Contrast-enhanced ultrasound evaluation of radioembolization treatment response - Project Summary Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and the incidence is increasing. The use of transarterial radioembolization (TARE) has been shown to be successful for the treatment and downstaging of HCC as well as liver metastases. While effective (complete response rates of 25-60%), evaluation of treatment response is problematic and frequently diagnosed on CT/MRI as equivocal or non- progressing for the first 4-6 months post treatment using the recently updated liver imaging and data reporting systems radiation-based treatment response algorithm (LI-RADS Radiation TRA v2024). Importantly, this delay in definitive diagnosis of tumor viability subsequently delays needed retreatment and can even serve as a barrier to transplantation. Contrast-enhanced ultrasound (CEUS) is a well-established technique for enhancing a wide range of vascular and oncologic ultrasound applications worldwide. Our prior work in HCC locoregional therapy has shown CEUS provides improved sensitivity in detecting viable tumor following transarterial chemoembolization relative to traditional cross-sectional imaging and results of our studies served as a foundation for the recently released CEUS Nonradiation LI-RADS TRA v2024. As part of a recently completed, randomized controlled clinical trial to use CEUS to augment radioembolization, we observed that changes in tumor vascularity could be detected as early as one week post TARE and that these changes correlated with longer term response. Consequently, we propose to evaluate both qualitative and quantitative CEUS as a tool for evaluating HCC TARE, while also investigating the role of a late phase (Kupffer cell-specific) agent. In the first specific aim we will evaluate the diagnostic performance of qualitative CEUS to assess treatment response of HCC to TARE at identical time points obtained on standard of care CT/MRI in a total of thirty patients with treatment naïve HCC. Sensitivity, specificity, positive and negative predictive value, and reader agreement will then be calculated for each exam and each time point using explant pathology (when available), or longer-term stability on CT/MRI follow-up as a reference standard. In the second aim, we will evaluate the diagnostic performance of quantitative CEUS to assess treatment response of HCC to TARE. Finally, in aim three we will explore the use of a Kupffer cell- specific contrast agent to improve diagnosis of viable HCC tumor following TARE using the ultrasound contrast agent Sonazoid Once fully validated, we expect CEUS to significantly improve treatment response evaluation and provide a foundation for the development of LI-RADS CEUS Radiation TRA.
