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December 15, 2020 — Radiology


Combined US-triggered microbubble destruction and hepatocellular carcinoma radioembolization showed improved treatment response compared with radioembolization alone and no changes in vital signs or liver function.


US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells.


To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC).

Materials and Methods

In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test.


Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02).


The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response.

Authors: John R. Eisenbrey1 , Flemming Forsberg1, Corinne E. Wessner1, Lauren J. Delaney1, Kristen Bradigan1, Sriharsha Gummadi1,5, Mohamed Tantawi1, Andrej Lyshchik1, Patrick O’Kane1, Ji-Bin Liu1, Charles Intenzo1, Jesse Civan2, Warren Maley3, Scott W. Keith4, Kevin Anton1, et al.

From Thomas Jefferson University: 1 Department of Radiology, 2 Department of Medicine, Division of Hepatology (J.C.), 3 Department of Surgery, 4 Department of Pharmacology and Experimental Therapeutics, Division of Biostatistics, 5 Department of Surgery, Lankenau Medical Center, Wynnewood, Pa

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