- Pope, Whitney B;
- Qiao, Xin Joe;
- Kim, Hyun J;
- Lai, Albert;
- Nghiemphu, Phioanh;
- Xue, Xi;
- Ellingson, Benjamin M;
- Schiff, David;
- Aregawi, Dawit;
- Cha, Soonmee;
- Puduvalli, Vinay K;
- Wu, Jing;
- Yung, Wai-Kwan A;
- Young, Geoffrey S;
- Vredenburgh, James;
- Barboriak, Dan;
- Abrey, Lauren E;
- Mikkelsen, Tom;
- Jain, Rajan;
- Paleologos, Nina A;
- Lada, Patricia;
- Prados, Michael;
- Goldin, Jonathan;
- Wen, Patrick Y;
- Cloughesy, Timothy
We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRI's from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 × 10(-6)mm(2)/s ± 224 (SD), and mean LCP was 0.71 ± 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L <1,209 and LCP >0.71 versus ADC-L >1,209 and LCP <0.71, there was a 2.28-fold reduction in the median time to progression, and a 1.42-fold decrease in the median OS. The predictive value of ADC histogram analysis, in which low ADC-L was associated with poor outcome, was confirmed in bevacizumab-treated patients with recurrent GBM in a post hoc analysis from the multi-center (BRAIN) study.