Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients

Abstract

Background. Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS. Methods. We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans ≤90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P =. 05. Results. Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm3) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P =. 009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P =. 08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P >. 51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P =. 025), the first post-bevacizumab enhancing volume (P =. 040), and the second post-bevacizumab enhancing volume (P =. 004). Conclusions. The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms.