Imaging necrosis during treatment is associated with worse survival in EORTC 26101 study.

Abstract

Imaging necrosis on MRI scans was assessed and compared to outcome measures of the European Organisation for Research and Treatment of Cancer 26101 phase III trial that compared single-agent lomustine with lomustine plus bevacizumab in patients with progressive glioblastoma. MRI in this post hoc analysis was available for 359 patients (lomustine = 127, lomustine + bevacizumab = 232). First, imaging necrosis at baseline being formally measurable (>10 × 10 mm, given 2 slices) was assessed. At weeks 6 and 12 of treatment, it was analyzed whether this necrosis remained stable or increased >25% calculated by 2 perpendicular diameters or whether necrosis developed de novo. Univariate and multivariate associations of baseline necrosis with overall survival (OS) and progression-free survival (PFS) were tested by log-rank test. Hazard ratios (HR) with 95% confidence interval were calculated by Cox model. Imaging necrosis at baseline was detected in 191 patients (53.2%) and was associated with worse OS and PFS in univariate, but not in multivariate analysis. Baseline necrosis was predictive for OS in the lomustine-only group (HR 1.46, p = 0.018). At weeks 6 and 12 of treatment, increase of baseline necrosis and de novo necrosis were strongly associated with worse OS and PFS in univariate and multivariate analysis (PFS both p < 0.001, OS univariate p < 0.001, multivariate p = 0.0046). Increase of and new development of imaging necrosis during treatment is a negative prognostic factor for patients with progressive glioblastoma. These data call for consideration of integrating the assessment of imaging necrosis as a separate item into the MRI response assessment criteria.