2003 Preoperative Embolization Improves Local Control and Reprograms Gene Expression in Atypical WHO Grade 2 Meningiomas

INTRODUCTION: While preoperative embolization is hypothesized to reduce blood loss and surgical time for resection of meningiomas, the impact of embolization on long-term outcomes and molecular profiling of meningiomas is incompletely understood. METHODS: A series of patients with grade 2 meningiomas who underwent resection at our institution from 1997 to 2021 were identified and reviewed. Available DNA methylation profiling and bulk RNA sequencing data were analyzed (n= 200, WHO grade 1 or 2). Univariate and multivariate analyses, Cox proportional hazards modeling, and propensity matching (sex, age at surgery, previous surgery, extent of resection, postop radiation) were utilized. RESULTS: A total of 357 WHO grade 2 meningioma patients were included, 129 (36.1%) underwent embolization and 228 (63.9%) did not undergo embolization. Mean age at diagnosis was 53.5 years and 61.4% of patients were female. There was no difference in time to recurrence with or without embolization for cases with gross total resection (229/357). Embolization was independently associated with improved local control for cases with subtotal resection even after accounting for postoperative radiotherapy (HR 0.49, 95% CI 0.32-2.20 p=0.028). Average time to recurrence of atypical WHO grade 2 meningioma was 3.3 years after subtotal resection and 6.7 years after embolization and subtotal resection (p<0.001, propensity matched). The distribution of Merlin-intact vs Immune-enriched vs Hypermitotic meningioma DNA methylation groups was equivalent with versus without embolization, but differential gene expression analysis of RNA sequencing data revealed enrichment of hypoxia related pathways after embolization that were unique to each DNA methylation group. CONCLUSIONS: These data show that embolization improves local control and reprograms gene expression in WHO grade 2 meningiomas. Additional investigation into the impact of embolization on clinical outcomes and gene expression for meningiomas, especially for higher-grade tumors, is warranted.