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

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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.

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Conflict of interest

Whitney B. Pope, Albert Lai, David Schiff, Lauren Abrey, Tom Mikkelsen, Nina A. Paleologos, and Timothy Cloughesy served on the Genentech/Roche advisory board; Albert Lai, Vinay K. Puduvalli, Tom Mikkelsen, and Patrick Y. Wen were supported by research funds from Genentech/Roche; Nina A. Paleologos, Lauren Abrey, and Tom Mikkelsen received honoraria from Genentech/Roche; All other authors declare no conflict of interest.

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This is to declare that the studies performed in this manuscript complied with current laws of the United States of America.

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Authors and Affiliations

  1. Department of Radiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA, 90095-1721, USA

    Whitney B. Pope, Xin Joe Qiao, Hyun J. Kim, Xi Xue, Benjamin M. Ellingson & Jonathan Goldin

  2. Department of Neurology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA

    Albert Lai, Phioanh Nghiemphu & Timothy Cloughesy

  3. Department of Neurology, Virginia Commonwealth University Health System, Richmond, VA, 23298, USA

    David Schiff

  4. Department of Radiology, University of Virginia Health System, Charlottesville, VA, 22908, USA

    Dawit Aregawi

  5. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA

    Soonmee Cha

  6. Department of Neuro-oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Vinay K. Puduvalli, Jing Wu & Wai-Kwan A. Yung

  7. Department of Radiology, Harvard Medical School, Boston, MA, 02115, USA

    Geoffrey S. Young

  8. Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA

    James Vredenburgh

  9. Department of Radiology, Duke University Medical Center, Durham, NC, 27710, USA

    Dan Barboriak

  10. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA

    Lauren E. Abrey

  11. Department of Neurology and Neurological Surgery, Henry Ford Hospital, Detroit, MI, 48202, USA

    Tom Mikkelsen

  12. Department of Radiology, Henry Ford Hospital, Detroit, MI, 48202, USA

    Rajan Jain

  13. Department of Neurology, Northshore University Health System, Evanston, IL, 60201, USA

    Nina A. Paleologos & Patricia Lada RN

  14. Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA

    Michael Prados

  15. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA

    Patrick Y. Wen

Authors
  1. Whitney B. Pope
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  2. Xin Joe Qiao
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  3. Hyun J. Kim
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  4. Albert Lai
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  7. Benjamin M. Ellingson
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  13. Wai-Kwan A. Yung
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  14. Geoffrey S. Young
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  15. James Vredenburgh
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  16. Dan Barboriak
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  17. Lauren E. Abrey
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  18. Tom Mikkelsen
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  19. Rajan Jain
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  20. Nina A. Paleologos
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  21. Patricia Lada RN
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  22. Michael Prados
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  23. Jonathan Goldin
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  24. Patrick Y. Wen
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  25. Timothy Cloughesy
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Corresponding author

Correspondence to Whitney B. Pope.

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Pope, W.B., Qiao, X.J., Kim, H.J. et al. Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study. J Neurooncol 108, 491–498 (2012). https://doi.org/10.1007/s11060-012-0847-y

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  • DOI: https://doi.org/10.1007/s11060-012-0847-y

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