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Journal of Neuro-Oncology

, Volume 131, Issue 2, pp 321–329 | Cite as

Early perfusion MRI predicts survival outcome in patients with recurrent glioblastoma treated with bevacizumab and carboplatin

  • Iwan E. Bennett
  • Kathryn M. Field
  • Christopher M. Hovens
  • Bradford A. Moffat
  • Mark A. Rosenthal
  • Katharine Drummond
  • Andrew H. Kaye
  • Andrew P. MorokoffEmail author
Clinical Study

Abstract

Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan–Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially load, correlated significantly with PFS and OS at both follow-up time-points. Patients with the greatest reduction in rCBVload by 8-weeks of therapy had a significantly increased median OS (30 weeks; p = 0.013). PWI may be of significant clinical utility in managing patients with rGBM, particularly those treated with anti-angiogenic agents such as bevacizumab. These findings need to be confirmed prospectively in larger studies.

Keywords

Bevacizumab Glioblastoma DSC MRI rCBV Perfusion 

Notes

Acknowledgments

The authors wish to thank Luisa Barassi, Linda Garrett, Simon Salinas and Chris Steward for their assistance in this project.

Funding

The CABARET trial was conducted by The Cooperative Trials Group for Neuro-Oncology (COGNO), and was funded in part by Roche. This analysis was supported in part by funding received from The Brain Foundation, the Neurosurgical Society of Australasia, the Cure for Life Foundation, and the Royal Australasian College of Surgeons.

Compliance with ethical standards

Conflict of interest

The CABARET trial was funded in part by Roche. No other potential conflicts of interest regarding the submission of this manuscript have been identified by any of the authors.

Supplementary material

11060_2016_2300_MOESM1_ESM.docx (120 kb)
Supplementary material 1 (DOCX 119 KB)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Iwan E. Bennett
    • 1
  • Kathryn M. Field
    • 3
  • Christopher M. Hovens
    • 1
  • Bradford A. Moffat
    • 2
  • Mark A. Rosenthal
    • 3
  • Katharine Drummond
    • 1
    • 4
  • Andrew H. Kaye
    • 1
    • 4
  • Andrew P. Morokoff
    • 1
    • 4
    Email author
  1. 1.Department of Surgery, The Royal Melbourne HospitalThe University of MelbourneParkvilleAustralia
  2. 2.Department of Radiology, The Royal Melbourne HospitalThe University of MelbourneParkvilleAustralia
  3. 3.Department of Medical OncologyThe Royal Melbourne HospitalParkvilleAustralia
  4. 4.Department of NeurosurgeryThe Royal Melbourne HospitalParkvilleAustralia

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