Pancreatic cancer: utility of dynamic contrast-enhanced MR imaging in assessment of antiangiogenic therapy.
OBJECTIVE
To prospectively evaluate the utility of dynamic contrast material-enhanced magnetic resonance (MR) imaging in predicting the response of locally advanced pancreatic cancer to combined chemotherapy and antiangiogenic therapy.


METHODS
This prospective, institutional review board-approved, HIPAA-compliant study with informed consent assessed dynamic contrast-enhanced MR imaging in 11 patients (mean age, 54.3 years; six men and five women) with locally invasive pancreatic cancer before and 28 days after combined chemotherapy and antiangiogenic therapy. Axial perfusion images were obtained after injection of 0.1 mmol gadopentetate dimeglumine per kilogram of body weight. Sagittal images of the upper abdominal aorta were obtained for arterial input function calculation. A two-compartment kinetic model was used to calculate the perfusion parameters K(trans) (the rate constant that represents transfer of contrast agent from the arterial blood into the extravascular extracellular space), K(ep) (the rate constant that represents transfer of contrast agent from the extravascular extracellular space to the blood plasma), and volume of distribution (v(e)). Semiquantitative measurements, peak tissue gadolinium concentration (C(peak)), maximum slope of gadolinium increase (slope), and area under the gadolinium curve at 60 seconds (AUC(60)) were also calculated. Perfusion parameters and tumor size changes were correlated with carbohydrate antigen 19-9 levels. Comparisons between pre- and posttreatment studies were performed by using the Wilcoxon signed rank test, and comparisons between responders and nonresponders were performed by using the Mann-Whitney test.


RESULTS
After therapy, K(trans), v(e), C(peak), slope, and AUC(60) decreased significantly (P = .02, .001, .002, .007, and .01, respectively). Tumor size and K(ep) were not significantly changed. Pretreatment K(trans) and K(ep) were significantly higher (P = .02 and .006, respectively) in tumors that showed marker response than in those that did not. A pretreatment K(trans) value (milliliters of blood per milliliter of tissue times minutes) of more than 0.78 mL/mL . min was 100% sensitive and 71% specific for subsequent tumor response. Semiquantative parameters and tumor size were not different between the groups.


CONCLUSIONS
Pretreatment K(trans) measurement in pancreatic tumors can predict response to antiangiogenic therapy. All perfusion parameters showed substantial reduction after 28 days of combined chemotherapy and antiangiogenic therapy.
Department of Radiology, Indiana University School of Medicine, 550 N University Blvd, Room 0279, Indianapolis, IN 46202, USA. makisik@iupui.edu
M Fatih
MF
Akisik
Kumaresan
K
Sandrasegaran
Guixue
G
Bu
Chen
C
Lin
Gary D
GD
Hutchins
Elena G
EG
Chiorean
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001557:Benzenesulfonates / Q000008:administration & dosage*; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077157:Sorafenib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D003287:Contrast Media; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D019786:Gadolinium DTPA