Hirohiko Tsujii

National Institute of Radiological Sciences, Tiba, Chiba, Japan

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Publications (300)782.56 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose To evaluate the safety and efficacy of carbon ion radiotherapy (CIRT) for locally advanced sinonasal adenocarcinoma. Material and methods Twenty-two patients with sinonasal adenocarcinoma were treated with CIRT. CIRT was the primary treatment for 16 patients. Four patients received CIRT for local recurrence after surgery and two for residual tumour after surgery or chemotherapy. At the start of CIRT, 1 patient had T-classification (T) 2 disease, 2 had T3 disease, 5 had T4a disease, and 14 had T4b disease. Fourteen patients were treated with 57.6 Gy equivalent (GyE)/16 fractions, and 8, with 64.0 GyE/16 fractions. Results The median follow-up period was 43 months for all patients. The 3-year local control and loco-regional control rates for all patients were 76.9% (95% confidence interval [CI] = 56.7–97.1%) and 61.3% (95% CI = 38.5–84.1%), respectively. The 3-year overall survival and disease-specific survival rates were 59.1% (95% CI = 38.6–79.6%) and 65.6% (95% CI = 44.9–86.3%), respectively. Acute reactions of grade 3 of the skin and mucosa were observed in 2 and 4 patients, respectively. Late reactions included lateral visual loss (5 patients), mucosal ulceration (1 patient), and brain necrosis with clinical symptoms (1 patient). In the 5 patients who developed visual loss, the optic nerve was close to the tumour. Conclusions CIRT was effective and generally safe for locally advanced sinonasal adenocarcinoma.
    Radiotherapy and Oncology. 10/2014;
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    ABSTRACT: Background: The prognosis of advanced squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear (ME) remains poor. Carbon ion radiotherapy (C-ion RT) has shown promise for locally advanced head and neck cancer. Therefore, we evaluated the safety and efficacy of C-ion RT for locally advanced SCC of the EAC and ME.Methods: The cases of 13 patients with advanced (T3 and T4) SCC of the EAC and ME who received C-ion RT as the primary treatment were reviewed.Results: The median follow-up for all patients and the seven surviving patients was 12 and 32 months, respectively. The 1-year and 3-year local control and overall survival rates were 72% and 54% and 70% and 40%, respectively. Severe temporal bone necrosis was observed in two patients.Conclusion: C-ion RT is effective and generally safe for locally advanced SCC of the EAC and ME. Head Neck, 2014
    Head & Neck 10/2014; · 2.83 Impact Factor
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    ABSTRACT: Background:The purpose of this study was to evaluate the feasibility of a new shortened 3-week treatment schedule of carbon ion radiotherapy (CIRT) for prostate cancer.Methods:Beginning in May 2010, patients with T1b-T3bN0M0, histologically proven prostate adenocarcinoma were enrolled in the phase II trial of CIRT. Patients received 51.6 GyE in 12 fractions over 3 weeks (protocol 1002). The primary end point was defined as the incidence of late adverse events that were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0. Biochemical failure was determined using the Phoenix definition (nadir +2.0 ng ml(-1)).Results:Forty-six patients were enrolled, and all patients were included in the analysis. The number of low-, intermediate-, and high-risk patients was 12 (26%), 9 (20%), and 25 (54%), respectively. The median follow-up period of surviving patients was 32.3 months. Two patients had intercurrent death without recurrence, and the remaining 44 patients were alive at the time of this analysis. In the analysis of late toxicities, grade 1 (G1) rectal haemorrhage was observed in 3 (7%) patients. The incidence of G1 haematuria was observed in 6 (13%) patients, and G1 urinary frequency was observed in 17 (37%) patients. No G2 late toxicities were observed. In the analysis of acute toxicities, 2 (4%) patients showed G2 urinary frequency, and no other G2 acute toxicities were observed.Conclusions:The new shortened CIRT schedule over 3 weeks was considered as feasible. The analysis of long-term outcome is warranted.British Journal of Cancer advance online publication, 10 April 2014; doi:10.1038/bjc.2014.191 www.bjcancer.com.
    British Journal of Cancer 04/2014; · 5.08 Impact Factor
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    ABSTRACT: Carbon ion radiotherapy (C-ion RT) for prostate cancer was started in 1995 using the Heavy-Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS), Japan. After preceding phase I/II dose-escalation studies of 20 fractions over 5 weeks, a phase II study was initiated in April 2000 using the treatment techniques and the recommended dose fractionations established by the phase I/II studies. This study was also successfully completed in October 2003 when the C-ion RT for solid tumors, including the prostate cancer, was approved as 'Advanced Medicine' by the Ministry of Health, Labor, and Welfare. Since then, more than 1400 patients have been treated with C-ion RT as of February 2012, and advancement of hypofractionation has also been achieved. In this paper, the treatment outcomes in 1144 patients who underwent the established C-ion RT between April 2000 and July 2012 were analyzed. Out of 1144 patients, 585 patients were categorized as high-risk group, which includes patients having at least one of the following conditions: T3 clinical stage, Gleason's score of 8 or higher and PSA of 20 or higher. One hundred and ninety-seven patients who met the conditions such as clinical stage of T2a or lower, Gleason's score of 6 or lower and PSA of <20 were categorized as low-risk group. Three hundred and sixty-two patients who were not included in either high- or low-risk group were categorized as intermediate-risk group. All patients were pathologically proven to have adenocarcinoma of the prostate, and Gleason's score was determined by the chief pathologist of our study group. Written consent was obtained from all patients included in the clinical study. Patients with the following conditions were not registered in the clinical trial: having distant metastases, having synchronous primary malignancy, not histologically proven cancer, without informed consent, post-operative/post-irradiation recurrence. All patients were treated with three field irradiations (vertical one field and horizontal opposing two fields). The prostate and proximal part of the seminal vesicle were contoured as clinical target volume (CTV), and planning target volume (PTV) was set with 5-10 mm margins around the CTV. On the way of radiotherapy, a part of irradiation field of the posterior side was cut to reduce the rectal dose. The 197 patients in the low-risk group did not undergo androgen deprivation therapy (ADT), whereas the 947 patients of intermediate- and high-risk groups underwent ADT. The patients of intermediate-risk group underwent about 6 months of neoadjuvant ADT, and the patients of high-risk group also underwent about 6 months of neoadjuvant ADT and sequential adjuvant ADT for more than 18 months. The median age of all patients was 68 years, and the median follow-up time was 48.7 months (range: 3.6-151.1 months). The 5-year overall survival rate and biochemical relapse-free rate of the entire groups was 95.7% and 91.0%, respectively. T-stage and Gleason's score were significant prognostic factors for both the biochemical control and patient survival and initial PSA was also a predictive factor for survival. Regarding the late radiation toxicity, the incidence of rectal toxicity of grade 2 or worse was 1.1% and that of genitourinary toxicity was 6.5%. These outcomes seemed to be better than those of the past publications [ 1- 4]. In addition, the incidence of toxicity in patients treated with more hypofractionated C-ion RT of 16 fractions over 4 weeks was lower than those of 20 fraction treatment. These favorable outcomes can be thought as apparent evidence of physical and biological advantages of the hypofractionated C-ion RT.
    Journal of Radiation Research 03/2014; 55 Suppl 1:i28-i29. · 1.45 Impact Factor
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    ABSTRACT: Introduction: In 1994, we started carbon-ion radiotherapy (CIRT) for peripheral stage I non-small-cell lung cancer (NSCLC). First, two phase I/II clinical trials demonstrated the optimal doses of 90.0 GyE in 18 fractions over 6 weeks (Protocol 9303) and 72.0 GyE in 9 fractions over 3 weeks (Protocol 9701) for achieving more than 95% local control with minimal pulmonary toxicity. As a next step, we conducted two successive phase II trials. The first trial (Protocol 9802) used a regimen of 72 GyE per 9 fractions over 3 weeks and the second trial (Protocol 0001) used a regimen of 4 fractions over 1 week, at a fixed dose of 52.8 GyE for stage IA and 60 GyE for IB. In these Phase II trials, the local control rate (LCR) for all patients was 91.5%, and those for T1 and T2 tumors were 96.3 and 84.7%, respectively. The 5-year cause-specific survival rate (CSS) was 67.0% (IA: 84.4, IB: 43.7), and overall survival (OS) was 45.3% (IA: 53.9, IB: 34.2). No adverse events greater than grade 2 occurred in the lung. In 2003, we also started a phase I/II clinical trial (Protocol 0201) as a dose escalation study using single fraction. The initial total dose was 28.0 GyE administered and escalated in increments of 2.0 GyE each, up to 50.0 GyE. This clinical trial ended in February 2012 and is still followed up. In this article, we investigated the preliminary results of this phase I/II trial. Materials and methods: In this prospective study, 151 primary stage I NSCLC were treated by CIRT monotherapy using a total dose of 36.0 GyE (n = 18), 38.0 GyE (n = 14), 40.0 GyE (n = 20), 42.0 GyE (n = 15), 44.0 GyE (n = 44), 46.0 GyE (n = 20), 48.0 GyE (n = 10) and 50.0 GyE (n = 10) using single fractionation. Mean age was 73.9 years, and size of tumor included T1 (n = 91) and T2 (n = 60). By type (cancer type was determined by biopsy), there were 104 adenocarcinomas, 46 squamous cell carcinomas and 1 large cell carcinoma. Medical inoperability was 55.6%. The patient is fixed on the rotational couch by using a custom-made immobilization device. Under free breathing conditions, planning CT images were acquired for treatment planning. The clinical target volume (CTV) was determined by adding >10-mm margin to the gross tumor volume (GTV). The planning target volume (PTV) was created by adding an internal margin to CTV as 5 mm in craniocaudal direction. The prescribed dose was delivered to PTV with different coplanar four beam angles. A respiratory-gated irradiation system was used in all irradiation sessions. Results: The median follow-up time was 45.6 months (range, 1.6-88.4 months). For 151 patients, the 5-year overall LCR was 79.2%, and those for T1 (n = 91) and T2 (n = 60) tumors were 83.6 and 72.2%, respectively. Also, local control in T1a, T1b, T2a and T2b were 96.8, 84.4, 80.2 and 20.0%, respectively. The OS was 55.1% and the CSS was 73.1%. No toxicity greater than grade 2 was observed in the lung and the skin. Conclusions: In patients with stage I NSCLC, CIRT using single fraction is considered as a promising curative modality. Especially for elderly and inoperable cases, CIRT could be a minimally invasive therapeutic option as a valid alternative to surgical resection (Fig. 1). Fig 1.Overall survival and local control in 151 patients with stage I non-small-cell lung cancer.
    Journal of Radiation Research 03/2014; 55 Suppl 1:i26-i27. · 1.45 Impact Factor
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    ABSTRACT: A novel risk assessment method, Japan Cancer of the Prostate Risk Assessment, has been developed based on database of patients receiving primary androgen deprivation therapy. To investigate the usefulness of Japan Cancer of the Prostate Risk Assessment for non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy. Patients with non-metastatic, high-risk prostate cancer (T3, initial prostate specific antigen level ≥20 ng/ml, and/or Gleason score ≥8) were included. The patients were treated with carbon ion radiotherapy (the total dose from 57.6 Gy (relative biological effectiveness)/16 fractions to 66.0 Gy(relative biological effectiveness)/20 fractions), and neoadjuvant as well as adjuvant androgen deprivation therapy for at least 24 months. Four hundred and twenty-six patients were included with the median follow-up of 68.1 months. Of 426, 210 (49.3%), 270 (63.4%) and 251 (58.9%) had Gleason 8-10, prostate specific antigen ≥20 ng/ml and T3, respectively. The 10-year progression-free and cause-specific survival rates in Japan Cancer of the Prostate Risk Assessment 1-2 group (76.5 and 98.9%) were significantly better than those in Japan Cancer of the Prostate Risk Assessment 3-6 group (52.6 and 93.1%), (P < 0.001 and P = 0.044, respectively). The median progression-free survivals in the Japan Cancer of the Prostate Risk Assessment 1-2 and 3-6 groups were 158.9 months and 125.9 months (95% confidence interval: 108.6-143.2 months), respectively. For non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy, Japan Cancer of the Prostate Risk Assessment score was useful for predicting the progression-free and cause-specific survivals.
    Japanese Journal of Clinical Oncology 02/2014; · 1.90 Impact Factor
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    ABSTRACT: BACKGROUND This study sought to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced adenocarcinoma of the uterine cervix in a phase 1/2 clinical trial. METHODS The treatment consisted of whole-pelvic irradiation of 36.0 gray equivalents (GyE) in 12 fractions and local boost with dose escalation from 26.4 to 38.4 GyE in 8 fractions. The dose escalation was performed with careful observation of acute normal tissue responses. Total dose to the cervical tumor was 62.4 to 74.4 GyE in 20 fractions. RESULTSBetween April 1998 and February 2010, 58 patients were treated with C-ion RT in this clinical trial. The number of patients with stage IIB, IIIB, and IVA disease were 20, 35, and 3, respectively. Median tumor size was 5.5 cm (range, 3.0-11.8 cm). Twenty-seven patients had pelvic lymph node metastases. The median follow-up period was 38 months. All patients completed the treatment schedule. Grade 2 or higher late toxicity was found in 8 patients: 5 with bladder and 2 with small intestine grade 2 toxicities, and 1 patient had grade 4 rectal complication, which was surgically salvaged. The 5-year local control rate, local control rate including salvage surgery, and overall survival rate in all cases were 54.5%, 68.2%, and 38.1%, respectively. CONCLUSIONS Dose escalation of C-ion RT for adenocarcinoma of the uterine cervix was accomplished without severe toxicities except in 1 case. Although the number of patients in this study was small, the results support continued investigation and analysis to confirm therapeutic efficacy. Cancer 2014. © 2014 American Cancer Society.
    Cancer 02/2014; · 5.20 Impact Factor
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    ABSTRACT: This study aimed to determine the risk factors for radiation-induced brain injury (RIBI) after carbon ion radiotherapy (CIRT) for treating skull base tumors. Between April 1997 and January 2009, CIRT at a total dose of 48.0-60.8Gy equivalent (GyE) was administered in 16 fractions to 47 patients with skull base tumors. Of these patients, 39 who were followed up with magnetic resonance imaging (MRI) for more than 24months were analyzed. RIBI was assessed according to the MRI findings based on the Late Effects of Normal Tissue-Subjective, Objective, Management, Analytic criteria; clinical symptoms were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer tables. The correlations of clinical and dosimetric parameters with incidence of ⩾grade 2 RIBI were retrospectively analyzed. The median follow-up period was 67months. The 5-year actuarial likelihoods of ⩾grade 2 RIBI and ⩾grade 2 clinical symptoms were 24.5% and 7.0%, respectively. Multivariate analysis demonstrated that the brain volume receiving more than 50GyE (V50) was a significant risk factor for the development of ⩾grade 2 RIBI (p=0.004). V50 was a significant risk factor for ⩾grade 2 RIBI after CIRT using a 16-fraction regimen.
    Radiotherapy and Oncology 12/2013; · 4.52 Impact Factor
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    ABSTRACT: Aim: The purpose of this study was to evaluate the role of FDG-PET regarding the indication of preoperative carbon-ion radiotherapy (CIRT) for pancreatic cancer patients. Patients with resectable pancreatic cancer underwent preoperative CIRT. The impact of baseline SUVmax on prognosis for patients was assessed by analyzing correlations with distant metastasis-free survival (DMFS) and overall survival (OS). Out of 21 patients, local recurrence was observed in no patient and distant metastasis was found in 13 patients (62%). 1-year DMFS and OS in low-SUVmax group were significantly higher than those in high-SUVmax group (91% vs. 20% and 91% vs. 56%). SUVmax was significantly correlated with DMFS and OS. Our data indicated a significant correlation between SUVmax and DMFS. FDG-PET might be useful for determining the indication of preoperative short-course CIRT for patients with resectable pancreatic cancer.
    Anticancer research 12/2013; 33(12):5579-84. · 1.71 Impact Factor
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    ABSTRACT: The authors performed phase I / II clinical trial to evaluate the toxicity and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced squamous cell carcinoma of the uterine cervix. Between April 2000 and January 2006, 22 patients for Protocol 9902 were treated with C-ion RT. The number of patients with stage IIB, IIIB, and IVA disease was 1, 18, and 3, respectively. All patients had bulky tumors measuring 4.0 - 12.0cm (median 6.2cm). The whole pelvic dose was fixed at 39.0 GyE for 13 fractions, and additional 15.0 GyE for 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, a dose-escalation study was planned for 2 fractions to GTV. Total dose to the cervical tumor was 64.0 - 72.0 GyE for 20 fractions. All patients completed the scheduled therapy and no patient developed Grade 2 or higher acute toxicity. There was no grade 3 or higher late complications at each dose. The 5-year overall survival rate and local control rate were 50.0% and 68.2%, respectively. Seven of 16 patients who received 64.0 - 68.0 GyE developed local recurrences, but all patients who received 72.0 GyE maintained local control. There were no severe acute or late complications in this trial. C-ion RT has the potential to improve the treatment for locally advanced bulky cervical cancer by applying a total dose of 72.0 GyE, with the results lending incentive to further investigations to confirm the therapeutic efficacy.
    Gynecologic Oncology 10/2013; · 3.93 Impact Factor
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    ABSTRACT: To assess 3-year health-related quality of life of patients treated with carbon ion radiotherapy for prostate cancer. A total of 213 patients received carbon-ion radiotherapy at a total dose of 66 Gy equivalent in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy were administered for high-risk patients for at least 12 months. A health-related quality of life assessment was carried out at four time-points (immediately before the initiation of carbon-ion radiotherapy, immediately after, 12 and 36 months after completion of carbon-ion radiotherapy) using Functional Assessment of Cancer Therapy General and for Prostate Cancer Patients. The evaluable response rates among all responses were more than 94%. Overall, a significant decrease in the scores of the health-related quality of life 12 months after carbon-ion radiotherapy returned to their baseline levels at 36 months. Additionally, no significant decrease was observed in the scores at any of the assessment time-points compared with their baseline scores in the group of carbon-ion radiotherapy without androgen deprivation therapy; however, the presence of morbidity and biochemical failure significantly worsened the scores, and the decreases in the scores did not improve even at 36 months after carbon-ion radiotherapy. An assessment based on a subjective scoring system shows a significant decrease in health-related quality of life at 12 months after carbon-ion radiation therapy, which tends to return to baseline levels at 36 months. The presence of morbidity and biochemical failure significantly worsen health-related quality of life scores. Further controlled studies focusing on health-related quality of life assessment in patients with prostate cancer are warranted.
    International Journal of Urology 10/2013; · 1.73 Impact Factor
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    ABSTRACT: The use of charged-particle radiation therapy (CPRT) is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields (radiation oncology, medical physics, radiobiology, research ethics and methodology), including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research.
    Journal of medical ethics 09/2013; · 1.42 Impact Factor
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    ABSTRACT: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m(2)) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.
    International journal of radiation oncology, biology, physics 09/2013; 87(1):100-5. · 4.59 Impact Factor
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    ABSTRACT: Spinal sarcomas have been one of the most challenging diseases for orthopedic surgeons. The objective of this study was to retrospectively analyze carbon ion radiotherapy (CIRT) treatment results for spinal sarcoma. Forty-seven patients with 48 medically unresectable spinal sarcomas, excluding sacral tumors, received treatment with CIRT between 1996 and 2011. All patients were enrolled in phase 1/2 and phase 2 clinical trials of CIRT for bone and soft tissue sarcoma. The applied dose ranged from 52.8 gray equivalents (GyE) to 70.4 GyE (median, 64.0 GyE) in 16 fixed fractions over 4 weeks. The median patient age was 54 years, and the cohort included 24 men and 23 women. Thirty-five patients were without prior treatment, and 12 patients had locally recurrent tumors after previous resection. The median follow-up was 25 months, and the median survival was 44 months (range, 5.2-148 months). The 5-year local control, overall survival, and progression free rates were 79%, 52%, and 48%, respectively. None of the 15 patients who had tumors measuring <100 cm(3) had a local recurrence. No fatal toxicities occurred during follow-up. One patient each had a grade 3 late skin reaction and a grade 4 late skin reaction. Vertebral body compression was observed in 7 patients. One patient had a grade 3 late spinal cord reaction. Twenty-two of the surviving 28 patients who had primary tumors remained ambulatory without supportive devices. CIRT appears to be both effective and safe for the treatment of patients with unresectable spinal sarcoma. Cancer 2013. © 2013 American Cancer Society.
    Cancer 08/2013; · 5.20 Impact Factor
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    ABSTRACT: To compare retrospectively outcome after photon radiotherapy alone, radiochemotherapy with temozolomide (TMZ), and carbon ion radiotherapy in patients with high-grade gliomas and to generate a hypothetical outcome curve for C12 and TMZ. Patients treated within a Phase I/II Trial with a carbon ion boost were compared retrospectively with randomly chosen patients treated with photons or photons in combination with TMZ in a retrospective analysis. Per treatment group, 16 patients with anaplastic astocytoma (AA), and 32 patients with glioblastoma (GBM) were included. Treatment outcome with focus on progression-free survival (PFS) and overall survival (OS) was analyzed. Median OS for patients with GBM was 9months with RT, 14months with RCHT group, and 18months in the C12 group. There was no significant difference between the C12 and the RCHT group. For patients with AA, median OS was 13months for RT, 39months for RCHT, and 35months after C12. The difference from RCHT to C12 was not significant. Median PFS for patients with GBM was 5months in the RT group, 6months in the RCHT group, and 8months in the C12 group. There was a significant difference between the RCHT group and the C12 group. For AA, median PFS was 15months with RT, 6months with RCHT, and 34 with C12. Comparing subgroups, C12 was significantly different from RCHT. Based on the significant OS increase from RT to RCHT, and from RT to C12, we projected the potential increase in outcome when combined C12 and TMZ would have been applied. A generated hypothetical curve based on the abovementioned outcome as well as preclinical examinations suggests there might be a benefit from the addition of C12 in patients with high-grade gliomas. This exploratory retrospective study suggests a potential benefit of carbon ions in patients with high-grade gliomas. This hypothesis is now being evaluated prospectively in GBM within the randomized CLEOPATRA clinical trial.
    Radiotherapy and Oncology 08/2013; · 4.52 Impact Factor
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    ABSTRACT: The prognosis of high-risk prostate cancer is poor with a high mortality rate. The Radiation Therapy Oncology Group (RTOG) has performed dose-escalation studies of external beam radiation therapy (EBRT) and has developed high-precision radiation therapy (RT) methods such as intensity-modulated RT, carbon ion therapy, and proton beam therapy. High-dose rate brachytherapy (HDR-BT) is also studied as an option for high-risk prostate cancer treatment. Past clinical trials have suggested that the local control rate of high-risk prostate cancer improves with total EBRT dose, even for doses >70Gy. Several randomized controlled trials, including RTOG 94-06, have shown significantly better prognoses with higher doses (>75Gy) than with lower doses (<70Gy). A proton beam therapy trial (PROG 95-09) also showed similar results. A phase II clinical trial (National Institute for Radiological Sciences, Japan; trial 9904) showed that carbon ion therapy resulted in very good biochemical recurrence-free survival rates among high-risk prostate cancer patients, demonstrating particle therapy to be a valid treatment option. RTOG 86-10 showed that short-term neo-adjuvant hormonal therapy (HT) was inadequate for high-risk prostate cancer but effective for intermediate-risk prostate cancer, whereas RTOG 92-02 and the European Organisation for Research and Treatment of Cancer (EORTC) 22863 showed significant improvements in the prognosis of high-risk groups receiving long-term (>2years) HT combined with definitive RT. Further studies are warranted to elucidate optimal irradiation doses, HT treatment durations, and combination therapy schedules.
    Cancer Treatment Reviews 05/2013; · 6.02 Impact Factor
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    ABSTRACT: AIM: Proton beam therapy is safe and more effective than conventional radiation therapy for the local control of nodular hepatocellular carcinoma (HCC). However, evaluating therapeutic response by imaging is not accurate during the early post-irradiation period. Therefore, we examined whether the histopathological study of biopsy specimens obtained at 3 weeks after irradiation can be used to more accurately assess therapeutic response. METHODS: Fifteen HCC lesions from 13 patients were treated with proton beam irradiation. Tissue biopsy samples were obtained using abdominal ultrasound-guided percutaneous fine-needle aspiration from the center of the tumor before, 3 weeks after and 1 year post-proton therapy. The specimens were examined after staining with hematoxylin/eosin (HE) and a MIB-1 antibody. RESULTS: MIB-1 labeling indices (LIs) before treatment were 13.0 ± 8.5% [0.6-27.0] (mean ± SD [range]), whereas those 3 weeks after proton therapy were significantly reduced to 3.2 ± 2.4% [0.6-8.9] (P<0.05). Although the tumor size was reduced, we did not observe a reduction in tumor blood flow by dynamic CT or degenerative changes by HE. All lesions that displayed reduced MIB-1 LIs at 3 weeks post-proton treatment were ultimately diagnosed as complete response at 1 year after treatment. In contrast, one case with increased MIB-1 LI at 3 weeks had significant tumor size progression at 1 year post-treatment. CONCLUSION: The percutaneous fine-needle aspiration biopsy of HCC is a safe and useful tool that can be used to evaluate the response to proton irradiation. In particular, MIB-1 LIs may provide additional information to assess the therapeutic response of HCC during the early post-irradiated period.
    Hepatology Research 04/2013; · 2.07 Impact Factor
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    ABSTRACT: SAGA HIMAT is now under construction in Tosu city, Saga prefecture, Kyushu island, Japan. It will open in 2013 and become the fourth carbon ion beam cancer therapy center in Japan. It is a collaborative project among the local governments, industries and universities in northern Kyushu area.
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    ABSTRACT: PURPOSE: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). METHODS AND MATERIALS: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. RESULTS: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. CONCLUSIONS: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.
    International journal of radiation oncology, biology, physics 02/2013; · 4.59 Impact Factor
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    ABSTRACT: The clinical results after carbon ion radiotherapy for the metastatic lung tumors believed to be in the state of oligo-recurrence were evaluated. One hundred and sixteen lesions in 91 patients with lung cancer metastasis were treated with carbon ion radiotherapy at our institute from April 1997 to February 2011. Regarding the prescribed dose, total dose ranged between 40 gray equivalents (GyE) and 80 GyE, and fraction size ranged from 1 to 16 fractions. After a median followup period of 2.3 years (range, 0.3-13.1 years), the statistical overall survival rate and local control rate were 71.2% and 91.9% at 2 years after treatment, respectively. Treatment-related side effects were not a clinical problem. When classified by the primary organ, there were 49 cases of lung cancer, 20 cases of colorectal cancer, and 22 cases of others. The overall survival rate and local control rate for lung metastasis cases from lung cancer at 2 years after treatment were 81.5% and 92.4%, respectively, and 65.0% and 92.0% regarding lung metastasis from colorectal cancer. Carbon ion beam therapy for the metastatic lung tumors is a safe therapy, and the therapeutic effect is comparable to the outcome obtained from reported surgical resections.
    Pulmonary medicine. 01/2013; 2013:219746.

Publication Stats

3k Citations
782.56 Total Impact Points


  • 1995–2014
    • National Institute of Radiological Sciences
      • Research Center for Charged Particle Therapy
      Tiba, Chiba, Japan
  • 2013
    • Saga University
      Сага Япония, Saga, Japan
    • Saitama Medical University
      Saitama, Saitama, Japan
  • 2012
    • University of Milan
      Milano, Lombardy, Italy
  • 2007–2012
    • Gunma University
      • Graduate School of Medicine
      Maebashi, Gunma Prefecture, Japan
    • Teikyo University Hospital
      Edo, Tōkyō, Japan
  • 1989–2012
    • University of Tsukuba
      • • Department of Radiation Oncology
      • • Institute of Clinical Medicine
      • • Department of Radiology
      • • Department of Neurosurgery
      • • Department of Urology
      Tsukuba, Ibaraki-ken, Japan
    • Hokkaido University Hospital
      • Department of Radiology
      Sapporo-shi, Hokkaido, Japan
  • 2009
    • National Institute of Mental Health (NIMH)
      Maryland, United States
  • 2001–2008
    • Chiba University
      • • Graduate School of Medicine
      • • Department of Neurological Surgery
      Chiba-shi, Chiba-ken, Japan
  • 2004
    • Tokyo Women's Medical University
      • Department of Cardiology
      Tokyo, Tokyo-to, Japan
  • 1994
    • Hokkaido University
      • Department of Radiobiology
      Sapporo-shi, Hokkaido, Japan