Histotripsy for Ablation of Liver Tumours in Asia

This will be a single-arm, multi-centre, prospective pilot study enrolling patients with:

A) Liver limited malignancies (primary or secondary) not eligible for/declined resection or other locoregional treatment modalities.

B) All solid cancer patients (e.g., HCC, colorectal, breast, pancreatic cancers etc) undergoing systemic therapy with oligoprogressive liver disease (defined as ≤ 3 liver limited progressive lesions, ≤ 3 cm in maximum diameter having received > 3 months of systemic therapy).

Patients will undergo baseline imaging and laboratory investigations, followed by histotripsy treatment under general anaesthesia. Post-procedure assessments will be performed at predefined intervals for clinical, radiologic, and biomarker evaluation.

Inclusion criteria

• Age ≥21 years at the time of consent.
• Histologically/cytologically confirmed cancers (imaging diagnosis as per AASLD allowed for HCC):

A) Liver limited malignancies (primary or secondary) not eligible for/declined resection or other locoregional treatment modalities.

B) All solid cancer patients (e.g., HCC, colorectal, breast, pancreatic cancers etc) undergoing systemic therapy with oligoprogressive liver disease (defined as ≤ 3 liver limited progressive lesions, ≤ 3 cm in maximum diameter having received > 3 months of systemic therapy).

• Characteristics of hepatic lesions intended for treatment:

• Up to 3 hepatic lesions.
• Tumour ≤ 3 cm in longest diameter.
• Lesion(s) must be visible and targetable by ultrasound.
• ECOG Performance Status 0-1.
• Child-Pugh class A or B7 liver function for patients with underlying cirrhosis.
• Adequate hematologic and organ function within 14 days prior to treatment:

• Haemoglobin ≥ 9.0 g/dL
• Platelets ≥ 75,000/mm³
• INR ≤ 1.5 × ULN
• Estimated (by Cockroft-Gault or Modification of Diet in Renal Disease (MDRD) or measured creatinine clearance ≥ 50ml/min.
• Total bilirubin ≤ 1.5 × upper limit normal or direct bilirubin ≤ ULN for participants with total bilirubin > 1.5 × ULN (participants with known history of elevated indirect bilirubin level suggestive of extrahepatic source of elevation e.g. Gilbert's disease may be recruited with bilirubin levels ≤ 3 × ULN)
• AST and ALT ≤ 5 × ULN
• Ability to undergo general anaesthesia, as confirmed by pre-anaesthetic assessment.
• Life expectancy ≥ 3 months in the opinion of the investigator.
• Willing and able to comply with study visits and procedures.
• Written informed consent obtained prior to any study-related procedures.

Exclusion criteria

• Extrahepatic disease progression requiring immediate systemic intervention, including new brain metastases or malignant ascites.
• Vascular invasion, defined as gross involvement or encasement of major portal vein or hepatic vein branches.
• Tumours located adjacent (<5 mm) to hollow viscera (e.g., stomach, colon) where histotripsy poses perforation risk.
• Lesions poorly visualized on ultrasound or not targetable due to overlying ribs or gas.
• Severe or uncontrolled comorbidities including:

• Uncontrolled hypertension or cardiovascular disease
• Active infection (requiring systemic therapy)
• Severe chronic obstructive pulmonary disease or hypoxia
• Contraindications to general anaesthesia or surgery.
• Pregnancy or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days prior to treatment.
• Participation in another interventional trial within 4 weeks prior to enrollment, or concurrent participation in a therapeutic study.
• Any condition that, in the investigator's judgment, may compromise the patient's safety or interfere with protocol adherence.