2008 Volume 17 Issue 6 Pages 440-448
Purpose: To report the preliminary results of phase I / II clinical trials for patients with skull base and paracervical tumors and central nervous system (CNS) tumors, treated with carbon ion radiotherapy. Materials and Methods: In carbon ion radiotherapy for skull base and paracervical tumors, dose escalation trials were performed up to the fourth-stage dose level: 48.0GyE (n = 4), 52.8GyE (n = 6), 57.6GyE (n = 9) and 60.8GyE (n = 9). Diffuse astrocytomas (Grade II) were treated with carbon ion radiotherapy alone. Carbon ion dose was escalated to the second stage - 50.4GyE (n = 9), and 55.2GyE (n = 5). For malignant gliomas, carbon ion radiotherapy was administered after x-ray therapy (50 Gy/25 fractions/5 weeks) by way of dose escalation up to the fifth stage (16.8, 18.4, 20.0, 22.4, and 24.8GyE). Results: Acute and late reactions were of a minor nature in all clinical trials. Carbon ion radiotherapy can therefore be described as presenting no clinical problems. Five-year local control rate by prescribed tumor dose of skull base and paracervical tumors was 75% for 48GyE, 67% for 52.8GyE, 78% for 57.6GyE, and 88% for 60.8GyE. Five-year overall survival rate of skull base and paracervical tumors was 50% for 48GyE, 100% for 52.8GyE, 100% for 57.6GyE, and 74% for 60.8GyE. Five-year progression free survival (PFS) rates of diffuse astrocytomas were 11% for the 50.4GyE group and 80% for the 55.2GyE group. Five-year overall survival rates were 22% for the 50.4GyE and 80% for the 55.2GyE. The 16 anaplastic astrocytoma (AA) patients had a median PFS time of 18 months and the 32 glioblastoma (GB) patients had a median PFS time of 7 months. The median survival time was 35 months for AA and 17 months for GB. These findings indicate that the survival rate tends to improve with higher carbon ion dose, and can be taken as evidence for the effectiveness of carbon ion radiotherapy for the treated diseases. Conclusion: The therapeutic effectiveness of carbon ion radiotherapy was particularly outstanding for CNS tumors and skull base and paracervical tumors, tumors that are intractable to photon radiotherapy. In view of these findings, it was decided to precede to the next phase I / II clinical trial a stage, for malignant gliomas stage consisting of carbon ion radiotherapy alone from April 2002. The phase I / II clinical trial for skull base and paracervical tumors was concluded in February 2004, and in April 2004 a phase II clinical trial was initiated under the Highly Advanced Medical Technology scheme with an irradiation schedule of 60.8GyE/16 fractions/4 weeks.
