Statistisch parametrisch raamwerk voor glioblastoomlocatie, behandeling en prognostische variabelen

PURPOSE: Brain tumor location is known to impact survival, but there is a lack of methodological tools for systematically studying the complex interplay between brain tumor location, prognostic variables, treatment schemes, and survival. EXPERIMENTAL DESIGN: 592 prospectively-enrolled patients with newly-diagnosed glioblastoma from the phase III AVAglio trial, randomized to post-surgical chemoradiation with or without bevacizumab, were retrospectively analyzed. Statistical parametric mapping (SPM) was conducted with multivariate Cox proportional hazard ratio models at the voxel-wise level, incorporating dedicated interaction variables to evaluate the impact of baseline tumor volume and treatment arm on survival for different tumor locations from MRI scans, with subsequent cluster-based correction for multiple testing, and mathematical estimation of regional survival curves. RESULTS: Tumor location in the right prefrontal cortex was an independent favorable prognostic factor (median HR=0.57) for survival, while tumor involvement in left-hemisphere eloquent areas with language and visual functions was unfavorable (median HR=1.69). Larger presurgical tumor volumes were associated with shorter survival independent from tumor location (HR=1.005), but the effect was larger for tumor locations including eloquent structures (HR ranging 1.008-1.015), whereas non-significant for anterior frontal locations. Bevacizumab appeared to grant a survival benefit when specific brain regions were involved or spared by the tumor, but this result was not confirmed after correction for multiple testing. CONCLUSIONS: This workflow allows to map the survival effects of variables onto specific brain tumor locations, revealing location-dependency of prognostic variables such as tumor volume, and potentially of treatment schemes, with relevant implications in risk stratification and clinical management.