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

J Neurooncol. 2013 Nov;115(2):267-76. doi: 10.1007/s11060-013-1225-0. Epub 2013 Aug 22.


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) mm(2)/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.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • DNA, Neoplasm / genetics
  • Disease Progression
  • ErbB Receptors / genetics*
  • Female
  • Follow-Up Studies
  • Glioma / drug therapy
  • Glioma / genetics
  • Glioma / mortality*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality*
  • Polymerase Chain Reaction
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Proteins / genetics*


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • DNA, Neoplasm
  • Tumor Suppressor Proteins
  • Bevacizumab
  • DNA Modification Methylases
  • MGMT protein, human
  • EGFR protein, human
  • ErbB Receptors
  • DNA Repair Enzymes