Preoperative embolization improves local control and modulates gene expression in atypical WHO grade 2 meningioma

Abstract Background Preoperative embolization is hypothesized to reduce blood loss and operative time for meningioma resection, but the impact of preoperative embolization on long-term oncological outcomes and molecular features of meningiomas is incompletely understood. Here we investigate how preoperative embolization influences perioperative and long-term outcomes and molecular features of atypical WHO grade 2 meningiomas. Methods Patients who underwent resection of WHO grade 2 meningiomas from 1997 to 2021 were retrospectively identified from an institutional database. Univariate and multivariate Cox proportional hazards modeling and propensity matching were used for clinical analyses. Available DNA methylation profiling, bulk RNA sequencing, and targeted gene expression profiling data were used to elucidate how preoperative embolization influences the molecular architecture of atypical WHO grade 2 meningiomas. Results A total of 319 patients with atypical WHO grade 2 meningiomas were identified, of which 106 (33.2%) underwent preoperative embolization without significant changes in perioperative outcomes, such as blood loss or operative time, in comparison to patients who did not undergo preoperative embolization. In propensity matched multivariate analyses, preoperative embolization was independently associated with longer recurrence free survival (RFS, HR 0.55, 95% CI 0.31-0.96, p=0.037), particularly in patients with subtotal resection (median RFS 16.2 years versus 5.9 years, p=0.045; HR 0.32, 95% CI 0.14-0.70, p=0.005). Bioinformatic analyses demonstrated that preoperative embolization led to enrichment of pathways linked to cellular differentiation and hypoxia, and suppression of pathways implicated in mitosis and cell cycle progression, suggesting that improved long-term oncological outcomes may occur through inhibition of the cell cycle in atypical WHO grade 2 meningiomas. Conclusions Preoperative embolization improves local control and modulates gene expression in atypical WHO grade 2 meningiomas, a subgroup of meningiomas that have intermediate clinical outcomes with standard interventions.