Onco-functional Outcome after Resection for Eloquent Glioblastoma (OFO): a Propensity-Score Matched Analysis of an International, Multicentre, Cohort Study

Background The combined impact of complete resection (oncological goal) and no functional loss (functional goal) in glioblastoma subgroups is currently unknown. This study aimed to develop a novel onco-functional outcome (OFO) to merge these two goals into one outcome, resulting in four classes: complete without deficits (OFO1), incomplete without deficits (OFO2), complete with deficits (OFO3), or incomplete with deficits (OFO4). Methods Between 2010-2020, 858 patients with tumor resection for eloquent glioblastoma were included. We analyzed the impact of OFO class on postoperative surgical outcomes using Cox proportional-hazards models with hazard ratios (HR) or logistic regression with odds ratios (OR), followed by specific subgroup analyses. We developed a risk model to predict OFO class preoperatively using logistic regression. Results The OFO classification stratified the four OFO classes for overall survival (OS:19.0 versus 14.0 versus 12.0 versus 9.0 months), progression-free survival (PFS), and adjuvant therapy. OFO1 was associated with improved OS [HR=0.67, (0.55-0.81); p<0.001], and PFS [HR=0.68, (0.57-0.81); p<0.001] in the overall cohort and all clinical and molecular subgroups, except for MGMT-unmethylated tumors; and higher rate of adjuvant therapy [OR=2.81, (1.71-4.84);p<0.001]. In patients≥70 years, only OFO1 improved their survival outcomes. Safe surgery was especially important in patients with a preoperative KPS≤80 to qualify for adjuvant treatment. Awake craniotomy more often led to OFO1 compared to asleep resection [OR=1.93, (1.19-3.14); p=0.008]. Conclusions OFO1 was associated with improved OS, PFS, and receipt of adjuvant therapy in all glioblastoma patients with IDH-wildtype and MGMT-methylated tumors. Awake craniotomy was associated with achieving this optimal OFO status. Preventing deficits was more important than complete surgery.