379 Meningioma Molecular Groups Predict Response to Adjuvant Radiotherapy Following Surgery

INTRODUCTION: Aside from surgery, radiotherapy (RT) remains the only treatment for meningiomas. However, patient selection for adjuvant RT remains controversial. METHODS: We utilized publicly available molecular datasets of meningiomas and generated de novo DNA-methylation and RNA-sequencing data. Meningiomas were classified into different molecular and methylation groups based on the methodologies of their original publications (Nassiri et al. [2021], Bayley et al. [2022], Choudhury et al. [2022], Sahm et al.[2017]) and progression-free survival (PFS) following surgery with and without adjuvant RT were analyzed. RESULTS: A total of 2029 meningiomas from 11 different institutions with adjuvant RT data were included. Adjuvant RT was associated with improved PFS in WHO grade 1 meningiomas following subtotal resection (STR), WHO grade 2 meningiomas following gross total resection (GTR) or STR, and immunogenic (COCA1) and NF2-wildtype (COCA2) meningiomas following STR. Multivariable analysis using Cox proportional hazards regression models showed that having a meningioma belonging to a hypermetabolic (COCA3) (HR 2.49, 95% CI 1.71-3.62), or proliferative (COCA4) (HR 3.77, 95% CI 2.78-5.10) group were associated with worse PFS when controlling for age, gender, extent of resection, and receipt of adjuvant RT. Meningiomas belonging to DKFZ MC-intermediate, MC-malignant, MenGC, and UCSF hypermitotic groups were also associated with worse outcomes. These relationships held true even in subgroup analysis with only WHO grade 2 meningiomas and following propensity score matching for the same clinical covariates above. Nearly all molecular and methylation classifications predicted 5-year PFS following surgery and adjuvant RT (area under the curve [AUC] 0.61-0.72) better than WHO grade (AUC 0.51). CONCLUSIONS: Molecular classification improves outcome prediction for meningiomas following surgery and adjuvant radiotherapy, supporting the rationale for molecularly informed treatment decisions and clinical trial stratification.