Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy for head-and-neck cancer in a Phase I/II dose escalation clinical trial.
Methods and materials: Between June 1994 and January 1997, 36 patients with locally advanced, histologically proven, and new or recurrent cancer of the head and neck were treated with carbon ions. A dose escalation study was conducted, delivering 18 fractions through 6 weeks for 17 patients (Group A) and 16 fractions through 4 weeks for 19 patients (Group B). Eligibility and ineligibility criteria were the same in both groups. The dosages were escalated in increments of 10% after careful observation of at least 3 patients treated with the same dosages. The endpoints of the study were a Grade 3 reaction of the skin and the mucous membrane or local control of the tumors.
Results: Follow-up time ranged from 77 to 108 months with a median of 90 months. Grade 3 acute reaction of the skin was detected in 1 of the 2 patients in Group A who were treated with 70.2 GyE/18 fractions/6 weeks. In Group B, Grade 3 acute skin reaction was detected in 20% (1/5), 27% (2/11), and 67% (2/3) patients treated with 52.8 GyE, 57.6 GyE, and 64.0 GyE through 16 fractions for 4 weeks, respectively. There was only 1 patient with a Grade 3 acute reaction of the mucous membrane. Only 1 patient developed a Grade 2 late reaction of the mucous membrane (superficial ulcer), which was located close to the tumor. No other Grade 2 or greater late reaction was noted until the time of analysis. Acute tumor reactions in 34 patients consisted of 10 patients of complete response 19 of partial response, 4 of no change, and 1 of progressive disease. Local control of 34 patients calculated by the Kaplan-Meier method was 75% at 5 years. Five years' local control of five malignant melanomas showed 100%, and that of 9 patients with adenoid cystic carcinoma was 90%. Also, local control of 8 patients of salivary glands and 4 patients of ears was 100% at 56 months and 5 years.
Conclusions: The dose fractionation methods of 70.2 GyE through 18 fractions for 6 weeks and 64.0 GyE through 16 fractions for 4 weeks showed equal clinical outcome in terms of morbidity and local control. The outcome of carbon ion radiotherapy showed a specific effectiveness in local control of non-squamous cell carcinoma such as adenoid cystic carcinomas and malignant melanomas. From the results of this study, it can be concluded that carbon ion radiotherapy will deliver a high local control rate without unacceptable injuries to the surrounding normal tissues.