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. 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.

Automated summary

Awake surgery has been shown to improve resection rates, reduce residual tumor rates, and achieve more supratotal resections compared to asleep surgery, benefiting the overall survival of IDH-wildtype glioblastoma patients.