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

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 q21days) 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.