Hypofractionated Carbon-Ion Radiation Therapy for Mucosal Malignant Melanoma in Head and Neck

Abstract

Mucosal malignant melanoma (MMM) in the head and neck is radio-resistant tumor, and carbon-ion radiotherapy (CIRT) is expected to overcome this refractory disease. We retrospectively evaluated the efficacy and safety of hypofractionated CIRT with or without DAV therapy (DTIC, ACNU, and VCR) for MMM patients. Between June 2011 and December 2016, 43 MMM patients were treated by CIRT. Median age was 71 years old (range: 32-91) and number of male patients was 23 (53%). T3/ T4a/ T4b diseases were 1/ 36/ 6, respectively, and all were N0M0. Nasal cavity tumors were observed in 35 patients (81%). All patients were treated using 16 fractions over 4 weeks. Thirty-nine patients received 64.0 Gy (relative biological effectiveness [RBE]) in and 4 patients received 57.6 Gy (RBE). Concurrent DAV therapy was used in 25 patients (58%) if patient met with our eligibility criteria; age ≦80, no severe liver and renal dysfunctions, and PS ≦2. Local control, progression free survival (PFS), and overall survival (OS) rates were statistically calculated by the Kaplan-Meier method and log-rank tests. A P value < 0.05 was defined as a statistical significance. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. This study was reviewed and approved by our Institutional Review Board. The median follow-up time for surviving patients was 26 months. Four patients developed local recurrence and the 2-year local control rate was 88%. There was not significant difference of local control rate irrespective of the use of DAV therapy (P = 0.58). During the follow-up, 21 patients died and the 2-year OS rate was 63%. The addition of DAV therapy was not prognostic factor for OS (P = 0.24). Lymph node and distant metastases were observed in 2 and 21 patients, and the 2-year PFS were 32%. Concurrent CIRT with DAV therapy had significantly better PFS than CIRT alone (P = 0.04), and the 2-year PFS rates were 40% and 20%, respectively. Acute grade ≧2 mucositis and dermatitis were 74% and 44%, which improved immediately with conservative therapy. Late grade ≧2 mucositis and dermatitis were 23% and 3%. There were no significant differences of the non-hematologic adverse event rates between CIRT with and without DAV therapy. Concurrent CIRT with DAV therapy developed higher rates of grade ≧2 hematologic adverse events than those of CIRT alone; leukopenia was 52% vs. 11% (P = 0.03), anemia was 12% vs. 0% (P = 0.08), thrombocytopenia was 40% vs. 0% (P = 0.01), respectively. Hypofractionated CIRT contributed to the excellent local control with tolerable toxicities for MMM in the head and neck. Concurrent CIRT with DAV therapy showed the better PFS than CIRT alone, and long-term observation will be necessary to confirm its significance. The addition of DAV therapy was associated with the hematologic adverse events, but not with the radiation-related mucositis and dermatitis.