IMG-51. Average necrotic cell number and extracellular fluid in FLAIR regions predict survival in glioblastoma patients undergoing subtotal and gross total resection

Abstract Glioblastoma (GBM) prognosis is influenced by both surgical resection extent and tumor microenvironmental features such as necrosis and extracellular fluid (ECF) accumulation. In this study, we hypothesize that MRI-based radio-pathomic maps (RPMs) of necrotic cell density and ECF volume provide prognostic information beyond standard imaging and vary by surgical resection extent. This study employed MRI-based RPMs to noninvasively characterize tumor microenvironment composition by generating voxel-wise maps of cell density and ECF volume using conventional MRI sequences. These RPMs were developed using a previously validated algorithm trained on spatially aligned histopathological tumor samples, enabling accurate estimation of microenvironment biomarkers outside standard imaging features. We retrospectively analyzed a cohort of 458 GBM patients —210 underwent subtotal resection (STR) and 248 underwent gross total resection (GTR) from the UCSF PDGM dataset. Preoperative T1, T1 post-contrast, ADC, and FLAIR images were processed to create whole tumor RPMs quantifying necrotic cell count and ECF volume. Average cell and ECF volume values were extracted from the RPMs within non-enhancing tumor regions, defined by FLAIR hyperintensity, for each patient. Cox proportional hazards models assessed the prognostic significance of MRI-derived necrosis and ECF metrics on overall survival for each resection type. Higher cell density correlated with poorer survival in the STR (B=2.208, p=0.027) group, whereas increased ECF volumes were associated with improved survival in STR (B=-2.571, p=0.010) and GTR (B=-2.291, p=0.022) patients. These findings demonstrate the effectiveness of integrating histologically informed radio-pathomic imaging biomarkers in the non-enhancing tumor margin for enhanced prognostication for different surgical outcomes, with necrotic presence in the tumor margin driving outcomes across surgical statuses and hypercellular presence specifically impacting subtotal resection patients. Future research could explore the biological mechanisms linking tumor necrosis, extracellular fluid dynamics, and clinical outcomes, as well as the evolution of tissue composition post-treatment.