NIMG-72. VOXEL-WISE, MULTIVARIABLE, COX PROPORTIONAL HAZARD STATISTICAL PARAMETER MAPPING TO INVESTIGATE THE INTERPLAY BETWEEN TUMOR LOCATION, PROGNOSTIC VARIABLES, AND EXPERIMENTAL TREATMENT IN A PHASE 3 TRIAL OF NEWLY-DIAGNOSED GLIOBLASTOMA TREATED WITH CHEMORADIATION WITH OR WITHOUT BEVACIZUMAB

Abstract

Abstract BACKGROUND Tumor location is known to impact overall survival (OS) in glioblastoma. However, there is a lack of quantitative tools for studying the interplay between tumor location, prognostic variables, and treatments. In the current study we develop a voxel-wise statistical parameter mapping technique using a multivariable Cox regression model to describe the influence of tumor location on treatment effects in newly diagnosed glioblastoma. METHODS 598 newly diagnosed glioblastoma patients from the phase 3 AVAglio trial were studied. Areas of T2/FLAIR hyperintensity and resection cavities on post-surgical MRI scans were segmented and aligned to MNI atlas space. Voxel-wise Cox proportional hazards models for OS were run for each image voxel and included tumor presence in a specific voxel, age, MGMT promoter methylation, baseline tumor volume, and treatment (chemoradiation with or without bevacizumab). Results. After adjusting for other variables, tumor location was an independent predictor of favorable OS for tumors with involvement in the right prefrontal cortex (p<0.05, HR ranging ~0.48–0.65) and a predictor of shorter OS for tumors in the left mesial/basal temporo-occipital areas (p<0.05, HR ~3–6.2) and in the left hemisplenium of the corpus callosum (p<0.05, HR ~2.5–3). Baseline tumor volume (HR ~4–6 x10-6), MGMT status (HR ~0.38–0.41), and age (HR ~1.020–1.025) were significative predictors regardless of location (p<0.05 in all locations). Interestingly, chemoradiation plus bevacizumab treatment showed a favorable OS compared with chemoradiation alone for tumors with involvement in the right corticospinal tract, right motor and sensory cortices, and left hemisplenium of the corpus callosum (p<0.05, HR ~0.82). CONCLUSIONS Tumor involvement in the prefrontal cortex is associated with favorable prognosis, while tumors in mesial/basal temporo-occipital areas or splenium of the corpus callosum are associated with shorter OS. Chemoradiation plus bevacizumab may improve OS for tumors involving eloquent motor areas and the corticospinal tract.