Poor Brain Reserve Increases Mortality Risk in Glioblastoma

Background Brain reserve refers to the structural capacity of the brain and correlates with age and Karnofsky Performance Status (KPS). While age and KPS are known independent predictors of survival in glioblastoma patients, the role of brain reserve in influencing glioblastoma outcomes remains unexplored. This study investigates the relationship between baseline brain reserve metrics and survival outcomes in IDH1-Wildtype (IDH1-WT) glioblastoma. Methods We analyzed 841 patients with IDH1-WT glioblastoma using clinical data and pre-surgical MR images sourced from four institutions. MRI-based tumor characteristics and quantitative brain reserve metrics were assessed using CaPTk (Cancer Imaging Phenomics Toolkit) and CAT12 (Computational Anatomy Toolbox). Statistical and survival analyses were conducted using MATLAB and R. Results Long-term survivors showed significantly higher residual functional gray matter volume (rfGM) (p < 0.001), gyrification (p = 0.001), and cortical thickness (p < 0.001) compared to medium and short-term survivors. Multivariable Cox analysis indicated significant associations between rfGM(p < 0.001) and gyrification (p = 0.008) with mortality after adjusting for clinical variables except age and KPS. After controlling for all clinical variables including age and KPS, gyrification (p = 0.01), sulcal depth (p = 0.02), and cortical thickness (p = 0.005) were significantly associated with mortality. Conclusion This multi-institutional study establishes significant associations between structural brain reserve metrics and glioblastoma outcomes, independent of age and KPS. The findings highlight the potential of brain reserve as a new biomarker for brain tumor prognosis and treatment planning.