastoma below 14 years old. The time horizon was set at 7.7 years after medulloblastoma treatment. The primary outcome was the incremental cost-effectiveness ratio (ICER), which was defined as the ratio of the difference in cost and lifetime attributable risk (LAR) between conventional X-ray therapy and PBT. The discount rate was set at 2% annually. Sensitivity analyses were performed to model uncertainty. Cost and LAR in conventional X-ray therapy and PBT were Japanese yen (JPY) 1 067 608 and JPY 2436061 and 42% and 7%, respectively. The ICER was JPY 3856398/LAR. In conclusion, PBT is more cost-effective than conventional X-ray therapy in reducing the risk of radiation-induced secondary cancers in pediatric medulloblastoma. Thus, our constructed ICER using LAR is one of the valid indicators for cost-effectiveness analysis in radiation-induced secondary cancer.

再照射 小児がんに対する陽子線再照射
橋本 孝之, 森 崇, 西岡 健太郎, 打浪 雄介, 安田 耕一, 木下 留美子, 田口 大志, 加藤 徳雄, 清水 伸一, 青山 英史
日本小児血液・がん学会雑誌, 58, 2, 89, 93, (一社)日本小児血液・がん学会, Aug. 2021
Japanese, 陽子線治療は通常のX線による放射線治療に比べて線量集中性に優れ,標的への線量を保ったまま周囲の正常組織線量を低減することで,小児がん患者の急性期並びに晩期有害事象の軽減が可能である.2016年4月からは20歳未満の限局性固形悪性腫瘍に対する根治的な陽子線照射が保険適応となり,各施設で小児がんの陽子線治療実施件数が増加傾向にある.局所領域再発に対する再照射は,腫瘍進行抑制・症状緩和と,時に治癒や長期の腫瘍制御による健康状態・QOLの維持をもたらす可能性がある.小児患者に対する再照射における重要臓器・器官の累積耐容線量や安全性は確立していないが,中枢神経腫瘍に対する陽子線再照射により,有害事象の発生を抑えた良好な治療成績が報告されている.今後,小児がん再発の治療選択肢における陽子線再照射の有用性については,前向き臨床試験での評価が必要と考える.(著者抄録)

Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines
Masashi Mizumoto, Hiroshi Fuji, Mitsuru Miyachi, Toshinori Soejima, Tetsuya Yamamoto, Norihiro Aibe, Yusuke Demizu, Hiromitsu Iwata, Takayuki Hashimoto, Atsushi Motegi, Atsufumi Kawamura, Keita Terashima, Takashi Fukushima, Tomohei Nakao, Akinori Takada, Minako Sumi, Junjiro Oshima, Kensuke Moriwaki, Miwako Nozaki, Yuji Ishida, Yoshiyuki Kosaka, Keisuke Ae, Ako Hosono, Hideyuki Harada, Etsuyo Ogo, Tetsuo Akimoto, Takashi Saito, Hiroko Fukushima, Ryoko Suzuki, Mitsuru Takahashi, Takayuki Matsuo, Akira Matsumura, Hidekazu Masaki, Hajime Hosoi, Naoyuki Shigematsu, Hideyuki Sakurai
Cancer Treatment Reviews, 98, 102209, 102209, Elsevier BV, Jul. 2021, [International Magazine]
English, Scientific journal, Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).

泌尿器癌に対する局所療法-超高齢社会の先端医療のあり方は? 筋層浸潤性膀胱癌に対する集学的治療 化学放射線療法による膀胱温存について
安部 崇重, 宮田 遥, 山田 修平, 菊地 央, 松本 隆児, 大澤 崇宏, 西岡 健太郎, 橋本 孝之, 清水 伸一, 篠原 信雄
日本老年泌尿器科学会誌, 34, 1, 50, 50, 日本老年泌尿器科学会, Apr. 2021
Japanese

Visualizing the urethra by magnetic resonance imaging without usage of a catheter for radiotherapy of prostate cancer
Takaaki Yoshimura, Kentaro Nishioka, Takayuki Hashimoto, Taro Fujiwara, Kinya Ishizaka, Hiroyuki Sugimori, Shoki Kogame, Kazuya Seki, Hiroshi Tamura, Sodai Tanaka, Yuto Matsuo, Yasuhiro Dekura, Fumi Kato, Hidefumi Aoyama, Shinichi Shimizu
Physics and Imaging in Radiation Oncology, 18, 1, 4, Apr. 2021
Scientific journal, The urethra position may shift due to the presence/absence of the catheter. Our proposed post-urination-magnetic resonance imaging (PU-MRI) technique is possible to identify the urethra without catheter. We aimed to verify the inter-operator difference in contouring the urethra by PU-MRI. The mean values of the evaluation indices of dice similarity coefficient, mean slice-wise Hausdorff distance, and center coordinates were 0.93, 0.17 mm, and 0.36 mm for computed tomography, and 0.75, 0.44 mm, and 1.00 mm for PU-MRI. Therefore, PU-MRI might be useful for identifying the prostatic urinary tract without using a urethral catheter. Clinical trial registration: Hokkaido University Hospital for Clinical Research (018-0221).

尿量の経日変化および前立腺体積が放射線治療時の前立腺の位置に与える影響(The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy)　　　　　　　　　　　　　　　
Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi
日本医学放射線学会学術集会抄録集, 80回, S193, S194, (公社)日本医学放射線学会, Mar. 2021
English

The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy(和訳中)　　　　　　　　　　　　　　　
Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi
日本医学放射線学会学術集会抄録集, 80回, S193, S194, (公社)日本医学放射線学会, Mar. 2021
English

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, 20210064, 20210064, British Institute of Radiology, Jan. 2021, [International Magazine]
English, 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.

Construction of a detachable artificial trachea model for three age groups for use in an endotracheal suctioning training environment simulator.
Takaaki Yoshimura, Noriyo Colley, Shunsuke Komizunai, Shinji Ninomiya, Satoshi Kanai, Atsushi Konno, Koichi Yasuda, Hiroshi Taguchi, Takayuki Hashimoto, Shinichi Shimizu
PloS one, 16, 3, e0249010, 2021, [International Magazine]
English, Scientific journal, Tracheal suctioning is an important procedure to maintain airway patency by removing secretions. Today, suctioning operators include not only medical staff, but also family caregivers. The use of a simulation system has been noted to be the most effective way to learn the tracheal suctioning technique for operators. While the size of the trachea varies across different age groups, the artificial trachea model in the simulation system has only one fixed model. Thus, this study aimed to construct multiple removable trachea models according to different age groups. We enrolled 20 patients who had previously received proton beam therapy in our institution and acquired the treatment planning computed tomography (CT) image data. To construct the artificial trachea model for three age groups (children, adolescents and young adults, and adults), we analyzed the three-dimensional coordinates of the entire trachea, tracheal carina, and the end of the main bronchus. We also analyzed the diameter of the trachea and main bronchus. Finally, we evaluated the accuracy of the model by analyzing the difference between the constructed model and actual measurements. The trachea model was 8 cm long for children and 12 cm for adolescents and young adults, and for adults. The angle between the trachea and bed was about 20 degrees, regardless of age. The mean model accuracy was less than 0.4 cm. We constructed detachable artificial trachea models for three age groups for implementation in the endotracheal suctioning training environment simulator (ESTE-SIM) based on the treatment planning CT image. Our constructed artificial trachea models will be able to provide a simulation environment for various age groups in the ESTE-SIM.

Diagnostic Capability of Cerebrospinal Fluid-Placental Alkaline Phosphatase Value in Intracranial Germ Cell Tumor.
Michinari Okamoto, Shigeru Yamaguchi, Yukitomo Ishi, Hiroaki Motegi, Takashi Mori, Takayuki Hashimoto, Yukayo Terashita, Shinsuke Hirabayashi, Minako Sugiyama, Akihiro Iguchi, Yuko Cho, Atsushi Manabe, Kiyohiro Houkin
Oncology, 99, 1, 23, 31, 2021, [International Magazine]
English, Scientific journal, OBJECTIVE: Most types of intracranial germ cell tumors (IGCTs) are sensitive to chemoradiation. However, biopsy specimens are usually small and thus cannot be used for obtaining an accurate pathological diagnosis. Recently, the cerebrospinal fluid (CSF) placental alkaline phosphatase (PLAP) value has been considered a new biomarker of IGCTs. The present study aimed to evaluate the discriminatory characteristics of the CSF-PLAP value upon diagnosis and at the time of recurrence in patients with IGCTs. METHODS: Between 2015 and 2019, this study included 37 patients with tumors located in the intraventricular and/or periventricular region. The CSF-PLAP level was assessed before the patients received any treatment. The PLAP level was evaluated during and after first-line chemoradiotherapy in 7 patients with IGCTs. The CSF-PLAP values were compared according to histological diagnosis, and the correlation between these values and radiographical features was assessed. The CSF-PLAP values of 6 patients with IGCTs with suspected recurrence were evaluated based on neuroimaging findings. RESULTS: The CSF-PLAP values were significantly higher in patients with IGCTs than in those with other types of brain tumor (n = 19 vs. 18; median: 359.0 vs. <8.0 pg/mL). The specificity and sensitivity were 88 and 95%, respectively, with a cutoff value of 8.0 pg/mL. In patients with IGCT, the CSF-PLAP value was higher in patients with germinoma than in those with nongerminomatous germ cell tumors (n = 12 vs. 7; median: 415.0 vs. 359.0 pg/mL). Regarding the time course, the CSF-PLAP value decreased to below the detection limit after the reception of first-line chemoradiotherapy in all 7 patients. A significant correlation was observed between the initial CSF-PLAP value and the tumor reduction volume after receiving first-line chemoradiotherapy (p < 0.0003, R2 = 0.6165, logY = 1.202logX - 1.727). Among the patients with suspected IGCT recurrence (n = 6), the CSF-PLAP value was high in patients with recurrence (n = 3; median: 259.0 pg/mL), and that in patients (n = 3) without recurrence was below the lower detection limit. CONCLUSIONS: The CSF-PLAP level is a useful biomarker during the initial diagnosis of IGCTs and at the time of recurrence. It may be associated with the volume of germinomatous components of tumors.

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.

Automatic Bladder Delineation on MR Images Using a Convolution Neural Network for Online Image-Guided Radiotherapy
K. Nishioka, Y. Nomura, T. Hashimoto, R. Kinoshita, N. Katoh, H. Taguchi, K. Yasuda, T. Mori, Y. Uchinami, M. Otsuka, T. Matsuura, S. Takao, R. Suzuki, S. Tanaka, T. Yoshimura, H. Aoyama, S. Shimizu
International Journal of Radiation Oncology*Biology*Physics, 108, 3, e288, e289, Elsevier BV, Nov. 2020
Scientific journal

画像誘導治療の今後について 画像誘導陽子線治療の将来展望　　　　　　　　　　　　　　　
田口 大志, 橋本 孝之, 加藤 徳雄, 木下 留美子, 安田 耕一, 西岡 健太郎, 森 崇, 打浪 雄介, 宮本 直樹, 高尾 聖心, 清水 伸一, 青山 英史
日本癌治療学会学術集会抄録集, 58回, SY14, 3, (一社)日本癌治療学会, Oct. 2020
English

【前立腺癌診療update-最新の診断と治療-】診断と治療 陽子線治療
清水 伸一, 西岡 健太郎, 橋本 孝之
日本臨床, 78, 6, 977, 982, (株)日本臨床社, Jun. 2020
Japanese

【泌尿器がんの新しい放射線治療戦略】前立腺がん 前立腺がんの陽子線治療
清水 伸一, 橋本 孝之, 西岡 健太郎
泌尿器科, 11, 4, 386, 391, (有)科学評論社, Apr. 2020
Japanese

Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.
Takaaki Yoshimura, Shinichi Shimizu, Takayuki Hashimoto, Kentaro Nishioka, Norio Katoh, Tetsuya Inoue, Hiroshi Taguchi, Koichi Yasuda, Taeko Matsuura, Seishin Takao, Masaya Tamura, Yoichi M Ito, Yuto Matsuo, Hiroshi Tamura, Kenji Horita, Kikuo Umegaki, Hiroki Shirato
Journal of applied clinical medical physics, 21, 2, 38, 49, Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot-scanning proton therapy with a gating function can be achieved in approximately 30-min time slots.

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.

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.

高リスク前立腺癌に対するロボット支援前立腺全摘除術と放射線療法の臨床的比較検討　　　　　　　　　　　　　　　
松本 隆児, 古御堂 純, 宮田 遥, 菊地 央, 大澤 崇宏, 安部 崇重, 西岡 健太郎, 橋本 孝之, 清水 伸一, 篠原 信雄
日本泌尿器内視鏡学会総会, 33回, P, 1, (一社)日本泌尿器内視鏡・ロボティクス学会, Nov. 2019
Japanese

高リスク前立腺癌に対するロボット支援前立腺全摘除術と放射線療法の臨床的比較検討　　　　　　　　　　　　　　　
松本 隆児, 古御堂 純, 宮田 遥, 菊地 央, 大澤 崇宏, 安部 崇重, 西岡 健太郎, 橋本 孝之, 清水 伸一, 篠原 信雄
日本泌尿器内視鏡学会総会, 33回, P, 1, (一社)日本泌尿器内視鏡・ロボティクス学会, Nov. 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

頭蓋内胚細胞腫瘍における放射線化学療法後のsalvage surgeryに関する病理所見からの検討　　　　　　　　　　　　　　　
山口 秀, 茂木 洋晃, 伊師 雪友, 岡本 迪成, 井口 晶裕, 長 祐子, 杉山 未奈子, 橋本 孝之, 岡田 宏美, 寳金 清博
Brain Tumor Pathology, 36, Suppl., 096, 096, 日本脳腫瘍病理学会, 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.

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, 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

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

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]

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, (一社)日本癌治療学会, Oct. 2018
English

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.

Prospective study to evaluate the safety of the world-first spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy system.
Nishioka K, Prayongrat A, Ono K, Onodera S, Hashimoto T, Katoh N, Inoue T, Kinoshita R, Yasuda K, Mori T, Onimaru R, Shirato H, Shimizu S
Journal of radiation research, 59, suppl_1, i63, i71, Mar. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, 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.

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, 192, 北海道整形災害外科学会, 24 Mar. 2017
Japanese

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

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

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, (NPO)日本小児血液・がん学会, Nov. 2016
English

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, Suppl., 5, 5, (公社)日本医学放射線学会, Feb. 2016
Japanese

キャンサーボードが機能した1症例　　　　　　　　　　　　　　　
遠藤 将吾, 寺坂 俊介, 小林 浩之, 山口 秀, 茂木 洋晃, 金子 貞洋, 井口 晶裕, 長 祐子, 大島 淳二郎, 寺坂 友佳代, 杉山 未奈子, 橋本 孝之, 鬼丸 力也, 清水 伸一, 有賀 正, 白戸 博樹, 寳金 清博
日本小児血液・がん学会雑誌, 52, 3, 343, 343, (NPO)日本小児血液・がん学会, Oct. 2015
Japanese

Proton beam therapy for unresectable intrahepatic cholangiocarcinoma
Ohkawa,Ayako, Mizumoto,Masashi, Ishikawa,Hitoshi, Abei,Masato, Fukuda,Kuniaki, Hashimoto,Takayuki, Sakae,Takeji, Tsuboi,Koji, Okumura,Toshiyuki, Sakurai,Hideyuki
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 30, 5, 957, 963, WILEY-BLACKWELL, May 2015, [Peer-reviewed]
English, Scientific journal

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis
MAKISHIMA,HIROKAZU, ISHIKAWA,HITOSHI, TERUNUMA,TOSHIYUKI, HASHIMOTO,TAKAYUKI, YAMANASHI,KOICHI, SEKIGUCHI,TAKAO, MIZUMOTO,MASASHI, OKUMURA,TOSHIYUKI, SAKAE,TAKEJI, SAKURAI,HIDEYUKI
Journal of Radiation Research, 56, 3, 568, 576, OXFORD UNIV PRESS, May 2015, [Peer-reviewed]
English, Scientific journal, Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy （CCRT）for esophageal cancer.The aim of this study was to examine the benefit of proton beam therapy（PBT）using clinical data and adaptive dosevolume histogram（DVH）analysis.The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays （n=19）or protons （n=25）.Experimental recalculation using protons was performed for the patient actually treated with X-rays ,and vice versa.Target coverage and dose constraints of normal tissues were conserved.Lung V5-V20,mean lung dose （MLD）,and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans.Potential toxicity was estimated using protons in patients actually treated with X-rays,and vice versa. Pulmonary events of Grade ≧2 occurred in 8/44 cases（18%）,and cardiac events were seen in 11 cases （25%）.Risk organ doses in patients with events of Grade ≧2 were significantly higher than for those with events of Grade ≦1.Risk organ doses were lower in proton plans compared with X-ray plans.All patients suffering toxicity who were treated with X-rays （n=13

Proton beam therapy combined with concurrent chemotherapy for esophageal cancer　　　　　　　　　　　　　　　
Ishikawa,Hitoshi, Hashimoto,Takayuki, Moriwaki,Toshikazu, Hyodo,Ichinosuke, Hisakura,Katsuji, Terashima,Hideo, Ohkohchi,Nobuhiro, Ohno,Toshiki, Makishima,Hirokazu, Mizumoto,Masashi, Ohnishi,Kayoko, Okumura,Toshiyuki, Sakurai,Hideyuki
Anticancer research, 35, 3, 1757, 1762, INT INST ANTICANCER RESEARCH, Mar. 2015
English, Scientific journal, The aim of the present study was to evaluate the outcomes of proton beam therapy (PBT) concurrently combined with chemotherapy consisting of cisplatin and 5-fluorouracil for esophageal cancer. Forty consecutive patients (stage I in 16 patients, II in 9 and III in 15) treated between 2008 and 2012 were evaluated. A total dose of 60 Gray equivalents (GyE) in 30 fractions was delivered, and an additional boost of 4-10 GyE was given when residual tumors were suspected. The median follow-up time was 24 months (range=7-66 months). No cardio-pulmonary toxicities of grade 3 or higher were observed. Recurrences were observed in 16 patients, and the 2-year rates of disease-specific survival and locoregional control were 77% and 66%, respectively. Irrespective of the small sample size and short follow-up time of the study, proton beam therapy combined with chemo therapy seems to be feasible for esophageal cancer.

Dose distribution of electrons from gold nanoparticles by proton beam irradiation　　　　　　　　　　　　　　　
Jihun Kwon, Kenneth Sutherland, Takayuki Hashimoto, Hiroyuki Date
International Journal of Medical Physics, Clinical Engineering and Radiation Oncology, 2015, 4, 49, 53, 2015, [Peer-reviewed]
English, Scientific journal

脳原発横紋筋肉腫に対する集学的治療の経験
長 祐子, 杉山 未奈子, 寺下 友佳代, 大島 淳二郎, 佐藤 智信, 井口 晶裕, 有賀 正, 小林 浩之, 寺坂 俊介, 橋本 孝之, 高桑 恵美
日本小児血液・がん学会雑誌, 51, 4, 282, 282, (一社)日本小児血液・がん学会, Oct. 2014
Japanese

Proton Beam Therapy Combined With Concurrent Chemotherapy for Esophageal Cancer　　　　　　　　　　　　　　　
Ishikawa.H, Okumura.T, Ohno.T, Makishima.H, Ohnishi.K, Mizumoto.M, Aihara.T, Numajiri.H, Hashimoto.T, Sakurai.H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 90, 1, S346, S346, ELSEVIER SCIENCE INC, Sep. 2014, [Peer-reviewed]
English, Scientific journal

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

Outcomes and Prognostic Factors for Recurrence After High-Dose Proton Beam Therapy for Centrally and Peripherally Located Stage I None-Small-Cell Lung Cancer
Ayae Kanemoto, Toshiyuki Okumura, Hitoshi Ishikawa, Masashi Mizumoto, Yoshiko Oshiro, Koichi Kurishima, Shinsuke Homma, Takayuki Hashimoto, Ayako Ohkawa, Haruko Numajiri, Toshiki Ohno, Takashi Moritake, Koji Tsuboi, Takeji Sakae, Hideyuki Sakurai
CLINICAL LUNG CANCER, 15, 2, E7, E12, CIG MEDIA GROUP, LP, Mar. 2014, [Peer-reviewed]
English, Scientific journal, This study was conducted to determine disease control rates and prognostic factors after high-dose proton beam therapy (PBT) for centrally and peripherally located stage I none-small-cell lung cancer (NSCLC). Eighty tumors were treated. The 3-year overall survival and local control rate were 76.7% and 81.8%. Radiation dose was shown to be the more significant prognostic factor for tumor control than tumor diameter and others. Introduction: This study was conducted to determine disease control rates and prognostic factors associated with recurrence of centrally and peripherally located stage I NSCLC treated using high-dose PBT. Patients and Methods: Seventy-four patients with 80 centrally or peripherally located stage I NSCLCs were treated with PBT. A protocol using 72.6 Gy (RBE) in 22 fractions was used for centrally located tumors, and 66 Gy (RBE) in 10 or 12 fractions was used for peripherally located tumors. Data were collected and control rates and prognostic factors for recurrence were evaluated retrospectively. Results: The median follow-up period was 31.0 months. The overall survival, disease-specific survival, and progression-free survival rates were 76.7%, 83.0%, and 58.6% at 3 years, respectively. Disease recurrence was noted in 30 patients and local recurrence of 11 tumors occurred. The 3-year local control rate was 86.2% for stage IA tumors and 67.0% for stage IB tumors. Radiation dose was identified as a significant prognostic factor for disease recurrence and local recurrence. Tumor diameter and age were only significantly associated with disease recurrence. The 3-year local control rate was 63.9% for centrally located tumors irradiated with 72.6 Gy (RBE) and 88.4% for peripherally located tumors irradiated with 66 Gy (RBE). Conclusion: Radiation dose was shown to be the most significant prognostic factor for tumor control in stage I NSCLC treated using high-dose PBT. Tumor diameter was not significant for local control. Further evaluation of PBT for centrally located tumors is warranted. (C) 2014 Elsevier Inc. All rights reserved.

A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma
Abei, Masato, Okumura, Toshiyuki, Fukuda, Kuniaki, Hashimoto, Takayuki, Araki, Masahiro, Ishige, Kazunori, Hyodo, Ichinosuke, Kanemoto, Ayae, Numajiri, Haruko, Mizumoto, Masashi, Sakae, Takeji, Sakurai, Hideyuki, Zenkoh, Junko, Ariungerel, Gerelchuluun, Sogo, Yu, Ito, Atsuo, Ohno, Tadao, Tsuboi, Koji
RADIATION ONCOLOGY, 8, 239, BIOMED CENTRAL LTD, Oct. 2013, [Peer-reviewed]
English, Scientific journal

Preliminary Results of Concurrent Chemoradiation Therapy Using Proton Beam Therapy for Esophageal Cancer　　　　　　　　　　　　　　　
Ishikawa,H, Hashimoto,T, Mizumoto,M, Ohno,T, Makishima,H, Takizawa,D, Sugawara,K, Okumura,T, Sakurai,H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 87, 2::S, S294, S294, ELSEVIER SCIENCE INC, Oct. 2013, [Peer-reviewed]
English, Scientific journal

Long-term Survival in Patients With Hepatocellular Carcinoma Initially Treated With Definitive Proton Beam Therapy　　　　　　　　　　　　　　　
Okumura,T, Fukuda,K, Hashimoto,T, Mizumoto,M, Ishikawa,H, Sakae,T, Abei,M, Tsuboi,K, Sakurai,H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 87, 2::S, S321, S321, ELSEVIER SCIENCE INC, Oct. 2013
English, Scientific journal

食道扁平上皮癌に対する同時化学療法併用陽子線治療の初期成績　　　　　　　　　　　　　　　
石川 仁, 橋本 孝之, 大野 豊然貴, 水本 斉志, 大西 かよ子, 粟飯原 輝人, 森脇 俊和, 久倉 勝治, 寺島 秀夫, 奥村 敏之, 櫻井 英幸
日本癌治療学会誌, 48, 3, 1178, 1178, (一社)日本癌治療学会, Sep. 2013
Japanese

Comparison of adverse effects of proton and X-ray chemoradiotherapy for oesophageal cancer using an adaptive dose-volume histogram analysis　　　　　　　　　　　　　　　
Makishima,H, Ishikawa,H, Terunuma,T, Hashimoto,T, Yamanashi,K, Sekiguchi,T, Mizumoto,M, Okumura,T, Tsuboi,K, Sakurai,H
EUROPEAN JOURNAL OF CANCER, 49, 2, S576, S576, ELSEVIER SCI LTD, Sep. 2013, [Peer-reviewed]
English, Scientific journal

Phase II Study of Concurrent Chemoradiotherapy at the Dose of 50.4 Gy with Elective Nodal Irradiation for Stage IIIII Esophageal Carcinoma
Ken Kato, Takako Eguchi Nakajima, Yoshinori Ito, Chikatoshi Katada, Hiromichi Ishiyama, Shin-ya Tokunaga, Masahiro Tanaka, Shuichi Hironaka, Takayuki Hashimoto, Takashi Ura, Takeshi Kodaira, Ken-ichi Yoshimura
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 43, 6, 608, 615, OXFORD UNIV PRESS, Jun. 2013, [Peer-reviewed]
English, Scientific journal, Definitive chemoradiotherapy is one of the curative options for resectable esophageal squamous cell carcinoma with organ preservation. We evaluated the efficacy and toxicity of radiotherapy at a dose of 50.4 Gy concurrent with chemotherapy for Stage IIIII esophageal cancer.Esophageal cancer patients with clinical Stage IIIII (T1N1M0 or T2-3N0-1M0) were eligible. Radiotherapy was administered to a total dose of 50.4 Gy with elective nodal irradiation of 41.4 Gy. Concurrent chemotherapy comprised two courses of 5-fluorouracil (1000 mg/m(2)/day) on days 14 and 2-h infusion of cisplatin (75 mg/m(2)) on Day 1; this was repeated every 4 weeks. Two courses of 5-fluorouracil with cisplatin were added.Fifty-one patients were enrolled in the study from June 2006 to May 2008. The characteristics of the 51 patients enrolled were as follows: median age 64 years; male/female, 45/6; performance status 0/1, 32/19 patients; Stage IIA/IIB/III, 9/20/22 patients, respectively. A complete response was achieved in 36 patients (70.6). The 1- and 3-year overall survival rate was 88.2 and 63.8, respectively. The median 1- and 3-year progression-free survival rate was 66.7 (80 CI: 5774) and 56.6 (80 CI: 47.164.9), respectively. Acute toxicities included Grade 3/4 anorexia (45), esophagitis (35) and febrile neutropenia (20). Eight patients (15.6) underwent salvage surgery due to residual or recurrent disease. There were no deaths related to salvage surgery.Chemoradiation therapy at a dose of 50.4 Gy with elective nodal irradiation is promising with a manageable tolerability profile in esophageal cancer patients.

Clinical results of proton beam therapy for advanced neuroblastoma
Yoshiko Oshiro, Masashi Mizumoto, Toshiyuki Okumura, Shinji Sugahara, Takashi Fukushima, Hitoshi Ishikawa, Tomohei Nakao, Takayuki Hashimoto, Koji Tsuboi, Haruo Ohkawa, Michio Kaneko, Hideyuki Sakurai
RADIATION ONCOLOGY, 8, 142, BIOMED CENTRAL LTD, Jun. 2013, [Peer-reviewed]
English, Scientific journal, Purpose: To evaluate the efficacy of proton beam therapy (PBT) for pediatric patients with advanced neuroblastoma.
Methods: PBT was conducted at 21 sites in 14 patients with neuroblastoma from 1984 to 2010. Most patients were difficult to treat with photon radiotherapy. Two and 6 patients were classified into stages 3 and 4, respectively, and 6 patients had recurrent disease. Seven of the 8 patients who received PBT as the initial treatment were classified as the high risk group. Twelve patients had gross residual disease before PBT and 2 had undergone intraoperative radiotherapy before PBT. Five patients received PBT for multiple sites, including remote metastases. Photon radiotherapy was used in combination with PBT for 3 patients. The PBT doses ranged from 19.8 to 45.5 GyE (median: 30.6 GyE).
Results: Seven patients are alive with no evidence of disease, 1 is alive with disease progression, and 6 died due to the tumor. Recurrence in the treatment field was not observed and the 3-year locoregional control rate was 82%. Severe acute radiotoxicity was not observed, but 1 patient had narrowing of the aorta and asymptomatic vertebral compression fracture at 28 years after PBT, and hair loss was prolonged in one patient.
Conclusion: PBT may be a better alternative to photon radiotherapy for children with advanced neuroblastoma, and may be conducted safely for patients with neuroblastoma that is difficult to manage using photon beams.

Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma
Ayae Kanemoto, Masashi Mizumoto, Toshiyuki Okumura, Hideto Takahashi, Takayuki Hashimoto, Yoshiko Oshiro, Nobuyoshi Fukumitsu, Takashi Moritake, Koji Tsuboi, Takeji Sakae, Hideyuki Sakurai
Acta Oncologica, 52, 3, 538, 544, 3, Apr. 2013, [Peer-reviewed]
English, Scientific journal, Background. Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT). Material and methods. The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients' characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography. Results. Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p ≥ 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy3 (RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2)
36 Gy3] and the AUCs of V30 to V120 (EQD2
18-72 Gy3) and Dmax to D10cm3 were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture. Conclusion. DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and Dmax to D10cm3 were also significant and clinically useful for estimating the risk of rib fracture after hypofractionated PBT. © 2013 Informa Healthcare.

Proton beam therapy for unresectable hepatoblastoma in children: Survival in one case
Yoshiko Oshiro, Toshiyuki Okumura, Masashi Mizumoto, Takashi Fukushima, Hitoshi Ishikawa, Takayuki Hashimoto, Koji Tsuboi, Michio Kaneko, Hideyuki Sakurai
Acta Oncologica, 52, 3, 600, 603, 3, Apr. 2013, [Peer-reviewed]
English

Comparison of the Effects of High-Energy Photon Beam Irradiation (10 and 18 MV) on 2 Types of Implantable Cardioverter-Defibrillators
Haruko Hashii, Takayuki Hashimoto, Ayako Okawa, Koichi Shida, Tomonori Isobe, Masahiro Hanmura, Tetsuo Nishimura, Kazutaka Aonuma, Takeji Sakae, Hideyuki Sakurai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 85, 3, 840, 845, ELSEVIER SCIENCE INC, Mar. 2013, [Peer-reviewed]
English, Scientific journal, Purpose: Radiation therapy for cancer may be required for patients with implantable cardiac devices. However, the influence of secondary neutrons or scattered irradiation from high-energy photons (>= 10 MV) on implantable cardioverter-defibrillators (ICDs) is unclear. This study was performed to examine this issue in 2 ICD models.
Methods and Materials: ICDs were positioned around a water phantom under conditions simulating clinical radiation therapy. The ICDs were not irradiated directly. A control ICD was positioned 140 cm from the irradiation isocenter. Fractional irradiation was performed with 18-MV and 10-MV photon beams to give cumulative in-field doses of 600 Gy and 1600 Gy, respectively. Errors were checked after each fraction. Soft errors were defined as severe (change to safety back-up mode), moderate (memory interference, no changes in device parameters), and minor (slight memory change, undetectable by computer).
Results: Hard errors were not observed. For the older ICD model, the incidences of severe, moderate, and minor soft errors at 18 MV were 0.75, 0.5, and 0.83/50 Gy at the isocenter. The corresponding data for 10 MV were 0.094, 0.063, and 0 /50 Gy. For the newer ICD model at 18 MV, these data were 0.083, 2.3, and 5.8 /50 Gy. Moderate and minor errors occurred at 18 MV in control ICDs placed 140 cm from the isocenter. The error incidences were 0, 1, and 0 /600 Gy at the isocenter for the newer model, and 0, 1, and 6 /600Gy for the older model. At 10 MV, no errors occurred in control ICDs.
Conclusions: ICD errors occurred more frequently at 18 MV irradiation, which suggests that the errors were mainly caused by secondary neutrons. Soft errors of ICDs were observed with high energy photon beams, but most were not critical in the newer model. These errors may occur even when the device is far from the irradiation field. (c) 2013 Elsevier Inc.

Reproducibility of image quality for moving objects using respiratory-gated computed tomography: A study using a phantom model
Nobuyoshi Fukumitsu, Masaya Ishida, Toshiyuki Terunuma, Masashi Mizumoto, Takayuki Hashimoto, Takashi Moritake, Toshiyuki Okumura, Takeji Sakae, Koji Tsuboi, Hideyuki Sakurai
Journal of Radiation Research, 53, 6, 945, 953, 6, Nov. 2012, [Peer-reviewed]
English, Scientific journal, To investigate the reproducibility of computed tomography (CT) imaging quality in respiratory-gated radiation treatment planning is essential in radiotherapy of movable tumors. Seven series of regular and six series of irregular respiratory motions were performed using a thorax dynamic phantom. For the regular respiratory motions, the respiratory cycle was changed from 2.5 to 4 s and the amplitude was changed from 4 to 10 mm. For the irregular respiratory motions, a cycle of 2.5 to 4 or an amplitude of 4 to 10 mm was added to the base data (i.e. 3.5-s cycle, 6-mm amplitude) every three cycles. Images of the object were acquired six times using respiratory-gated data acquisition. The volume of the object was calculated and the reproducibility of the volume was decided based on the variety. The registered image of the object was added and the reproducibility of the shape was decided based on the degree of overlap of objects. The variety in the volumes and shapes differed significantly as the respiratory cycle changed according to regular respiratory motions. In irregular respiratory motion, shape reproducibility was further inferior, and the percentage of overlap among the six images was 35.26 in the 2.5- and 3.5-s cycle mixed group. Amplitude changes did not produce significant differences in the variety of the volumes and shapes. Respiratory cycle changes reduced the reproducibility of the image quality in respiratory-gated CT. © 2012 The Author 2012. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology.

Designed-seamless irradiation technique for extended whole mediastinal proton-beam irradiation for esophageal cancer
Noriyuki Okonogi, Takatuki Hashimoto, Masaya Ishida, Toshiki Ohno, Toshiyuki Terunuma, Toshiyuki Okumura, Takeji Sakae, Hideyuki Sakurai
RADIATION ONCOLOGY, 7, BIOMED CENTRAL LTD, Oct. 2012
English, Scientific journal, Background: Proton-beam therapy (PBT) provides therapeutic advantages over conformal x-ray therapy in sparing organs at risk when treating esophageal cancer because of the fundamental physical dose distribution of the proton-beam. However, cases with extended esophageal lesions are difficult to treat with conventional PBT with a single isocentric field, as the length of the planning target volume (PTV) is longer than the available PBT field size in many facilities. In this study, the feasibility of a practical technique to effectively match PBT fields for esophageal cancer with a larger regional field beyond the available PBT field size was investigated.
Methods: Twenty esophageal cancer patients with a larger regional field than the available PBT single-field size (15 cm in our facility) were analyzed. The PTV was divided into two sections to be covered by a single PBT field. Subsequently, each PTV isocenter was aligned in a cranial-caudal (CC) axis to rule out any influence by the movement of the treatment couch in anterior-posterior and left-right directions. To obtain the appropriate dose distributions, a designed-seamless irradiation technique (D-SLIT) was proposed. This technique requires the following two adjustments: (A) blocking a part of the PTV by multi-leaf collimator(s) (MLCs); and (B) fine-tuning the isocenter distance by the half-width of the MLC leaf (2.5 mm in our facility). After these steps, the inferior border of the cranial field was designed to match the superior border of the caudal field. Dose distributions along the CC axis around the field junction were evaluated by the treatment-planning system. Dose profiles were validated with imaging plates in all cases.
Results: The average and standard deviation of minimum dose, maximum dose, and dose range between maximum and minimum doses around the field junction by the treatment-planning system were 95.9 +/- 3.2%, 105.3 +/- 4.1%, and 9.4 +/- 5.2%. The dose profile validated by the imaging plate correlated with the results of the treatment-planning system in each case, with an error range within 4.3%.
Conclusions: Dose distributions around the field junction were applied using D-SLIT. D-SLIT can be a useful treatment strategy for PBT of extended esophageal cancer.

Verification of beam delivery using fibrosis after proton beam irradiation to the lung tumor
Nobuyoshi Fukumitsu, Yoshiko Oshiro, Takayuki Hashimoto, Toshiyuki Okumura, Masashi Mizumoto, Takashi Moritake, Koji Tsuboi, Takeji Sakae, Hideyuki Sakurai
LUNG CANCER, 77, 1, 83, 88, ELSEVIER IRELAND LTD, Jul. 2012, [Peer-reviewed]
English, Scientific journal, Background and purpose: To investigate the geometrical accuracy in proton beam therapy (PBT) to the lung by comparing the location of the fibrosis after PBT and the tumor using less invasive method.
Patients and methods: We examined 50 lung tumors that had been treated by respiratory-gated PBT(33-74 Gray equivalents). Image registration and re-slicing of computed tomography (CT) before and after PBT were performed using an image analysis software system. We investigated whether the location of fibrosis was accurate with the tumor site and which factor among the respiratory rhythm, tumor volume, location, fixation, beam direction and clinical outcome was affected with accuracy.
Results: The area of fibrosis was accurate with the tumor in 45 tumors (Group A) and not accurate in 5 tumors (Group B). All lesions with a small irregularity of respiratory rhythm showed fibrosis in an area accurate with the tumor. This percentage (100%) was higher than that of the lesions with a large irregularity of respiratory rhythm (67%, p = 0.037). Radiation pneumonitis was found for 1 lesion in group A and 2 lesions in Group B (p = 0.0009).
Conclusion: The geometrical accuracy of beam delivery to the lung was higher in the patients with a regular respiratory rhythm in PBT. The patients of Group B had greater risk of pneumonitis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

肝細胞癌に対する陽子線治療における予後と治療前肝機能の関連性　　　　　　　　　　　　　　　
水本斉志, 奥村敏之, 橋本孝之, 石川仁, 福田邦明, 安部井誠人, 石毛和紀, 兵頭一之介, 坪井康次, 櫻井英幸
第48回日本肝癌研究会, Jul. 2012, [Peer-reviewed]
Japanese, Research society

Spindle cell sarcoma of the penis: A case report
Tomokazu Kimura, Takehiro Oikawa, Atsushi Ikeda, Takayuki Yoshino, Takahiro Suetomi, Jun Miyazaki, Toru Shimazui, Takayuki Hashimoto, Shintaro Sugita, Masayuki Noguchi, Hiroyuki Nishiyama
Acta Urologica Japonica, 58, 6, 299, 305, 6, Jun. 2012, [Peer-reviewed]
Japanese, Scientific journal, A 75-year-old man, with a past history of radiation therapy for prostatic carcinoma ten years ago, was referred to our hospital with complaints of penile tumor. After pathological examination by core biopsy, the patient was treated by radical penectomy for a penile tumor. Pathological examinations demonstrated that the tumor was composed of pleomorphic spindle cells without any differentiation tendency and diagnosed as spindle cell sarcoma. Although the patient had a past history of radiation therapy for the prostate, the causal relation of development of penile sarcoma with the radiation therapy was uncertain because the main tumor was very near but outside of the irradiation field. The sarcoma rarely occurs in the penis, and this is the first report of penile spindle cell sarcoma, to our knowledge.

Outcome of T4 (International Union Against Cancer Staging System, 7th edition) or Recurrent Nasal Cavity and Paranasal Sinus Carcinoma Treated With Proton Beam
Nobuyoshi Fukumitsu, Toshiyuki Okumura, Masashi Mizumoto, Yoshiko Oshiro, Takayuki Hashimoto, Ayae Kanemoto, Haruko Hashii, Ayako Ohkawa, Takashi Moritake, Koji Tsuboi, Keiji Tabuchi, Tetsuro Wada, Akira Hara, Hideyuki Sakurai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 83, 2, 704, 711, ELSEVIER SCIENCE INC, Jun. 2012, [Peer-reviewed]
English, Scientific journal, Purpose: To investigate the clinical features, prognostic factors, and toxicity of treatment for unresectable carcinomas of the nasal cavity and paranasal sinus (NCPS) treated with proton beam therapy (PBT).
Methods and Materials: Seventeen patients (13 men, 4 women) with unresectable carcinomas of the NCPS who underwent PBT at the University of Tsukuba between 2001 and 2007 were analyzed. The patients' median age was 62 years (range, 30-83 years). The tumors were located in the nasal cavity in 3 patients, the frontal sinus in 1, the ethmoid sinus in 9, and the maxillary sinus in 4. The clinical stage was Stage IVA in 5 cases, IVB in 10, and recurrent in 2. The tumors were deemed unresectable for medical reasons in 16 patients and because of refusal at a previous hospital 4 months earlier in 1 patient. All the patients received PBT irradiation dose of 22-82.5 GyE and a total of 72.4-89.6 GyE over 30-64 fractions (median 78 GyE over 36 fractions) with X-ray, with attention not exceeding the delivery of 50 GyE to the optic chiasm and brain-stem.
Results: The overall survival rate was 47.1% at 2 years and 15.7% at 5 years, and the local control rate was 35.0% at 2 years and 17.5% at 5 years. Invasion of the frontal or sphenoid sinus was a prognostic factor for overall survival or local control. Late toxicity of more than Grade 3 was found in 2 patients (brain necrosis in 1 and ipsilateral blindness in 1); however, no mortal adverse effects were observed.
Conclusion: Proton beam therapy enabled a reduced irradiation dose to the optic chiasm and brainstem, enabling the safe treatment of unresectable carcinomas in the NCPS. Superior or posterior extension of the tumor influenced patient outcome. (C) 2012 Elsevier Inc.

[Advances in highly conformal radiotherapy for prostate cancer: past, current, and future]
Ishikawa Hitoshi, Hashimoto Takayuki, Makishima Hirokazu, Mizumoto Masashi, Okumura Toshiyuki, Sakurai Hideyuki
Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics, 32, 3, 138, 147, Japan Society of Medical Physics, Apr. 2012
English, Scientific journal, Recent advance in the field of radiation oncology, especially in medical physics for radiation therapy (RT), has considerably improved treatment outcomes of various cancers including prostate cancer with regard to both of tumor control and morbidity. Three-dimensionally conformal RT with image-guided radiotherapeutic modalities for accurate tumor localization, such as brachytherapy, intensity-modulated radiation therapy (IMRT), and charged particle beam RT can thereby deliver a large dose to the tumor and allow the sparing of surrounding normal tissues. It is thought that prostate cancer is one of representative cancers which have been treated with RT as a curative intent and benefited from novel conformal RT techniques. Because the number of prostate cancer patients has been increasing year by year in Japan as results from wide spread of PSA screening and rapid change in life style, RT has been recently playing much more important roles in the curative treatment for patients with prostate cancer. Hence, we will review the outcomes of RT for prostate cancer and introduce the benefit of modern RT modalities from clinical aspect. In addition, our future prospect to further yield bett

Evaluation of Liver Function After Proton Beam Therapy for Hepatocellular Carcinoma
Masashi Mizumoto, Toshiyuki Okumura, Takayuki Hashimoto, Kuniaki Fukuda, Yoshiko Oshiro, Nobuyoshi Fukumitsu, Masato Abei, Atsushi Kawaguchi, Yasutaka Hayashi, Ayako Ohkawa, Haruko Hashii, Ayae Kanemoto, Takashi Moritake, Eriko Tohno, Koji Tsuboi, Takeji Sakae, Hideyuki Sakurai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 82, 3, E529, E535, ELSEVIER SCIENCE INC, Mar. 2012, [Peer-reviewed]
English, Scientific journal, Purpose: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function.
Methods and Materials: The subjects were 259 patients treated with PBT at the University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effect of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event.
Results: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of >= 2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively.
Conclusion: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required. (C) 2012 Elsevier Inc.

INVESTIGATION OF THE GEOMETRIC ACCURACY OF PROTON BEAM IRRADIATION IN THE LIVER
Nobuyoshi Fukumitsu, Takayuki Hashimoto, Toshiyuki Okumura, Masashi Mizumoto, Eriko Tohno, Kuniaki Fukuda, Masato Abei, Takeji Sakae, Hideyuki Sakurai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 82, 2, 826, 833, ELSEVIER SCIENCE INC, Feb. 2012, [Peer-reviewed]
English, Scientific journal, Purpose: To investigate the geometric accuracy of proton beam irradiation to the liver by measuring the change in Hounsfield units (HUs) after irradiation.
Methods and Materials: We examined 21 patients with liver tumors who were treated with respiratory-gated proton beam therapy (PBT). The radiation dose was 66 GyE in 12 patients and 726 GyE in 9 patients. image registration and reslicing of the computed tomography (CT) results obtained within 1 month before and 3 months after PBT was performed, referring to the planning CT image. The resliced CT images obtained after PBT were subtracted from the images obtained before PBT. We investigated whether the area of the large HU change was consistent with the high-dose distribution area using the location of the largest change in HU around the tumor (peak) on the subtracted CT image and the 90% dose distribution area of the planning CT image.
Results: The number of patients (n = 20) whose left right peaks were within the 90% dose distribution area was significantly larger than the number of patients whose anterior posterior peaks and superior-inferior peaks were within the 90% dose distribution area (n = 14, n = 13, p = 0.034, and p = 0.02, respectively). Twelve patients exhibited a peak within the 90% dose distribution area in all directions. Nine of the 11 patients with smaller 90% confidence intervals of the percent normalization of the beam cycle (BC; 90% BC) showed a peak within the 90% dose distribution area in six directions, and this percentage was higher than that among the patients with larger 90% BC (3/10, p = 0.03).
Conclusion: The geometric accuracy of proton beam irradiation to the liver was higher in the left-right direction than in the other directions. Patients with an irregular respiratory rhythm have a greater risk of a reduced geometric accuracy of PBT in the liver. (C) 2012 Elsevier Inc.

Results of Proton Beam Therapy without Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer
Yoshiko Oshiro, Masashi Mizumoto, Toshiyuki Okumura, Takayuki Hashimoto, Nobuyoshi Fukumitsu, Ayako Ohkawa, Ayae Kanemoto, Haruko Hashii, Toshiki Ohno, Takeji Sakae, Koji Tsuboi, Hideyuki Sakurai
JOURNAL OF THORACIC ONCOLOGY, 7, 2, 370, 375, LIPPINCOTT WILLIAMS & WILKINS, Feb. 2012, [Peer-reviewed]
English, Scientific journal, Introduction: This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone.
Methods: The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE).
Results: Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2-28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9-78.0%) and 39.4% (25.353.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1-49.4%) and 24.9% (12.7-37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-year local control rates were 79.1% (66.8-91.3%) and 64.1% (47.5-80.7%), respectively. Grade >= 3 lung toxicity was seen in six patients, esophageal toxicity occurred at grade <= 2, and there was no cardiac toxicity.
Conclusion: The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that highdose PBT is beneficial and tolerable for these patients.

Roles and problems of proton beam radiation therapy for the treatment of pediatric cancer　　　　　　　　　　　　　　　
H.,Sakurai, Y.,Oshiro, M.,Mizumoto, T.,Hashimoto, H.,Ishikawa, T.,Okumura, K.,Tsuboi, T.,Sakae, N.,Fukumitsu, R.,Sumazaki
Second International Conference on Real-time Tumor-tracking Radiation Therapy with 4D Molecular Imaging Technique(第2回分子追跡放射線治療国際会議）, 29, Feb. 2012, [Peer-reviewed]
English, International conference proceedings

Influence of secondary neutrons induced by proton radiotherapy for cancer patients with implantable cardioverter defibrillators
Takayuki Hashimoto, Tomonori Isobe, Haruko Hashii, Hiroaki Kumada, Hiroshi Tada, Toshiyuki Okumura, Koji Tsuboi, Takeji Sakae, Kazutaka Aonuma, Hideyuki Sakurai
RADIATION ONCOLOGY, 7, 10, BIOMED CENTRAL LTD, Jan. 2012, [Peer-reviewed]
English, Scientific journal, Background: Although proton radiotherapy is a promising new approach for cancer patients, functional interference is a concern for patients with implantable cardioverter defibrillators (ICDs). The purpose of this study was to clarify the influence of secondary neutrons induced by proton radiotherapy on ICDs.
Methods: The experimental set-up simulated proton radiotherapy for a patient with an ICD. Four new ICDs were placed 0.3 cm laterally and 3 cm distally outside the radiation field in order to evaluate the influence of secondary neutrons. The cumulative in-field radiation dose was 107 Gy over 10 sessions of irradiation with a dose rate of 2 Gy/min and a field size of 10 x 10 cm(2). After each radiation fraction, interference with the ICD by the therapy was analyzed by an ICD programmer. The dose distributions of secondary neutrons were estimated by Monte-Carlo simulation.
Results: The frequency of the power-on reset, the most serious soft error where the programmed pacing mode changes temporarily to a safety back-up mode, was 1 per approximately 50 Gy. The total number of soft errors logged in all devices was 29, which was a rate of 1 soft error per approximately 15 Gy. No permanent device malfunctions were detected. The calculated dose of secondary neutrons per 1 Gy proton dose in the phantom was approximately 1.3-8.9 mSv/Gy.
Conclusions: With the present experimental settings, the probability was approximately 1 power-on reset per 50 Gy, which was below the dose level (60-80 Gy) generally used in proton radiotherapy. Further quantitative analysis in various settings is needed to establish guidelines regarding proton radiotherapy for cancer patients with ICDs.

Nutrition support for head and neck squamous cell carcinoma patients treated with chemoradiotherapy: how often and how long?
Ishiki H, Onozawa Y, Kojima T, Hironaka S, Fukutomi A, Yasui H, Yamazaki K, Taku K, Machida N, Boku N, Hashimoto T, Nishimura T
ISRN oncology, 2012, 274739, 2012, [Peer-reviewed]

Results of Proton Beam Therapy without Concurrent Chemotherapy for Patients with Unresectable Stage III Non-small Cell Lung Cancer
Y.,Oshiro, M.,Mizumoto, T.,Okumura, T.,Hashimoto, N.,Fukumitsu, A.,Ohkawa, A.,Kanemoto, H.,Hashii, T.,Ohno, T.,Sakae, K.,Tsuboi, H.,Sakurai
J Thorac Oncol, 7, 2, 370, 375, Jan. 2012, [Peer-reviewed]
English, Scientific journal, [INTRODUCTION] This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone.

[METHODS] The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE).

[RESULTS] Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2-28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9-78.0%) and 39.4% (25.3-53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1-49.4%) and 24.9% (12.7-37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-

Proton beam therapy for liver metastasis from breast carcinoma: Five cases reports and a review of the literatures　　　　　　　　　　　　　　　
A.,Kanemoto, H.,Ishikawa, M.,Mizumoto, T.,Okumura, T.,Hashimoto, Y.,Oshiro, N.,Fukumitsu, K.,Tsuboi, T.,Sakae, H.,Sakurai
International Cancer Conference Journal, 1, 4, 210, 214, Jan. 2012, [Peer-reviewed]
English, Scientific journal

肝細胞癌に対する陽子線治療 ～筑波大学での治療経験～　　　　　　　　　　　　　　　
福田邦明, 奥村敏之, 安部井誠人, 石川仁, 橋本孝之, 石毛和紀, 兵頭一之介, 坪井康次, 櫻井英幸
第48回日本肝癌研究会, 2012, [Peer-reviewed]
Japanese, Research society

Clinical Features of Refractory Radiation Esophageal Ulcer after Proton Beam Therapy and Its Management in a Patient with Esophageal Cancer
Hisakura,Katsuji, Terashima,Hideo, Nagai,Kentaro, Kohno,Keisuke, Tadano,Sosuke, Enomoto,Tsuyoshi, Inagawa,Satoshi, Hashimoto,Takayuki, Sakurai,Hideyuki, Ohkohchi,Nobuhiro
Jpn J Gastroenterol Surg, 45, 12, 1145, 1152, The Japanese Society of Gastroenterological Surgery, 2012
Japanese, Scientific journal, It has been reported that proton beam therapy is an effective treatment method for patients with locally confined esophageal cancer. However, there seems to be serious problems related to post-radiotherapy (RT) esophageal ulcers. We treated 7 patients who developed post-RT esophageal ulcers with the earliest symptom of esophageal stenosis, which was observed 7–17 months (median, 10.0) after completion of RT. Five of the patients had unhealed ulcers leading to lethal events such as perforation or penetration. The mean time between the appearance of the earliest symptom and lethal episode was no more than 2 months (mean, 2.1). The first 3 patients who underwent conservative therapies died from severe complications caused by perforation or penetration of post-RT esophageal ulcers. In the case of 2 consecutive patients, we performed surgical treatment as soon as possible since there were indications of penetration in post-RT developed esophageal ulcers. Therefore, they could be cured by a salvage operation which was subtotal esophagectomy using the stomach for esophageal replacement. Through the above-mentioned experience, we discussed surgical management for esophageal ulcers after

PROTON BEAM THERAPY FOR HEPATOCELLULAR CARCINOMA: A COMPARISON OF THREE TREATMENT PROTOCOLS
Masashi Mizumoto, Toshiyuki Okumura, Takayuki Hashimoto, Kuniaki Fukuda, Yoshiko Oshiro, Nobuyoshi Fukumitsu, Masato Abei, Atsushi Kawaguchi, Yasutaka Hayashi, Ayako Ookawa, Haruko Hashii, Ayae Kanemoto, Takashi Moritake, Eriko Tohno, Koji Tsuboi, Takeji Sakae, Hideyuki Sakurai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, 4, 1039, 1045, ELSEVIER SCIENCE INC, Nov. 2011, [Peer-reviewed]
English, Scientific journal, Background: Our previous results for treatment of hepatocellular carcinoma (HCC) with proton beam therapy revealed excellent local control with low toxicity. Three protocols were used to avoid late complications such as gastrointestinal ulceration and bile duct stenosis. In this study, we examined the efficacy of these protocols.
Methods and Materials: The subjects were 266 patients (273 HCCs) treated by proton beam therapy at the University of Tsukuba between January 2001 and December 2007. Three treatment protocols (A, 66 GyE in 10 fractions; B, 72.6 GyE in 22 fractions; and C, 77 GyE in 35 fractions) were used, depending on the tumor location.
Results: Of the 266 patients, 104, 95, and 60 patients were treated with protocols A, B, and C, respectively. Seven patients with double lesions underwent two different protocols. The overall survival rates after 1, 3 and 5 years were 87%, 61%, and 48%, respectively (median survival, 4.2 years). Multivariate analysis showed that better liver function, small clinical target volume, and no prior treatment (outside the irradiated field) were associated with good survival. The local control rates after 1, 3, and 5 years were 98%, 87%, and 81%, respectively. Multivariate analysis did not identify any factors associated with good local control.
Conclusions: This study showed that proton beam therapy achieved good local control for HCC using each of three treatment protocols. This suggests that selection of treatment schedules based on tumor location may be used to reduce the risk of late toxicity and maintain good treatment efficacy. (C) 2011 Elsevier Inc.

HYPERFRACTIONATED CONCOMITANT BOOST PROTON BEAM THERAPY FOR ESOPHAGEAL CARCINOMA
Masashi Mizumoto, Shinji Sugahara, Toshiyuki Okumura, Takayuki Hashimoto, Yoshiko Oshiro, Nobuyoshi Fukumitsu, Akira Nakahara, Hideo Terashima, Koji Tsuboi, Hideyuki Sakurai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, 4, E601, E606, ELSEVIER SCIENCE INC, Nov. 2011, [Peer-reviewed]
English, Scientific journal, Purpose: To evaluate the efficacy and safety of hyperfractionated concomitant boost proton beam therapy (PBT) for patients with esophageal cancer.
Methods and Materials: The study participants were 19 patients with esophageal cancer who were treated with hyperfractionated photon therapy and PBT between 1990 and 2007. The median total dose was 78 GyE (range, 70-83 GyE) over a median treatment period of 48 days (range, 38-53 days). Ten of the 19 patients were at clinical T Stage 3 or 4.
Results: There were no cases in which treatment interruption was required because of radiation-induced esophagitis or hematologic toxicity. The overall 1- and 5-year actuarial survival rates for all 19 patients were 79.0% and 42.8%, respectively, and the median survival time was 31.5 months (95% limits: 16.7-46.3 months). Of the 19 patients, 17 (89%) showed a complete response within 4 months after completing treatment and 2 (11%) showed a partial response, giving a response rate of 100% (19/19). The 1- and 5-year local control rates for all 19 patients were 93.8% and 84.4 %, respectively. Only 1 patient had late esophageal toxicity of Grade 3 at 6 months after hyperfractionated PBT. There were no other nonhematologic toxicities, including no cases of radiation pneumonia or cardiac failure of Grade 3 or higher.
Conclusions: The results suggest that hyperfractionated PBT is safe and effective for patients with esophageal cancer. Further studies are needed to establish the appropriate role and treatment schedule for use of PBT for esophageal cancer. (C) 2011 Elsevier Inc.

進行非小細胞肺癌に対する化学放射線療法における正常肺DVH解析 －X線と陽子線の比較－　　　　　　　　　　　　　　　
大野豊然貴, 水本斉志, 大城佳子, 橋本孝之, 金本彩恵, 榮武二, 坪井康次, 奥村敏之, 櫻井英幸
日本放射線腫瘍学会第24回学術大会抄録集, 257, 257, Nov. 2011, [Peer-reviewed]
Japanese, Research society

Radiotherapy for Patients with Symptomatic Intramedullary Spinal Cord Metastasis
Haruko Hashii, Masashi Mizumoto, Ayae Kanemoto, Hideyuki Harada, Hirofumi Asakura, Takayuki Hashimoto, Kazuhisa Furutani, Hirohisa Katagiri, Yoko Nakasu, Tetsuo Nishimura
JOURNAL OF RADIATION RESEARCH, 52, 5, 641, 645, JAPAN RADIATION RESEARCH SOC, Sep. 2011, [Peer-reviewed]
English, Scientific journal, The study was performed to evaluate radiotherapy for patients with intramedullary spinal cord metastasis (ISCM) and to identify the clinical features of ISCM. The subjects were 18 patients (8 men, 10 women) with ISCM who underwent radiotherapy between September 2002 and February 2008. The primary lesions were lung cancer in 8 patients (2 small cell, 6 non-small cell), breast cancer in 6, malignant melanoma in 2, renal cell carcinoma in 1, and rectal cancer in 1 patient. Diagnosis, symptoms and survival of these patients were compared with those for 544 patients with vertebral metastases who underwent radiotherapy at the same institute between September 2002 and November 2006. In the 18 patients with ISCM, the 6-month survival rate after radiotherapy was 36% and the median survival period was 4.0 months. Ten patients had neurological improvement or pain relief after radiotherapy. Brain metastases were six fold more frequent in the patients with ISCM than in those with vertebral metastasis [89% vs. 15%, p = 0.001]. At the time of radiotherapy, back pain in patients with vertebral metastasis was more frequent [97% vs. 33%, p = 0.001] but neurological deficits were less common [24% vs. 100%, p = 0.001]. Most ISCM cases were diagnosed by contrast-enhanced MRI, with detection by contrast-enhanced CT in only 3/18 cases (17%). ISCM has a poor prognosis and most patients have neurological deficits that impair quality of life. Early diagnosis by MRI is important for suspected ISCM to allow initiation of radiotherapy before development of neurological deficits.

乳癌肝転移に対する陽子線治療症例の検討　　　　　　　　　　　　　　　
金本 彩恵, 水本 斉志, 奥村 敏之, 橋本 孝之, 大城 佳子, 福光 延吉, 大川 綾子, 橋井 晴子, 榮 武二, 坪井 康次, 櫻井 英幸
日本乳癌学会総会プログラム抄録集, 19回, 325, 325, (一社)日本乳癌学会, Sep. 2011
Japanese

Occurrence and Clinical Features of Brain Metastasis after Chemoradiotherapy for Esophageal Carcinoma
Ayae Kanemoto, Takayuki Hashimoto, Hideyuki Harada, Hirofumi Asakura, Hirofumi Ogawa, Kazuhisa Furutani, Narikazu Boku, Yoko Nakasu, Tetsuo Nishimura
JOURNAL OF RADIATION RESEARCH, 52, 4, 509, 515, JAPAN RADIATION RESEARCH SOC, Jul. 2011, [Peer-reviewed]
English, Scientific journal, Brain metastasis from esophageal carcinoma has been considered rare and survival following esophageal carcinoma with distant metastasis is poor. The purpose of this report was to clarify cumulative incidence and risk factors for brain metastasis after chemoradiotherapy for esophageal carcinoma, and to consider recommended treatments for brain metastasis from esophageal carcinoma. We reviewed 391 patients treated with chemoradiotherapy. Median age was 65 years. Clinical stages were I, II, III, and IV in 32, 47, 150, and 162 patients, respectively. Brain imaging was performed usually when patients revealed neurological symptoms. The 3-year cumulative incidence of brain metastasis after chemoradiotherapy was 6.6%. There were 4 patients with single metastasis and 8 with multiple metastases. Initial clinical stages were II, III, and IV in 1, 2, and 9 patients, respectively. Histology included squamous cell carcinoma in 10 patients and others in 2 patients. Univariate analysis demonstrated M factor, distant lymph node relapse, and recurrent lung and liver metastasis as significant risk factors of brain metastasis (P < 0.05). Median survival time after diagnosis of brain metastasis was 2.1 months. Brain metastasis was not directly related to cause of mortality. The causes were extracranial tumor deterioration in 8 patients and infection in 4 patients. Brain metastasis may increase in the future with improving survival from esophageal carcinoma. However, considering the poor survival after diagnosis of brain metastasis, short-term palliative therapy for brain metastasis appears preferable to vigorous long-term therapy.

Efficacy and limitation of radiation therapy for hepatocellular carcinoma complicated with liver cirrhosis　　　　　　　　　　　　　　　
Abei,M, Fukuda,K, Okumura,T, Fukumitsu,N, Hashimoto,T, Mizumoto,M, Ishige,K, Ohkohchi,N, Tsuboi,K, Hyodo,I, Sakurai,H
2nd Asia-Pacific Primary Liver Cancer Expert Meeting. Workshop "Radiotherapy of HCC", Jul. 2011, [Peer-reviewed]
English, International conference proceedings

Displacement of hepatic tumor at time to exposure in end-expiratory-triggered-pulse proton therapy
Yoshiko Oshiro, Toshiyuki Okumura, Masaya Ishida, Shinji Sugahara, Masashi Mizumoto, Takayuki Hashimoto, Kiyoshi Yasuoka, Koji Tsuboi, Takeji Sakae, Hideyuki Sakurai
RADIOTHERAPY AND ONCOLOGY, 99, 2, 124, 130, ELSEVIER IRELAND LTD, May 2011, [Peer-reviewed]
English, Scientific journal, Purpose: This study is to evaluate reproducibility of hepatic tumors in end-expiration and end-inspiration on free-breathing, also measure shift of hepatic tumor location in pulsed proton beams exposure in end-expiration in order to estimate feasible planning target volume (PTV) margin.
Materials and methods: Pairs (1232) of anterior and lateral radiographs from 30 patients (628 end-expiration and 604 end-inspiration phases) were analyzed using fiducial markers adjacent to the tumors. By using the co-ordinates of the marker centroid of mass related to the isocenter, intrafractional variation was compared in end-expiration and end-inspiration, and a feasible PTV margin was generated using the measured motion.
Results: The average internal motion in end-expiration was 1.1 mm, which was significantly smaller than that in end-inspiration. The mean deviation from the plan was -0.1, 0.3, and 0.1 mm in the left-right (LR), cranio-cepharal (CC), and anterior-posterior (AP) directions, respectively. The estimated PTV margins were 3.2, 3.5, and 4.6 mm, in the LR. CC, and AP directions, respectively.
Conclusions: It was indicated that localization of the targets was more reproducibility in end-expiration than that in end-inspiration. Also, feasible and practical margin values were obtained. These should contribute accuracy of respiration synchronized proton radiotherapy for liver tumors. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 99 (2011) 124-130

Pediatric nasopharyngeal carcinoma treated with proton beam therapy. Two case reports
Yoshiko Oshiro, Shinji Sugahara, Takashi Fukushima, Toshiyuki Okumura, Tomohei Nakao, Masashi Mizumoto, Takayuki Hashimoto, Koji Tsuboi, Michio Kaneko, Hideyuki Sakurai
ACTA ONCOLOGICA, 50, 3, 470, 473, INFORMA HEALTHCARE, Apr. 2011, [Peer-reviewed]
English

Palliative radiotherapy for bleeding from advanced gastric cancer: is a schedule of 30 Gy in 10 fractions adequate?
Hirofumi Asakura, Takayuki Hashimoto, Hideyuki Harada, Masashi Mizumoto, Kazuhisa Furutani, Noriaki Hasuike, Masaki Matsuoka, Hiroyuki Ono, Narikazu Boku, Tetsuo Nishimura
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 137, 1, 125, 130, SPRINGER, Jan. 2011, [Peer-reviewed]
English, Scientific journal, To evaluate the effectiveness of short-course radiotherapy (RT) with 30 Gy in 10 fractions for bleeding from advanced gastric cancer.
We reviewed the data for all patients with gastric cancer requiring blood transfusions due to gastric bleeding who were treated with RT at the Shizuoka Cancer Center Hospital between September 2002 and March 2007. Patients with curative-intent chemoradiotherapy or previous irradiation were excluded. RT was planned to deliver a total of 30 Gy at 3 Gy per fraction. We defined RT as effective if the patients did not require blood transfusions for 1 or more months after RT.
Twenty-two out of 30 patients (73%) responded to RT, and rebleeding occurred in 11 (50%) of 22 patients responding to RT. The median actuarial time to rebleeding was 3.3 months. Twelve patients received concurrent chemoradiotherapy and had a significantly lower rebleeding rate than patients undergoing RT alone (P = 0.001). Among patients receiving CRT, 1 with grade 3 non-hematological toxicity and 5 with grade 3-4 hematological toxicity were observed. No Grade 3 or higher adverse events were observed in patients treated with RT alone.
RT with 30 Gy in 10 fractions is an adequate treatment for bleeding from advanced gastric cancer, especially in patients with poor prognosis.

RADIOTHERAPY FOR PATIENTS WITH METASTASES TO THE SPINAL COLUMN: A REVIEW OF 603 PATIENTS AT SHIZUOKA CANCER CENTER HOSPITAL
Masashi Mizumoto, Hideyuki Harada, Hirofumi Asakura, Takayuki Hashimoto, Kazuhisa Furutani, Haruko Hashii, Hideki Murata, Tatsuya Takagi, Hirohisa Katagiri, Mitsuru Takahashi, Tetsuo Nishimura
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 79, 1, 208, 213, ELSEVIER SCIENCE INC, Jan. 2011, [Peer-reviewed]
English, Scientific journal, Purpose: Long- and short-course radiotherapy have similar outcomes in the treatment of spinal metastases. Long-course radiotherapy is recommended for patients with good predicted survival to reduce the risk of in-field recurrence, whereas short-course radiotherapy is used for those with poor predicted survival. Therefore, prediction of prognosis and local control is required for selecting the optimal course of radiotherapy.
Methods and Materials: The subjects were 603 patients with spinal metastases who received radiotherapy at the Shizuoka Cancer Center Hospital between September 2002 and February 2007. Factors associated with survival and local control were retrospectively investigated by multivariate analyses. Local recurrence was defined as regrowth within the irradiated field or exacerbation of symptoms such as pain and motor deficits.
Results: Of the 603 patients, 555 (92%) were followed for 12 months or until death. The survival rates after 6, 12, and 2 months were 50%, 32%, and 19%, respectively, with a median survival of 6.2 months. The median survival periods after long- and short-course radiotherapy were 7.9 and 1.8 months, respectively. In multivariate analysis, primary tumor site, good performance status, absence of previous chemotherapy, absence of visceral metastasis, single bone metastasis, younger age, and nonhypercalcemia were associated with good survival. The local control rates after 6, 12, and 24 months were 91%, 79%, and 69%, respectively, and non-mass-type tumor, breast cancer, and absence of previous chemotherapy were predictors of good local control.
Conclusions: Identification of factors associated with good local control and survival may allow selection of an optimal radiotherapy schedule for patients with spinal metastases. (C) 2011 Elsevier Inc.

Designed-Seamless Irradiation Technique (D-SLIT) for Extended Whole Mediastinal Proton-Beam Irradiation for Esophageal Cancer　　　　　　　　　　　　　　　
Okonogi, N, Hashimoto, T, Ishida, M, Terunuma, T, Okumura, T, Sakae, T, Sakurai, H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, 2::Suppl. S, S313, S313, ELSEVIER SCIENCE INC, Jan. 2011, [Peer-reviewed]
English, Scientific journal

Evaluation of Secondary Neutron Dose in Particle and High Energy X-ray Therapy　　　　　　　　　　　　　　　
Isobe, T, Hashimoto, T, Kumada, H, Hashii, H, Takada, K, Matsufuji, N, Hanmura, M, Fukuda, S, Sakurai, H, Sakae, T
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, 2::Suppl. S, S875, S876, ELSEVIER SCIENCE INC, Jan. 2011, [Peer-reviewed]
English, International conference proceedings

Application of the multi-modal Monte-Carlo treatment planning system combined with PHITS to proton radiotherapy　　　　　　　　　　　　　　　
Kumada, H, Sakae, T, Saito, K, Isobe, T, Hashimoto, T, Sakurai, H
Progress in Nuclear Science and Technology, 2, 213, 218, Jan. 2011, [Peer-reviewed]
English, Scientific journal

Effects of secondary neutron beam generated in radiotherapy on electronic medical devices．　　　　　　　　　　　　　　　
Isobe,T, Kumada,H, Takada,K, Hashimoto,T, Hashii,H, Shida,K, Tadano,K, Fujibuchi,T, Hanmura,M, Sakurai,H, Sakae,T
Progress in Nuclear Science and Technology, 2, 524, 529, 2011, [Peer-reviewed]
English, Scientific journal

Hyperfractionated Concomitant Boost Proton Radiotherapy for Supratentorial Glioblastoma Multiforme: Analysis of Long Survival Patients　　　　　　　　　　　　　　　
Mizumoto, M, Tsuboi, K, Okumura, T, Hashimoto, T, Oshiro, Y, Fukumitsu, N, Hayashi, Y, Ohkawa, A, Sakae, T, Sakurai, H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, 2::Suppl. S, S278, S278, ELSEVIER SCIENCE INC, Jan. 2011, [Peer-reviewed]
English, International conference proceedings

Proton Beam Therapy for Metastatic Liver Cancer　　　　　　　　　　　　　　　
Hashimoto, T, Okumura, T, Kanemoto, A, Hashii, H, Ohkawa, A, Oshiro, Y, Mizumoto, M, Fukumitsu, N, Tsuboi, K, Sakurai, H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, 2::Suppl. S, S353, S353, ELSEVIER SCIENCE INC, Jan. 2011, [Peer-reviewed]
English, Scientific journal

Results Of Proton Beams Radiotherapy Without Concurrent Chemotherapy For Patients With Unresectable Stage III Non-small Cell Lung Cancer　　　　　　　　　　　　　　　
Oshiro, Y, Okumura, T, Mizumoto, M, Hashimoto, T, Fukumitsu, N, Ohkawa, A, Kanemoto, A, Hashii, H, Tsuboi, K, Sakurai, H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 81, 2::Suppl. S, S576, S577, ELSEVIER SCIENCE INC, Jan. 2011, [Peer-reviewed]
English, Scientific journal

Influence of Neutron Generated in 10 MV-X-ray Irradiation and Proton Beam on Implatable Cardioverter Defibrillators(ICDs)　　　　　　　　　　　　　　　
Isobe, T, Kumada, H, Hashimoto, T, Hashii, H, Sakurai, H, Sakae, T
The Radiological Society of North America（RSNA）96 t Scientific Assembly and Annual Meeting, Dec. 2010, [Peer-reviewed]
English, International conference proceedings

肝腫瘍陽子線治療の照射精度の検討　　　　　　　　　　　　　　　
福光延吉, 橋本孝之, 奥村敏之, 橋井晴子, 金本彩恵, 大川綾子, 水本斉志, 榮武二, 坪井康次, 櫻井英幸
日本放射線腫瘍学会第23回学術大会, Nov. 2010, [Peer-reviewed]
Japanese, Research society

A case of large intrahepatic cholangiocarcinoma treated with concurrent proton beam therapy and TS-1　　　　　　　　　　　　　　　
Takayuki Hashimoto
Liver Cancer, 16, 2, 164-170, 癌と化学療法社, Nov. 2010, [Peer-reviewed]
Japanese, Scientific journal

Application of Monte-Carlo treatment planning system “JCDS-FX with PHITS”to proton radiotherapy　　　　　　　　　　　　　　　
Kumada, H, Sakae, T, Saito, K, Isobe, T, Hashimoto, T, Sakurai, H
Joint International Conference on Supercomputiong in Nuclear Applications + Monte Carlo 2010, Oct. 2010, [Peer-reviewed]
English, International conference proceedings

Radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma　　　　　　　　　　　　　　　
Kanemoto, A, Mizumoto, M, Okumura, T, Moritake, T, Hashimoto, T, Ohshiro, Y Ohkawa, A, Hashii H, Sakae, T, Tsuboi K, Sakurai, H
European Society for Therapeutic Radiology and Oncology(ESTRO 29), Sep. 2010, [Peer-reviewed]
English, International conference proceedings

がんの放射線治療のなかでの陽子線治療の位置付け
櫻井英幸, 奥村敏之, 橋本孝之, 水本斉志, 大城佳子, 大川綾子, 金本彩恵, 橋井晴子, 盛武敬, 坪井康次, 磯辺智範, 照沼利之, 安岡聖, 熊田博明, 榮武二
癌の臨床, 55, 12, 829-846, 836, 篠原出版社, Aug. 2010, [Peer-reviewed]
Japanese, Scientific journal

肝癌の放射線治療－粒子線治療の立場から-　　　　　　　　　　　　　　　
櫻井英幸, 奥村敏之, 橋本孝之, 水本斉志, 大城佳子, 福光延吉, 盛武敬, 坪井康次, 榮武二
第22回日本高精度放射線外部照射研究会, 31, Jul. 2010, [Peer-reviewed]
Japanese, Research society

転移性肝癌に対する陽子線治療成績　　　　　　　　　　　　　　　
橋本孝之, 福田邦明, 金本彩恵, 橋井晴子, 大川綾子, 大城佳子, 水本斉志, 森健作, 盛武敬, 安部井誠人, 奥村敏之, 坪井康次, 兵頭一之介, 櫻井英幸
第46回日本肝癌研究会, Jul. 2010, [Peer-reviewed]
Japanese, Research society

肝内胆管癌に対する陽子線治療の経験　　　　　　　　　　　　　　　
奥村敏之, 安部井誠人, 大川綾子, 正田純一, 福田邦明, 橋本孝之, 水本斉志, 大城佳子, 盛武敬, 森建作, 廣島良規, 金本彩恵, 橋井晴子, 坪井康次, 櫻井英幸
第46回日本肝癌研究会, Jul. 2010, [Peer-reviewed]
Japanese, Research society

Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer
Hirofumi Asakura, Takayuki Hashimoto, Sadamoto Zenda, Hideyuki Harada, Koichi Hirakawa, Masashi Mizumoto, Kazuhisa Furutani, Shuichi Hironaka, Hiroshi Fuji, Shigeyuki Murayama, Narikazu Boku, Tetsuo Nishimura
RADIOTHERAPY AND ONCOLOGY, 95, 2, 240, 244, ELSEVIER IRELAND LTD, May 2010, [Peer-reviewed]
English, Scientific journal, Purpose: To evaluate dose-volume histogram (DVH) parameters as predictors of radiation pneumonitis (RP) in esophageal cancer patients treated with definitive concurrent chemoradiotherapy.
Patients and methods: Thirty-seven esophageal cancer patients treated with radiotherapy with concomitant chemotherapy consisting of 5-fluorouracil and cisplatin were reviewed. Radiotherapy was delivered at 2 Gy per fraction to a total of 60 Gy. For most of the patients, two weeks of interruption was scheduled after 30 Gy. The percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively), and the mean lung dose (MLD) were analyzed.
Results: Ten (27%) patients developed RP of grade 2; 2 (5%), grade 3: 0 (0%), grade 4; and 1 (3%), grade 5. By univariate analysis, all DVH parameters (i.e., V5-V50 and MLD) were significantly associated with grade >= 2 RP (p < 0.01). The incidences of grade >= 2 RP were 13%, 33%, and 78% in patients with V20s of <= 24%, 25-36%, and >= 37% respectively. The optimal V20 threshold to predict symptomatic RP was 30.5% according to the receiver operating characteristics curve analysis.
Conclusion: DVH parameters were predictors of symptomatic RP and should be considered in the evaluation of treatment planning for esophageal cancer. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 95 (2010) 240-244

Estimation for incidental doses caused by secondary neutrons and photons in proton radiotherapy by Monte-Carlo simulations using PHITS and JCDS.　　　　　　　　　　　　　　　
Kumada, H, Sakae, T, Isobe, T, Hashimoto, T, Terunuma, T, Saito, K
The Third Asian and Oceanic Congress on Radiation Protecrion, May 2010, [Peer-reviewed]
English, International conference proceedings

Estimations for incidental doses caused by secondary neutrons and photons in proton therapy by Monte-Calro simulation with PHITS　　　　　　　　　　　　　　　
Kumada, H, Sakae, T, Terunuma, T, Isobe, T, Hashimoto, T, Saito, K, 櫻井, 英幸
The 49th Particle Therapy Co-Operative Group, 132, May 2010, [Peer-reviewed]
English, International conference proceedings

Radiological Response and Clinical Outcome in Patients with Femoral Bone Metastases after Radiotherapy
Hideyuki Harada, Hirohisa Katagiri, Minoru Kamata, Yasuo Yoshioka, Hirofumi Asakura, Takayuki Hashimoto, Kazuhisa Furutani, Mitsuru Takahashi, Harumi Sakahara, Tetsuo Nishimura
JOURNAL OF RADIATION RESEARCH, 51, 2, 131, 136, OXFORD UNIV PRESS, Mar. 2010, [Peer-reviewed]
English, Scientific journal, We evaluated the radiological response and clinical outcome in patients with femoral bone metastases after radiotherapy. 102 consecutive patients with femoral metastases without pathological fracture were treated by surgery or radiotherapy between 2002 and 2005. Twelve of them initially treated with surgery were excluded from this study. The remaining 90 patients with 102 lesions underwent radiation therapy as the initial treatment. Twelve patients who died within 30 days by disease progression and 6 who were lost to follow-up were excluded. The remaining 72 patients with 84 lesions including 43 impending fractures were enrolled in this analysis. Radiological changes were categorized into complete response, partial response, no change, and progressive disease based on plain radiograph findings. Pain relief was reviewed for 77 painful lesions. The median radiation dose was 30 Gy. No re-irradiation was performed. 35 lesions (42%) achieved radiological responses median 3 months after radiotherapy. Pain relief was obtained in 36 of 77 lesions (47%). There was no significant correlation between radiological response and pain relief (P = 0.166). Eleven lesions eventually required surgery and considered as treatment failure. The treatment failure rate in the radiological progressive disease (PD) group (8/19, 42%) was significantly higher than that in the non-PD group (3/65, 5%) (P < 0.001). Among 43 impending fracture lesions, 15 lesions (36%) experienced radiological response and 35 lesions (81%) required no surgical interventions. Our data suggest that radiotherapy can enable metastatic bone healing and avoid surgery in many lesions. However, radiological PD lesions often require surgery after radiotherapy.

Proton beam therapy for hepatocellular carcinoma　　　　　　　　　　　　　　　
Hideyuki,Sakurai, Toshiyuki,Okumura, Takayuki,Hashimoto, Masashi,Mizumoto, Yoshiko,Ohshiro, Takashi,Moritake, Koji,Tsuboi, Takeji,Sakae
IX Annual International Cancer Confernce(RGCON2010), 128, 129, Mar. 2010, [Peer-reviewed]
English, International conference proceedings

PMRCにおけるパッチ照射接合部の検証法　　　　　　　　　　　　　　　
石田 真也, 榮 武二, 宮本 俊男, 照沼 利之, 佐藤 勝, 橋本 孝之, 藤崎 達也
日本放射線技術学会総会学術大会予稿集, 66回, 286, 286, (公社)日本放射線技術学会, Feb. 2010
Japanese

肝癌治療における放射線科の現状と未来 粒子線治療の立場から　　　　　　　　　　　　　　　
櫻井 英幸, 奥村 敏之, 橋本 孝之, 水本 斉志, 大城 佳子, 大川 綾子, 金本 彩恵, 橋井 晴子, 盛武 敬, 坪井 康次
日本医学放射線学会学術集会抄録集, 69回, S75, S75, (公社)日本医学放射線学会, Feb. 2010
Japanese

肝腫瘍に対する陽子線治療後肋骨骨折をきたした５例の検討　　　　　　　　　　　　　　　
金本彩恵, 水本斉志, 橋本孝之, 大城佳子, 大川綾子, 橋井晴子, 盛武敬, 坪井康次, 奥村敏之, 櫻井英幸
第69回日本医学放射線学会総会抄録集, 69回, S364, S364, (公社)日本医学放射線学会, Feb. 2010, [Peer-reviewed]
Japanese, Research society

肝内胆管癌に対する陽子線治療成績　　　　　　　　　　　　　　　
大川綾子, 橋本孝之, 金本彩恵, 橋井晴子, 大城佳子, 水本斉志, 盛武敬, 奥村敏之, 坪井康次, 櫻井英幸
第69回日本医学放射線学会総会抄録集, 69回, S363-4, S364, (公社)日本医学放射線学会, Feb. 2010, [Peer-reviewed]
Japanese, Research society

Proton beam therapy at PMRC, University of Tsukuba -present and future　　　　　　　　　　　　　　　
Sakurai, H, Okumura, T, Hashimoto, T, Mizumoto, M, Oshiro, Y, Ohkawa, A, Hashii, H, Kanemoto, A, Moritake, T, Tsuboi, K, Terunuma, T, Yasuoka, K, Kumada, H, Sakae, T
Scientific Meeting, PTCOG 49, 7, Jan. 2010, [Peer-reviewed]
English, International conference proceedings

Proton Beam Therapy for Intrahepatic Cholangiocarcinoma　　　　　　　　　　　　　　　
Ohkawa, A, Hashimoto, T, Okumura, T, Abei, M, Fukuda, K, Mizumoto, M, Oshiro, Y, Sakae, T, Tsuboi, K, Sakurai, H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 78, 3::Suppl. S, 0, 0, ELSEVIER SCIENCE INC, Jan. 2010, [Peer-reviewed]
English, Scientific journal

T1-3前立腺癌に対する陽子線治療の成績　　　　　　　　　　　　　　　
宮永直人, 橋本孝之, 菅原信二, 小野澤瑞樹, 水本斉志, 及川剛宏, 宮崎淳, 関戸哲利, 河合弘二, 奥村敏之, 島居徹, 櫻井英幸, 赤座英之
泌尿器外科, 23, 8, 1189, 1192, Jan. 2010, [Peer-reviewed]
Japanese, Scientific journal

Influence of Particle Therapy on Implantable Cardiac Devices: An Experimental Study　　　　　　　　　　　　　　　
Hashimoto, T, Hashii, H, Isobe, T, Ohkawa, A, Yonai, S, Matsufuji, N, Fukuda, S, Sakae, T, Aonuma, K, Sakurai, H
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 78, 3::Suppl. S, 0, 0, ELSEVIER SCIENCE INC, Jan. 2010, [Peer-reviewed]
English, Scientific journal

RESIDUAL MOTION AND DUTY TIME IN RESPIRATORY GATING RADIOTHERAPY USING INDIVIDUALIZED OR POPULATION-BASED WINDOWS
Hiroshi Fuji, Yoshihiro Asada, Masumi Numano, Haruo Yamashita, Tetsuo Nishimura, Takayuki Hashimoto, Hideyuki Harada, Hirofumi Asakura, Shigeyuki Murayama
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 75, 2, 564, 570, ELSEVIER SCIENCE INC, Oct. 2009, [Peer-reviewed]
English, Scientific journal, Purpose: The efficiency and precision of respiratory gated radiation therapy for tumors is affected by variations in respiration-induced tumor motion. We evaluated the use of individualized and population-based parameters for such treatment.
Methods and Materials: External respiratory signal records and images of respiration-induced tumor motion were obtained from 42 patients undergoing respiratory gated radiation therapy for liver tumors. Gating window widths were calculated for each patient, with 2, 4, and 10 mm of residual motion, and the mean was defined as the population-based window width. Residual motions based on population-based and predefined window widths were compared. Duty times based on whole treatment sessions, at various window levels, were calculated. The window level giving the longest duty time was defined as the individualized most efficient level (MEL). MELs were also calculated based on the first 10 breathing cycles. The duty times for population-based MELs (defined as mean MELs) and individualized MELs were compared.
Results: Tracks of respiration-induced tumor motion ranged from 3 to 50 mm. Half of the patients had larger actual residual motions than the assigned residual motions. Duty times were greater when based on individualized, rather than population-based, window widths. The MELs established during whole treatment sessions for 2 rum and 4 mm of residual motion gave significantly increased duty times, whereas those calculated using the first 10 breathing cycles showed only marginal increases.
Conclusions: Using individualized window widths and levels provided more precise and efficient respiratory gated radiation therapy. However, methods for predicting individualized window levels before treatment remain to be explored. (C) 2009 Elsevier Inc.

OPTIMAL TIMING OF ENDOSCOPIC EVALUATION OF THE PRIMARY SITE OF ESOPHAGEAL CANCER AFTER CHEMORADIOTHERAPY OR RADIOTHERAPY: A RETROSPECTIVE ANALYSIS
Sadamoto Zenda, Shuichi Hironaka, Keisei Taku, Hiroshi Sato, Takayuki Hashimoto, Noriaki Hasuike, Narikazu Boku, Yasuhiro Tsubosa, Hiroyuki Ono, Tetsuo Nishimura
DIGESTIVE ENDOSCOPY, 21, 4, 245, 251, WILEY-BLACKWELL PUBLISHING, INC, Oct. 2009, [Peer-reviewed]
English, Scientific journal, Background:
Although use of gastrointestinal endoscopy for response evaluation in patients with esophageal cancer undergoing chemoradiotherapy or radiotherapy (CRT/RT) treatment is widely accepted, optimal timing for evaluation has not been sufficiently investigated. Here, we investigated optimal timing of primary site response evaluation in esophageal cancer patients treated with CRT/RT.
Patients and Methods:
This study examined esophageal cancer patients who underwent CRT/RT between September 2002 and December 2004. Time to complete response (CR) at the primary site was assessed in patients designated as CR at the primary site, while progression-free survival at the primary site (PFSp) was assessed in patients designated as incomplete response at the primary site.
Results:
Eighty-three patients were enrolled in this study. Median total RT dose was 60 Gy (range, 50-60 Gy), and median RT duration was 53 days (range, 35-74 days). Mean time to CR at the primary site was 97 days (range, 52-201 days). In four patients, although initial examination of biopsy specimens found evidence of viable cancer cells within 75 days of treatment initiation, subsequent examination found no such evidence, and the patients were thus designated as CR. Median PFSp was 149 days (range, 67-399 days), and PFSp rate at 90 days was 97%. Median interval between the previous examination and initial primary progressive disease was 37 days.
Conclusion:
Recommended time of first response evaluation for esophageal cancer following initiation of CRT/RT was found to be between 75 and 90 days. Subsequent evaluation should be carried out approximately one month following non-CR/non-progressive disease declassification.

長径2.5cm以上の脳動静脈奇形に対する陽子線分割照射療法　　　　　　　　　　　　　　　
奥村敏之, 坪井康次, 橋本孝之, 水本斉志, 大城佳子, 林靖孝, 大川綾子, 橋井晴子, 金本彩恵, 櫻井英幸
日本放射線腫瘍学会第22回学術大会, Sep. 2009, [Peer-reviewed]
Japanese, Research society

頭蓋底脊索腫/軟骨肉腫に対する陽子線照射の治療成績　　　　　　　　　　　　　　　
水本斉志, 奥村敏之, 林靖孝, 橋本孝之, 大城佳子, 大川綾子, 金本彩恵, 橋井晴子, 櫻井英幸, 坪井康次
日本放射線腫瘍学会第22回学術大会, Sep. 2009, [Peer-reviewed]
Japanese, Research society

進行食道癌に対して化学療法と陽子線治療を併用した3症例　　　　　　　　　　　　　　　
橋井晴子, 奥村敏之, 橋本孝之, 大城佳子, 水本斉志, 盛武敬, 大川綾子, 金本彩恵, 坪井康次, 櫻井英幸
日本放射線腫瘍学会第22回学術大会, Sep. 2009, [Peer-reviewed]
Japanese, Research society

陽子線治療時に呼吸同期照射を行った肝腫瘍例のPTV marginの検討　　　　　　　　　　　　　　　
金本彩恵, 大城佳子, 奥村敏之, 水本斉志, 橋本孝之, 盛武敬, 大川綾子, 橋井晴子, 坪井康次, 櫻井英幸
日本放射線腫瘍学会第22回学術大会, Sep. 2009, [Peer-reviewed]
Japanese, Research society

The use of image analysis software system to evaluate the geometrical accuracy of proton beam irradiation in the liver　　　　　　　　　　　　　　　
Nobuyoshi,Fukumitsu, Haruko,Hashii, Yoshiko,Ohshiro, Masashi,Mizumoto, Takayuki,Hashimoto, Toshiyuki,Okumura, Takeji,Sakae, Koji,Tsuboi, Hideyuki,Sakurai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 75, 3::Suppl. S, ELSEVIER SCIENCE INC, Jan. 2009, [Peer-reviewed]
English, International conference proceedings

FEASIBILITY OF PROTON BEAM THERAPY FOR PEDIATRIC TUMOR
FUJI Hiroshi, ISHIDA Yuji, MURAYAMA Shigeyuki, YAMASHITA Haruo, HASHIMOTO Takayuki, HARADA Hideyuki, ASAKURA Hirofumi, FURUTANI Kazuhisa, NISHIMURA Tetsuo
The Journal of JASTRO, 20, 4, 143, 149, 25 Dec. 2008
Japanese

Proton beam therapy interference with implanted cardiac pacemakers
Yoshiko Oshiro, Shinji Sugahara, Mio Noma, Masato Sato, Yuzuru Sakakibara, Takeji Sakae, Yasutaka Hayashi, Hidetsugu Nakayama, Koji Tsuboi, Nobuyoshi Fukumitsu, Ayae Kanemoto, Takayuki Hashimoto, Koichi Tokuuye
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 72, 3, 723, 727, ELSEVIER SCIENCE INC, Nov. 2008, [Peer-reviewed]
English, Scientific journal, Purpose: To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function.
Methods and Materials: After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33-77 gray equivalents (GyE) in dose fractions of 2.2-6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation held. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined before and after PBT.
Results: The phantom study showed no effect of neutron scatter oil pacemaker generators. In the study changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course.
Conclusions: PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore. patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT. (C) 2008 Elsevier Inc.

Prognostic Factors and a Scoring System for Survival After Radiotherapy for Metastases to the Spinal Column A Review of 544 Patients at Shizuoka Cancer Center Hospital
Masashi Mizumoto, Hideyuki Harada, Hirofumi Asakura, Takayuki Hashimoto, Kazuhisa Furutani, Haruko Hashii, Tatsuya Takagi, Hirohisa Katagiri, Mitsuru Takahashi, Tetsuo Nishimura
CANCER, 113, 10, 2816, 2822, JOHN WILEY & SONS INC, Nov. 2008, [Peer-reviewed]
English, Scientific journal, BACKGROUND. To optimize selection of a radiotherapy schedule for patients with spinal metastases, the authors analyzed prognostic factors and developed a scoring system to predict Survival in Such patients.
METHODS. Five-hundred forty-four patients with spinal metastases received radiotherapy at Shizuoka Cancer Center Hospital between September 2002 and November 2006. Prognostic factors for survival were studied using a Cox proportional hazards model, and a scoring system was developed based on regression coefficients: Three points were given for an unfavorable tumor type and bad performance status (>= 3); 2 points were given for hypercalcemia, visceral metastases, and previous chemotherapy; and 1 point was given for multiple bone metastases and age >= 71 years.
RESULTS. The overall survival rates after 6 months, 12 months, and 24 months were 49%, 32%, and 19%, respectively, and the median survival was 5.9 months (95% confidence interval, 4.9-6.8 months). In total, 503 patients (93%) were followed for >= 12 months or until death. These patients were separated into Groups A, 13, and C based on scores of 0 to 4, 5 to 9, and 10 to 14, respectively. These groups included 24%, 57%, and 19% of patients, respectively; and the mean median survival for Groups A, B, and C was 27.1 months, 5.4 months, and 1.8 months, respectively. Overall survival rates after 6 months, 12 months, and 24 months were 89%, 77%, and 54% in Group A; 46%, 22%, and 9% in Group B; and 7%, 4%, and 0% in Group C, respectively (P < .001).
CONCLUSIONS. The scoring system was able to predict the survival of patients with spinal metastases and may be useful for selecting an optimal radiotherapy schedule. Cancer 2008; 113:2816-22. (C) 2008 American Cancer Society

Results of a retrospective analysis of gemcitabine as a second-line treatment after chemoradiotherapy and maintenance chemotherapy using 5-fluorouracil in patients with locally advanced pancreatic cancer
Koichi Taira, Narikazu Boku, Akira Fukutomi, Yusuke Onozawa, Shuichi Hironaka, Takayuki Yoshino, Hirofumi Yasui, Kentaro Yamazaki, Keisei Taku, Takayuki Hashimoto, Tetsuo Nishimura
JOURNAL OF GASTROENTEROLOGY, 43, 11, 875, 880, SPRINGER JAPAN KK, Nov. 2008, [Peer-reviewed]
English, Scientific journal, Many studies of concurrent chemoradiation therapy with 5-fluorouracil (5-FU) for locally advanced pancreatic cancer have been reported with a median survival time of approximately 10 months. Recently, gemcitabine (GEM) has been administered immediately after chemoradiation. The clinical outcome of chemoradiation therapy in conjunction with 5-FU and second-line chemotherapy with GEM after disease progression has not been clarified.
Patients with locally advanced pancreatic cancer were treated with concurrent radiation therapy (1.8 Gy/fraction; total dose, 50.4 Gy) with 5-FU (200 mg/m2 every day) until disease progression, followed by GEM (1000 mg/m2, days 1, 8, 15, and every 4 weeks) as second-line therapy.
Of the 18 patients with locally advanced pancreatic cancer who received chemoradiation therapy with 5-FU, there were three partial responses, giving a response rate of 17%. The median time to progression was 170 days. The median survival time was 443 days. During chemoradiation therapy, the incidences of grade 3 or 4 anorexia, nausea, mucositis, and gastric ulcer were 33%, 22%, 17%, and 17%, respectively. Sixteen patients received second-line chemotherapy with GEM, of whom one patient had a partial response. The median time to progression from the initiation of GEM was 113 days, and median overall survival time was 231 days. Major toxicities were hematological toxicities: grade 3 or 4 leukopenia in 75% and anemia in 31%.
The treatment strategy with concurrent chemoradiation and maintenance chemotherapy with 5-FU followed by second-line chemotherapy with GEM may be an option for locally advanced pancreatic cancer.

食道癌化学放射線療法後の心毒性の検討—dose‐volume histogramを用いた評価—第2報
橋本孝之, 朝倉浩文, 全田貞幹, 金本彩恵, 小川洋史, 原田英幸, 古谷和久, 清水伸一, 白土博樹, 西村哲夫
日本放射線腫よう学会誌, 20, Supplement 1, 164, 22 Sep. 2008
Japanese

Proton beam therapy interference with implanted cardiac pacemakers
Oshiro,Y, Sugahara,S, Noma,M, Sato,M, Sakakibara,Y, Sakae,T, Hayashi,Y, Nakayama,H, Tsuboi,K, Fukumitsu,N, Kanemoto,A, Hashimoto,T, Tokuuye,K
Int J Radiat Oncol Biol Phys, 72, 3, 723, 727, Jan. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal, [PURPOSE] To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function.

[METHODS AND MATERIALS] After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33-77 gray equivalents (GyE) in dose fractions of 2.2-6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation field. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined before and after PBT.

[RESULTS] The phantom study showed no effect of neutron scatter on pacemaker generators. In the study, changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course.

[CONCLUSIONS] PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore, patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT.

RADIOTHERAPY FOR PATIENTS WITH MALIGNANT DISEASES AGED 85 YEARS OR OLDER
ASAKURA Hirofumi, MIZUMOTO Masashi, ZENDA Sadamoto, HARADA Hideyuki, HASHIMOTO Takayuki, HIRAKAWA Koichi, NUMANO Masumi, FUJI Hiroshi, MURAYAMA Shigeyuki, NISHIMURA Tetsuo
The Journal of JASTRO, 19, 4, 283, 287, 25 Dec. 2007
Japanese

Classical tandem-source dwelling covering the entire uterus: Essential in modern intracavitary radiotherapy for cervical cancer?
Kiyoshi Ohara, Keiko Nemoto, Kayoko Ohnishi, Takayuki Hashimoto, Nobuyoshi Fukumitsu, Masaharu Hata, Shinji Sugahara, Koichi Tokuuye, Yasuyuki Akine
Radiation Medicine - Medical Imaging and Radiation Oncology, 25, 8, 386, 392, 8, Oct. 2007, [Peer-reviewed]
English, Scientific journal, Purpose. We investigated whether conventional tandem-source dwelling to cover the entire uterus, classically regarded as the target volume, is necessary in modern intracavitary radiotherapy (ICRT) for cervical cancer. Materials and methods. The study included 95 cervical squamous cell carcinoma patients treated by high-dose-rate ICRT (point A dose was 6.0 Gy, with three to five insertions per patient) after external beam radiotherapy (EBRT), with central pelvic doses of 12-50 Gy. The tandem-source dwell length was adjusted to the target volume specified by magnetic resonance (MR) imaging. A tandem applicator was inserted as far as the uterine fundus in accordance with the post-EBRT MR-assessed cavity length. The pre-EBRT MR-specified target volume was used for the dwell-length adjustment. The safety of the dwell-length adjustment was assessed in terms of treatment failure. Results. The dwell-length adjustment was made in 248 of 366 total insertions with a dwell-length reduction of 5-55 mm (median 15 mm) at the corpus. Pelvic failure was identified in 22 patients with a 2-year pelvic disease-free survival rate of 75.6% but without evidence of failure at dwelling-skipped corpuses. Conclusion. Given after pelvic EBRT and ICRT of full-length dwelling in part, which may have eradicated possible subclinical extension, adjustment of the tandem-source dwell length to the MR-specified target volume appeared to be safe. © 2007 Japan Radiological Society.

Proton irradiation in a single fraction for hepatocellular carcinoma patients with uncontrollable ascites
Masaharu Hata, Koichi Tokuuye, Shinji Sugahara, Eriko Tohno, Nobuyoshi Fukumitsu, Takayuki Hashimoto, Kayoko Ohnishi, Keiko Nemoto, Kiyoshi Ohara, Takeji Sakae, Yasuyuki Akine
STRAHLENTHERAPIE UND ONKOLOGIE, 183, 8, 411, 416, URBAN & VOGEL, Aug. 2007, [Peer-reviewed]
English, Scientific journal, Purpose: To present technical considerations and results of proton irradiation in a single fraction for hepatocellular carcinoma ( HCC) patients with uncontrollable ascites.
Patients and Methods: Three HCC patients with uncontrollable ascites underwent proton irradiation of 24 Gy in a single fraction. Hepatic tumors were solitary in two patients, and multiple in one, and tumor sizes were 30, 30, and 33 mm in maximum diameter. No patient had lymph node or distant metastases. The center position of radiation fields was determined and the beam range was adjusted, using CT data taken immediately before irradiation to compensate for changes in the volume of ascites. Adjustment of the beam range was within 6 mm in water- equivalent thickness.
Results: All irradiated tumors showed objective responses, and were controlled during the follow- up period. Of the three patients, two were alive with no evidence of disease at 13 and 30 months, respectively, after treatment. The remaining patient died of ruptured esophageal varices 6 months after treatment. No therapy- related toxicity of grade 3 or more was observed.
Conclusion: Proton beams were successfully adjusted immediately before irradiation. Single- dose irradiation with precisely adjusted proton beams may be tolerable for HCC patients with uncontrollable ascites.

Hypofractionated high-dose proton beam therapy for stage I non-small-cell lung cancer: Preliminary results of a phase I/II clinical study
Masaharu Hata, Koichi Tokuuye, Kenji Kagei, Shinji Sugahara, Hidetsugu Nakayama, Nobuyoshi Fukumitsu, Takayuki Hashimoto, Masashi Mizumoto, Kiyoshi Ohara, Yasuyuki Akine
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 68, 3, 786, 793, ELSEVIER SCIENCE INC, Jul. 2007, [Peer-reviewed]
English, Scientific journal, Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC).
Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites.
Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade !:3 was observed.
Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC. (c) 2007 Elsevier Inc.

Proton beam therapy for hepatocellular carcinoma with inferior vena cava tumor thrombus: Report of three cases
Masashi Mizumoto, Koichi Tokuuye, Shinji Sugahara, Masaharu Hata, Nobuyoshi Fukumitsu, Takayuki Hashimoto, Kayoko Ohnishi, Keiko Nemoto, Kiyoshi Ohara, Yasushi Matsuzaki, Eriko Tohno, Yasuyuki Akine
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 37, 6, 459, 462, OXFORD UNIV PRESS, Jun. 2007, [Peer-reviewed]
English, Scientific journal, Three patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) were treated using proton beam therapy at the University of Tsukuba, Japan. A total dose of 50-70 Gy in 10-35 fractions was given to the primary tumor and lVCTT. All the patients survived for more than 1 year from the beginning of proton beam therapy (13-55 months) and no treatment-related toxicity of grade 3 or higher was observed. These cases suggest that proton beam therapy is safe and effective for patients with HCC associated with lVCTT.

Explanation for the failure of neoadjuvant chemotherapy to improve outcomes after radiotherapy for locally advanced uterine cervical cancer from the standpoint of the tumor regression rate
Kiyoshi Ohara, Hajime Tsunoda, Yumiko Oishi Tanaka, Kayoko Ohnishi, Keiko Nemoto, Takayuki Hashimoto, Nobuyoshi Fukumitsu, Masaharu Hata, Shinji Sugahara, Koichi Tokuuye, Hiroyuki Yoshikawa, Yasuyuki Akine
Radiation Medicine - Medical Imaging and Radiation Oncology, 25, 2, 53, 59, 2, Feb. 2007, [Peer-reviewed]
English, Scientific journal, Purpose. Treatment outcomes for patients with locally advanced cervical cancer are no better with neoadjuvant chemotherapy (NAC) combined with radiotherapy (RT) than with RT alone. We investigated the reason for this failure from the standpoint of the tumor regression rate (RR). Materials and methods. A total of 48 patients with clinical stage IIB-IVA cervical squamous cell carcinoma were treated clinically with cisplatin-based NAC plus RT (n = 15) or RT alone (n = 33). The RR was defined as the slope of a tumor shrinkage curve derived with magnetic resonance images. The local control rate (LCR) and disease-free rate (DFR) were estimated by clinical stage (IIB vs. III-IVA), pretreatment volume (≤ median vs. >
median), lymph node status (negative vs. positive), treatment type, overall treatment time (≤8 weeks vs. >
8 weeks), and RR (≤ median vs. >
median) using univariate and multivariate analyses. Results. RR during NAC or during NAC and RT (n = 15) was not significantly higher than RR by RT alone (n = 33). Low RR and positive nodal status were significantly powerful prognostic factors for both the LCR and DFR, whereas the others were not. Conclusion. Although effective in reducing tumor volume prior to RT, NAC showed no overall effect in increasing the RR, which was shown to be the most powerful prognostic factor. © 2007 Japan Radiological Society.

Sequential evaluation of hepatic functional reserve by (99m)Technetium-galactosyl human serum albumin scinitigraphy after proton beam therapy: a report of three cases and a review of the literatures
Hiroshi Igaki, Koichi Tokuuye, Tohoru Takeda, Shinji Sugahara, Masaharu Hata, Takayuki Hashimoto, Nobuyoshi Fukumitsu, Jin Wu, Kayoko Ohnishi, Kiyoshi Ohara, Yasuyuki Akine
ACTA ONCOLOGICA, 45, 8, 1102, 1107, TAYLOR & FRANCIS AS, Dec. 2006, [Peer-reviewed]
English, Scientific journal, The treatment strategy for malignant liver tumors should be appropriately determined because post-treatment quality of life greatly depends on the patients' residual hepatic function. In this report, we present three patients with malignant liver tumors treated by proton beam therapy in whom pre- and post-therapeutic hepatic functional reserves were evaluated sequentially for more than a year by (99m)Technetium-galactosyl human serum albumin (Tc-99m-GSA) scintigraphy. All three patients exhibited the distinctive time course of Tc-99m-GSA uptake efficiency, which suggested a transient decline in the ratio of liver activity to heart and liver activity at 15 minutes (LHL15) 3-6 months after proton beam therapy. This change was not in parallel with that expected from a functioning normal liver tissue volume. In a year after proton beam therapy, LHL15 recovered nearly to the pre-treatment level in all three patients. Our observations may be related to the upregulation of receptor-mediated Tc-99m-GSA uptake during hepatic regeneration after proton beam therapy.

A patient surviving for eight years after proton and x-ray irradiation for advanced esophageal cancer
Nobuyoshi Fukumitsu, Koichi Tokuuye, Shinji Sugahara, Takayuki Hashimoto, Masaharu Hata, Kiyoshi Ohara, Takeshi Shibahara, Akira Nakahara, Yasuyuki Akine
ACTA ONCOLOGICA, 45, 8, 1132, 1134, TAYLOR & FRANCIS AS, Dec. 2006, [Peer-reviewed]
English

Proton beam therapy for hepatocellular carcinoma patients with severe cirrhosis
Masaharu Hata, Koichi Tokuuye, Shinji Sugahara, Nobuyoshi Fukumitsu, Takayuki Hashimoto, Kayoko Ohnishi, Keiko Nemoto, Kiyoshi Ohara, Yasushi Matsuzaki, Yasuyuki Akine
STRAHLENTHERAPIE UND ONKOLOGIE, 182, 12, 713, 720, URBAN & VOGEL, Dec. 2006, [Peer-reviewed]
English, Scientific journal, Background and Purpose: Hepatocellular carcinoma (HCC) patients with severe cirrhosis are usually treated with supportive care because of their poor prognosis. However, the survival of severe cirrhotic patients has recently improved due to advanced treatments. The aim of this study was to define the role of proton beam therapy for HCC patients with severe cirrhosis.
Patients and Methods: 19 HCC patients with Child-Pugh class C cirrhosis received proton beam therapy. The hepatic tumors were solitary in 14 patients and multiple in five, and the tumor size was 25-80 mm (median 40 mm) in maximum diameter. No patient had regional Lymph node or distant metastasis. Total doses of 50-84 Gy (median 72 Gy) in ten to 24 fractions (median 16) were delivered to the tumors.
Results: Of the 19 patients, six, eight and four died of cancer, Liver failure and intercurrent diseases, respectively, during the follow-up period of 3-63 months (median 17 months) after treatment. A remaining patient was alive with no evidence of disease 33 months after treatment. ALL but one of irradiated tumors were controlled during the follow-up period. Ten patients had new intrahepatic tumors outside the irradiated volume. The overall and progression-free survival rates were 53% and 47% at 1 year, respectively, and 42% each at 2 years. Performance status and Child-Pugh score were significant prognostic factors for survival. Therapy-related toxicity of grade 3 or more was not observed.
Conclusion: Proton beam therapy for HCC patients with severe cirrhosis was tolerable. It may improve survival for patients with relatively good general condition and liver function.

Proton beam therapy for hepatocellular carcinoma with limited treatment options
Masaharu Hata, Koichi Tokuuye, Shinji Sugahara, Nobuyoshi Fukumitsu, Takayuki Hashimoto, Kayoko Ohnishi, Keiko Nemoto, Kiyoshi Ohara, Yasushi Matsuzaki, Yasuyuki Akine
CANCER, 107, 3, 591, 598, JOHN WILEY & SONS INC, Aug. 2006, [Peer-reviewed]
English, Scientific journal, BACKGROUND. The authors conducted a retrospective review to define the usefulness of proton beam therapy for patients who had hepatocellular carcinoma (HCC) with limited treatment options.
METHODS. Twenty-one patients with HCC for whom other treatment modalities either were contraindicative or were unfeasible because of coexisting diseases and unfavorable conditions received proton beam therapy. Four patients had renal failure, 2 patients had severe heart disease, 9 patients had severe cirrhosis, 1 patient had aplastic anemia, 1 patient had a dissecting abdominal aortic aneurysm before treatment, and 4 patients had bleeding tendency or unresectable tumors. Moreover, 2 of the latter 4 patients were allergic to iodine, and 2 other patients were unable to be catheterized for transcatheter arterial chemoembolization. Hepatic tumors were solitary in 14 patients and multiple in 7 patients, and the tumors ranged in greatest dimension from 25 mm to 100 mm (median, 40 mm). No patient had regional lymph node or distant metastasis. Total doses of 63 grays (Gy) to 84 Gy (median, 73 Gy) in 13 to 27 fractions (median, 18 fractions) were used for tumor treatments.
RESULTS. All but I of the irradiated tumors were controlled at a median follow-up of 3.3 years. The objective response rate was 81%, and the primary site-control rate was 93% at 5 years. Eleven patients had intrahepatic recurrences, and 2 patients had distant metastases in the lungs. Four of 11 patients with intrahepatic recurrences received a second course of proton beam therapy, and all recurrent tumors were controlled. The overall and cause-specific survival rates were 62% and 82% at 2 years, respectively, and 33% and 67% at 5 years, respectively. Grade >= 3 therapy-related toxicities were not observed.
CONCLUSIONS. Proton beam therapy was safe and effective for a variety of patients with HCC. The current results suggested that this method was tolerable and effective, even for patients with HCC who had limited treatment options.

Repeated proton beam therapy for hepatocellular carcinoma
T Hashimoto, K Tokuuye, N Fukumitsu, H Igaki, M Hata, K Kagei, S Sugahara, K Ohara, Y Matsuzaki, Y Akine
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 65, 1, 196, 202, ELSEVIER SCIENCE INC, May 2006, [Peer-reviewed]
English, Scientific journal, Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC).
Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at the University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively.
Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure.
Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A. (c) 2006 Elsevier Inc.

Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy
M Hata, N Miyanaga, K Tokuuye, Y Saida, K Ohara, S Sugahara, K Kagei, H Igaki, T Hashimoto, K Hattori, T Shimazu, H Akaza, Y Akine
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 64, 5, 1371, 1379, ELSEVIER SCIENCE INC, Apr. 2006, [Peer-reviewed]
English, Scientific journal, Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer.
Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT23N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy.
Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently, proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2.
Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation. (c) 2006 Elsevier Inc.

Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors
K Ohara, A Oki, YO Tanaka, K Onishi, N Fukumitsu, T Hashimoto, T Satoh, H Tsunoda, M Hata, S Sugahara, K Tokuuye, Y Akine, H Yoshikawa
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 64, 4, 1179, 1182, ELSEVIER SCIENCE INC, Mar. 2006, [Peer-reviewed]
English, Scientific journal, Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer.
Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day(-1)) of the shrinkage curve by fitting to an exponential equation.
Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day(-1) (median, 0.021 day(-1)) and late-assessed radioresponse from 0.009 to 0.091 day(-1) (median, 0.021 day(-1)), with no significant difference between them (p=0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R-2=0.714, p=0.0005).
Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness. (C) 2006 Elsevier Inc.

Proton beam therapy for hepatocellular carcinoma with portal vein tumor thrombus
M Hata, K Tokuuye, S Sugahara, K Kagei, H Igaki, T Hashimoto, K Ohara, Y Matsuzaki, N Tanaka, Y Akine
CANCER, 104, 4, 794, 801, JOHN WILEY & SONS INC, Aug. 2005, [Peer-reviewed]
English, Scientific journal, Background. Treatment modalities for patients with hepatocellular carcinoma (HCC) who have portal vein turner thrombus (PVTT) are limited and controversial; furthermore, the prognosis for these patients is extremely poor. The authors conducted a retrospective review to determine the role of proton beam therapy in the treatment of patients who had HCC with PVTT.
Methods. Twelve patients with HCC who had tumor thrombus in the main trunk or major branches of the portal vein (clinical T3-T4N0M0) were treated with proton beam therapy. At the time they received proton beam irradiation, patients. ranged in age from 42 years to 80 years (median, 62 years), and their tumors ranged in size from 40 mm to 110 mm (median, 60 mm) in greatest dimension. A total dose of 50-72 gray (Gy) (median, 55 Gy) in 10-22 fractions was delivered to the tumors, including PVTT.
Results. All tumors that were treated with proton beam therapy remained controlled at a median follow-up of 2.3 years (range, 0.3-7.3 years). Among 12 patients, 10 patients had new liver tumors outside the irradiated volume 0.1-2.4 years after proton beam therapy, and 3 patients also had distant metastases; consequently, 8 patients died of disease, and 2 patients were salvaged by further therapies. The remaining two patients were alive with no evidence of disease 4.3 years and 6.4 years after proton beam therapy. The progression-free survival rates were 67% at 2 years and 24% at 5 years. The median progression-free survival was 2.3 years. According to the Acute Radiation Morbidity Scoring Criteria (Radiation Therapy Oncology Group), therapy-related toxicity-Grade 3 was not observed.
Conclusions. Proton beam therapy for patients with HCC who had PVTT was feasible and effective. It appeared to improve survival and local control significantly for these patients.

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, H Shirato, M Kato, K Yamazaki, N Kurauchi, T Morikawa, S Shimizu, YC Ahn, Y Akine, K Miyasaka
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 61, 5, 1559, 1564, ELSEVIER SCIENCE INC, Apr. 2005, [Peer-reviewed]
English, Scientific journal, Purpose: To evaluate the feasibility of real-time monitoring of a fiducial marker in/near the digestive tract and to analyze the motion of organs at risk to determine a reasonable internal margin.
Methods and Materials: We developed two methods to insert a fiducial marker into/near the digestive tract adjacent to the target volume. One method involves an intraoperative insertion technique, and the other involves endoscopic insertion into the submucosal layer of the normal digestive tract. A fluoroscopic real-time tumor-tracking radiotherapy system was used to monitor the marker.
Results: Fourteen markers (2 in the mediastinum and 12 in the abdomen) were implanted intraoperatively in 14 patients with no apparent migration. Seventeen of 20 markers (13/14 in the esophagus, 1/2 in the stomach, and 3/4 in the duodenum) in 18 patients were implanted using endoscopy without dropping. No symptomatic adverse effects related to insertion were observed. The mean/standard deviation of the range of motion of the esophagus was 3.5/1.8, 8.3/3.8, and 4.0/2.6 mm for lateral, craniocaudal and anteroposterior directions, respectively, in patients with intrafractional tumor motion less than 1.0 cm.
Conclusion: Both intraoperative and endoscopic insertions of a fiducial marker into/near the digestive tract for monitoring of organs at risk were feasible. The margin for internal motion can be individualized using this system. (c) 2005 Elsevier Inc.

Clinical results of proton beam therapy for skull base chordoma
H Igaki, K Tokuuye, T Okumura, S Sugahara, K Kagei, M Hata, K Ohara, T Hashimoto, K Tsuboi, S Takano, A Matsumura, Y Akine
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 60, 4, 1120, 1126, ELSEVIER SCIENCE INC, Nov. 2004, [Peer-reviewed]
English, Scientific journal, Purpose: To evaluate clinical results of proton beam therapy for patients with skull base chordoma.
Methods and Materials: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months).
Results: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery.
Conclusion: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy. (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.

PROTON BEAM THERAPY FOR LARGE HEPATOCELLULAR CARCINOMA
NEMOTO Keiko, TOKUUE Koichi, ONISHI Kayoko, MIZUMOTO Masashi, HASHIMOTO Takayuki, IGAKI Hiroshi, HATA Masaharu, KAGEI Kenji, SUGAHARA Shinji, OHARA Kiyoshi, AKINE Yasuyuki
The Journal of JASTRO, 16, 3, 177, 182, (公社)日本放射線腫瘍学会, 25 Sep. 2004
Japanese, 医学的理由で手術が困難あるいは手術拒否された巨大肝細胞癌症例に対する陽子線治療についてその有効性と安全性を後ろ向きに検討した.肝細胞癌に対し陽子線治療を行った235例中,巨大肝細胞癌症例は9例であった.このうち肝内多発例2例,他臓器転移(肺転移)のある1例を除いた6例を解析の対象とした.短い観察期間ではあるが6例全例において局所制御が達成された.陽子線治療により長期間に亘って腫瘍が制御され,局所が制御されることにより長期生存が可能となり,巨大な腫瘍に対して高線量を投与した後も,その治療による肝機能の低下,肝不全は起こらないことが同時に示唆された.巨大肝細胞癌に対しても陽子線治療は効果的な治療法で,現在において唯一の有効な治療法とされている手術療法に取って代わりうる治療法であることが示唆された

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.

Initial Experience of Proton Beam Therapy at the New Facility of the University of Tsukuba
Kagei Kenji, Akine Yasuyuki, Ohara Kiyoshi, Hashimoto Takayuki, Igaki Hiroshi, Hata Masaharu, Sugahara Shinji, Tokuuye Koichi
日本医学放射線学会雑誌, 64, 4, 225, 230, 日本医学放射線学会, 25 May 2004
Japanese

Initial experience of proton beam therapy at the new facility of the University of Tsukuba
Kagei Kenji, Tokuuye Koichi, Sugahara Shinji, Hata Masaharu, Igaki Hiroshi, Hashimoto Takayuki, Ohara Kiyoshi, Akine Yasuyuki
Nippon Acta Radiologica, 64, 4, 225, 230, 4, 25 May 2004, [Peer-reviewed]
Japanese, Scientific journal, Purpose: To present the initial experience with proton beam therapy at the new Proton Medical Research Center (PMRC) of the University of Tsukuba. Materials and Methods: The new facility has a synchrotron with maximum energy of 250MeV and two rotational gantries. We treated 105 patients with 120 lesions with proton beams in the first year, beginning in September 2001. The most common lesion treated was primary liver cancer (40 lesions) followed by lung cancer, head and neck cancers, and prostate cancer. Concurrent X-ray radiotherapy was given for 38 of the 120 lesions. Results: The median follow-up period was 11 months (range, 1-19 months). Of the 105 patients, 97% had Grade 0-2 RTOG/ EORTC acute morbidities, while the remaining 3% had Grade 3. Tumor response after irradiation was CR for 35% of the lesions, PR for 25%, SD for 22%, PD for 9%, and not evaluated for 9%. Conclusion: The proton beam therapy conducted at the new facility of the University of Tsukuba was safe and effective.

Proton therapy for head and neck malignancies at Tsukuba
K Tokuuye, Y Akine, K Kagei, M Hata, T Hashimoto, T Mizumoto, Y Ohshiro, S Sugahara, K Ohara, T Okumura, J Kusakari, H Yoshida, F Otsuka
STRAHLENTHERAPIE UND ONKOLOGIE, 180, 2, 96, +, URBAN & VOGEL, Feb. 2004, [Peer-reviewed]
German, Scientific journal, Purpose: To evaluate the effectiveness and feasibility of proton therapy for head and neck cancers.
Patients and Methods: From 1983 to 2000, 33 patients with head and neck malignancies but no history of surgical resection were treated with 250-MeV protons with or without X-ray irradiation. This study retrospectively evaluated Local control, survival, and treatment sequelae of these patients. The median total target dose using protons with or without X-rays was 76 Gy (range: 42-99 Gy) and the median proton dose per fraction 2.8 Gy (range: 1.5-6.0 Gy).
Results: Overall 5-year survival and Local control rates were 44% and 74%, respectively. One (3%) and six patients (18%) suffered from treatment-related acute and Late toxicity > grade 3 (RTOG/EORTC acute and Late radiation morbidity scoring criteria). One patient with a history of radiotherapy suffered from acute toxicity > grade 3.
Conclusion: Proton therapy appeared to offer high local control rates with few toxicities relative to conventional radiotherapy. However, Late toxicity was seen in areas where large radiation doses had been given.

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

RESULTS OF A SAFETY TEST FOR PROTON BEAM THERAPY EQUIPMENT AT THE PROTON MEDICAL RESEARCH CENTER (PMRC), UNIVERSITY OF TSUKUBA
TOKUUYE Koichi, AKINE Yasuyuki, SHIOYAMA Yoshiyuki, KAGEI Kenji, SUGAHARA Shinji, IGAKI Hiroshi, HATA Masaharu, OHARA Kiyoshi, HASHIMOTO Takayuki
The Journal of JASTRO, 15, 4, 277, 283, Japanese Society for Therapeutic Radiology and Oncology, 25 Dec. 2003
Japanese, A new hospital-based proton radiotherapy facility having two treatment rooms with a rotating gantry each and an experiment room with two horizontal beam ports was built at the Proton Medical Research Center (PMRC), University of Tsukuba. We started proton beam therapy as a clinical study to test the safety of the treatment equipment in September 2001. Six patients, a patient with liver metastases from ovarian carcinoma, two patients with lung carcinoma, a patient with cholangiocarcinoma, a patient with local recurrence of rectal carcinoma and a patient with bone metastasis from breast carcinoma, were enrolled in the study. They were considered unsuitable for other modalities of treatment, and were treated by proton beam therapy alone according to the methods used in the old facility at the University of Tsukuba. They were evaluated with regard to unexpected occurrences due to treatment equipment failures and treatment related toxicities. We observed no occurrence of hazardous events to the patients and no toxicities greater than grade II skin toxicities in the six patients. The results showed that the treatment system was safe and reliable for proton beam therapy.

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

Use of small pelvic field instead of whole pelvic field in postoperative radiotherapy for node-negative, high-risk stages I and II cervical squamous cell carcinoma
K Ohara, H Tsunoda, M Nishida, S Sugahara, T Hashimoto, Y Shioyama, K Hasezawa, H Yoshikawa, Y Akine, Y Itai
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 13, 2, 170, 176, BLACKWELL PUBLISHING INC, Mar. 2003, [Peer-reviewed]
English, Scientific journal, We investigated whether a small pelvic (SP) field that covers primarily the pericervical regions in postoperative radiotherapy for cervical squamous cell carcinoma is adequate for a subgroup of node-negative patients. Of 84 patients with stage I-II disease treated with postoperative radiotherapy due to pathologic risk factors, 42 node-negative patients received SP-field radiotherapy, whereas remaining 42 node-positive patients were treated with a conventional whole pelvic (WP) field that also covered pelvic lymph nodes, both with 50.0-50.4 Gy/25-28 fractions. The pathologic risk factors included positive nodes, deep stromal invasion (greater than or equal to2 /3 thickness), parametrial extension, and positive or close surgical margin. Recurrence was identified for 20 patients: three in the SP group and 17 in the WP group. Intrapelvic recurrence accounted for all three recurrences in the SP group and for four in the WP group; 5-year pelvic-control rate did not differ significantly between the SP (93%) and WP (90%) groups. Extrapelvic recurrence (n = 11) was identified exclusively in the WP group. Patterns of recurrence indicate that use of an SP field instead of a WP field may be adequate in postoperative radiotherapy for a subgroup of node-negative, high-risk patients.

Nonoperative assessment of nodal status for locally advanced cervical squamous cell carcinoma treated by radiotherapy with regard to patterns of treatment failure
K Ohara, YO Tanaka, H Tsunoda, S Sugahara, T Hashimoto, K Kagei, K Tokuuye, Y Akine, H Yoshikawa, Y Itai
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 55, 2, 354, 361, ELSEVIER SCIENCE INC, Feb. 2003, [Peer-reviewed]
English, Scientific journal, Purpose: Lymph node metastasis is a major prognostic factor in the treatment of cervical cancer, but its nonsurgical assessment is not necessarily accurate, particularly in small nodes. We evaluated whether nodenegative status could be accurately assessed using a low cutoff measure.
Methods and Materials: The subjects were 84 patients with Stage IIB-IVA cervical squamous cell carcinoma treated by definitive radiotherapy. Nodal status was assessed by CT as negative (<5 mm), possibly positive (5-10 mm), or probably positive (>10 mm). Cause-specific survival and the disease-free rate, including the pelvic recurrence-free and distant metastasis-free rates, were estimated.
Results: The cause-specific survival, disease-free rate, and pelvic recurrence-free rate at 5 years were significantly higher for the 32 patients with node-negative disease (83.5%, 86.1%, and 86.1%) and the 17 patients with possibly node-positive disease (59.2%, 93.8%, and 93.8%) than for the 35 patients with probably node-positive disease (32.6%, 22.0%, and 46.8%), respectively. No significant difference was found between negative and possibly node-positive status. In contrast, the distant metastasis-free rate differed significantly among nodenegative (96.4%), possibly node-positive (59.3%), and probably node-positive (35.1%) status.
Conclusion: Node-negative status assessed using a strict cutoff measure may be useful as a strong predictor of cervical cancer being confined to the pelvis. (C) 2003 Elsevier Science Inc.

Treatment of intracranial immature teratoma with serum AFP elevation
山口秀, 伊師雪友, 大木聡悟, 茂木洋晃, 長谷河昌孝, 寺下友佳代, 平林真介, 西岡健太郎, 橋本孝之, 真部淳, 藤村幹, 小児の脳神経(Web), 49, 2, 2024

免疫チェックポイント阻害薬と放射線治療—Clinical evidences for the combination of immune checkpoint inhibitor and radiation therapy—特集 がん免疫療法の展望 : 免疫チェックポイント阻害薬の併用療法に中心に ; 免疫チェックポイント阻害薬の併用療法のエビデンス
安田 耕一, 志藤 元泰, 小泉 富基, 高橋 周平, 藤田 祥博, 大塚 愛美, 宮﨑 智彦, 西川 昇, 打浪 雄介, 森 崇, 西岡 健太郎, 木下 留美子, 田口 大志, 加藤 徳雄, 橋本 孝之, 青山 英史, 腫瘍内科 = Clinical oncology / 腫瘍内科編集委員会 編, 30, 1, 23, 28, Jul. 2022
Japanese

Evaluation of Visualizing the Prostatic Urinary Tract in MRI With a Super Resolution Deep Learning Model for Urethra Sparing Radiotherapy
T. Yoshimura, K. Nishioka, T. Hashimoto, S. Kogame, K. Seki, H. Sugimori, H. Yamashina, F. Kato, H. Aoyama, K. Kudo, S. Shimizu, International Journal of Radiation Oncology*Biology*Physics, 111, 3, e121, e122, Nov. 2021, [Peer-reviewed]
Elsevier BV, English

Proton beam therapy for reirradiation in pediatric cancer
橋本孝之, 森崇, 西岡健太郎, 打浪雄介, 安田耕一, 木下留美子, 田口大志, 加藤徳雄, 清水伸一, 青山英史, 日本小児血液・がん学会雑誌(Web), 58, 2, 2021

陽子線治療—Proton therapy for prostate cancer—特集 前立腺癌診療update : 最新の診断と治療 ; 診断と治療
清水 伸一, 西岡 健太郎, 橋本 孝之, 日本臨床 = Japanese journal of clinical medicine, 78, 6, 977, 982, Jun. 2020
日本臨床社, Japanese

前立腺がんの陽子線治療—Proton therapy for prostate cancer—特集 泌尿器がんの新しい放射線治療戦略 ; 前立腺がん
清水 伸一, 橋本 孝之, 西岡 健太郎, 泌尿器科 = Urology / 泌尿器科編集委員会 編, 11, 4, 386, 391, Apr. 2020
科学評論社, Japanese

画像誘導陽子線治療の将来展望
田口大志, 橋本孝之, 橋本孝之, 加藤徳雄, 木下留美子, 安田耕一, 西岡健太郎, 西岡健太郎, 森崇, 打浪雄介, 宮本直樹, 高尾聖心, 清水伸一, 清水伸一, 青山英史, 日本癌治療学会学術集会(Web), 58th, 2020

筋層浸潤性膀胱癌に対する膀胱温存治療後患者のHealth-related quality of life
大澤崇宏, 安部崇重, 西岡健太郎, 菊地央, 松本隆児, 橋本孝之, 清水伸一, 青山英史, 村井祥代, 篠原信雄, 日本泌尿器内視鏡学会(Web), 34th, 2020

頭蓋内胚細胞腫瘍における放射線化学療法後のsalvage surgeryに関する病理所見からの検討　　　　　　　　　　　　　　　
山口 秀, 茂木 洋晃, 伊師 雪友, 岡本 迪成, 井口 晶裕, 長 祐子, 杉山 未奈子, 橋本 孝之, 岡田 宏美, 寳金 清博, Brain Tumor Pathology, 36, Suppl., 096, 096, May 2019
日本脳腫瘍病理学会, Japanese

ヒステリーや発達障害と評価され診断が遅れた頭蓋内胚細胞腫瘍の2例
本田譲, 原和也, 寺下友佳代, 杉山未奈子, 長祐子, 井口晶裕, 山口健史, 中村明枝, 真部淳, 岡本迪成, 伊師雪友, 茂木洋晃, 山口秀, 森崇, 橋本孝之, 鬼丸力也, 平松泰好, 植竹公明, 佐藤正夫, 日本小児科学会雑誌, 123, 11, 2019

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

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

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

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

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

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

Targeting integrins with RGD-conjugated gold nanoparticles in radiotherapy decreases the invasive activity of breast cancer cells
Ping Hsiu Wu, Yasuhito Onodera, Yuki Ichikawa, Yuki Ichikawa, Erinn B. Rankin, Amato J. Giaccia, Yuko Watanabe, Wei Qian, Takayuki Hashimoto, Hiroki Shirato, Hiroki Shirato, Hiroki Shirato, Jin Min Nam, Jin Min Nam, Jin Min Nam, International Journal of Nanomedicine, 12, 5069, 5085, 14 Jul. 2017
© 2017 Wu et al. 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.

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

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

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

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

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 and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms, 384, 113, 120, 01 Oct. 2016
© 2016 Elsevier B.V. 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 sub ) were then evaluated. The spatial DEF distributions showed hot spots in the distal radial region from the proton beam axis. The spatial D sub 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.

Treatment Time and Dose Rate Analysis for Respiratory Moving Liver Tumor Using Real-time-image Gated Spot Scanning Proton Beam Therapy System
SHIMIZU Shinichi, KATOH Norio, TAKAO Seishin, MATSUURA Taeko, MIYAMOTO Naoki, HASHIMOTO Takayuki, NISHIOKA Kentaro, YOSHIMURA Takaaki, UMEGAKI Kikuo, SHIRATO Hiroki, 日本医学放射線学会総会抄録集, 75th, S225, S225, 29 Feb. 2016
(公社)日本医学放射線学会, English

Particle Therapy Using Protons or Carbon Ions for Cancer Patients With Cardiac Implantable Electronic Devices (CIEDs): A Retrospective Japan Radiological Society Multi-institutional Study
T. Hashimoto, Y. Demizu, T. Isobe, H. Numajiri, S. Fukuda, M. Wakatsuki, H. Yamashita, S. Murayama, S. Takamatsu, H. Katoh, K. Murata, R. Kohno, T. Arimura, T. Matsuura, Y. M. Ito, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 93, 3, E563, E564, Nov. 2015
ELSEVIER SCIENCE INC, English, Summary international conference

Development of a Real-Time Image Gated Proton Beam Therapy (RGPT) System and Its Initial Clinical Application to Respiratory Moving Liver Tumors
S. Shimizu, N. Katoh, S. Takao, T. Matsuura, N. Miyamoto, T. Hashimoto, K. Nishioka, T. Yoshimura, Y. Matsuzaki, R. Kinoshita, Y. Nishikawa, R. Onimaru, K. Umegaki, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 93, 3, S42, S42, Nov. 2015
ELSEVIER SCIENCE INC, English, Summary international conference

The invasion activity after radiation treatment is suppressed by RGD peptide conjugated gold nanoparticles in breast cancer cells
P. Wu, Y. Onodera, Y. Ichikawa, Y. Watanabe, W. Qian, T. Hashimoto, H. Shirato, J. Nam, MOLECULAR BIOLOGY OF THE CELL, 26, 2015
AMER SOC CELL BIOLOGY, English, Summary international conference

キャンサーボードが機能した1症例
遠藤将吾, 寺坂俊介, 小林浩之, 山口秀, 茂木洋晃, 金子貞洋, 井口晶裕, 長祐子, 大島淳二郎, 寺坂友佳代, 杉山未奈子, 橋本孝之, 鬼丸力也, 清水伸一, 有賀正, 白戸博樹, 寳金清博, 日本小児血液・がん学会雑誌(Web), 52, 3, 2015

食道癌に対する化学放射線療法の有害事象 X線と陽子線の比較　　　　　　　　　　　　　　　
牧島 弘和, 石川 仁, 橋本 孝之, 大野 豊然貴, 菅原 香織, 奥村 敏之, 櫻井 英幸, 日本食道学会学術集会プログラム・抄録集, 68回, 59, 59, Jul. 2014
(NPO)日本食道学会, Japanese

食道がん治療戦略のUp to Date 食道癌の化学放射線療法と陽子線治療の役割　　　　　　　　　　　　　　　
石川 仁, 奥村 敏之, 水本 斉志, 大西 かよ子, 菅原 香織, 牧島 弘和, 大野 豊然貴, 森脇 俊和, 兵頭 一之介, 久倉 勝治, 田村 孝史, 寺島 秀人, 大河内 信弘, 橋本 孝之, 櫻井 英幸, 日本癌治療学会誌, 49, 3, 770, 770, Jun. 2014
(一社)日本癌治療学会, Japanese

前立腺放射線治療における膀胱容量の再現性
布施拓, 石川仁, 石川仁, 石田真也, 宮本俊男, 佐藤勝, 橋本孝之, 橋本孝之, 櫻井英幸, 櫻井英幸, 日本放射線技術学会総会学術大会予稿集, 69th, 2013

原発性肝癌の陽子線治療
奧村敏之, 橋本孝之, 福田邦明, 安部井誠人, 福光延吉, 水本斉志, 沼尻晴子, 大西かよ子, 石川仁, 坪井康次, 福永潔, 大河内信弘, 櫻井英幸, 日本癌治療学会学術集会(CD-ROM), 51st, ROMBUNNO.OS24-4, 2013
Japanese

３．SLIT法を用いた食道癌同時併用化学陽子線治療の初期成績
小此木 範之, 橋本 孝之, 榮 武二, 石田 真也, 奥村 敏之, 櫻井 英幸, The Kitakanto medical journal, 62, 2, 225, 225, 01 May 2012
北関東医学会, Japanese

肝がんの陽子線治療
奥村敏之, 橋本孝之, 福光延吉, 水本斉志, 福永潔, 佐々木亮孝, 盛武敬, 榮武二, 坪井康次, 大河内信弘, 櫻井英幸, 日本外科系連合学会誌, 36, 3, 341, 30 May 2011
Japanese

Radiotherapy Today 2011 放射線治療最前線 高精度放射線治療の適応と成果,そして課題 II)高精度放射線治療の適応と課題:疾患別の検討 6.肝がんの最新放射線治療 粒子線治療―陽子線治療の適応と課題を中心に
奥村敏之, 橋本孝之, 福光延吉, 水本斉志, 大城佳子, 大川綾子, 金本彩恵, 橋井晴子, 大野豊然貴, 小此木範之, 榮武二, 坪井康次, 櫻井英幸, Innervision, 26, 3, 65, 67, 25 Feb. 2011
肝がんは原発性肝がん、転移性肝がんに分類される。わが国においては、前者の多くは肝細胞がんであり、後者のうち放射線治療の適応となるものとしては結直腸原発がんの転移が代表的なものであろう。いずれにしても、放射線治療はそれらの疾患の標準治療の地位にはない。その理由として、肝がんは多発する傾向が強いことや、正常な肝組織の放射線感受性が高く、高線量の放射線照射は、照射野内の肝機能喪失を容易に招いてしまうことなどが挙げられる。しかし近年、外照射の照準精度が格段の進歩を遂げたこと、および、肝臓は並列臓器であるという認識が浸透したことにより、肝予備能と線量分布を適正に評価することができれば、限局した肝内病変に高線量な放射線治療を行うことが可能であるという報告が多数見られるようになった。当大学では、局所根治をめざした肝臓の放射線治療が始まって二十数年が経過した。特に、陽子線治療はこの領域を重点的に扱ってきた。いまだその経験は、肝がんの放射線治療の意義を評価するに十分なものとは言えないが、これまでに得られた知見の一端を本稿で紹介したい。(著者抄録), (株)インナービジョン, Japanese

肝細胞癌の術後巨大肝内再発に対し,血管内治療と陽子線治療による集学的治療を行った1例
奥村敏之, 安部井誠人, 森健作, 金本彩恵, 福田邦明, 阿部孝志, 橋本孝之, 水本斉志, 大城佳子, 福光延吉, 大川綾子, 橋井晴子, 盛武敬, 榮武二, 坪井康次, 櫻井英幸, Liver Cancer, 16, 2, 155, 161, 19 Nov. 2010
52歳男性。患者は他院にて肝細胞癌(HCC)に対し肝右葉後区域切除術を施行され、病理組織学的にHCCはpt3n0m0と診断された。その後、CTでS3およびS7に再発結節を指摘され、肝動脈より化学塞栓療法(TACE)が施行、加えてUFT投与にて経過観察されていたが、結節の増大傾向を認めたため、著者らの施設へ紹介となった。腹部CTでは腫瘍径はS7が110mm、S3の2つは58mm、46mmといずれも著明に増大しており、また腫瘤も被膜をもつが一部では不明瞭化し、単純結節周囲増殖型と診断された。以後、治療として巨大腫瘍を含む多発再発に対しTACEをはじめ肝動脈塞栓療法(TAE)、陽子線治療(PBT)による集学的治療が行なわれ、PBT後はCal TUMPによる免疫アジュバント局注療法が行なわれたが、結果的には残肝に再々発が生じ、2度のTACEが必要となった。尚、患者はこのTACE後、再発病巣はみられなくなり、全身状態も良好となった。, (株)アークメディア, Japanese

3種類の治療プロトコールを用いた肝細胞癌に対する陽子線治療
水本斉志, 奥村敏之, 橋本孝之, 福田邦明, 大城佳子, 福光延吉, 安部井誠人, 大川綾子, 金本彩恵, 橋井晴子, 盛武敬, 東野英利子, 坪井康次, 栄武二, 櫻井英幸, 日本癌治療学会誌, 45, 2, 589, 589, 21 Sep. 2010
(一社)日本癌治療学会, Japanese

Roles of proton beam therapy as a cancer radiotherapy
櫻井 英幸, 奥村 敏之, 橋本 孝之, Japanese journal of cancer clinics, 55, 12, 829, 836, Dec. 2009
篠原出版新社, Japanese

治療談話会記録 粒子線治療装置の新展開
橋本 孝之, 臨床放射線, 54, 7, 915, 917, Jul. 2009
金原出版, Japanese

Cardiac toxicities after concurrent chemoradiotherapy for esophageal cancer - Dose-volume histogram (DVH) analysis
T. Hashimoto, H. Asakura, S. Zenda, H. Hashii, M. Mizumoto, H. Harada, K. Furutani, H. Fuji, S. Murayama, T. Nishimura, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 72, 1, S130, S130, 2008
ELSEVIER SCIENCE INC, English, Summary international conference

Prognostic impact of total tumor volume in stage III non-small-cell lung cancer treated with concurrent chemoradiotherapy
Harada Hideyuki, Nobuyuki Yamamoto, Toshiaki Takahashi, Hirfumi Asakura, Takayuki Hashimoto, Koichi Hirakawa, Masashi Mizumoto, Hiroshi Fuji, Shigeyuki Murayama, Tetsuo Nisimura, JOURNAL OF THORACIC ONCOLOGY, 2, 8, S450, S450, Aug. 2007
LIPPINCOTT WILLIAMS & WILKINS, English, Summary international conference

Analysis of dose-volume histogram parameters for radiation pneumonitis after concurrent chemoradiotherapy for esophageal cancer
H. Asakura, T. Hashimoto, S. Zenda, H. Harada, K. Hirakawa, M. Mizumoto, H. Yamashita, H. Fuji, S. Murayama, T. Nishimura, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 69, 3, S302, S302, 2007
ELSEVIER SCIENCE INC, English, Summary international conference

I期の非小細胞肺癌に対する少分割陽子線治療の初期成績
幡多政治, 徳植公一, 菅原信二, 影井兼司, 中山秀次, 福光延吉, 橋本孝之, 水本斉志, 大原潔, 秋根康之, 日本放射線腫よう学会誌, 18, Supplement 1, 162, 25 Oct. 2006
Japanese

Conventional source dwelling up to the uterine fundus may not be mandatory in intracavitary radiotherapy for cervical cancer
K. Ohara, K. Ohnishi, K. Nemoto, T. Hashimoto, N. Fukumitsu, M. Hata, S. Sugahara, K. Tokuuye, Y. Akine, RADIOTHERAPY AND ONCOLOGY, 81, S254, S254, Oct. 2006
ELSEVIER IRELAND LTD, English, Summary international conference

Clinical results of proton beam therapy for locoregionally advanced esophageal cancer
S. Sugahara, K. Tokuuye, A. Nakahara, M. Hata, H. Terashima, N. Fukumitsu, T. Shibahara, H. Nakayama, T. Hashimoto, K. Ohara, Y. Akine, RADIOTHERAPY AND ONCOLOGY, 81, S358, S358, Oct. 2006
ELSEVIER IRELAND LTD, English, Summary international conference

5.肺・胸膜・肝内転移を繰り返し,腎障害・心筋障害も来たした,2002年登録肝芽腫難治症例における治療経過(続報) : CPT-11,陽子線照射,ラジオ波焼灼(RFA)の効果(日本小児肝癌スタディグループ研究会2006,研究会)
平井 みさ子, 金子 道夫, 堀 哲夫, 小室 広昭, 瓜田 泰久, 渡邊 美穂, 星野 論子, 福島 敬, 高橋 実穂, 松枝 清, 橋本 孝之, 小児がん : 小児悪性腫瘍研究会記録, 43, 2, 258, 258, 30 Sep. 2006
日本小児がん学会, Japanese

限局性前立腺癌に対する陽子線治療
宮永直人, 赤座英之, 及川剛宏, 関戸哲利, 樋之津史郎, 河合弘二, 島居徹, 幡多政治, 徳植公一, 橋本孝之, 福光延吉, 菅原信二, 秋根康之, 泌尿器外科, 19, 8, 951, 954, 15 Aug. 2006
Japanese

消化管に近接した肝細胞癌に対する陽子線治療の初期成績
徳植公一, 橋本孝之, 福光延吉, 幡多政治, 菅原信二, 根本景子, 大西かよ子, 大原潔, 秋根康之, 日本医学放射線学会学術集会抄録集, 65th, S217, 25 Feb. 2006
Japanese

合併症により治療法が制限された肝細胞癌患者に対する陽子線治療
幡多政治, 徳植公一, 菅原信二, 福光延吉, 橋本孝之, 大西かよ子, 根本景子, 大原潔, 秋根康之, 日本医学放射線学会学術集会抄録集, 65th, S315, 25 Feb. 2006
Japanese

子宮頚癌治療におけるネオアジュバント化学療法併用が放射線単独治療に比べ有効でなかった理由
大原潔, 田中優美子, 大西かよ子, 根本景子, 橋本孝之, 福光延吉, 菅原信二, 幡多政治, 徳植公一, 秋根康之, 日本医学放射線学会学術集会抄録集, 65th, S312, 25 Feb. 2006
Japanese

消化器がんに対する放射線治療 2 各論 (4) 消化器がんに対する陽子線治療
秋根康之, 徳植公一, 菅原信二, 幡多政治, 福光延吉, 橋本孝之, 臨床消化器内科, 21, 3, 315, 322, 20 Feb. 2006
Japanese

Preliminary results of hypofractionated proton beam therapy for hepatocellular carcinoma
N. Fukumitsu, K. Tokuuye, T. Hashimoto, S. Sugahara, M. Hata, K. Ohara, E. Tohno, Y. Akine, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 66, 3, S279, S280, 2006
ELSEVIER SCIENCE INC, English, Summary international conference

Repeated proton beam therapy for previously irradiated hepatocellular carcinoma - Dose-volume histogram (DVH) analysis
T. Hashimoto, K. Tokuuye, K. Ohnishi, N. Fukumitsu, M. Hata, S. Sugahara, K. Ohara, E. Tohno, T. Nishimura, Y. Akine, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 66, 3, S303, S303, 2006
ELSEVIER SCIENCE INC, English, Summary international conference

陽子線治療により視神経が温存された横紋筋肉腫の1例
根本景子, 菅原信二, 徳植公一, 奥村敏之, 影井兼司, 幡多政治, 井垣浩, 大原潔, 橋本孝之, 福光延吉, 秋根康之, 茨城県臨床医学雑誌, 41, 33, 01 Dec. 2005
Japanese

門脈腫よう栓を伴う肝細胞癌に対する陽子線治療の初期成績
大西かよ子, 幡多政治, 徳植公一, 根本景子, 橋本孝之, 福光延吉, 影井兼司, 菅原信二, 大原潔, 秋根康之, 日本放射線腫よう学会誌, 17, Supplement 1, 89, 25 Oct. 2005
Japanese

ペースメーカー装着患者に対する陽子線治療経験
橋本孝之, 野間美緒, 徳植公一, 福光延吉, 幡多政治, 影井兼司, 菅原信二, 大原潔, 榊原謙, 秋根康之, 日本放射線腫よう学会誌, 17, Supplement 1, 168, 25 Oct. 2005
Japanese

巨大肝細胞癌に対する陽子線治療成績
根本景子, 徳植公一, 大西かよ子, 橋本孝之, 福光延吉, 幡多正治, 影井兼司, 菅原信二, 大原潔, 秋根康之, 日本放射線腫よう学会誌, 17, Supplement 1, 90, 25 Oct. 2005
Japanese

重症肝硬変症をともなう肝細胞癌患者に対する陽子線治療
幡多政治, 徳植公一, 菅原信二, 影井兼司, 福光延吉, 橋本孝之, 大西かよ子, 根本景子, 大原潔, 秋根康之, 日本放射線腫よう学会誌, 17, Supplement 1, 106, 25 Oct. 2005
Japanese

Preliminary results of hypofractionated proton beam therapy for hepatocellular carcinoma
N. Fukumitsu, K. Tokuuye, T. Hashimoto, S. Sugahara, K. Kagei, M. Hata, K. Ohara, Y. Akine, EJC SUPPLEMENTS, 3, 2, 206, 206, Oct. 2005
PERGAMON-ELSEVIER SCIENCE LTD, English, Summary international conference

Preliminary results of proton beam therapy for hepatocellular carcinoma with portal vein tumor thrombus
K. Ohnishi, M. Hata, K. Tokuuye, K. Nemoto, T. Hashimoto, N. Fukumitsu, S. Sugahara, K. Ohara, Y. Matsuzaki, Y. Akine, EJC SUPPLEMENTS, 3, 2, 223, 223, Oct. 2005
PERGAMON-ELSEVIER SCIENCE LTD, English, Summary international conference

Proton beam therapy for hepatocellular carcinoma patients with severe cirrhosis
M. Hata, K. Tokuuye, S. Sugahara, K. Kagei, N. Fukumitsu, T. Hashimoto, K. Ohnishi, K. Ohara, Y. Matsuzaki, Y. Akine, EJC SUPPLEMENTS, 3, 2, 224, 225, Oct. 2005
PERGAMON-ELSEVIER SCIENCE LTD, English, Summary international conference

Dose-response relationship of proton beam therapy for hepatocellular carcinoma
K. Tokuuye, Y. Akine, T. Hashimoto, Y. Fukumitsu, S. Hata, S. Sugahara, K. Ohara, K. Ohnishi, K. Nemoto, Y. Matsuzaki, EJC SUPPLEMENTS, 3, 2, 223, 223, Oct. 2005
PERGAMON-ELSEVIER SCIENCE LTD, English, Summary international conference

肝細胞癌に対する陽子線単独治療の治療成績
徳植公一, 橋本孝之, 井垣浩, 幡多政治, 影井兼司, 菅原信二, 大城佳子, 福光延吉, 大原潔, 日本医学放射線学会学術集会抄録集, 64th, S160, 25 Feb. 2005
Japanese

^99mTc‐GSAによる肝腫よう陽子線治療後の肝予備能の経時的評価
井垣浩, 徳植公一, 菅原信二, 影井兼司, 幡多政治, 武田徹, 福光延吉, 橋本孝之, 大原潔, 日本医学放射線学会学術集会抄録集, 64th, S180, 25 Feb. 2005
Japanese

Clinical results of proton beam therapy for esophageal cancer at the University of Tsukuba
S Sugahara, K Tokuuye, A Nakahara, H Igaki, M Hata, K Kagei, H Terashima, T Hashimoto, N Fukumitsu, T Shibahara, K Ohara, Y Akine, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 63, 2, S163, S164, 2005
ELSEVIER SCIENCE INC, English, Summary international conference

Repeated proton beam therapy for hepatocellular carcinoma
T Hashimoto, K Tokuuye, K Nemoto, K Onishi, N Fukumitsu, H Igaki, M Hata, K Kagei, S Sugahara, K Ohara, Y Matsuzaki, Y Akine, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 63, 2, S159, S160, 2005
ELSEVIER SCIENCE INC, English, Summary international conference

Clinical results of proton beam therapy for skull base chordoma
H Iqaki, K Tokuuye, T Okumura, S Sugahara, K Kagei, M Hata, K Ohara, K Tsuboi, T Hashimoto, Y Akine, RADIOTHERAPY AND ONCOLOGY, 73, S258, S258, Oct. 2004
ELSEVIER IRELAND LTD, English, Summary international conference

Objective assessment of cervical cancer radioresponse by serum squamous cell carcinoma antigen and magnetic resonance imaging
K Ohara, S Sugahara, K Kagei, M Hata, H Igaki, T Hashimoto, K Tokuuye, Y Akine, RADIOTHERAPY AND ONCOLOGY, 73, S291, S291, Oct. 2004
ELSEVIER IRELAND LTD, English, Summary international conference

Proton beam therapy for hepatocellular carcinoma with portal vein tumor thrombus
M Hata, K Tokuuye, K Ohara, S Sugahara, K Kagei, H Igaki, T Hashimoto, Y Matsuzaki, N Tanaka, Y Akine, RADIOTHERAPY AND ONCOLOGY, 73, S318, S318, Oct. 2004
ELSEVIER IRELAND LTD, English, Summary international conference

神経膠腫に対する陽子線治療成績　　　　　　　　　　　　　　　
井垣 浩, 徳植 公一, 坪井 康次, 菅原 信二, 影井 兼司, 幡多 政治, 橋本 孝之, 大原 潔, 秋根 康之, 日本放射線腫瘍学会誌, 16, Suppl.1, 128, 128, Oct. 2004
(公社)日本放射線腫瘍学会, Japanese

肝細胞癌の下大静脈腫瘍栓に対する陽子線治療　　　　　　　　　　　　　　　
水本 斉志, 徳植 公一, 橋本 孝之, 幡多 政治, 影井 兼司, 井垣 浩, 菅原 信二, 大原 潔, 秋根 康之, 日本放射線腫瘍学会誌, 16, Suppl.1, 171, 171, Oct. 2004
(公社)日本放射線腫瘍学会, Japanese

門脈腫瘍栓をともなう肝細胞癌に対する陽子線治療　　　　　　　　　　　　　　　
幡多 政治, 徳植 公一, 菅原 信二, 影井 兼司, 井垣 浩, 橋本 孝之, 水本 斉志, 大原 潔, 秋根 康之, 日本放射線腫瘍学会誌, 16, Suppl.1, 171, 171, Oct. 2004
(公社)日本放射線腫瘍学会, Japanese

肝細胞癌の放射線治療計画における臨床標的体積の治療医間でのばらつきの検討　　　　　　　　　　　　　　　
橋本 孝之, 徳植 公一, 水本 斉志, 井垣 浩, 幡多 政治, 影井 兼司, 菅原 信二, 大原 潔, 秋根 康之, 日本放射線腫瘍学会誌, 16, Suppl.1, 171, 171, Oct. 2004
(公社)日本放射線腫瘍学会, Japanese

血清SCC抗原による子宮頸癌の放射線反応評価 MR画像による評価との比較　　　　　　　　　　　　　　　
大原 潔, 橋本 孝之, 影井 兼司, 幡多 政治, 井垣 浩, 菅原 信二, 水本 斉志, 徳植 公一, 秋根 康之, 日本放射線腫瘍学会誌, 16, Suppl.1, 180, 180, Oct. 2004
(公社)日本放射線腫瘍学会, Japanese

金マーカーの埋め込みを上部消化管内視鏡下に行ったReal-time Tumor Tracking Radiotherapy　　　　　　　　　　　　　　　
森 康明, 小野 雄司, 桂田 武彦, 小野 尚子, 山本 純司, 中川 学, 三浦 洋輔, 工藤 真弓, 結城 敏志, 武居 正明, 宮下 憲暢, 小松 嘉人, 浅香 正博, 中川 宗一, 清水 勇一, 加藤 元嗣, 橋本 孝之, 白土 博樹, Gastroenterological Endoscopy, 46, Suppl.2, 1895, 1895, Sep. 2004
(一社)日本消化器内視鏡学会, Japanese

Initial experience of proton beam therapy at the new facility of the University of Tsukuba
Kagei Kenji, Tokuuye Koichi, Sugahara Shinji, Hata Masaharu, Igaki Hiroshi, Hashimoto Takayuki, Ohara Kiyoshi, Akine Yasuyuki, Nippon Acta Radiologica, 64, 4, 225, 230, 25 May 2004
Purpose: To present the initial experience with proton beam therapy at the new Proton Medical Research Center (PMRC) of the University of Tsukuba. Materials and Methods: The new facility has a synchrotron with maximum energy of 250MeV and two rotational gantries. We treated 105 patients with 120 lesions with proton beams in the first year, beginning in September 2001. The most common lesion treated was primary liver cancer (40 lesions) followed by lung cancer, head and neck cancers, and prostate cancer. Concurrent X-ray radiotherapy was given for 38 of the 120 lesions. Results: The median follow-up period was 11 months (range, 1-19 months). Of the 105 patients, 97% had Grade 0-2 RTOG/ EORTC acute morbidities, while the remaining 3% had Grade 3. Tumor response after irradiation was CR for 35% of the lesions, PR for 25%, SD for 22%, PD for 9%, and not evaluated for 9%. Conclusion: The proton beam therapy conducted at the new facility of the University of Tsukuba was safe and effective., Japanese

MR画像誘導陽子線治療システムおよび磁場下の治療計画・検証技法に関する基盤開発
科学研究費助成事業
01 Apr. 2024 - 31 Mar. 2028
松浦 妙子, 宮本 直樹, 打浪 雄介, 高尾 聖心, 陳 叶, 橋本 孝之, 栗山 靖敏, 加藤 徳雄
日本学術振興会, 基盤研究(B), 北海道大学, 24K02389

An Integrated Approach for Uncertainty Reduction of DIR-based Dose Accumulation in Adaptive Radiotherapy
Grants-in-Aid for Scientific Research
01 Apr. 2024 - 31 Mar. 2027
小橋 啓司, 橋本 孝之, 吉村 高明, 西岡 健太郎
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24K10878

肺癌に対する陽子線治療の選択基準確立に向けた心肺相互作用勘案NTCPモデル構築
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
青山 英史, 鈴木 隆介, 宮本 直樹, 高尾 聖心, 金平 孝博, 橋本 孝之, 小橋 啓司, 西岡 健太郎, 田口 大志
日本学術振興会, 基盤研究(B), 北海道大学, 22H03008

AIを活用した小児がん陽子線照射のトリプルハイブリッド遠隔治療計画システムの開発
科学研究費助成事業
01 Apr. 2022 - 31 Mar. 2025
橋本 孝之, 高尾 聖心, 小橋 啓司, 吉村 高明, 西岡 健太郎
日本学術振興会, 基盤研究(C), 北海道大学, 22K07631

超高線量率陽子線治療に適したリアルタイム飛程検出法の開発
科学研究費助成事業
09 Jul. 2021 - 31 Mar. 2024
松浦 妙子, 田中 創大, 富岡 智, 橋本 孝之, 栗山 靖敏
FLASH放射線治療は，通常の放射線治療の線量率の数百倍から数千倍高い線量率（40 Gy/s程度以上）を用いる超高線量率照射法である。抗腫瘍効果を変えずに正常組織の障害発生を顕著に抑制できることが知られており，これまでの治療様式を大きく変えるインパクトがある．本研究では，数年以内に臨床利用が期待される超高線量率陽子線治療に適用する心電図検査式リアルタイム飛程検出法の実用化に向けた基盤技術開発を行うことを目標とした研究開発を行っている．本年度はまず，シミュレーション検討に用いるためにCT及び超音波の両方のイメージングに対応した人体ファントムを選定し（Model 057A，CIRS社製），音波伝搬シミュレーションの構築を開始した．まず人体ファントムを陽子線治療計画用のCT装置で撮影し，各ボクセルのCT値に対して陽子線治療に用いられているCT-相対阻止能テーブルを用いて水密度を割り当て，モンテカルロシミュレーションによって陽子線線量分布を計算した．一方で，音波発生・伝搬シミュレーションの準備として，文献を参照しながら各ボクセルに対してCT値に応じた音響特性（音速や音響インピーダンス，グルネイセン係数など）を割り当てた．人体ファントムに対して，FLASH線量率で陽子線を照射し，これを音源とした音波伝搬をシミュレーションした．音波は体表面に配置した複数のセンサーで受信する設定とした．本年度はまた，次年度予定している陽子線照射実験に用いる予定の寒天をベースとしたファントムの構造と形状の検討を行い，試作を行った．
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 21K19434

Research and development about helium and proton hybrid system with proton CT and Immuno-radiotherapy
Grants-in-Aid for Scientific Research
01 Apr. 2019 - 31 Mar. 2024
白土 博樹, 宮本 直樹, 高尾 聖心, 茶本 健司, 橋本 孝之, Nam JinMin, 西岡 健太郎, 小野寺 康仁, 松浦 妙子, 梅垣 菊男, 平田 雄一, 田中 創大, 清水 伸一
① 2019年度に決定した、短時間（0.1秒以下）でエネルギー変更可能な小型加速器の基本設計に基づき、小型加速器の要素技術の設計を行い、短時間（0.1秒以下）でエネルギー変更を可能とする回転ガントリーを含む照射・輸送系の磁場制御設計を行った。
② 陽子からヘリウムに短時間で加速粒子を変更できる混合加速方式を検討、2023年度に制作開始するべく、陽子線CTの機器としての仕様を検討した。
③ 陽子線CT値-ヘリウムSPR変換プロセスと、X線CT値利用時の精度を比較し、高エネルギー陽子線CTに必要な要素機器と制御方式の仕様を明確化した。
④ 高エネルギー陽子線ビームを照射する場合に、ビームの人体への入射方向を意図的に偏心させ、ノズルの外側から照射野中心に向かったビームアングルとするための加速器・照射系の検討を行った。
⑤ PD-1阻害剤およびPD-L1阻害剤を用いて、がん細胞の制御に最適なLET、ROSとミトコンドリアの分布を計測し、放射線と阻害剤の組み合わせによる相関を検討した。T細胞のPD-1阻害に関する条件検討を行っていたところ、当初の想定に反し、がん細胞での観察と類似の条件ではT細胞の観察が困難であることが判明した。T細胞を観察した上で条件決定することが不可欠であるため、T細胞のPD-1阻害に関する条件決定のための追加検討事項として、培養条件や使用する蛍光色素の種類を複数追加し、T細胞を観察するための至適条件の検討を行った。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H03591

Challenge to elucidate and optimize the radiation sensitizing effect of gold nanoparticles by quantum life science approach
Grants-in-Aid for Scientific Research
01 Apr. 2018 - 31 Mar. 2022
Hashimoto Takayuki
Radiation effects on metals, such as gold nanoparticles, was investigated to improve the results of radiotherapy for intractable cancers. Observation of gold particles in cellular microstructure was delayed due to damage to an ultra-high voltage electron microscope caused by the great earthquake, and proton irradiation experiments using gold nanoparticles that can be administered into the body were not conducted during the period due to the intermittent issuance of a state of emergency declaration and priority measures to prevent spread of the COVID-19. In relation to the interaction between metals in the body and radiation, we published papers on proton therapy for pediatric cancer, in which the radiosensitizing effect of gold particles is expected to be clinically applicable, and on a comparative study of the effects of proton beams and carbon ion beams on implantable medical devices such as pacemakers, respectively.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 18K07660

Development of minimum invasive real-time markerless image guided radiotherapy technique using minimum space information.
Grants-in-Aid for Scientific Research
01 Apr. 2018 - 31 Mar. 2021
Shimizu Shinichi
In the real-time tumor tracking radiotherapy, feature point information, that is used for gating, is obtained by fluoroscopic X-ray images. There still problems exist:1.X-ray exposure from diagnostic X ray that used for gating 2.insertion of a gold marker etc. as a feature pointReduce or eliminate X-ray exposure by making the observing area through diagnostic X-rays as small as possible to acquire target movement information or establishing the method of processing gating information obtained using MRI technology without using fluoroscopy were considered to be the goal of this study.
X-rays are still optimal for acquiring organ motion information within human body necessary for gating treatment in real time, but a method for limiting the range was achieved in this study. In addition, we succeeded in trying to visualize the position of organs with MRI image data without using X-rays when preparing for treatment, and there were expectations for the promotion of future research.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 18H02758

Development of a real-time tumor-tracking proton beam therapy with molecular imaging for intractable cancers using gold nanoparticles preparation
Grants-in-Aid for Scientific Research
01 Apr. 2014 - 31 Mar. 2017
Hashimoto Takayuki, HASHIMOTO Shintaro, Kwon Jihun, Sutherland Kenneth L
We conducted basic researches for developing a novel proton beam therapy as one of the multimodal therapies to improve treatment results of intractable cancers using gold nanoparticles (GNPs) as a radiosensitizer. The spatial dose distributions and dose enhancement ratio around the proton beam axis in the presence and absence of a GNPs were calculated using the Geant4 Monte Carlo simulation toolkit under various conditions. GNPs form clusters when taken up by tumor cells and shield a part of secondary electrons. Our results suggest the improvement of treatment accuracy in clinical use, because the dose enhancement is overestimated without considering energy absorption by the clustered GNPs. It is necessary to evaluate the sufficient safety including animal test before clinical application of GNPs preparation, which is highly concentrated enough to distinguish the difference of CT value as the tumor imaging agent or the fiducial marker.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 26461876

Novel approaches to cancer treatment based on DNA damage and tumor immunity activation induced by proton beam irradiation
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2015
TSUBOI Koji, SAKAE Takeji, KUMADA Hiroaki, MORITAKE Takashi, HASHIMOTO Takayuki, SUZUKI Kenshi, ITO Atsuo, OHNO Tadao
1) The “complex DNA damages” induced by irradiation make a significant impact on cell inactivation or transformation. Although complex DNA damage formation was dependent on radiation quality in the early phase after irradiation, senescence-like growth arrest was suggested to be the major cellular response in the later phase, regardless of radiation quality.
2) A selective Cox-2 inhibitor “celecoxib” sensitized malignant brain tumor cells to gamma-rays by loading ER stress. The major modality of cell death induced was autophagy, suggesting that celecoxib is a promising candidate for radosensitizing refractory malignant brain tumors.
3) Local cancer radiotherapy may have an effect as an immune adjuvant. We found that a tumor-specific immune system was activated when the primary tumor was cured by irradiation. This “abscopal effect” was effective even in the brain. In contrast, primary tumor recurrence after irradiation resulted in suppression of tumor immunity.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), University of Tsukuba, 24390287

Basic research for particle therapy using high enrgy proton in next generation
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2015
SAKURAI Hideyuki, MATSUMOTO Hideki, ISHIKAWA Hitoshi, OKUMURA Toshiyuki, MORITAKE Takashi, HASHIMOTO Takayuki, MIZUMOTO Masashi, MATSUMOTO Yoshitaka
There is high possibility to increase cure rate of cancer by using new radiation therapy, proton beam therapy and boron neutron capture therapy (BNCT). We performed not only basic research of these two particle therapy, but also clinical studies of chemoproton therapy for esophageal cancer, locally advanced lung cancer, and cholangiocarcinoma. As a result, chemoproton therapy, which was new field of cancer therapy, showed high treatment effect with less toxicity for the heart and lung. We also carried out clinical study of proton for pediatric cancer, and started long term to follow up of 150 patients. For clinical study of BNCT, the treatments were finalized in 4 patients.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), University of Tsukuba, 24390286

A translational research for promotion of multimodality therapy combined with proton beam therapy
Grants-in-Aid for Scientific Research
2009 - 2011
SAKURAI Hideyuki, MATSUMOTO Hideki, OHNO Tatsuya, MORITAKE Takashi, MIZUMOTO Masashi, OKUMURA Toshiyuki, HASHIMOTO Takayuki
The aim of this study is to promote translational research for multimodality therapy combined with proton beam therapy (PBT). We found increasing radiobiological effect on late phase of bragg peak, and also detected apoptosis in the crypt cells irradiated with very low dose of proton. For normal tissue reaction, dose-volume relationship was clearly found both in rib fracture on PBT for liver cancer and in pneumonistis on PBT combined with chemotherapy for advanced lung cancer. Finally, from these translational researches, we have started clinical trials for advanced lung cancer and pediatric cancer as a multimodality therapy combined with PBT.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), University of Tsukuba, 21390338