Prospective, Randomized Study of Radiation Dose Escalation With Combined Proton-Photon Therapy for Benign Meningiomas

Purpose To assess the outcomes of benign meningiomas (BM) treated to two radiation dose levels. Methods and Materials We randomly assigned patients (1:1) with incompletely resected or recurrent BM to 2 radiation doses: 55.8 Gy(relative biological effectiveness [RBE]) and 63.0 Gy(RBE) of fractionated combined proton–photon radiation therapy. The primary endpoint was local control with hypothesis of improved tumor control with higher dose. Secondary endpoints included progression-free survival, overall survival, and rates of treatment-related toxicities. Results Between 1991 and 2000, 47 patients were randomized. Three patients were excluded for nonbenign histology; therefore, 44 patients were analyzed: 22 who received 55.8 Gy(RBE) and 22 who received 63.0 Gy(RBE). The median follow-up was 17.1 years. Local control for the entire cohort was 98% at 10 years and 90% at 15 years. Of the 5 patients with local recurrence, 4 occurred after 10 years of follow-up, and 3 were in the lower dose group (P=.322). In the modified intention to treat analysis, there was no difference in progression-free survival (P=.234) and overall survival (P=.271) between arms. A total of 26 patients (59%) experienced a grade 2 or higher late toxicity, including 9 patients (20%) incurring a cerebrovascular accident (CVA), 7 of which were deemed at least possibly attributable to irradiation. The median time between completion of radiation therapy and CVA was 5.6 years (range, 1.4-14.0 years). Conclusions Fractionated combined proton–photon radiation therapy is effective for BM, with no apparent benefit in dose escalation. Further investigation is needed to better define the risk of late toxicities, including CVA after cranial radiation therapy.