Neurocognitive functioning, seizure control, and return to work after awake surgery with or without adjuvant therapy in IDH-mutant grade 3 diffuse gliomas

Purpose: The optimal oncological management of adult patients with IDH-mutant CNS WHO grade 3 diffuse gliomas remains debated, particularly given the potential neurotoxic effects of adjuvant therapies on cognition and health-related quality-of-life. Methods: We conducted a retrospective single-center cohort study including 87 consecutive patients with IDH-mutant CNS WHO grade 3 glioma who underwent awake craniotomy. Patients were stratified into a surgery only group (n = 23) or an adjuvant oncological group (radiotherapy with or without chemotherapy; n = 64). Neurocognitive outcomes, seizure control, and return-to-work rates were assessed. Voxel-wise lesion-symptom mapping was performed to identify associations between radiation dose distribution and postoperative neurocognitive performance. Results: Patients who did not receive postoperative adjuvant therapy showed better language (100% vs. 73.4%, p = 0.005) and executive and social function (95.6% vs. 70.1%, p = 0.013) outcomes. Left-sided tumor location and adjuvant treatment were independent predictors of poorer language and executive and social function outcomes, while adjuvant therapy was the only independent predictor of impaired executive and social function recovery. Voxel-wise lesion-symptom mapping analyses revealed significant associations between radiation exposure of specific white matter tracts involved in language and executive and social networks and postoperative neurocognitive decline. Seizure control did not differ between groups. Patients managed with surgery alone had higher 6-month employment rates and returned to work earlier. Conclusion: In this cohort, adjuvant therapy was associated with preliminary worse neurocognitive outcomes and reduced return-to-work rates, potentially reflecting the impact of radiation exposure on brain connectivity preserved during awake surgery. For selected patients, a watch-and-wait strategy following maximal safe resection may help preserve mid-term neurocognitive functioning.