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

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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.

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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.

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Authors and Affiliations

  1. Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, 6th Floor, Clinical Sciences Building, Royal Parade, Parkville, VIC, 3050, Australia

    Iwan E. Bennett, Christopher M. Hovens, Katharine Drummond, Andrew H. Kaye & Andrew P. Morokoff

  2. Department of Radiology, The Royal Melbourne Hospital, The University of Melbourne, 1st Floor, 300 Grattan St, Parkville, VIC, 3050, Australia

    Bradford A. Moffat

  3. Department of Medical Oncology, The Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia

    Kathryn M. Field & Mark A. Rosenthal

  4. Department of Neurosurgery, The Royal Melbourne Hospital, 300 Grattan St, Parkville, VIC, 3050, Australia

    Katharine Drummond, Andrew H. Kaye & Andrew P. Morokoff

Authors
  1. Iwan E. Bennett
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  2. Kathryn M. Field
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  3. Christopher M. Hovens
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  4. Bradford A. Moffat
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  8. Andrew P. Morokoff
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Correspondence to Andrew P. Morokoff.

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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.

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Bennett, I.E., Field, K.M., Hovens, C.M. et al. Early perfusion MRI predicts survival outcome in patients with recurrent glioblastoma treated with bevacizumab and carboplatin. J Neurooncol 131, 321–329 (2017). https://doi.org/10.1007/s11060-016-2300-0

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  • DOI: https://doi.org/10.1007/s11060-016-2300-0

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