Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab--initial experience.
OBJECTIVE
To retrospectively compare three dynamic contrast material-enhanced magnetic resonance (MR) imaging (dynamic MR imaging) analytic methods to determine the parameter or combination of parameters most strongly associated with changes in tumor microvasculature during treatment with bevacizumab alone and bevacizumab plus chemotherapy in patients with inflammatory or locally advanced breast cancer.


METHODS
This study was conducted in accordance with the institutional review board of the National Cancer Institute and was compliant with the Privacy Act of 1974. Informed consent was obtained from all patients. Patients with inflammatory or locally advanced breast cancer were treated with one cycle of bevacizumab alone (cycle 1) followed by six cycles of combination bevacizumab and chemotherapy (cycles 2-7). Serial dynamic MR images were obtained, and the kinetic parameters measured by using three dynamic analytic MR methods (heuristic, Brix, and general kinetic models) and two region-of-interest strategies were compared by using two-sided statistical tests. A P value of .01 was required for significance.


RESULTS
In 19 patients, with use of a whole-tumor region of interest, the authors observed a significant decrease in the median values of three parameters measured from baseline to cycle 1: forward transfer rate constant (Ktrans) (-34% relative change, P=.003), backflow compartmental rate constant extravascular and extracellular to plasma (Kep) (-15% relative change, P<.001), and integrated area under the gadolinium concentration curve (IAUGC) at 180 seconds (-23% relative change, P=.009). A trend toward differences in the heuristic slope of the washout curve between responders and nonresponders to therapy was observed after cycle 1 (bevacizumab alone, P=.02). The median relative change in slope of the wash-in curve from baseline to cycle 4 was significantly different between responders and nonresponders (P=.009).


CONCLUSIONS
The dynamic contrast-enhanced MR parameters Ktrans, Kep, and IAUGC at 180 seconds appear to have the strongest association with early physiologic response to bevacizumab. Clinical trial registration no. NCT00016549
Thukral
Arpi
A
Medical Oncology Branch, Molecular Imaging Program, and Biostatistics and Data Management Section, Center for Cancer Research, NCI, and Diagnostic Radiology Department, Warren G. Magnuson Clinical Center, NIH, Bethesda, MD 20889-5015, USA.
Thomasson
David M
DM
Chow
Catherine K
CK
Eulate
Reyes
R
Wedam
Suparna B
SB
Gupta
Sandeep N
SN
Wise
Betty J
BJ
Steinberg
Seth M
SM
Liewehr
David J
DJ
Choyke
Peter L
PL
Swain
Sandra M
SM
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D006801:Humans; D007249:Inflammation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab; D019786:Gadolinium DTPA