Clinical Study

Journal of Neuro-Oncology

, Volume 108, Issue 3, pp 491-498

First online:

Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study

  • Whitney B. PopeAffiliated withDepartment of Radiology, David Geffen School of Medicine at UCLA Email author 
  • , Xin Joe QiaoAffiliated withDepartment of Radiology, David Geffen School of Medicine at UCLA
  • , Hyun J. KimAffiliated withDepartment of Radiology, David Geffen School of Medicine at UCLA
  • , Albert LaiAffiliated withDepartment of Neurology, David Geffen School of Medicine at UCLA
  • , Phioanh NghiemphuAffiliated withDepartment of Neurology, David Geffen School of Medicine at UCLA
  • , Xi XueAffiliated withDepartment of Radiology, David Geffen School of Medicine at UCLA
  • , Benjamin M. EllingsonAffiliated withDepartment of Radiology, David Geffen School of Medicine at UCLA
  • , David SchiffAffiliated withDepartment of Neurology, Virginia Commonwealth University Health System
  • , Dawit AregawiAffiliated withDepartment of Radiology, University of Virginia Health System
    • , Soonmee ChaAffiliated withDepartment of Radiology and Biomedical Imaging, University of California
    • , Vinay K. PuduvalliAffiliated withDepartment of Neuro-oncology, University of Texas MD Anderson Cancer Center
    • , Jing WuAffiliated withDepartment of Neuro-oncology, University of Texas MD Anderson Cancer Center
    • , Wai-Kwan A. YungAffiliated withDepartment of Neuro-oncology, University of Texas MD Anderson Cancer Center
    • , Geoffrey S. YoungAffiliated withDepartment of Radiology, Harvard Medical School
    • , James VredenburghAffiliated withDepartment of Medicine, Duke University Medical Center
    • , Dan BarboriakAffiliated withDepartment of Radiology, Duke University Medical Center
    • , Lauren E. AbreyAffiliated withDepartment of Neurology, Memorial Sloan-Kettering Cancer Center
    • , Tom MikkelsenAffiliated withDepartment of Neurology and Neurological Surgery, Henry Ford Hospital
    • , Rajan JainAffiliated withDepartment of Radiology, Henry Ford Hospital
    • , Nina A. PaleologosAffiliated withDepartment of Neurology, Northshore University Health System
    • , Patricia Lada RNAffiliated withDepartment of Neurology, Northshore University Health System
    • , Michael PradosAffiliated withDepartment of Neurological Surgery, University of California
    • , Jonathan GoldinAffiliated withDepartment of Radiology, David Geffen School of Medicine at UCLA
    • , Patrick Y. WenAffiliated withDana Farber Cancer Institute, Harvard Medical School
    • , Timothy CloughesyAffiliated withDepartment of Neurology, David Geffen School of Medicine at UCLA

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Abstract

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 × 10−6mm2/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.

Keywords

Apparent diffusion coefficient Glioblastoma multiforme Progression-free survival