SURG-23. REOPERATION IN MOLECULAR SUBTYPES OF RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Recurrent glioblastoma (rGBM) treatment is not well defined and multiple therapeutic approaches have been proposed, none of which has shown to prolong survival in randomized trials. The role of reoperation for rGBM is still unclear. While most studies demonstrate improve overall survival (OS) and post-progression survival (PPS), recent studies employing time-dependent analysis appear to undermine the OS benefit in reoperated patients. Moreover, the relevance of rGBM molecular subtypes that benefit from reoperation is an important question that may guide clinical decision-making. METHODS A retrospective review of rGBM demographics, clinical, molecular, and outcome characteristics was performed for all cases managed by us between 01/2005 to 10/2019 at our institution. IDH1/IDH2 status was determined by immunohistochemistry and/or next-generation sequencing (NGS). A genetic subanalysis was conducted for most rGBM IDH-wildtype (IDH-WT) by NGS. The primary outcome was PPS. Kaplan-Meier method, multivariable Cox proportional-hazards model, and accelerated failure time model were performed in survival analysis. Random survival forest was applied to identify variable importance. RESULTS 284 rGBM patients fulfill inclusion criteria, 145 (51.1%) had reoperation at their 1st recurrence. Reoperated patients were significantly younger, had better performance status, and had a higher extent of resection at initial surgery; meanwhile, they were less likely to receive bevacizumab. Patients undergoing reoperation experienced superior PPS (11.5 vs. 7.4, months, log-rank test: p= 0.002), which kept consistent in multivariable Cox model (HR: 0.62, p= 0.001). Moreover, reoperated rGBM IDH-WT (N= 238) had 37% reduced risk of post-progression death compared to non-reoperated patients. A subanalysis of rGBM IDH-WT molecular subtypes identified that EGFR mutant, NF1 wildtype, and TP53 wildtype subgroups could benefit from reoperation (all p< 0.008). CONCLUSIONS Maximal safe re-resection improved the PPS of rGBM regardless of their IDH status. Reoperation for 1st recurrence was especially beneficial for GBM IDH-WT harboring EGFR alteration, TP53 WT, and NF1-WT.