Dose Escalation study of Carbon Ion Radiotherapy for Locally Advanced Carcinoma of the Uterine Cervix

Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had stage IIIB disease and 14 patients had stage IVA disease. Median tumor size was 6.5 cm (4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalent (GyE) (2.2 to 3.0 GyE/fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose: 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were over 60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rates for patients in the first and second studies were 45% and 79%, respectively. When treated with 62.4 GyE or more, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors > 6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to less than 60 GyE to avoid major complications. Although the number of patients was small, the results supported the continued investigation to confirm therapeutic efficacy.