Days Gained Response Discriminates Treatment Response in Patients with Recurrent Glioblastoma Receiving Bevacizumab-based Therapies

Abstract

PurposeAccurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma multiforme (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze Days Gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies.\n\nExperimental DesignDays Gained response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N=62). Kaplan-Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM.\n\nResultsIn patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan-Meier analysis showed significant differences in OS and PFS at previously identified DG cutoffs consistent with previous DG analyses using gadolinium-enhanced T1 weighted MR imaging. DG scores for bevacizumab monotherapy only approached significance for PFS. Cox regression showed that increases of 25 DG were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy.\n\nConclusionDays Gained has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.