Changes in tumor blood flow as measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) may predict activity of single agent bevacizumab in recurrent epithelial ovarian (EOC) and primary peritoneal cancer (PPC) patients: an exploratory analysis of a Gynecologic Oncology Group Phase II study

Gynecol Oncol. 2012 Sep;126(3):375-80. doi: 10.1016/j.ygyno.2012.06.002. Epub 2012 Jun 7.

Abstract

Objective: To explore feasibility of measuring tumor blood flow as marker for antiangiogenic activity using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) in women with recurrent EOC/PPC treated with bevacizumab.

Methods: In a phase II study, 62 patients with recurrent/persistent EOC/PPC were treated with bevacizumab (15 mg/kg IV q21 days) until disease progression. DCE-MRI was performed pre-cycle 1 and 4 of bevacizumab. Images were analyzed retrospectively by a single experienced blinded radiologist. Tumor and muscle contrast enhancement was measured by region of interest signal intensity within the same DCE-MRI images. Flow rates were obtained with concentration of dye as a function of time. Relative blood flow (RBF) was calculated as a ratio of average blood flow into tumor to muscle tissue. Associations between RBF and characteristics/outcomes were explored.

Results: Sixty-two patients were eligible for study. Unfortunately, only 14 (23%) patients had imaging data available for analysis at baseline and 13 of those same patients (21%) had imaging data available for analysis pre-cycle 4. The RBF distribution was similar from pre-cycle 1 to 4. RBF remained stable for the majority of the cases (median change -0.21). Baseline RBF was not significantly associated with being progression-free at 6 months, microvessel density, 17 month overall survival, tumor response, or platinum sensitivity. However, increases in blood flow rates were associated with likelihood to be progression-free at 6 months.

Conclusion: Functional imaging of tumor blood flow is a potential research endpoint that may be explored further. Consideration should be given to timing of endpoint and standardizing the technique.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Blood Vessels / pathology
  • Carcinoma, Ovarian Epithelial
  • Contrast Media
  • Disease-Free Survival
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / blood supply*
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neovascularization, Pathologic / pathology
  • Ovarian Neoplasms / blood supply*
  • Ovarian Neoplasms / drug therapy
  • Peritoneal Neoplasms / blood supply*
  • Peritoneal Neoplasms / drug therapy
  • Predictive Value of Tests
  • Regional Blood Flow / drug effects
  • Single-Blind Method

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Contrast Media
  • Bevacizumab