Sustained focal antitumor activity of bevacizumab in recurrent glioblastoma

Neurology. 2014 Jul 15;83(3):227-34. doi: 10.1212/WNL.0000000000000594. Epub 2014 Jun 13.

Abstract

Objectives: To investigate the relevance of bevacizumab (BEV)-induced diffusion-restricted lesions and T1-hyperintense lesions in patients with recurrent glioblastoma.

Methods: We prospectively screened 74 BEV-treated patients with recurrent glioblastoma for (1) diffusion-restricted lesions and/or, (2) lesions with a hyperintense signal on precontrast T1-weighted images. We further evaluated overall survival (OS), histopathology of the lesions, and patterns of progression.

Results: Twenty-five of 74 patients (34%) developed T1-hyperintense lesions, whereas diffusion-restricted lesions could be detected in 35 of 74 patients (47%). In 21 of 74 patients (28%), the lesions displayed both features ("double-positive"). OS for patients with double-positive lesions was 13.0 months; patients with neither of these lesions had an OS of 6.6 months (p < 0.005). Histologic evaluation of double-positive lesions revealed extensive calcified necrosis in 4 of 4 patients. Notably, these double-positive lesions were rarely involved in further tumor progression. However, they were associated with an increase in distant recurrences at BEV failure.

Conclusions: BEV-induced double-positive MRI lesions are a predictive imaging marker associated with a substantial survival benefit and with improved local control in patients with recurrent glioblastoma. Our data suggest that these lesions are the result of a sustained focal antitumor activity of BEV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / pharmacology*
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Bevacizumab
  • Biomarkers, Pharmacological
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Gliosarcoma / drug therapy*
  • Gliosarcoma / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Prospective Studies
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Pharmacological
  • Bevacizumab