Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab

Clin Transl Oncol. 2017 Jan;19(1):51-57. doi: 10.1007/s12094-016-1502-4. Epub 2016 Mar 30.

Abstract

Background and purpose: In glioblastoma, tumor progression appears to be triggered by expression of VEGF, a regulator of blood vessel permeability. Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response. Our objectives were: (1) to evaluate whether changes in DSC perfusion MRI-derived leakage could predict survival in recurrent glioblastoma, and (2) to estimate whether leakage at baseline was related to treatment outcome.

Materials and methods: We retrospectively analyzed DSC perfusion MRI in 24 recurrent glioblastomas treated with bevacizumab as second line chemotherapy. Leakage at baseline and changes in maximum leakage between baseline and the first follow-up after treatment were selected for quantitative analysis. Survival univariate analysis was made constructing survival curves using Kaplan-Meier method and comparing subgroups by log rank probability test.

Results: Leakage reduction at 8 weeks after initiation of bevacizumab treatment had a significant influence on overall survival (OS) and progression-free survival (PFS). Median OS and PFS were 2.4 and 2.8 months longer for patients with leakage reduction at the first follow-up. Higher leakage at baseline was associated with leakage reduction after treatment. Odds ratio of treatment response was 9 for patients with maximum leakage at baseline >5.

Conclusions: Leakage decrease may predict OS and PFS in recurrent glioblastomas treated with bevacizumab. Leakage reduction postulates as a potential biomarker for treatment response evaluation. Leakage at baseline seems to predict response to treatment, but was not independently associated with survival.

Keywords: Bevacizumab; Brain; Glioblastoma; Leakage; Perfusion.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Contrast Media*
  • Female
  • Follow-Up Studies
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism
  • Glioblastoma / mortality*
  • Glioblastoma / pathology
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Perfusion
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Angiogenesis Inhibitors
  • Contrast Media
  • Bevacizumab