Microbubble Ultrasound Compared to Dynamic Contrast Mri and Ct for the Assessment of Vascular Response to Sunitinib in Renal Cell Carcinoma.

e15039 Background: A novel ultrasound method employing microbubble (MB) contrast offers portable, noninvasive dynamic assessment of tumor blood flow. A MB contrast agent (Definity, Lantheus, Boston) is infused to produce vascular enhancement on nonlinear ultrasound imaging. The MBs, the size of red blood cells, remain intravascular. MBs are disrupted with an ultrasound pulse and the wash-in of new bubbles is imaged. This method, DCE-US, measures blood flow, velocity and vascular volume in multiple planes. Methods: Untreated patients (pts) with metastatic renal cell cancer (RCC) and a large abdominal tumor suitable for imaging were eligible for study and received Sunitinib 50 mg for 4 weeks on a 6-week cycle. DCE-US, contrast enhanced CT and DCE-MRI were performed on the first treatment course at baseline and on day 14. Blood samples for circulating endothelial cells (CECs) were obtained at the same time points. Results: The abdominal tumors imaged in 20 pts were the RCC primary (15pts), local recurrence (2), liver metastasis (1), retroperitoneal nodes (1) and a pancreas metastasis (1). In 16 pts progression free at 2 months, baseline vs. day 14 studies showed a significant (p < 0.05) decrease in blood volume in each of 13/16 pts (81%) on DCE-US, and a significant decrease in Ktrans and kep (Ktrans/ve) in 9/15 pts (60%) and 8/15 pts (53%) respectively on DCE-MRI. By RECIST criteria on CT, 3/16 (19%) and 13/16 (81%) were designated as partial response (PR) and stable disease (SD) respectively. By modified Choi criteria on CT, 8/13 (62%) and 5/13 (38%) were designated as PR and SD respectively. The number of viable CECs decreased in 10/14 (71%) and of apoptotic CECs in 9/14 (64%) pts. In 4 pts that progressed during the first sunitinib course, DCE-US showed a significant increase in blood volume in 1/4, no change in 2/4 and a decrease in 1/4. There was no increase in Ktrans or kep in progressing pts. The coefficient of variation of the same image plane scanned multiple times with DCE-US was 10%. Conclusions: DCE-US at 14 days is at least as good as DCE-MRI and a contrast enhanced CT at predicting progression-free survival at 2 months. This method is reproducible and takes advantage of a non-diffusible tracer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Philips Ultrasound, Supersonic Imagine Inc. Pfizer Lantheus Medical Imaging, Inc., Pfizer