291 Supra-maximal Extent of Resection is Associated With Improved Progression-Free Survival in Patients With IDH Wild-Type Glioblastoma Once Negative TERT Promoter Molecular Margins are Achieved

Abstract

INTRODUCTION: The standard of care for isocitrate dehydrogenase (IDH) wild-type GBM involves safe maximal resection with subsequent chemoradiation. TERT promoter (TERTp) mutations are clonal in >85% of IDH wild-type GBMs, detectable in all tumor cells. Advances in surgical management have focused on optimizing maximal resection given the positive correlation between extent of resection (EOR) and post-operative outcomes. METHODS: TERTp mutation detection in margin specimens was performed via a novel 30min qPCR-based method. A machine learning algorithm incorporating preoperative anatomic and intraoperative characteristics was developed using 148 patients to predict EOR. This model was prospectively applied to 44 patients to assess the correlation between a TERTp mutation negative margin and survival in cases when GTR was predicted. RESULTS: Retrospective analysis of 148 patients who underwent resection of GBM revealed significant improvement in 36-month survival with residual volume (RV) <4.9 cc). The primary predictive characteristics for achieving this RV were tumor volume, ventricular contact, multifocality, and Sawaya grade. Prospective analysis of 44 patients showed that, in cases where GTR was predicted and achieved, 26% obtained a TERTp negative margin. Although small, this group's PFS was significantly prolonged (0% vs 75% event-free at 30 months, p = 0.02), and a numerically superior prolonged OS was observed, while survival in GTR with positive molecular margin was indistinguishable from STR. CONCLUSIONS: These findings provide novel evidence supporting the utility of supramaximal resection targeting a “molecular margin” to maximize postoperative survival for a subset of patients with “localized” GBM. Further study is warranted to assess intraoperative, quantitative testing of TERTp mutation in GBM specimens to guide marginal resection in these patients.