2D and 3D Contrast-enhanced Ultrasound Evaluation of Chemoembolization.

Project Summary Transarterial chemoembolization (TACE) is the recommended treatment option for patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma (HCC) but may also be used as a bridge therapy in HCC patients who are potential transplant candidates. Additionally, this locoregional therapy is frequently used for the treatment of other primary (cholangiocarcinoma) and metastatic liver cancers (colorectal cancer, breast cancer, melanoma, neuroendocrine tumors, and some soft tissue sarcomas). Incomplete TACE treatment (observed in up to two-thirds of patients) is defined as persistence of enhancing areas inside the treated lesions seen at the first imaging follow up. Initial guidelines recommend follow-up contrast-enhanced MR or CT imaging 4-6 weeks after all tumor-bearing areas have been treated. The inherent limitations of these modalities initially led our group to pursue the use of contrast-enhanced ultrasound (CEUS) imaging as an alternative for assessing HCC response to TACE earlier as part of this NIH grant R01 CA194307. Our prospective multi-center trial demonstrated an improved sensitivity for detecting residual disease following TACE relative to clinical standard of care CT/MR imaging (91.4% vs. 67.8%; p≤0.008) and an ability to identify patients requiring retreatment as early as one-week post treatment. Importantly, data from this grant has in part lead to the recent decision by the American College of Radiology to incorporate CEUS into its liver imaging reporting and data system (LI-RADS) treatment response algorithm, supporting full clinical adoption. In this funding cycle, we plan to build on this momentum to expand the role of CEUS within TACE while also overcoming limitations in our prior study. First, we plan to evaluate the diagnostic performance of CEUS for assessing TACE response in non-HCC tumors (which vary in vascularity and now makes up the majority of cases at many institutions). Secondly, we plan to investigate the ability and diagnostic performance of TACE intra-operatively. While treatment will not be altered as part of this proposal, once properly validated this could enable immediate tumor retreatment and improve the overall response rates of TACE. Thirdly, we plan to investigate a variety of advanced ultrasound techniques including improved volumetric CEUS, frequency spectrum analysis, and off-line techniques for improving resolution of vascular structures. We hypothesize these approaches will improve on the suboptimal specificity observed in our initial studies. Finally, we propose to quantify tumor vascular morphology and blood flow dynamics prior to treatment as a means for predicting treatment response (and ultimately personalizing the selection of locoregional therapy). Ultimately, this work will continue to expand the role of CEUS in the setting of TACE by demonstrating applicability to a variety of solid tumors, guiding treatment, and improving on the technique’s overall specificity.