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 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.


CONCLUSIONS
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.
Gynecologic Oncology, Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013 USA.
Dana M
DM
Chase
Michael W
MW
Sill
Bradley J
BJ
Monk
Mark D
MD
Chambers
Kathleen M
KM
Darcy
Ernest S
ES
Han
Barbara J
BJ
Buening
Joel I
JI
Sorosky
John P
JP
Fruehauf
Robert A
RA
Burger
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000068258:Bevacizumab; D001808:Blood Vessels / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D003287:Contrast Media; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D010534:Peritoneal Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D011237:Predictive Value of Tests; D012039:Regional Blood Flow / Q000187:drug effects; D016037:Single-Blind Method
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab