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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. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the applicability of carbon ion beams for the treatment of carcinoma of the lacrimal gland with regard to normal tissue morbidity and local tumor control. Methods and materials Between April 2002 and January 2011, 21 patients with locally advanced primary epithelial carcinoma of the lacrimal gland were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy (CIRT) at the National Institute of Radiological Sciences. Acute radiation toxicity was the primary endpoint of this dose-escalation study and the late toxicity, local control, and overall survival were additionally evaluated as secondary endpoints. Of the 21 subjects enrolled, all patients were followed for more than 6 months and analyzed. Results The radiation dose was increased from the initial dose of 48.0 Gy equivalents (GyE)/12 fractions at 10% increments up to 52.8 GyE. Of the 21 patients, five received a total dose of 48.0 GyE, and 16 received a total dose of 52.8 GyE. No patient developed grade 3 or higher skin toxicity. As late ocular/visual toxicity, three patients had grade 3 retinopathy and seven patients lost their vision. Among the 10 patients treated until May 2005, five patients had local recurrence, three of whom had marginal recurrence. Therefore, the margin for the CTV (clinical target volume) was set to a range according to the orbital exenteration since June 2005. After the application of the extended margin, no local recurrence has been observed. The three-year overall survival and local control rates were 82.2% and 79.0%, respectively. Conclusion CIRT can be applied for primary epithelial carcinoma of the lacrimal gland, with a borderline acceptable morbidity and sufficient antitumor effect when an extended margin is adopted. [ABSTRACT FROM AUTHOR]

Background & Aims: Carbon‐ion radiation therapy has shown encouraging results in hepatocellular carcinoma patients in single‐centre studies. We evaluated the effectiveness and safety of short‐course carbon‐ion radiation therapy for hepatocellular carcinoma in a multicentre study conducted by the Japan Carbon Ion Radiation Oncology Study Group. Methods: Consecutive hepatocellular carcinoma patients who were treated with carbon‐ion radiation therapy in four or fewer fractions at four Japanese institutions between April 2005 and November 2014 were analysed retrospectively. The primary outcome was overall survival; secondary outcomes were local control rate, treatment‐related toxicity and radiation‐induced liver disease. Results: A total of 174 patients were included in this study. Prescribed carbon‐ion radiation therapy doses were (relative biological effectiveness): 48.0 Gy in two fractions (n = 46), and 52.8 Gy (n = 108) and 60.0 Gy (n = 20) in four fractions. The median follow‐up period was 20.3 (range, 2.9‐103.5) months. The overall survival and local control rates at 1, 2 and 3 years were 95.4%, 82.5% and 73.3%; and 94.6%, 87.7% and 81.0% respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status 1‐2, Child‐Pugh class B, maximum tumour diameter ≥3 cm, multiple tumours and serum alpha foetoprotein level >50 ng/mL were significant prognostic factors of overall survival. No treatment‐related death occurred during the follow‐up period. Grades 3 or 4 treatment‐related toxicities were observed in 10 patients (5.7%); radiation‐induced liver disease was observed in three patients (1.7%). Conclusions: Short‐course carbon‐ion radiation therapy is a safe, effective and potentially curative therapy for hepatocellular carcinoma. See Editorial on Page 2132 [ABSTRACT FROM AUTHOR]

Highlights • We analyzed 64 LAPC patients treated with C-ion RT at single institution. • The median survival time and 2-year OS were 25.1 months and 53%. • Only four patients experienced acute grade 3 toxicities. • C-ion RT for LAPC showed relatively favorable outcome and limited toxicity. Abstract Purpose The aim of this study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for unresectable locally advanced pancreatic cancer (LAPC). Methods and materials Patients with LAPC treated with definitive C-ion RT between April 2014 and July 2017 were analyzed retrospectively. The prescribed dose was 55.2 Gy (relative biological effectiveness [RBE] weighted absorbed dose) in 12 fractions. Overall survival (OS), local control (LC), progression free survival (PFS), and toxicity were evaluated. Results Sixty-four patients were enrolled. All patients completed planned course of C-ion RT. The median follow-up time for survivors from the initiation of C-ion RT was 24.4 months (range, 5.1–46.1 months). Median survival time was 25.1 months. Two-year OS, LC, and PFS were 53% (95% confidence interval [CI], 39%–66%), 82% (95% CI, 66%–91%), and 23% (95% CI, 14%–36%), respectively. Four patients experienced acute grade 3 toxicities including 3 gastrointestinal (GI) toxicities. There was no grade 3 or more late toxicity. Conclusions The clinical results of C-ion RT for LAPC at our institution were comparable to those of a recent multi-institutional analysis. [ABSTRACT FROM AUTHOR]

Background and purpose A multi-institutional observational study (J-CROS1501PR) has been carried out to analyze outcomes of carbon-ion radiotherapy (CIRT) for patients with prostate cancer. Patients and methods Data of the patients enrolled in prospective studies of following 3 CIRT institutions were analyzed: National Institute of Radiological Sciences (NIRS; Chiba, Japan), Gunma University Heavy Ion Medical Center (GHMC; Gunma, Japan), and Ion Beam Therapy Center, SAGA HIMAT Foundation (HIMAT; Saga, Japan). Endpoints of the clinical trial are biochemical recurrence-free survival (bRFS), overall survival (OS), cause-specific survival (CSS), local control rate (LCR), and acute/late adverse effects. Results A total of 2157 patients’ data were collected from NIRS ( n = 1432), GHMC ( n = 515), and HIMAT ( n = 210). The number of patients in low-risk, intermediate-risk, and high-risk groups was 263 (12%), 679 (31%), and 1215 (56%), respectively. The five-year bRFS in low-risk, intermediate-risk, and high-risk patients was 92%, 89%, and 92%, respectively. The five-year CSS in low-risk, intermediate-risk, and high-risk patients was 100%, 100%, and 99%, respectively. The incidence of grade 2 late GU/GI toxicities was 4.6% and 0.4%, respectively, and the incidence of ⩾G3 toxicities were 0%. Conclusions Favorable overall outcomes of CIRT for prostate cancer were suggested by the analysis of the first multi-institutional data. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to clarify the incidence, clinical risk factors, and dose–volume relationship of upper gastrointestinal (GI) ulcer after carbon-ion radiotherapy (C-ion RT) for pancreatic cancer. Materials and methods Fifty-eight pancreatic cancer patients were treated with C-ion RT from April 2014 to December 2015. The total dose was 55.2 Gy (RBE) in 12 fractions. D 2cm3 of GI tracts were restricted under 46 Gy (RBE); RBE-weighted absorbed dose. The association between dosimetric parameters (V 10–50 , D max , D 1cm3 , D 2cm3 ) and GI ulcer was examined using Spearman’s correlation. The incidence of GI ulcer was compared between the two groups divided by the cutoff value. Results Twelve patients (21%) experienced gastric ulcer including only one (2%) grade 3 ulcer. There was no grade 4/5 toxicity or duodenal ulcer. V 10–30 was significantly associated with gastric ulcer. The 1-year estimated risk of gastric ulcer for the determined cutoff values were 51% vs. 10% (V 10 , ⩾102 cm 3 or less), 42% vs. 9% (V 20 , ⩾24 cm 3 or less), 34% vs. 4% (V 30 , ⩾6 cm 3 or less). Conclusions The incidence of GI ulcer after C-ion RT was very low with the dose constraint of D 2cm3 <46 Gy (RBE). To further minimize the risk of GI ulcer, V 10–30 should also be reduced. [ABSTRACT FROM AUTHOR]

Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy. [ABSTRACT FROM AUTHOR]