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Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival

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Abstract

Although bevacizumab represented an important advance in treatment of recurrent high-grade gliomas (HGG), responses occur in fewer than half of patients. There are no validated biomarkers for anti-angiogenic therapy that are available for routine clinical use. We assessed the prognostic values of imaging and molecular markers in this patient population. MRI scans from 191 patients with recurrent HGG obtained prior to initiating bevacizumab were reviewed for areas of enhancement, necrosis, T2/FLAIR abnormality, and ADC values. Serial MRI scans following the initiation of bevacizumab were evaluated for response and progression. Non-radiographic markers including EGFR and MGMT status were also assessed with respect to response and patient survival. 65 of 191 patients (34 %) showed complete or partial response at the time of their best response MRI and demonstrated longer progression free survival (PFS) and overall survival (OS) compared to the group without response (PFS: 6.9 vs 3.5 months, OS: 10.9 vs 6.1 months). Minimum ADC values within enhancing and non-enhancing regions were lower in responders compared to those of non-responders (1,099 vs 984 × 10−6 mm2/s, p = 0.006). Smaller enhancing area was associated with longer OS (HR = 1.99, p = 0.017). The ratio of T2/FLAIR to enhancing area was prognostic of OS for only the Grade III HGG subgroup (HR = 0.14, p = 0.004). Area of enhancing tumor at baseline can stratify survival in patients with recurrent HGG treated with bevacizumab. The extent of edema relative to enhancing area may have a prognostic role specific to Grade III HGG.

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Acknowledgments

This study was supported by institutional funds.

Conflict of interest

Dr. Wen discloses that he serves on the Genentech advisory board. Other authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Harvard Medical School, 250 Longwood Avenue, Boston, MA, 02115, USA

    Christina Chen, Raymond Huang, Srinivasan Mukundan, Patrick Y. Wen & Andrew D. Norden

  2. Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Raymond Huang, Srinivasan Mukundan, Patrick Y. Wen & Andrew D. Norden

  3. Mid-Atlantic Permanente Medical Group, 2101 East Jefferson Street, Rockville, MD, 20852, USA

    Ainsley MacLean

  4. Massachusetts General Hospital Biostatistics Center, 50 Staniford Street, Boston, MA, 02114, USA

    Alona Muzikansky

  5. Center for Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA

    Patrick Y. Wen & Andrew D. Norden

Authors
  1. Christina Chen
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  2. Raymond Huang
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  3. Ainsley MacLean
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  4. Alona Muzikansky
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  5. Srinivasan Mukundan
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  6. Patrick Y. Wen
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  7. Andrew D. Norden
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Corresponding author

Correspondence to Andrew D. Norden.

Additional information

Christina Chen and Raymond Huang contributed equally to this project and should be considered co-first authors.

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Chen, C., Huang, R., MacLean, A. et al. Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival. J Neurooncol 115, 267–276 (2013). https://doi.org/10.1007/s11060-013-1225-0

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  • DOI: https://doi.org/10.1007/s11060-013-1225-0

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