Histotripsy x Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with 5-year survival around 12% despite advances in surgery, chemotherapy, and radiotherapy. Existing ablative therapies (RFA, microwave, irreversible electroporation) are limited by thermal injury risk, proximity to vessels/ducts. Novel local therapies that can be integrated with systemic regimens are urgently needed. Histotripsy is a non-thermal focused ultrasound modality that uses controlled cavitation to mechanically liquefy tissue without thermal coagulation or ionizing radiation, with precision under real-time ultrasound guidance. Preclinical and early translational work in pancreatic models shows that histotripsy can safely ablate pancreatic tissue while sparing major vessels and ducts in large-animal models, and can alter the tumour microenvironment (TME) with increased release of damage-associated molecular patterns (DAMPs), enhanced dendritic cell and macrophage activation, and increased CD8+ T-cell infiltration in murine pancreatic tumours. This proposal aims to evaluate the safety, local tumour control, and immunologic effects of histotripsy in pancreatic cancer especially PDAC, positioning it as a platform to enhance responsiveness to contemporary systemic therapies. The HistoSonics Histotripsy System is now registered in the Medical Device Administration Control System from Department of Health in Hong Kong (HKMD no: 252842).

Inclusion Criteria: * Age ≥ 18 years old * Fit for general anaesthesia * Unresectable pancreatic cancer with, or without vascular encasement * With or without distant metastasis * Without portal vein thrombosis * Good performance status: 1. Tumour visible and targetable by ultrasound with acceptable acoustic windows 2. Adequate hematologic, hepatic, and renal function Exclusion Criteria: * Refusal to take part in clinical trial * Portal vein thrombosis present * Not fit for general anaesthesia * Poor general condition with limited life expectancy * Uncontrolled coagulopathy * Extensive bowel interposition preventing safe targeting, per recent porcine safety data linking mis-targeting to bowel injury