A Prospective Multi-Institutional Study of Clinical Outcomes for Meningioma Patients Treated with Proton Beam Radiotherapy

Abstract

To report on the patient outcomes and treatment-related toxicities associated with proton beam radiotherapy (PBT) for patients with meningiomas. Patients with newly diagnosed or recurrent meningiomas treated with fractionated external beam PBT were analyzed from a prospective multi-institutional PBT registry. Treatment-related toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Of the 209 patients included in this study, the median age at treatment was 61 years (Range: 18 - 92 years). 126 patients (60%) were treated for newly diagnosed disease and 83 patients (40%) were treated for recurrent disease. 46 patients (22%) had previously received photon radiotherapy before salvage PBT. 144 patients (69%) underwent resection prior to PBT at a median of 5.6 months (Range: 1 - 356 months). 56 patients (27%) had WHO Grade I disease, 68 patients (33%) had Grade II disease, 12 patients (6%) had Grade III disease, and 73 (35%) patients had an unknown grade at time of treatment. The median PBT dose was 54 Gy in 30 fractions (Range: 45 - 68 Gy). Of the 147 patients with clinical follow-up and 131 patients with imaging follow-up, the median follow-up was 14 months (Range: 2 - 65 months) and 16 months (Range: 2 - 65 months), respectively. The 24-month overall survival (OS) for all patients with WHO Grade I disease was 100%, for Grade II disease was 71% (95% CI: 55%-91%), and for Grade III disease was 42% (95% CI: 16%-100%), while patients with an unknown grade had an OS of 82% (95% CI: 71%-94%) (p=0.004). The 24-month overall survival was 89% (95% CI: 81-97%) in patients with newly diagnosed disease and 70% (95% CI: 57 - 86%) in those with recurrent disease (p=0.025). The 24-month progression free survival in patients with newly diagnosed disease was 90% (95% CI: 81%-99%) and 70% (95% CI: 56%-86%) in patients with recurrent disease (p=0.006). Ten patients (7%) experienced a Grade ≥3 toxicity, most commonly muscle weakness, ataxia, and optic disorder, half (5/10) of whom had received prior radiotherapy. The 12-month risk of Grade ≥2 toxicity was 32% for newly diagnosed patients (95% CI: 21-41%) and 46% for patients with recurrent disease (95% CI: 31 - 58%) (p=0.22). This study represents the largest prospective multi-institutional registry study of patients treated with PBT for meningiomas, including patients with recurrent disease, documenting clinical efficacy of this treatment technique. Grade 2 and 3 adverse events were expectedly more common in the cohort with recurrent disease. However, even here, the Grade ≥3 toxicity is acceptable. Prospective neurocognitive and quality-of-life studies are needed to determine additional benefits of this treatment technique in this patient population with benign tumors.