Feasibility, Safety and Impact on Overall Survival of Awake Resection for Newly Diagnosed Supratentorial IDH-Wildtype Glioblastomas in Adults

SIMPLE SUMMARY: A few studies have suggested the benefits of awake surgery by maximizing the extent of resection while preserving neurological function and improving survival in high-grade glioma patients. However, the histomolecular heterogeneity in these series, mixing grade 3 with grade 4, and IDH-mutated with IDH-wildtype gliomas, represents a major selection bias that may influence survival analyses. For the first time, in a large homogeneous single-institution cohort of newly diagnosed supratentorial IDH-wildtype glioblastoma in adult patients, we assessed feasibility, safety and efficacy of awake surgery using univariate, multivariate and case-matched analysis. Awake surgery was associated with higher resection rates, lower residual tumor rates, and more supratotal resections than asleep resections, allowed standard radiochemotherapy to be performed systematically within a short time between surgery and radiotherapy, and was an independent predictor of progression-free survival and overall survival in the whole series, together with the extent of resection, MGMT promoter methylation status, and standard. ABSTRACT: Background: Although awake resection using intraoperative cortico-subcortical functional brain mapping is the benchmark technique for diffuse gliomas within eloquent brain areas, it is still rarely proposed for IDH-wildtype glioblastomas. We have assessed the feasibility, safety, and efficacy of awake resection for IDH-wildtype glioblastomas. Methods: Observational single-institution cohort (2012–2018) of 453 adult patients harboring supratentorial IDH-wildtype glioblastomas who benefited from awake resection, from asleep resection, or from a biopsy. Case matching (1:1) criteria between the awake group and asleep group: gender, age, RTOG-RPA class, tumor side, location and volume and neurosurgeon experience. Results: In patients in the awake resection subgroup (n = 42), supratotal resections were more frequent (21.4% vs. 3.1%, p < 0.0001) while partial resections were less frequent (21.4% vs. 40.1%, p < 0.0001) compared to the asleep (n = 222) resection subgroup. In multivariable analyses, postoperative standard radiochemistry (aHR = 0.04, p < 0.0001), supratotal resection (aHR = 0.27, p = 0.0021), total resection (aHR = 0.43, p < 0.0001), KPS score > 70 (HR = 0.66, p = 0.0013), MGMT promoter methylation (HR = 0.55, p = 0.0031), and awake surgery (HR = 0.54, p = 0.0156) were independent predictors of overall survival. After case matching, a longer overall survival was found for awake resection (HR = 0.47, p = 0.0103). Conclusions: Awake resection is safe, allows larger resections than asleep surgery, and positively impacts overall survival of IDH-wildtype glioblastoma in selected adult patients.