Investigate the impact of histotripsy dosing on liver cancer therapeutic outcomes

Histotripsy has been shown to inhibit local and abscopal tumor progression, reduce metastasis development and improve survival. Following promising preclinical studies and clinical trials, histotripsy received FDA clearance for treating liver cancer in 2023. However, clinically, a fixed histotripsy dose (defined by the number of histotripsy pulses) is used, which has not been optimized to maximize therapeutic outcomes based on cancer type. The aim of this study is to investigate the impact of histotripsy dose and tumor stages on treatment outcomes in a well-established orthotopic immunocompetent HCC model. We quantitatively demonstrate that histotripsy dose affects the level of tumor cellular damage, with downstream effects on immune response and other long-term treatment outcomes including local tumor control, metastasis inhibition, abscopal response, and survival. Importantly, we found that higher doses that result in overtreatment do not improve histotripsy outcomes, rather they had worse outcomes compared to the optimal dose. Overall, our data emphasizes the need for optimizing and personalizing histotripsy doses for different types of cancer types.