Correlation of radiological and immunochemical parameters with clinical outcome in patients with recurrent glioblastoma treated with Bevacizumab

Clin Transl Oncol. 2019 Oct;21(10):1413-1423. doi: 10.1007/s12094-019-02070-6. Epub 2019 Mar 15.

Abstract

Background: Some phase 2 trials had reported encouraging progression-free survival with Bevacizumab in monotherapy or combined with chemotherapy in glioblastoma. However, phase 3 trials showed a significant improvement in progression free survival without a benefit in overall survival. To date, there are no predictive biomarker of response for Bevacizumab in glioblastoma.

Methods: We used Immunochemical analysis on tumor samples and pretreatment and post-treatment perfusion-MRI to try to identify possible predictive angiogenesis-related biomarkers of response and survival in patients with glioblastoma treated with bevacizumab in the first recurrence. We analyzed histological parameters: vascular proliferation, mitotic number and Ki-67 index; molecular factors: MGMT promoter methylation, EGFR amplification and EGFR variant III; immunohistochemical: MET, Midkine, HIF1, VEGFA, VEGF-R2, CD44, Olig2, microvascular area and microvascular density; and radiological: rCBV.

Results: In the statistical analysis, no significant correlation of any histological, molecular, microvascular or radiological parameters could be demonstrated with the response rate, PFS or OS with bevacizumab treatment.

Conclusion: Unfortunately, in this histopathological, molecular, immunohistochemical and neuroradiological study we did not find any predictive biomarker of response or survival benefit for Bevacizumab in glioblastoma.

Keywords: Bevacizumab; Biomarkers; Glioblastoma; Microvacular density; Microvascular area.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / chemistry
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Cerebrovascular Circulation
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / metabolism
  • Female
  • Gene Amplification
  • Genes, erbB-1
  • Glioblastoma / blood supply
  • Glioblastoma / chemistry
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / drug therapy*
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Male
  • Methylation
  • Microvessels / pathology
  • Middle Aged
  • Mitotic Index
  • Neoplasm Recurrence, Local / blood supply
  • Neoplasm Recurrence, Local / chemistry
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / drug therapy*
  • Retrospective Studies
  • Tissue Array Analysis
  • Tumor Suppressor Proteins / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Tumor Suppressor Proteins
  • Bevacizumab
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes