Cholangiocarcinoma Non-resectable
Conditions
Keywords
Perihilar cholangiocarcinoma, Hepatic artery embolization, Vascular invasion, Surgical conversion, Radical resection
Brief summary
This is a prospective, multicenter, single-arm study investigating the efficacy and safety of preoperative right hepatic artery embolization (PHAE) followed by surgical resection in patients with locally advanced Bismuth IIIb or IV perihilar cholangiocarcinoma (PHCC) involving the right hepatic artery. The standard treatment for such cases is often considered unresectable due to the high risk of hepatic ischemia after arterial resection without reconstruction. This study proposes a strategy: preoperative embolization of the tumor-involved right hepatic artery to stimulate the development of collateral arterial circulation (e.g., from the right inferior phrenic artery), enabling subsequent radical resection of the right hepatic artery without reconstruction. The primary objective is to evaluate the 1-year overall survival rate. Secondary objectives include surgical conversion rate, R0 resection rate, 1-year/3-year recurrence-free survival, 3-year overall survival rate and safety assessment. A total of 33 participants will be enrolled across multiple centers in China.
Detailed description
This study aims to validate a novel surgical strategy for locally advanced Bismuth IIIb or IV perihilar cholangiocarcinoma (PHCC) where the tumor involves the right hepatic artery (RHA), rendering the tumor conventionally unresectable due to the high risk of postoperative right hepatic lobe ischemia if the artery is resected without reconstruction. The intervention involves preoperative selective embolization of the tumor-involved RHA using coils. This procedure is intended to induce the development of collateral arterial supply to the right liver lobe from extrahepatic arteries (e.g., right inferior phrenic, adrenal, intercostal arteries) over a 2-4 week period. Following confirmation of collateral circulation via imaging, patients undergo radical left hepatectomy or left trisectionectomy with en-bloc resection of the involved RHA without arterial reconstruction. The study employs a single-arm design. The primary endpoint is the 1-year overall survival (OS) . The study is designed to detect an improvement to 75%, compared to a historical control rate of 54% observed with chemoimmunotherapy for unresectable disease. Secondary endpoints include surgical conversion rate, R0 resection rate, 1-year/3-year recurrence-free survival (RFS), 3-year OS, and safety profiles (incidence of liver abscess, bile leak, post-hepatectomy liver failure, and other Clavien-Dindo ≥ Grade III complications). The study involves multiple phases: screening/preparation (including biliary drainage and portal vein embolization if needed), the PHAE procedure, radical surgery (2-4 weeks post-PHAE), and a 3-year follow-up period. Statistical analysis will be performed on the intention-to-treat (FAS), per-protocol (PPS), and safety (SS) populations.
Interventions
PROCEDUREPreoperative Right Hepatic Artery Embolization
Participants receive preoperative selective embolization of the tumor-involved right hepatic artery, followed 2-4 weeks later by radical left hepatectomy or left trisectionectomy with resection of the involved artery without reconstruction.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent. * Age 18-80 years. * Clinical diagnosis of Bismuth IIIb or IV perihilar cholangiocarcinoma, deemed suitable for radical resection via left hepatectomy or left trisectionectomy. * Imaging (CTA/MRA) confirms tumor invasion of the right hepatic artery (RHA) that is assessed as "unable to be safely reconstructed after resection" (e.g., involvement of RHA branches or requiring vascular graft for reconstruction). * Portal vein on the side of the future liver remnant is not invaded or is reconstructable. * ECOG performance status 0-1. * Child-Pugh score ≤ 7 (Class A or B). * Adequate organ function (bone marrow, liver, kidney) as per protocol-defined laboratory values. * Expected survival ≥ 12 weeks.
Exclusion criteria
* Evidence of distant metastasis (M1). * History of other malignancies within the past 5 years (except cured basal cell carcinoma or cervical carcinoma in situ). * Severe cardiac, pulmonary, renal, or cerebrovascular disease as specified in the protocol (e.g., recent myocardial infarction, severe COPD, chronic renal failure stage ≥ III). * Uncontrolled active infection or diabetes. * Pregnancy or lactation. * Allergy to iodinated contrast media. * Postoperative pathology confirms non-cholangiocarcinoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-Year Overall Survival | 1 year post-surgery | The proportion of patients alive at 1 year after the radical surgery date. Overall survival is defined as the time from surgery to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgical Conversion Rate | At the time of surgery | The proportion of enrolled patients who successfully undergo radical resection. |
| R0 Rate | At the time of surgery | The proportion of resected patients achieving microscopically negative cut margins at the axial and radial of bile duct tumor. |
| 1-Year and 3-Year Recurrence-Free Survival Rate | 1 year and 3 years post-surgery | The proportion of patients alive and free of tumor recurrence at 1 and 3 years after surgery. Recurrence-free survival is defined as the time from surgery to the first documented recurrence or death from any cause. |
| 3-Year Overall Survival | 3 years post-surgery | The proportion of patients alive at 3 years after the radical surgery date. |
| Incidence of Major Complications (Clavien-Dindo ≥ Grade III) | 90 days post-surgery | The proportion of patients experiencing post-procedural (embolization or surgery) complications graded as Clavien-Dindo III or higher within 90 days after surgery. |
Contacts
CONTACTXiangde Shi, Doctor
CONTACTChao Liu, Doctor
Outcome results
None listed