2025 Proffered Presentations
S240: THE IMPACT OF MRI-DEFINED EXTENT OF RESECTION ACROSS MENINGIOMA DNA METHYLATION GROUPS: RE-EVALUATING SURGERY IN THE ERA OF MENINGIOMA MOLECULAR CLASSIFICATION
Ramin Morshed, MD1; Minh P Nguyen1; Abrar Choudhury1; Stephen Magill, MD, PhD2; Nadeem Al-Adli1; Alexander F Haddad1; Kanish Mirchia1; Calixto-Hope G Lucas3; Michael McDermott4; William Chen1; David Raleigh1; 1UCSF; 2Northwestern University; 3Johns Hopkins University; 4Miami Neuroscience Institute
Extent of resection (EOR) has been consistently identified as prognostic for meningioma outcomes across histology-defined WHO grades. Recent meningioma risk stratification systems based on molecular features such as DNA methylation profiling shed light on biological drivers and therapeutic vulnerabilities, and correlate with local freedom from recurrence (LFFR) and overall survival (OS). The goal of this retrospective, international study was to re-evaluate the impact of surgical extent of resection on these clinical outcomes across meningioma DNA methylation groups. Patients with NF2-related schwannomatosis were excluded. Gross vs subtotal resection (GTR vs STR, respectively) was determined based on postoperative magnetic resonance imaging (MRI). The Kaplan-Meier method and Log-rank statistics were used to evaluate the impact of EOR on LFFR and OS, and a LogNormal distribution was used for modeling of time-to-event estimates. Overall, 588 patients (Male: 195, Female: 392) underwent surgical resection of 644 meningiomas (GTR: 438, 68%; STR: 206, 32%). There were 124 surgeries (19.3%) for recurrent meningiomas. The cohort was comprised of 375 (58.2%) WHO grade 1, 202 (31.4%) grade 2, and 67 (10.4%) 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 DNA methylation groups (Log-rank: Merlin-intact p<.0001; Immune enriched p=0.013; Hypermitotic p=0.001) and was associated with longer OS for Hypermitotic meningiomas (Log-rank: p=0.0022) (Figure 1, Table 1). Similarly, GTR was associated with longer LFFR across all three WHO grades (Log-rank: Grade 1 p=0.0017; Grade 2 p=0.025; Grade 3 p=0.0083) and was associated with longer OS for Grade 3 meningiomas (Log-rank: p=0.026). In multivariable Cox Proportional Hazard analyses including age, sex, EOR, newly diagnosed versus recurrent presentation, and adjuvant radiotherapy, 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). In summary, 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, even in the era of molecular classification of meningiomas.
