Contrast-enhanced ultrasound (CEUS) presents an ideal modality to evaluate the enhancement curve of a tumor. With the continuous imaging of ultrasound, a video clip of enhancement over time can be obtained, in order to produce a time-intensity curve (TIC). The TIC is of increasing interest in radiologic evaluation of tumors, in that it allows for quantifiable parameters to be extracted from imaging data. We wish to exploit this tool to monitor the response to therapy of primary or metastatic RCC, being treated with the novel agent sEphB4-HSA in the neoadjuvant setting. An anti-angiogenic and antineoplastic agent, sEphB4-HSA is known to decrease microvascular density within tumors, and has been studied in many types of epithelial tumors. We expect that the decreased microvascular density produced by this anti-angiogenic agent will be able to be evaluated and quantified using CEUS with TIC analysis, when pre- and post-treatment TICs are compared. 

The assembled study team has extensive research experience investigating novel therapies and quantitative imaging techniques for the treatment and therapy response assessment, respectively, for RCC. The study PI has already received pilot funding for projects related to contrast enhanced ultrasound for other tumor types and is extending his work to explore utility of CEUS with TIC as a potential response assessment biomarker to novel neoadjuvant therapeutic agents. This group is already working productively together, and meets regularly.

The present application represents a focused synergistic collaboration, which will enable the investigators to pool their resources and scientific expertise in addressing these unmet clinical needs which could not be achieved by the individual investigators working independently.
The successful validation and integration of CEUS with TIC analysis as a novel quantitative imaging methodology has the potential to allow better identification of patients who would benefit from neoadjuvant therapy, allow detection of early changes in microvascular density associated with response to therapy such that non-responders could be identified early and offered alternative treatment options. This potential, if actualized, could help establish new guidelines for neoadjuvant therapy and response assessment to improve outcomes and minimize complications. Increasing the use of quantitative imaging techniques should make patient care more objective, consistent, and personalized.

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