Histotripsy for the Treatment of Cholangiocarcinoma in a Patient-Derived Xenograft Mouse Model

Abstract

Histotripsy is a focused ultrasound ablation therapy being developed for the treatment of liver tumors. A recent study investigating the feasibility of using histotripsy for the ablation of cholangiocarcinoma (CC), bile duct cancer that is difficult to treat with current therapies because of its location near critical structures and fibrous tissue, reported the feasibility of treating CC in an acute mouse model. Here, we investigate histotripsy for the in vivo ablation of CC in a chronic study using a 1-MHz transducer at an applied dose of 500 pulses/point. A pilot study determined that treating the CC tumors plus a 1- to 2-mm margin induced significant injuries to intestinal tissues, thus precluding the use of this strategy. Next, histotripsy was applied to CCs (n = 6) with the treatment contained to the tumor. Post-treatment, the ablation was visualized using ultrasound, and subjects were monitored over time. Histotripsy achieved an average of 73% reduction of tumor diameter 26 d after treatment, with no significant adverse events. Notably, three of six treated tumors were undetectable after 2.5 wk. The treated animals were found to have significantly increased tumor progression-free and overall survival. Overall, results indicate that histotripsy can be used as a safe and effective method for treating CC.

Keywords: Cholangiocarcinoma; Focused ultrasound; Histotripsy; Liver cancer; Tumor ablation.