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

Albert Cy Chan; Vince Wh Lau; Gordon Tc Wong; Y W Chan; Kwan Man; L Y Ng; Huanhuan Ma; Abdullah Husain; Irene Ol Ng

doi:10.1097/JS9.0000000000003856

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

Int J Surg. 2025 Nov 10. doi: 10.1097/JS9.0000000000003856. Online ahead of print.

Authors

Albert Cy Chan^{1

2}, Vince Wh Lau³, Gordon Tc Wong⁴, Y W Chan⁴, Kwan Man^{1

2}, L Y Ng^{2

5}, Huanhuan Ma^{2

5}, Abdullah Husain^{2

5}, Irene Ol Ng^{2

5}

Affiliations

¹ Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong.
² State Key Laboratory of Liver Research, The University of Hong Kong.
³ Department of Radiology, Gleneagles.
⁴ Department of Anaesthesia, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong.
⁵ Department of Pathology, LKS Faculty of Medicine, School of Clinical Medicine, Queen Mary Hospital.

PMID: 41217432
DOI: 10.1097/JS9.0000000000003856

Abstract

Background: Histotripsy was an innovative, non-invasive ultrasound-based technology that mechanically disrupts liver tumour tissues at cellular level through acoustic cavitation. It offered precise swith minimal collateral damage. This study evaluated the safety and efficacy of this novel treatment with biomolecular analysis.

Methods: From August to 30 December 2024 patients with malignant liver cancers, Child A liver function, and tumours <10 cm were recruited. Treatments were performed under general anaesthesia using histotripsy with tailored approaches for left and right liver tumours. Technical success and treatment efficacy were assessed by contrast-enhanced MRI at 36 hours and one month post-procedure. Complications were classified by Clavien-Dindo criteria. Plasma cytokine profiles were analysed pre-treatment, 1-day, and 1-month post-treatment. A cytokine score predictive of clinical outcomes was derived via LASSO regression and ROC analysis.

Results: 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 tumours with a median tumour diameter of 1.8 cm and a median tumour 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 IL-6. A four-cytokine panel (IL-7, IL-6, IL-1α, CXCL1) generated a cytokine score that strongly predicted complete tumour response (AUC = 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 tumours, demonstrating promising clinical outcomes and systemic immune activation. These findings supported further investigation into its long-term efficacy and potential synergy with immunotherapy.

Keywords: ablation; hepatocellular carcinoma; histotripsy; liver metastasis; liver tumour.