Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

Neuroradiology. 2015 Dec;57(12):1269-80. doi: 10.1007/s00234-015-1582-9. Epub 2015 Sep 12.

Abstract

Introduction: The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas.

Methods: Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V(tot)), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V(CE-T1) and V(NON-CE-T1), respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K(trans) maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease.

Results: Responding patients showed a larger reduction in V(NON-CE-T1) after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K(trans), after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V(tot) was predictive of overall survival (OS), while V(CE-T1) showed a tendency of correlation with OS.

Conclusion: Tumor subvolumes with increased nIAUGC and K(trans) showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation.

Keywords: Bevacizumab; DCE MRI; High-grade glioma; Perfusion MRI; Quantitative image analysis.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Bevacizumab / administration & dosage*
  • Biomarkers
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology*
  • Contrast Media
  • Drug Monitoring / methods
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neoplasm Grading

Substances

  • Angiogenesis Inhibitors
  • Biomarkers
  • Contrast Media
  • Bevacizumab