Outcomes of early versus late radiotherapy in grade 2 meningiomas: a National retrospective analysis from the TROD neuro-oncology group

Purpose: The optimal timing of radiotherapy (RT) in patients with WHO grade 2 meningiomas remains controversial, particularly following gross total resection (GTR). This multicenter study compared long-term outcomes of early RT versus late RT, focusing on progression-free survival (PFS), overall survival (OS), and tumor-related mortality. Methods and materials: This retrospective multicenter cohort study included 263 adult patients with histopathologically confirmed WHO grade 2 meningiomas treated between 2005 and 2023. Patients were stratified by RT timing: early adjuvant RT after initial surgery versus late RT administered after radiologic or clinical progression. Outcomes were analyzed in the overall cohort and in a prespecified GTR subgroup. PFS and OS were estimated using the Kaplan–Meier method. Tumor-related mortality was assessed using cause-specific Cox and Fine–Gray competing-risk models. Results: With a median follow-up exceeding 7 years, early RT was associated with a significant improvement in PFS compared with late RT. In the overall cohort, 10-year PFS was 84.8% with early RT versus 18.6% with late RT (p < 0.001). Among patients undergoing GTR, 10-year PFS remained high with early RT (89.3%) but declined markedly after late RT (18.8%; p < 0.001). RT timing was the strongest independent predictor of PFS in multivariable models, although its effect attenuated over time. Tumor-related mortality was approximately sixfold higher in the late RT group (16.7% vs 2.7%; p = 0.011), whereas all-cause mortality did not differ significantly (24.2% vs 14.7%; p = 0.198). Mitotic count and Ki-67 index were independently associated with early and long-term PFS, whereas male sex, older age, and subtotal resection predicted tumor-related mortality. Conclusions: Early RT provides a durable and clinically meaningful PFS benefit over late RT in WHO grade 2 meningiomas, including after GTR, without conferring an OS advantage. These findings emphasize the importance of RT timing and tumor biology in postoperative risk stratification and support consideration of early RT in selected patients, pending results from randomized trials.