Improved progression-free survival following dose-escalated vs. standard dose post-operative radiation therapy for high-risk meningiomas: An International Multicenter Individual Patient Level Meta-Analysis (FIRESTORM).

Abstract

We performed an individual patient level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) vs. standard-dose post-operative radiation therapy (SD-RT). A total of 7 institutions participated. DE-RT was defined as treatment with a biological effective dose (BED10) of ≥79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared PFS with DE-RT vs. SD-RT via Kaplan-Meier analysis and log-rank t-tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT vs.SD-RT. The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One-hundred and eighty-eight cases(75.8%) were WHO Grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was STR in 182/248(75.2%). Three- and 5-year PFS rates were 62.8%(95% CI: 55.8-69.0%) and 45.0%(95% CI: 37.3-52.3%), respectively. DE-RT was associated with superior PFS rates (p=0.0022), with 3- (95% CI: 86.4% vs. 55.6%) and 5-year (95% CI: 65.8% vs. 38.8%) PFS rates favoring DE-RT. On MVA, DE-RT was associated with superior PFS (hazard ratio (HR)= 0.40 (95% CI: 0.24-0.69; p=0.001). On IPTW, DE-RT continued to be associated with superior PFS (HR=0.45 (95% CI: 0.24-0.83; p=0.01)). A greater incidence of any grade RN was observed following DE-RT (20/59; 33.9%) vs. SD-RT (25/189; 13.2%) (p=0.001) but with similar Grade 3 or greater RN events [DE-RT (5.1%) vs. SD-RT (3.2%)]. DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.