Optical imaging for monitoring tumor oxygenation response after initiation of single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer patients

PLoS One. 2014 Jun 6;9(6):e98715. doi: 10.1371/journal.pone.0098715. eCollection 2014.

Abstract

Purpose: Optical imaging techniques for measuring tissue hemoglobin concentration have been recently accepted as a way to assess tumor vascularity and oxygenation. We investigated the correlation between early optical response to single-agent bevacizumab and treatment outcome.

Methods: Seven patients with advanced or metastatic breast cancer were treated with single-agent bevacizumab followed by addition of weekly paclitaxel. Optical imaging of patient's breasts was performed to measure tumor total hemoglobin concentration (tHb) and oxygen saturation (stO2) at baseline and on days 1, 3, 6, 8, and 13 after the first infusion of bevacizumab. To assess early metabolic response, 2-deoxy-2-(18F)-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT), 18F-fluoromisonidazole (FMISO)-PET/CT, and magnetic resonance imaging were performed at baseline and after two cycles of the regimen.

Results: Seven patients were grouped as responders (n = 4) and nonresponders (n = 3) on the basis of metabolic response measured by FDG-PET/CT. The responders showed remarkable tumor shrinkage and low accumulations of FMISO tracer relative to those of the nonresponders at the completion of two cycles of chemotherapy. Tumors of both groups showed remarkable attenuation of mean tHb as early as day 1 after therapy initiation. The nonresponders had lower baseline stO2 levels compared with adjacent breast tissue stO2 levels along with a pattern of steadily low stO2 levels during the observation window. On the other hand, the responders appeared to sustain high stO2 levels with temporal fluctuation.

Conclusions: Low tumor stO2 level after single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Bevacizumab
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / physiopathology
  • Cytotoxins / pharmacology*
  • Cytotoxins / therapeutic use
  • Female
  • Fluorodeoxyglucose F18
  • Hemodynamics / drug effects
  • Hemoglobins / metabolism
  • Humans
  • Middle Aged
  • Multimodal Imaging
  • Optical Imaging*
  • Oxygen / metabolism*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Cytotoxins
  • Hemoglobins
  • Fluorodeoxyglucose F18
  • Bevacizumab
  • Oxygen

Grant support

This work was supported by JSPS KAKENHI Grant Number 25830105 and Hidaka Research Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.