Dose escalated radiotherapy is associated with improved outcomes for high grade meningioma

: The optimal modern radiotherapy (RT) approach after surgery for atypical and malignant meningioma is unclear. We present results of dose-escalation in a single institution cohort spanning 2000-2021. : Consecutive patients with histopathologic grade 2 or 3 meningioma treated with RT were reviewed. A dose-escalation cohort [≥66Gy equivalent dose in 2 Gy fractions using an a/b=10 (EQD2)], was compared to a standard dose cohort (<66Gy). Outcomes were progression-free survival (PFS), cause-specific survival (CSS), overall survival (OS), local failure (LF) and radiation necrosis. : 118 patients (111 Grade 2, 94.1%) were identified; 54/118 (45.8%) received dose-escalation and 64/118 (54.2%) standard dose. Median follow-up was 45.4 months (IQR:24.0-80.0 months) and median OS was 9.7 years (Q1:4.6 years, Q3:not reached). All dose-escalated patients had residual disease vs. 65.6% in the standard dose cohort (p<0.001). PFS at 3-, 4- and 5-years in the dose-escalated vs. standard dose cohort were 78.9%, 72.2% and 64.6% vs. 57.2%, 49.1% and 40.8%, respectively, (p=0.030). On multivariable (MVA) analysis, dose-escalation (HR:0.544,p=0.042) was associated with improved PFS, whereas ≥2 surgeries (HR:1.989,p=0.035) and older age (HR:1.035,p<0.001) were associated with worse PFS. The cumulative risk of LF was reduced with dose-escalation (p=0.016). MVA confirmed dose-escalation protective for LF (HR: 0.483,p=0.019), whereas ≥2 surgeries prior to RT predicted for LF (HR:2.145,p=0.008). A trend was observed for improved CSS and OS in the dose-escalation cohort (p<0.1). Seven patients (5.9%) developed symptomatic radiation necrosis (RN) with no significant difference between the two cohorts. : Dose-escalated radiotherapy with ≥66Gy for high grade meningioma is associated with improved local control and PFS with an acceptable risk of RN.