Search

The long-term oncologic outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12/16-fraction CIRT at our institution outside of clinical trials. The outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. The diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In four of five patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney, or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although one case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. The local control rate, and disease-free, cancer-specific, and overall survival rates at 5- years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yielding favorable treatment outcomes, even in inoperable cases. This article is protected by copyright. All rights reserved.

The aim of this study was to prospectively assess 5-year health-related quality of life (HRQOL) of patients treated with carbon ion radiotherapy (C-ion RT) for clinically localized prostate cancer. A total of 417 patients received carbon ion radiotherapy at a total dose of 63-66 Gray-equivalents (GyE) in 20 fractions over 5 weeks, and neoadjuvant and adjuvant androgen deprivation therapy (ADT) were administered for intermediate and high-risk patients. A HRQOL assessment was performed at five time points (immediately before the initiation of C-ion RT, immediately after, and at 12, 36 and 60 months after completion of C-ion RT) using Functional Assessment of Cancer Therapy (FACT) questionnaires. FACT-G and FACT-P scores were significantly decreased; however, the absolute change after 60 months was minimal. The transient decreases in the Trial Outcome Index (TOI) score returned to their baseline levels. Use of ADT, presence of adverse events, and biochemical failure were related to lower scores. Scores of subdomains of FACT instruments indicated characteristic changes. The pattern of HRQOL change after C-ion RT was similar to that of other modalities. Further controlled studies focusing on a HRQOL in patients with prostate cancer are warranted.

BACKGROUND: Whether biochemical recurrence (BR) is a significant predictive factor of mortality after definitive radiation therapy for prostate cancer remains unknown. The aim of the current study was to investigate the relation between BR and overall mortality (OAM) in high-risk prostate cancer patients who were treated with carbon-ion radiotherapy (CIRT) and had long-term follow-up in 2 prospective trials. METHODS: In the 2 phase 2 clinical trials, which involved 466 prostate cancer patients who received 63.0 to 66.0 Gy of CIRT (relative biological effect) in 20 fractions between 2000 and 2007, 324 patients who were deemed to be at high risk on the basis of the modified D'Amico classification criteria and received CIRT along with androgen-deprivation therapy (ADT) were examined. The OAM rate was adjusted for the ADT duration, and multivariate analyses using a Cox proportional hazards model were performed for OAM with BR as a time-dependent covariate. RESULTS: The median follow-up period was 107.4 months, and the 5- and 10-year OAM rates after adjustments for the ADT duration were 7.0% (95% confidence interval [CI], 4.0%-9.4%) and 23.9% (95% CI, 16.4%-26.2%), respectively. A multivariate analysis revealed that the presence of BR (hazard ratio, 2.82; 95% Cl, 1.57-5.08; P = .001) was one of the predictive factors for OAM. On the other hand, the duration of ADT had no impact on OAM. CONCLUSIONS: BR after CIRT combined with ADT is an independent predictive factor for OAM in high-risk prostate cancer patients. The results of this study could be applied to other high-dose radiation therapies. Cancer 2016. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Purpose: To determine the prognostic factors for biochemical recurrence (BR) and mortality in patients with high-risk localized prostate cancer after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT). Methods and Materials: A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding T4 disease, 614 patients received CIRT combined with LTADT for high- or very-high-risk disease, according to the National Comprehensive Cancer Network (NCCN) classification system. Results: Median follow-up time was 78.7 months, and 5-year rates of BR-free, prostate cancer-specific survival, and overall survival were 90.4% (95% confidence interval [CI]: 87.6 - 92.7), 98.5% (95% CI: 97.2 - 99.2), and 94.7% (95% CI: 92.8 - 96.5), respectively. T3a/b disease, Gleason score (GS) 9-10, percentage of positive biopsy cores (PPCs) > 75%, and age > 75 years had a significant impact on BR. Moreover, patients with T3b disease, GS 9-10, and PPCs > 75% had significantly higher prostate cancer-specific mortality (p = 0.007, p = 0.009, and p = 0.015, respectively) and overall mortality (p = 0.035, p = 0.025, and p < 0.001, respectively), on multivariate analyses. Conclusions: Prognostic factors for BR and mortality were identified. Patients with T3b disease, GS 9-10, and PPCs > 75% should be considered to have very-high-risk disease requiring a new treatment strategy., the 56th Annual Conference of the Particle Therapy Co-operative Group (PTCOG56)

： A clinical trial of carbon ion radiotherapy (C-ion RT) for prostate cancer was started in 1995 at the National Institute of Radiological Sciences (NIRS), taking advantage of the quality of carbon ion beams to distinguish dose concentrations and establish a high anticancer efficacy. First, two phase I/II dose escalation studies with a fractionation of 20 fractions over five weeks were conducted to establish techniques using carbon ion beams to determine the optimal dose of fractionation. Then, a phase II study of 20 fractions was performed to validate the feasibility and efficacy of C-ion RT delivered in 20 fractions, which was successfully completed in 2003. Thereafter, a study of hypofractionated C-ion RT in16 fractions over four weeks was performed. Consequently, the incidence of late radiation toxicity decreased without an increase in tumor recurrence. Currently, hypofractionated radiotherapy in 12 fractions over three weeks with scanning irradiation is being evaluated in clinical practice. Up to February 2013, 1,733 patients underwent C-ion RT, including 552 patients treated with 20 fractions, 1,107 patients treated with 16 fractions, and 64 patients treated with 12 fractions. Of these patients, 53% were categorized as high-risk. The five-year overall survival rate and biochemical relapse-free rate in the entire group were 95.1% and 90.7%, respectively. All risk factors had a significant influence on both biochemical control and patient survival. Biochemical control was not affected by the alteration of dose fractionation; however, the incidence of late radiation toxicity decreased in association with a decrease in the fraction number.

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).

BACKGROUND: To clarify how a multidisciplinary cancer board (CB) influences treatment decisions. \nMETHODS: From March 2010 to June 2011, a total of 475 cases were discussed at our CB and the minutes of the board were reviewed for this study. \nRESULTS: Of the 475 patients, minor changes in treatment methods were made in 42 patients (9 %) and major changes were made in 28 patients (6 %). Further diagnostic procedures, further publication surveys and reconfirmation of patient's wishes were recommended in 80 patients (17 %). In the 392 patients for whom treatment was recommended, the CB's recommendation was realized in 349 patients (89 %) and was not realized in 20 (5 %) patients. \nCONCLUSIONS: It is obvious that a CB has a great influence on cancer treatment decisions, but the effectiveness of the CB in our hospital should be verified in the future by analyzing treatment outcomes.

BACKGROUND: The purpose of this phase I trial of S-1 chemotherapy in combination with pelvic radiotherapy for locally recurrent rectal cancer was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of S-1. \nMETHODS: We enrolled 9 patients between April 2005 and March 2009. Radiotherapy (total dose, 60 Gy in 30 fractions) was given to the gross local recurrent tumor and pelvic nodal metastases using three-dimensional radiotherapy planning. We administered oral S-1 twice a day on days 1-14 and 22-35 during radiotherapy. The dose of S-1 was initially 60 mg/m(2)/day and was increased to determine the MTD and RD for this regimen. \nRESULTS: DLT appeared at dose level 2 (70 mg/m(2)/day) in 2 patients, who experienced grade 3 enterocolitis and consequently required suspension of S-1 administration for longer than 2 weeks. Hematological toxicity was mild and reversible. At the initial evaluation, complete regression and partial regression were seen in 1 patient (11%) and 2 patients (22%), respectively. \nCONCLUSION: This phase I trial of S-1 chemotherapy with pelvic radiotherapy for locally recurrent rectal cancer revealed that the MTD for S-1 was 70 mg/m(2)/day and the RD was 60 mg/m(2)/day.

PURPOSE: Renal cell carcinoma (RCC) is known as a radioresistant tumor, and there are few reports on radiotherapy for primary RCC. We evaluated the efficacy of carbon ion radiotherapy (CIRT) for patients with RCC. METHODS AND MATERIALS: Data for patients with RCC who received CIRT were analyzed. A median total dose of 72 GyE (gray equivalents) in 16 fractions was administered without any additional treatment. Clinical stage was determined based on TNM classification by the International Union Against Cancer (UICC). Local recurrence was defined as definite tumor regrowth after treatment. RESULTS: Data for 10 patients were included in the analyses, including 7 patients with Stage I and 3 patients with Stage IV (T4NxM0 or TxN2M0) disease. The median maximum diameter of the tumor was 43 mm (24-120 mm). The median follow-up for surviving patients was 57.5 months (9-111 months). The 5-year local control rate, progression-free survival rate, cause-specific survival rate, and overall survival rates were 100%, 100%, 100%, and 74%, respectively. Interestingly, treated tumors showed very slow shrinkage, and the tumor in 1 case has been shrinking for 9 years. One patient with muscular invasion (T4 tumor) developed Grade 4 skin toxicity, but no other toxicity greater than Grade 2 was observed. CONCLUSIONS: This is one of the few reports on curative radiotherapy for primary RCC. The response of the tumor to treatment was uncommon. However despite inclusion of T4 and massive tumors, favorable local controllability has been shown. The results indicate the possibility of radical CIRT, as well as surgery, for RCC.

NIRS-CNAO Joint Symposium on Carbon Ion Radiotherapy

Background: The carbon ion radiotherapy (C-ion RT) for the 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 fractionation established by the phase I/II studies. This study was also successfully completed in October 2003 when the C-ion RT for the solid tumors including the prostate cancer was approved as ,Advanced Medicine, from the Ministry of Health, Labor, and Welfare. Materials and methods: A phase II study of C-ion RT (9904[1]-[3]) for localized prostate cancer (T1b-T3bN0M0) was started from April 2000. A C-ion RT schedule of 66.0GyE/20fr./5weeks, 63.0GyE/20fr./5w and 57.6GyE/16fr./4w were used in 9904[1], 9904[2] and 9904[3] trials, respectively. The patients with low-risk prostate cancer were treated with C-ion RT alone, and the patients with intermediate-risk and high-risk prostate cancer were treated with C-ion RT combined with hormonal therapy of 6 months and >24 months, respectively. Biochemical failure was defined as PSA increase of 2.0ng/ml above nadir after the treatment. Results: A total of 1,144 patients were enrolled to the clinical study. Out of 1,144 patients, more than 50% patients were categorized as high-risk group with T3 clinical stage, Gleason,s score of 8 or higher, or PSA of 20 or higher. The 5-year overall survival rate and biochemical relapse free rate of the entire group was 95.7% and 91.0%, respectively. Biochemical relapse free rates of low-, intermediate- and high-risk patients were 90.1%, 94.2% and 89.7%, respectively. T-stage, Gleason score was 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, incidence of rectal toxicity of grade 2 or worse was 1.1% and that of genitourinary toxicity was 6.5%, respectively. In addition, incidence of the toxicity in the patients treated with more hypofractionated C-ion RT of 16 fractions over 4 weeks were lower than those of 20 fraction-treatment. Conclusions: These favorable outcomes can be thought as apparent evidence of physical and biological advantages of the hypofractionated C-ion RT., The 17th ECCO- 38th ESMO- 32nd ESTRO European Cancer Congress

The 17th ECCO- 38th ESMO- 32nd ESTRO European Cancer Congress

The carbon ion radiotherapy (C-ion RT) for the 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 fractionation established by the phase I/II studies. This study was also successfully completed in October 2003 when the C-ion RT for the solid tumors including the prostate cancer was approved as'Advanced Medicine'from the Ministry of Health, Labor, and Welfare. Since then more than 1,400 patients have treated with carbon-ion radiotherapy as of February 2012 and advancement of hypofractionation has been also achieved. In this paper, treatment outcomes in 1,144 patients who underwent the established C-ion RT between April 2000 and July 2012 were analyzed. Out of 1,144 patients, more than 50% patients were categorized as high-risk group with T3 clinical stage, Gleason's score of 8 or higher, or PSA of 20 or higher. The 5-year overall survival rate and biochemical relapse free rate of the entire group was 95.7% and 91.0%, respectively. T-stage, Gleason score was 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, incidence of rectal toxicity of grade 2 or worse was 1.1% and that of genitourinary toxicity was 6.5%, respectively. In addition, incidence of the toxicity in the patients treated with more hypofractionated C-ion RT of 16 fractions over 4 weeks were 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., Heavy Ion in Therapy and Space Radiation Symposium 2013(HITSRS2013)

NIRS-Mayo Clinic Joint Symposium 2013 on Carbon Ion Therapy

Purpose: The aim of this study was to evaluate intrafractional target motion under respiratory gating with the device "Abches". Methods: (A) Patients with lung cancer were performed computed tomography (CT) for radiotherapy planning (RTP) using respiratory gating system. RTP-CT were performed 5 times, continuously, and 3 dimentional errors of the target (lung tumor = GTV: gross tumor volume) motion were measured. (B) Cone Beam CT was performed for 5 times per day and was performed 5 days during clinical treatment. Distances from tumor edge to the calculated ITV (internal target volume) margin were measured and analysed. Results: Five patients with lung tumor were analyzed in this study. (A) The errors (1.96SD) of anterior, posterior, left, right, superior and inferior directions were2.5,2.6,2.2,1.1,3.6 and 2.1 mm, respectively. (B) The errors (mean 1.65SD) of distances from tumor edge to the calculated ITV (internal target volume) margin [anterior, posterior, left, right, superior and inferior] were 2.7, 0.2, 2.4, 2.7, 4.5 and 2.7 mm, respectively. Conclusion: Respiratory target motion was well reduced by the respiratory gating system "Abches". Five millimeter of ITV margins were seemed to be sufficient (includes 95% data) in the A-P and L-R directions, and 7 mm of ITV margins were seemed sufficient in the S-I direction. Five millimeter of planning target volume (PTV) margin were seemed to be sufficient in the A-P and L-R directions, and 7 mm margin was sufficient for PTV margin in S-I directions. Further study is needed., The 6th S. Takahashi Memorial Symposium & The 6th Japan-US Cancer Therapy international Joint Symposium

1. Introduction The NIRS has been challenging the prostate cancer treatment from June 1995 taking the advantage of the quality of carbon ion beam which has distinguished dose convergence and high anticancer efficacy. The safety and efficacy of C-ion RT was confirmed with clinical studies, and government approval for its use as an advanced medicine was obtained in November 2003. 2. Materials and methods A total of 1,593 prostate cancer patients have received carbon ion radiotherapy from the start of clinical trial to July 2012. We treated 96 cases in the early dose escalation trials, 175 cases in the phase II clinical trial, thereafter 1,322 cases were treated. The annual cases are gradually increasing, especially greatly increased in 2003 when we gained the government approval of advanced medicine and in 2007 when we shortened the therapy term from 20 fractions in 5 weeks to 16 fractions in 4 weeks. When we started the phase II study, the irradiated dose was fixed at 63.0GyE or 66.0GyE/20fractions as the recommended dose fractionation schedule established in the two previous phase I/II studies. In addition, more hypofractionated schedule of 57.6GyE/16fractionas was applied since September 2007. Furthermore, a new clinical trial of C-ion RT of 12 fractions over 3 weeks was also conducted in 2010. In the near future all prostate cancer patients will be treated with 12-fraction carbon ion therapy. 3. Results As for the treatment morbidity, in the lower urinary tract, the incidence of grade 2 or worse late toxicity was approximately the same in 63.0GyE/20fractions carbon ion radiotherapy, intensity modulated radiation therapy and proton, which is interesting that it shows that this dose has comparable impact against lower urinary tract tissues. While for the 57.6GyE/16 fractions, the lowering of incidence was realized as a real outcome for shortening the treatment term. As for the rectal toxicity, even 63.0GyE showed lower rate than X-ray or proton, this is thought to be the proof of eminent dose convergence of carbon ion beam. In addition, 57.6GyE gained further lowering. Adding shortening to the high dose convergence, significant reduction of toxicity was obtained. Regarding the antitumor effect, especially in the high-risk groups, high survival rate was gained. It is caused by the carbon ion's excellent curative effect along with the distinguished treatment strategy. There was no difference in relapse-free rate and survival rate between 20 fractions and 16 fractions, while the result showed that the toxicity was less in 16 fractions. Therefore reducing the fractions to 16 made it possible to achieve not only the improvement of efficiency but also the improvement of outcome from therapy. Recently the pencil beam scanning irradiation has become available. Comparing the dose-volume of the rectum with scanning irradiation to that of passive irradiation in the treatment of prostate cancer, better rectum sparing can be obtained with scanning , though the difference is not large. Therefore, scanning irradiation was started to apply to the prostate cancer patients and will be applied to all the prostate cancer in the near future., MMND & IPCT Workshop