Fractionated radiotherapy adjuvant to surgery of WHO-2 meningioma with and without gross total resection: a multicenter, retrospective cohort study of 1,452 patients

PURPOSE: The role of adjuvant fractionated radiotherapy (aFRT) after gross total resection (GTR) of WHO-2 meningiomas remains unclear. We aimed to estimate the effect of aFRT on recurrence risk and survival following GTR and subtotal resection (STR). METHODS: We analyzed 1452 patients with WHO-2 from our international, multicenter database (followed between 1989 and 2019). Outcomes were recurrence (10-year follow-up) and death (5-year follow-up). Risk estimates were obtained using competing risks and survival analysis. Average treatment effects were estimated by G-computation, adjusted for potential confounding by age, sex, Simpson grade, Ki-67 proliferation index, location, country group (universal healthcare or not), and year of treatment initiation. The robustness of findings was examined through sensitivity analyses. RESULTS: Overall, 276 of 1452 patients (19.0%) received aFRT. Among GTR patients, unadjusted analysis showed comparable recurrence proportions between irradiated and non-irradiated patients (25.5% vs. 22.8% within 5 years). Adjusted analyses provided no evidence that aFRT reduced the risk of recurrence (largest difference: −2.7%, 95% CI −5.6 to 0.2); although, the CIs include the possibility of small beneficial effects. In STR patients, aFRT was associated with reduced recurrence risk in both unadjusted and adjusted analyses. Unexpectedly, a higher mortality was observed among irradiated GTR patients, largely driven by older patients with low Ki-67 PI receiving aFRT. Sensitivity analyses showed similar results for patients with STR but discrepancy in estimates for those with GTR. CONCLUSION: Adjuvant FRT showed a consistent reduction in recurrence risk after STR while inconsistent recurrence risk estimates were observed for patients with GTR. The findings reflect efficacy of aFRT using real-world data without standardized guidelines.