Dose escalation study of carbon ion radiotherapy for locally advanced head-and-neck cancer

To evaluate the toxicity and efficacy of carbon ion radiotherapy for head-and-neck cancer in a Phase I/II dose escalation clinical trial.

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.

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.

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.