A Prospective, Randomized Controlled Phase II Clinical Study of Sequential or Non-sequential Irreversible Electroporation After Chemotherapy Induction in Patients With Locally Advanced Unresectable Perihilar Cholangiocarcinoma
Irreversible electroporation is a non-thermal ablative technology that uses high-voltage electric pulses to create permanent nanopores in tumor cell membranes, leading to apoptosis or other forms of cell death. Because the mechanism is primarily non-thermal, IRE may better preserve extracellular matrix, bile ducts, vessels, and other critical structures than thermal ablation, which is relevant for tumors adjacent to major vascular or biliary anatomy. The main anticipated clinical value of IRE in these protocols is local disease control and potential survival benefit when used after induction therapy in patients with non-progressive disease. The procedure may be performed by open or percutaneous access according to tumor location, safety considerations, and institutional expertise. Perioperative management, imaging guidance, and post-procedure monitoring will follow institutional standards. Post-IRE gastrointestinal dysfunction may occur. Symptom-directed supportive care, including electroacupuncture where appropriate and approved by the investigator, may be used as supportive management. Such care is not intended to replace oncologic treatment and will be recorded as concomitant treatment when administered.
• \- Age 18-75 years, both sexes
• Histologically or cytologically confirmed locally advanced perihilar cholangiocarcinoma (Bismuth-Corlette type III/IV or equivalent)
• Non-progressive disease (PR or SD) after 3 cycles of standard induction chemotherapy
• MDT-confirmed unresectable disease after induction therapy
• No prior palliative systemic therapy
• At least one measurable lesion per RECIST 1.1
• ECOG Performance Status 0-1
• Adequate organ and marrow function: Hb ≥9.0 g/dL, ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, TBIL ≤3×ULN, AST/ALT ≤5×ULN, serum creatinine ≤1.5×ULN or CrCl \>60 mL/min
• Life expectancy ≥3 months
• Willing to use contraception if of childbearing potential
• Written informed consent