Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients

Neuro Oncol. 2016 May;18(5):735-43. doi: 10.1093/neuonc/nov268. Epub 2015 Nov 3.

Abstract

Background: Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS.

Methods: We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans ≤90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05.

Results: Median OS was 9.1 months (95% CI = 7.2-14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm(3)) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003-1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004).

Conclusions: The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms.

Keywords: (ADC); apparent diffusion coefficient; bevacizumab; diffusion; glioblastoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / mortality
  • Glioblastoma / pathology*
  • Humans
  • Image Interpretation, Computer-Assisted / methods*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Bevacizumab