Prognostic associations of surgical resection and adjuvant radiotherapy in meningioma defined by an exome–sequencing–based grading

Abstract Molecular classifications of meningiomas improve biological and prognostic stratification, but their complexity can hinder routine implementation, and their treatment implications remain unclear. This study aimed to establish a whole-exome sequencing (WES)–based molecular grading (MG) system, evaluate its prognostic utility, and examine the associations of gross total resection (GTR) and postoperative adjuvant radiotherapy (RT) with recurrence-free survival (RFS). We retrospectively analyzed 456 patients who underwent resection of intracranial meningiomas (1999–2024) with WES-based MG and the prognostic associations of GTR and adjuvant RT for RFS were evaluated within each MG using propensity score–matched analysis. MG A was defined by the presence of NF2 mutation/22q loss and absence of high-risk molecular alterations; MG B by the absence of both NF2 mutation/22q loss and high-risk alterations; and MG C by the presence of high-risk molecular alterations. RFS differed significantly among MG A, B, and C in the entire cohort and in the subset of patients with WHO grade 1 meningiomas (all pairwise FDR-adjusted p values < 0.05). GTR was associated with longer RFS in matched MG B and MG C (both FDR-adjusted p < 0.01), whereas no statistically significant association was observed in MG A. In exploratory analyses, postoperative adjuvant RT was associated with longer RFS in the matched MG B cohort (FDR-adjusted p = 0.005), whereas analyses in MG A and MG C were inconclusive. This simplified WES-based grading system stratified RFS and enabled exploratory evaluation of treatment-associated outcomes within molecular subgroups.