Extent of Resection Thresholds in Molecular Subgroups of IDH-Wildtype Glioblastoma

Abstract

INTRODUCTION: Maximizing the extent of resection (EOR) improves outcomes in glioblastoma (GBM). However, prior GBM studies have not addressed the impact of EOR in molecular subgroups of GBM beyond IDH1/IDH2 status. Therefore, it remains unclear whether EOR confers a benefit in all GBM subtypes or only in particular molecular subgroups. METHODS: Patients with newly diagnosed GBM IDH-wildtype undergoing resection were prospectively included in a database (n=138). EOR and RTV were quantified with semi-automated software. Formalin-fixed paraffin-embedded tumor tissues were analyzed by targeted next-generation sequencing. The association between recurrent genomic alterations and EOR/RTV was evaluated using a recursive partitioning analysis (RPA) to identify thresholds of EOR or RTV that may predict survival. The Kaplan-Meier methods and multivariable Cox proportional hazards regression methods were applied for survival analysis. RESULTS: Patients with EOR = 95.9% and younger than 67.5 years experienced improved survival compared to older patients with EOR <95.9% (Hazard ratio [HR] 5.85, p < 0.002). Patients with alterations in the TP53 pathway and EOR <88.72% showed reduced OS (mOS: 10.5 vs. 18.8 months; HR: 2.78, p = 0.013). However, EOR/RTV was not associated with OS in patients without alterations in the TP53 pathway. Among patients with EOR <87.69%, PTEN altered had significantly worse overall survival than PTEN wildtype (9.5 vs. 15.4 months; HR: 4.53, p < 0.001). CONCLUSIONS: Our results suggest that a subset of molecularly defined GBMs IDH-wildtype may benefit more from aggressive resections. Re-resections to optimize EOR might be beneficial in a subset of molecularly defined GBMs. Molecular alterations should be taken into consideration for surgical treatment decisions in GBM IDH-wildtype.