The Impact of Mri-defined Extent of Resection Across Meningioma DNA Methylation Groups: Re-evaluating Surgery in the Era of Meningioma Molecular Classification

Introduction: Extent of resection (EOR) is prognostic for meningioma outcomes across histological grades. Recent meningioma molecular risk stratification systems, such as those based on DNA methylation profiling, shed light on biological drivers and therapeutic vulnerabilities. The goal of this study was to re-evaluate the impact of EOR on clinical outcomes across meningioma DNA methylation groups.

Methods: Patients with sporadic meningiomas that underwent resection from a multicenter, international cohort were retrospectively reviewed. Gross vs. subtotal resection (GTR vs. STR, respectively) was determined based on postoperative magnetic resonance imaging (MRI). The Kaplan-Meier method, Log-rank statistics, and multivariable Cox proportional hazard analyses were performed to evaluate the impact of EOR on local freedom from recurrence (LFFR) and overall survival (OS).

Results: 587 patients (Male: 195, Female: 392) underwent 644 surgeries for intracranial meningioma (GTR: 438, STR: 206), with 124 surgeries (19.3%) for recurrent intracranial meningiomas. The cohort included 375 (58.2%) WHO grade 1, 202 (31.4%) WHO grade 2, and 67 (10.4%) WHO grade 3 meningiomas based on histological criteria. DNA methylation profiling was used to categorize meningiomas as Merlin-intact (N=214, 33.2%), Immune-enriched (N=236, 36.6%), or Hypermitotic (N=194, 30.1%). GTR was associated with longer LFFR across all meningioma DNA methylation groups (Merlin-intact p<.0001; Immune-enriched p=0.013; Hypermitotic p=0.001) and was associated with longer OS for Hypermitotic meningiomas (p=0.0022). In multivariable Cox proportional hazard analyses, EOR was significantly associated with LFFR across all DNA methylation groups and WHO grades but was significantly associated with OS only for Hypermitotic meningiomas (HR [GTR vs STR] 0.64, 95% CI 0.43-0.97, p=0.034).

Conclusion : MRI-defined GTR is associated with improved LFFR across all meningioma DNA methylation groups and improved OS for patients with Hypermitotic meningiomas. These data continue to support maximal safe resection when feasible and demonstrate how molecular classification systems complement rather than supersede the prognostic impact of surgery.