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.

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.

• Authors: Dana M Chase, Michael W Sill, Bradley J Monk, Mark D Chambers, Kathleen M Darcy, Ernest S Han, Barbara J Buening, Joel I Sorosky, John P Fruehauf, Robert A Burger
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 126 Issue 3 Pg. 375-80 (Sep 2012) ISSN: 1095-6859 [Electronic] United States
• PMID: 22683587 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Aged
• Angiogenesis Inhibitors (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized (pharmacology, 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, drug therapy)
• Neovascularization, Pathologic (pathology)
• Ovarian Neoplasms (blood supply, drug therapy)
• Peritoneal Neoplasms (blood supply, drug therapy)
• Predictive Value of Tests
• Regional Blood Flow (drug effects)
• Single-Blind Method