Volumetric Study Reveals the Relationship Between Outcome and Early Radiographic Response During Bevacizumab-Containing Chemoradiotherapy for Unresectable Glioblastoma

Abstract

Purpose: Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBMs), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of the early radiographic responses in nd-GBMs treated with BEV.Methods: Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. Early responses in fluid-attenuated inversion-recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI) were interpreted by an experienced neuroradiologist. Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response assessment in neuro-oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan-Meier analysis.Results: The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p=0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologist-interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in RANO criteria; however, even less stringent neuroradiologist-interpretation could successfully predict OS prolongation (improved vs. non-improved: p=0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20 to 50% (20%, p=0.0315; 30%, p=0.087; 40%, p=0.0456).Conclusions: Early response during BEV-containing chemoradiation can be a predictive indicator for patient outcome in unresectable nd-GBMs.