Early perfusion changes in patients with recurrent high-grade brain tumor treated with Bevacizumab: preliminary results by a quantitative evaluation

J Exp Clin Cancer Res. 2012 Apr 11;31(1):33. doi: 10.1186/1756-9966-31-33.

Abstract

Background: To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up.

Methods: Sixteen patients were enrolled in the present study. For each patient, two PCT examinations, before and after the first dose of bevacizumab, were acquired. Areas of abnormal Cerebral Blood Volume (CBV) were manually defined on the CBV maps, using co-registered T1- weighted images, acquired before treatment, as a guide to the tumor location. Different perfusion metrics were derived from the histogram analysis of the normalized CBV (nCBV) maps; both hyper and hypo-perfused sub-volumes were quantified in the lesion, including tumor necrosis. A two-tailed Wilcoxon test was used to establish the significance of changes in the different perfusion metrics, observed at baseline and during treatment. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated.

Results: Significant reductions in mean and median nCBV were detected throughout the entire patient population, after only a single dose of bevacizumab. The nCBV histogram modifications indicated the normalization effect of bevacizumab on the tumor abnormal vasculature. An improvement in hypoxia after a single dose of bevacizumab was predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up.

Conclusions: These preliminary results show that a quantification of changes in necrotic intra-tumoral regions could be proposed as a potential imaging biomarker of tumor response to anti-VEGF therapies.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Bevacizumab
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Female
  • Glioblastoma / blood supply
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology
  • Glioma / blood supply
  • Glioma / diagnostic imaging
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood supply
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Perfusion
  • Prospective Studies
  • Tomography, X-Ray Computed / methods

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab