Prospective analysis on the outcomes of histotripsy for primary and metastatic liver tumors

BACKGROUND: Histotripsy is an innovative, non-invasive ultrasound-based technology that mechanically disrupts liver tumor tissues at the cellular level through acoustic cavitation. It offered precise tissue destruction with minimal collateral damage. This study evaluated the safety and efficacy of this novel treatment through clinical and biomolecular analysis. METHODS: From August to 30 December 2024 patients with malignant liver cancers, Child-Pugh A liver function, and tumors <10 cm were recruited. Treatments were performed under general anesthesia using histotripsy with tailored approaches for left and right liver tumors. Technical success and treatment efficacy were assessed by contrast-enhanced MRI at 36 hours and 1 month post-procedure. Complications were classified by Clavien-Dindo criteria. Plasma cytokine profiles were analyzed pre-treatment, at 1-day, and 1-month post-treatment. A cytokine score predictive of clinical outcomes was derived via Least Absolute Shrinkage and Selection Operator regression and Receiver Operating Characteristic analysis. RESULTS: A total of 19 patients (63.3%) had hepatocellular carcinoma while the remaining 11 patients had liver metastases from different origins including colorectal, pancreas, breast, and thyroid. A total of sixty tumors with a median tumor diameter of 1.8 cm and a median tumor number per patient of 2 were treated. The 36-hour technical success rate was 95% and 1-month efficacy rate was 82.5%. Procedure-related complications were mild, including transient fever and abdominal discomfort controlled by analgesics; no grade III or above complications occurred. Cytokine profiling revealed a significant systemic inflammatory response at 1-day post-treatment, notably increased Interleukin 6 (IL-6). A four-cytokine panel (IL-7, IL-6, IL-1α, CXCL1) generated a cytokine score that strongly predicted complete tumor response (area under the curve = 0.955). Higher cytokine scores correlated with greater treatment volume and elevated liver enzymes indicative of an immunomodulatory effect. CONCLUSION: Histotripsy was a safe and effective non-invasive treatment for liver tumors, demonstrating promising clinical outcomes and systemic immune activation. These findings supported further investigation into its long-term efficacy and potential synergy with immunotherapy.