Radiosensitization of intrahepatic cholangiocarcinoma and metastatic disease in the liver using microbubble cavitation: results from a phase 2 clinical trial.

Ultrasound triggered microbubble destruction (UTMD) has been shown to sensitize tumors to radiation. This study evaluated the feasibility, safety, and efficacy of using UTMD for radiosensitization in participants with intrahepatic cholangiocarcinoma (ICC) and/or metastatic disease to the liver (MDL) receiving Yttrium-90 transarterial radioembolization (Y90-TARE). This was a prospective single-center IRB-approved clinical trial. Participants received four contrast ultrasound sessions: 1-2 weeks prior to Y90-TARE, 1-4 h post-treatment, and 1 week and 2 weeks post-Y90-TARE. The control group consisted of 1:1 nearest-neighbor propensity score matched historical controls participants that received Y90-TARE as part of standard-of-care. Safety was evaluated through general lab values, physiological monitoring and adverse events. Treatment response was determined by a 1-6 month CT/MRI and evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Final analysis included 15 participants in each group. There were no differences in general lab values between groups (p > 0.15). In study participants, there were no differences in physiological monitoring between pre and post UTMD sessions (p > 0.20). There was a trend toward a better response distribution in the study group compared to the control group (study group: 0 % progressive disease (0/14), 29 % participants with stable disease (4/14), 21 % participants with partial response (3/14), 50 % participants with complete response (7/14) and control group: 33 % participants with progressive disease (5/15), 27 % with stable disease (4/15), 13 % with partial response (2/15), 27 % with complete response (4/15) when evaluating long-term imaging, p = 0.06). The addition of UTMD in participants that received Y90-TARE was feasible, safe, and might deliver improved treatment response.