To evaluate the efficacy and safety of carbon-ion radiation therapy (RT) for mucosal melanoma of the head and neck (MMHN) in the Japan Carbon-Ion Radiation Oncology Study Group study. Patients with MMHN with N0-1M0 status who were treated with carbon-ion RT at 4 institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. Two hundred sixty patients (male, 111; female, 149; median age, 68 years) with histologically proven MMHN were enrolled. Primary sites included the nasal cavity in 178 patients, paranasal sinuses in 43, oral cavity in 27, and pharynx in 12. Eighty-six patients had T3 tumors, 147 had T4a tumors, and 27 had T4b tumors. Two hundred fifty-one patients were diagnosed with N0 disease, and 9 with N1 disease. The median total dose and number of fractions were 57.6 Gy RBE (relative biological effectiveness) and 16, respectively. Chemotherapy including dimethyl traizeno imidazole carboxamide was used concurrently in 129 patients. The median follow-up duration was 22 months (range, 1-132 months). The 2-year overall survival and local control rates were 69.4% and 83.9%, respectively. Multivariate analysis showed that gross tumor volume and concurrent chemotherapy were significant prognostic factors for overall survival. Grade 3 and grade 4 late morbidities were observed in 27 and 7 patients (5 developed ipsilateral blindness, 1 mucosal ulcer, and 1 second malignant disease in the irradiated volume), respectively. No patients developed grade 5 late morbidities. Carbon-ion RT is a promising treatment option for MMHN.

To evaluate the safety and efficacy of carbon-ion radiation therapy (C-ion RT) for locally advanced sinonasal malignant tumors in a multicenter retrospective study (J-CROS 1402 HN). Clinical data were collected for patients who had sinonasal malignant tumors of stage N0-1M0 and received C-ion RT at 4 institutions in Japan between November 2003 and December 2014. Of the 458 patients, 393 had naïve tumors and 65 had recurrent tumors. The tumors were located in the nasal cavity (n = 263), maxillary sinus (n = 109), ethmoid sinus (n = 71), and other locations (n = 15). The histologic types were mucosal melanoma (n = 221, 48%), adenoid cystic carcinoma (n = 122, 27%), squamous cell carcinoma (n = 31, 7%), olfactory neuroblastoma (n = 30, 7%), adenocarcinoma (n = 21, 5%), and other types (n = 33, 7%). Of the 458 patients, 300 (66%) had T4 tumors. All patients received definitive C-ion RT. The median follow-up period was 25.2 months for all patients (range, 1.4-132.3 months). The 2-year overall survival and local control rates were 79.6% and 84.1%, respectively. As analyzed according to histology, the 2-year overall survival rate was 68.0% for mucosal melanoma, 96.8% for adenoid cystic carcinoma, 70.0% for squamous cell carcinoma, 96.7% for olfactory neuroblastoma, and 89.7% for adenocarcinoma. Regarding late toxicities, 17% of patients developed grade 3 and 4 toxicities, of which visual impairment was the most common. The results of our multicenter study have demonstrated that C-ion RT can provide excellent clinical outcomes with acceptable late toxicities in patients who have locally advanced sinonasal malignant tumors.

Locoregional recurrence after carbon-ion radiotherapy (CIRT) for primary head and neck malignancies, such as malignant mucosal melanoma, adenoid cystic carcinoma, and sarcoma, occurs occasionally. However, the treatment options are limited. We report on the toxicity and efficacy of re-irradiation using carbon ions for recurrent head and neck malignancies after CIRT. Data of 48 patients with recurrent head and neck malignancies treated with re-irradiation with CIRT at our institution (2007-2016) were retrospectively analyzed. Twenty-one patients (43.8%) had malignant mucosal melanoma, 17 (35.4%) had adenoid cystic carcinoma, six (12.5%) had bone and soft tissue sarcomas, and four patients (8.3%) had other disease types. Tumor recurrences at re-irradiation were located in the paranasal cavity (n = 18, 37.5%), nasal cavity (n = 9, 18.8%), nasopharynx (n = 4, 8.3%), orbit (n = 3, 6.3%), cavernous sinus (n = 3, 6.3%), and at other sites (n = 11, 22.9%). The median dose of initial CIRT and that at re-irradiation were 57.6 Gy and 54.0 Gy (relative biological effectiveness [RBE]), respectively. None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 27.1 months. Five patients (10.4%) developed Grade 3 acute toxicities and 18 (37.5%) developed Grade ≥3 late toxicities, including Grade 5 central nervous system necrosis in one patient. The 2-year local control, locoregional control, progression-free survival, and overall survival rates were 40.5, 33.5%, 29.4%, and 59.6%, respectively. Re-irradiation using carbon ions may be a reasonable treatment option with tolerable toxicity for patients with recurrent head and neck malignancies after CIRT.

A retrospective multicenter study was carried out 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 four 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, seven patients had grade 3 mucositis and seven had grade 3 dermatitis. Regarding late toxicities, one patient had grade 3 dysphagia and one 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.

Oral mucosal malignant melanoma (OMM) is extremely rare and has a poor prognosis. Owing to its rarity, it has not yet been possible to establish an optimal treatment modality. The objective of this study was to evaluate the long-term efficacy of carbon-ion radiotherapy (C-ion RT) for OMM. Between 1997 and 2013, 19 patients with OMM were treated with C-ion RT alone. Patient ages ranged from 44 to 84 years (median, 69 years). Nine men and 10 women were included. OMMs were restaged in accordance with the seventh edition of the tumour/node/metastasis (TNM) Staging System of the International Union Against Cancer. Before treatment, 14 patients had T3 disease and 5 had T4a disease. Three patients were classified as having N1 disease. All patients were classified as having M0. The hard palate was the most frequently involved oral subsite. All patients were treated with 57.6 Gy (relative biological effectiveness) in 16 fractions. The median follow-up period was 61 months (range, 8–190 months). The 5-year local control, overall survival and progression-free survival rates were 89.5%, 57.4% and 51.6%, respectively. For local control and overall survival, T classification was found to be a significant prognostic factor. Grade 2 and 3 osteoradionecrosis was observed in three and four patients, respectively. The presence of teeth within the planning target volume was a significant risk factor for developing osteoradionecrosis. C-ion RT was an effective treatment option with acceptable toxicity for OMM.