Abstract
BackgroundAccurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma (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.MethodsDG 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.ResultsIn patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan–Meier analysis showed significant differences in OS and PFS at DG cutoffs consistent with previously identified values from newly diagnosed GBM using T1-weighted gadolinium-enhanced magnetic resonance imaging (T1Gd). DG scores for bevacizumab monotherapy patients only approached significance for PFS. Cox regression showed that increases of 25 DG on T1Gd imaging 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 patients.ConclusionDG 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.
Highlights
In the era of precision-based medicine, clinicians strive to understand the unique evolution of disease in individual patients in order to provide the most effective care
Reports from the AV37018g and NCI 06-C-0046E trials of bevacizumab for recurrent glioblastoma multiforme (GBM) were promising for improved progression-free survival (PFS), but improvements were not observed for overall survival (OS) [7,8]
In this work, we examined the use of a patient-specific response metric, Days Gained, for the discrimination of OS and PFS in patients with recurrent GBM who received bevacizumab with or without concurrent cytotoxic therapy
Summary
In the era of precision-based medicine, clinicians strive to understand the unique evolution of disease in individual patients in order to provide the most effective care. In patients with glioblastoma multiforme (GBM), the most common and aggressive form of glioma, assessing tumor response to therapy has proven difficult. To address the challenge of treatment appraisal in the setting of recurrent GBM, we evaluated patients receiving bevacizumab with and without concurrent cytotoxic therapies using a personalized model-based response metric, Days Gained, that utilizes volumetric image measurements to account for differing tumor growth dynamics between patients. Reports from the AV37018g and NCI 06-C-0046E trials of bevacizumab for recurrent GBM were promising for improved progression-free survival (PFS), but improvements were not observed for overall survival (OS) [7,8]. While subsequent clinical trials have not provided conclusive evidence that bevacizumab improves OS, they have solidified the impact of bevacizumab on PFS and clinicians continue to use it both as a monotherapy and in combination with cytotoxic agents [9]
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