Journal of Neuro-Oncology

, Volume 108, Issue 3, pp 491–498

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. Pope
  • Xin Joe Qiao
  • Hyun J. Kim
  • Albert Lai
  • Phioanh Nghiemphu
  • Xi Xue
  • Benjamin M. Ellingson
  • David Schiff
  • Dawit Aregawi
  • Soonmee Cha
  • Vinay K. Puduvalli
  • Jing Wu
  • Wai-Kwan A. Yung
  • Geoffrey S. Young
  • James Vredenburgh
  • Dan Barboriak
  • Lauren E. Abrey
  • Tom Mikkelsen
  • Rajan Jain
  • Nina A. Paleologos
  • Patricia Lada RN
  • Michael Prados
  • Jonathan Goldin
  • Patrick Y. Wen
  • Timothy Cloughesy
Clinical Study

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 

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Whitney B. Pope
    • 1
  • Xin Joe Qiao
    • 1
  • Hyun J. Kim
    • 1
  • Albert Lai
    • 2
  • Phioanh Nghiemphu
    • 2
  • Xi Xue
    • 1
  • Benjamin M. Ellingson
    • 1
  • David Schiff
    • 3
  • Dawit Aregawi
    • 4
  • Soonmee Cha
    • 5
  • Vinay K. Puduvalli
    • 6
  • Jing Wu
    • 6
  • Wai-Kwan A. Yung
    • 6
  • Geoffrey S. Young
    • 7
  • James Vredenburgh
    • 8
  • Dan Barboriak
    • 9
  • Lauren E. Abrey
    • 10
  • Tom Mikkelsen
    • 11
  • Rajan Jain
    • 12
  • Nina A. Paleologos
    • 13
  • Patricia Lada RN
    • 13
  • Michael Prados
    • 14
  • Jonathan Goldin
    • 1
  • Patrick Y. Wen
    • 15
  • Timothy Cloughesy
    • 2
  1. 1.Department of RadiologyDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Department of NeurologyDavid Geffen School of Medicine at UCLALos AngelesUSA
  3. 3.Department of NeurologyVirginia Commonwealth University Health SystemRichmondUSA
  4. 4.Department of RadiologyUniversity of Virginia Health SystemCharlottesvilleUSA
  5. 5.Department of Radiology and Biomedical ImagingUniversity of CaliforniaSan FranciscoUSA
  6. 6.Department of Neuro-oncologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Department of RadiologyHarvard Medical SchoolBostonUSA
  8. 8.Department of MedicineDuke University Medical CenterDurhamUSA
  9. 9.Department of RadiologyDuke University Medical CenterDurhamUSA
  10. 10.Department of NeurologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  11. 11.Department of Neurology and Neurological SurgeryHenry Ford HospitalDetroitUSA
  12. 12.Department of RadiologyHenry Ford HospitalDetroitUSA
  13. 13.Department of NeurologyNorthshore University Health SystemEvanstonUSA
  14. 14.Department of Neurological SurgeryUniversity of CaliforniaSan FranciscoUSA
  15. 15.Dana Farber Cancer InstituteHarvard Medical SchoolBostonUSA

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