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Takatori K.,Kasai City Hospital | Terashima K.,Hyogo Ion Beam Medical Center | Yoshida R.,Kasai City Hospital | Horai A.,Kasai City Hospital | And 6 more authors.
Journal of Gastroenterology | Year: 2014

Background: Little is known about acute upper gastrointestinal (GI) complications associated with gemcitabine-concurrent proton radiotherapy (GPT) for inoperable pancreatic cancer. We investigated acute GI complications following GPT in patients with inoperable pancreatic cancer using small-bowel endoscopy. Methods: This prospective single center observational study was conducted at the Hyogo Ion Beam Medical Center from January 2010 to January 2012. Ninety-one patients who had clinically and medically inoperable pancreatic cancer treated by GPT were analyzed. Endoscopic examinations were performed before and after GPT to clarify the incidence rates of radiation-induced ulcers, GI hemorrhage, and GI perforation associated with GPT. Results: Post-treatment endoscopic examinations revealed that 45 (49.4 %) patients had radiation-induced ulcers in the stomach and duodenum. Of those, many ulcerative lesions were found in the lower stomach (51 %) and horizontal part of the duodenum (39 %), regardless of the primary tumor site in the pancreas. Neither GI hemorrhage, nor perforation, was found in post-treatment endoscopy examinations. Conclusion: Approximately half of the patients treated with GPT for inoperable pancreatic cancer exhibited radiation-induced ulcers in the stomach and duodenum. © 2013 Springer.


Iwata H.,Nagoya City University | Iwata H.,Hyogo Ion Beam Medical Center | Murakami M.,Hyogo Ion Beam Medical Center | Demizu Y.,Hyogo Ion Beam Medical Center | And 8 more authors.
Cancer | Year: 2010

BACKGROUND: A study was undertaken to evaluate the clinical outcome of particle therapy for stage I nonsmall cell lung cancer (NSCLC). METHODS: From April 2003 to April 2007, 80 patients with stage I NSCLC were treated with proton therapy or carbon-ion therapy (57 with proton therapy and 23 with carbon-ion therapy) using 3 treatment protocols. In the first protocol, 80 gray equivalents (GyE) of proton therapy was given in 20 fractions, and the second proton therapy protocol used 60 GyE in 10 fractions. For carbon-ion therapy, 52.8 GyE was given in 4 fractions. After achieving promising preliminary results for the first protocol, the authors started to use the second proton therapy protocol to shorten the overall treatment time. Carbon-ion therapy was started in 2005, and thereafter, both proton and carbon-ion therapy plans were made for each patient, and the 1 that appeared superior was adopted. Patient age ranged from 48 to 89 years (median, 76 years). Thirty-seven patients were medically inoperable, and 43 refused surgery. Forty-two patients had T1 tumors, and 38 had T2 tumors. RESULTS: The median follow-up period for living patients was 35.5 months. For all 80 patients, the 3-year overall survival, cause-specific survival, and local control rates were 75% (IA: 74%; IB: 76%), 86% (IA: 84%; IB: 88%), and 82% (IA: 87%; IB: 77%), respectively. There were no significant differences in treatment results among the 3 protocols. Grade 3 pulmonary toxicity was observed in only 1 patient. CONCLUSIONS: Proton therapy and carbon-ion therapy are safe and effective for stage I NSCLC. Further investigation of particle therapy for stage I NSCLC is warranted. © 2010 American Cancer Society.


Someya M.,Sapporo Medical University | Yamamoto H.,St. Marianna University School of Medicine | Nojima M.,Tokyo Medical University | Hori M.,Sapporo Medical University | And 7 more authors.
Radiotherapy and Oncology | Year: 2015

Background and purpose: Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. Materials and methods: Four patients each with grade 0-1 or grade 2-3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4 Gy of X-ray ex-vivo. Results: In the discovery cohort, grade 2-3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ≥1.09 group (P = 0.011). In radiation-induced expression of miR-99a, grade 2-3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(-) >0.93 group compared with ≤0.93 group (P = 0.013). Most patients with grade 2-3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. Conclusion: A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy. © 2015 Elsevier Ireland Ltd. All rights reserved.


Nihei K.,Hospital East | Ogino T.,Hospital East | Onozawa M.,Hospital East | Murayama S.,Proton Therapy | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2011

Purpose: Proton beam therapy (PBT) is theoretically an excellent modality for external beam radiotherapy, providing an ideal dose distribution. However, it is not clear whether PBT for prostate cancer can clinically control toxicities. The purpose of the present study was to estimate prospectively the incidence of late rectal toxicities after PBT for organ-confined prostate cancer. Methods and Materials: The major eligibility criteria included clinical Stage T1-T2N0M0; initial prostate-specific antigen level of ≤20 ng/mL and Gleason score ≤7; no hormonal therapy or hormonal therapy within 12 months before registration; and written informed consent. The primary endpoint was the incidence of late Grade 2 or greater rectal toxicity at 2 years. Three institutions in Japan participated in the present study after institutional review board approval from each. PBT was delivered to a total dose of 74 GyE in 37 fractions. The patients were prospectively followed up to collect the data on toxicities using the National Cancer Institute-Common Toxicity Criteria, version 2.0. Results: Between 2004 and 2007, 151 patients were enrolled in the present study. Of the 151 patients, 75, 49, 9, 17, and 1 had Stage T1c, T2a, T2b, T2c, and T3a, respectively. The Gleason score was 4, 5, 6, and 7 in 5, 15, 80 and 51 patients, respectively. The initial prostate-specific antigen level was <10 or 10-20 ng/mL in 102 and 49 patients, respectively, and 42 patients had received hormonal therapy and 109 had not. The median follow-up period was 43.4 months. Acute Grade 2 rectal and bladder toxicity temporarily developed in 0.7% and 12%, respectively. Of the 147 patients who had been followed up for >2 years, the incidence of late Grade 2 or greater rectal and bladder toxicity was 2.0% (95% confidence interval, 0-4.3%) and 4.1% (95% confidence interval, 0.9-7.3%) at 2 years, respectively. Conclusion: The results of the present prospective study have revealed a valuable piece of evidence that PBT for localized prostate cancer can achieve a low incidence of late Grade 2 or greater rectal toxicities. © 2011 Elsevier Inc.


Demizu Y.,Hyogo Ion Beam Medical Center | Fujii O.,Hyogo Ion Beam Medical Center | Terashima K.,Hyogo Ion Beam Medical Center | Mima M.,Hyogo Ion Beam Medical Center | And 6 more authors.
Strahlentherapie und Onkologie | Year: 2014

Purpose: To retrospectively analyze treatment outcomes after particle therapy using protons or carbon ions for mucosal melanoma of the head and neck (HNMM) at the Hyogo Ion Beam Medical Center, as well as to compare proton therapy (PT) and carbon ion therapy (CIT). Patients and methods: Data from 62 HNMM patients without metastasis, treated with PT or CIT between October 2003 and April 2011 were analyzed. Median patient age was 70.5 years (range 33-89 years). Of the total patients, 33 (53 %) had received PT and 29 (47 %) had undergone CIT. Protocols for 65 or 70.2 GyE in 26 fractions were used for both ion types. Results: Median follow-up was 18.0 months (range 5.2-82.7 months). The 1-/2-year overall survival (OS) and local control (LC) rates were 93 %/61 % and 93 %/78 % for all patients, 91 %/44 % and 92 %/71 % for the PT patients and 96 %/62 % and 95 %/59 % for the CIT patients, respectively. No significant differences were observed between PT and CIT. Local recurrence was observed in 8 patients (PT: 5, CIT: 3) and 29 (PT: 18, CIT: 11) experienced distant metastases. Acute reactions were acceptable and all patients completed the planned radiotherapy. Regarding late toxicity, grade 3 or greater events were observed in 5 patients (PT: 3, CIT: 2), but no significant difference was observed between PT and CIT. Conclusion: Our single-institution retrospective analysis demonstrated that particle therapy for HNMM achieved good LC, but OS was unsatisfactory. There were no significant differences between PT and CIT in terms of either efficacy or toxicity. © 2013 Springer Heidelberg Berlin.


Demizu Y.,Hyogo Ion Beam Medical Center
Japanese Journal of Clinical Radiology | Year: 2013

Particle therapy, such as proton therapy and carbon ion therapy, is capable of delivering high-dose radiation to tumors while minimizing the dose delivered to organs at risk because of its precise dose distribution, as compared with conventional photon therapy. Little is known about particle therapy for oligometastases and oligo-recurrence, however, published reports and our unpublished data suggest that particle therapy can achieve favorable local control with acceptable toxicities. More data accumulation is warranted.


Komatsu S.,Kobe University | Komatsu S.,Hyogo Ion Beam Medical Center | Murakami M.,Hyogo Ion Beam Medical Center | Fukumoto T.,Kobe University | And 3 more authors.
British Journal of Surgery | Year: 2011

Background: Particle radiotherapy is a novel treatment for malignant tumours. The present study aimed to evaluate risk factors for overall survival and local control after particle radiotherapy of single small hepatocellular carcinoma (HCC), and to identify suitable candidates for this treatment. Methods: All patients with a single HCC smaller than 5 cm in diameter treated by particle radiotherapy between 2001 and 2008 were identified retrospectively from a prospectively collected database. Clinical outcomes and prognostic factors were analysed. Results: A total of 150 patients were included. Five-year overall survival and local control rates were 50·9 and 92·3 per cent respectively. Multivariable analysis revealed that several factors, including age and Child-Pugh classification, significantly influenced overall survival. Proximity to the digestive tract and Child-Pugh classification were independent risk factors for local recurrence. Other tumour factors including size, gross classification, previous treatment, macroscopic vascular invasion, and tumour location in relation to the diaphragm and large vessels did not influence local control rate. Conclusion: Particle radiotherapy seems safe and effective, and may be a novel treatment for small HCC. Recurrences are more frequent when the tumour is located close to the gut. © 2011 British Journal of Surgery Society Ltd.


Komatsu S.,Kobe University | Komatsu S.,Hyogo Ion Beam Medical Center | Fukumoto T.,Kobe University | Demizu Y.,Hyogo Ion Beam Medical Center | And 7 more authors.
Cancer | Year: 2011

BACKGROUND: The objective of this study was to evaluate the clinical outcome of proton and carbon ion therapy for hepatocellular carcinoma (HCC). METHODS: In total, 343 consecutive patients with 386 tumors, including 242 patients (with 278 tumors) who received proton therapy and 101 patients (with 108 tumors) who received carbon ion therapy, were treated on 8 different protocols of proton therapy (52.8-84.0 gray equivalents [GyE] in 4-38 fractions) and on 4 different protocols of carbon ion therapy (52.8-76.0 GyE in 4-20 fractions). RESULTS: The 5-year local control and overall survival rates for all patients were 90.8% and 38.2%, respectively. Regarding proton and carbon ion therapy, the 5-year local control rates were 90.2% and 93%, respectively, and the 5-year overall survival rates were 38% and 36.3%, respectively. These rates did not differ significantly between the 2 therapies. Univariate analysis identified tumor size as an independent risk factor for local recurrence in proton therapy, carbon ion therapy, and in all patients. Multivariate analysis identified tumor size as the only independent risk factor for local recurrence in proton therapy and in all patients. Child-Pugh classification was the only independent risk factor for overall survival in proton therapy, in carbon ion therapy, and in all patients according to both univariate and multivariate analyses. No patients died of treatment-related toxicities. CONCLUSIONS: Proton and carbon ion therapies for HCC were comparable in terms of local control and overall survival rates. These therapies may represent innovative alternatives to conventional local therapies for HCC. © 2011 American Cancer Society.


Yamashita T.,Hyogo Ion Beam Medical Center | Akagi T.,Hyogo Ion Beam Medical Center | Aso T.,Nagaoka University of Technology | Kimura A.,Ashikaga Institute of Technology | Sasaki T.,High Energy Accelerator Research Organization
Physics in Medicine and Biology | Year: 2012

The pencil beam algorithm (PBA) is reasonably accurate and fast. It is, therefore, the primary method used in routine clinical treatment planning for proton radiotherapy; still, it needs to be validated for use in highly inhomogeneous regions. In our investigation of the effect of patient inhomogeneity, PBA was compared with Monte Carlo (MC). A software framework was developed for the MC simulation of radiotherapy based on Geant4. Anatomical sites selected for the comparison were the head/neck, liver, lung and pelvis region. The dose distributions calculated by the two methods in selected examples were compared, as well as a dose volume histogram (DVH) derived from the dose distributions. The comparison of the off-center ratio (OCR) at the iso-center showed good agreement between the PBA and MC, while discrepancies were seen around the distal fall-off regions. While MC showed a fine structure on the OCR in the distal fall-off region, the PBA showed smoother distribution. The fine structures in MC calculation appeared downstream of very low-density regions. Comparison of DVHs showed that most of the target volumes were similarly covered, while some OARs located around the distal region received a higher dose when calculated by MC than the PBA. © 2012 Institute of Physics and Engineering in Medicine.


Terashima K.,Hyogo Ion Beam Medical Center
Japanese Journal of Clinical Radiology | Year: 2016

Focal liver reaction was observed corresponding to particle therapy (PT) using proton or carbon-ion beam for liver tumor, presented with significant low intensity at hepatobiliary phase on gadoxetate acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging. The imaging findings appeared 8 weeks after PT with threshold dose of 19.9 and 24.3 gray equivalents (GyE) at 10 and 20 fractions for proton beam, 21.9 and 25.5 GyE at 10 and 20 fractions for carbon-ion beam. These results could serve as a basis for an optimal management of radiation induced liver disease. © 2016, Kanehara Shuppan Co. Ltd. All rights reserved.

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