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Efficacy and safety of carbon-ion radiotherapy (CIRT) for locally advanced non-small-cell lung cancer (LA-NSCLC) remain unclear. We reported the clinical outcomes of CIRT for LA-NSCLC. Data of 141 eligible patients who received CIRT between 1995 and 2015 were retrospectively analyzed. Local control (LC), locoregional control (LRC), progression-free survival (PFS), and OS were calculated using Kaplan-Meier method. The median age was 75.0 years. Overall, 21, (14.9%), 57 (40.4%), 43 (30.5%), and 20 (14.2%) patients had T1, T2, T3, and T4 disease, respectively. Moreover, 51 (36.2%), 45 (31.9%), 40 (28.4%), and 5 (3.5%) patients had N0, N1, N2, and N3 disease, respectively. Furthermore, 34 (24.1%), 42 (29.8%), 45 (31.9%), and 20 (14.2%) patients had stages IIA, IIB, IIIA, and ΙΙΙB disease, respectively. Overall, 62 (44.0%), 60 (42.6%), 8 (5.7%), and 11 (7.8%) patients had adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and others, respectively. The median dose was 72.0 Gy (relative biological effectiveness). No patient received concurrent chemotherapy. Median follow-up periods were 29.3 (1.6-207.7) and 40.0 (10.7-207.7) months for all patients and survivors, respectively. Two-year LC, PFS, and OS rates were 80.3%, 40.2%, and 58.7%, respectively. Overall, 1 (0.7%), 5 (3.5%), and 1 (0.7%) patient developed Grades 4 (mediastinal hemorrhage), 3 (radiation pneumonitis), and 3 (bronchial fistula) toxicities, respectively. Multivariate analysis showed adenocarcinoma and N2/3 classification as significant poor prognosticators of PFS. CIRT is an effective treatment with acceptable toxicity for LA-NSCLC, especially for elderly patients or patients with severe comorbidities who cannot be treated with surgery or chemoradiotherapy. This article is protected by copyright. All rights reserved.

Prognosis is usually grim for those who cannot receive resection with liver metastasis from colorectal cancer (CRC). Radiation therapy can be an option for those unsuitable for resection, and carbon-ion radiotherapy (CIRT) would be expected higher effective and less toxic than X-ray due to its physio-biological characteristics. The objective of this study is to identify the optimal dose of single fraction CIRT for colorectal cancer liver metastasis. Thirty-one patients with liver metastasis from CRC were enrolled. Twenty-nine patients received a single-fraction CIRT, escalating dose from 36 Gy (RBE) in 5 to 10% increments until unacceptable incidence of dose-limiting toxicity is observed. Dose-limiting toxicity was defined as grade ≥ 3 acute toxicity attributed to radiotherapy. The prescribed doses were: 36 Gy (RBE) (3 cases), 40 (2), 44 (4), 46 (6), 48 (3), 53 (8), and 58 (3). Dose-limiting toxicity was not observed but late grade 3 liver toxicity due to biliary obstruction was observed in 2 patients at 53 Gy (RBE). Both cases had lesions close to the hepatic portal region, and therefore dose was escalated to 58 Gy (RBE) limited to peripheral lesions. Three-year actuarial overall survival rate of all 29 patients was 78%, and median survival time was 65 months. Local control improved significantly at ≥53 Gy (RBE), with 3-year actuarial local control rate of 82%, compared to 28% in lower doses. Treatment for CRC liver metastasis with single-fraction CIRT appeared to be safe up to 58Gy (RBE) as long as the central hepatic portal region is avoided. This article is protected by copyright. All rights reserved.

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.

Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors.

A retrospective multicenter study was conducted to assess the clinical outcomes of carbon-ion radiotherapy for head and neck malignancies (Japan Carbon-Ion Radiation Oncology Study Group [J-CROS] study: 1402 HN). We evaluated the safety and efficacy of carbon-ion radiotherapy in patients with major salivary gland carcinoma. Sixty-nine patients treated with carbon-ion radiotherapy at 4 Japanese institutions were analyzed. Thirty-three patients (48%) had adenoid cystic carcinomas, 10 (14%) had mucoepidermoid carcinomas, and 26 (38%) had other disease types. Three patients (4%) had T1 disease, 8 (12%) had T2, 25 (36%) had T3, and 33 (48%) had T4. The median radiation dose was 64 Gy (relative biological effectiveness) in 16 fractions. The median gross tumor volume was 27 mL. The median follow-up period was 32.7 months. The 3-year local control rate and overall survival rate were 81% and 94%, respectively. Regarding acute toxicities, 7 patients had grade 3 mucositis and 7 had grade 3 dermatitis. Regarding late toxicities, 1 patient had grade 3 dysphagia and 1 had a grade 3 brain abscess. No grade 4 or worse late reactions were observed. In conclusion, definitive carbon-ion radiotherapy was effective with acceptable toxicity for major salivary gland carcinomas.

Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 (211At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that 211At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test a-particle radioimmunotherapy with 211At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of 211At-trastuzumab (1 MBq) was a more efficient means of delivery of 211At into metastatic tumors than i.v.injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of 211At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA doublestrand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered 211At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with 211At-trastuzumab may offer a new treatment option for HER2-positive PMGC.