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.