Hepatic Artery Infusion Pump Chemotherapy Associated Biliary Sclerosis After Treatment for Colorectal Cancer Liver Metastasis.

Abstract

Hepatic artery infusion pump chemotherapy (HAIC) improves colorectal liver metastasis (CRLM) outcomes, but treatment-associated biliary sclerosis (BS) is a major complication. This study evaluates the incidence of and risk factors for BS after HAIC for CRLM. This was a single-center retrospective analysis including all patients with CRLM treated with floxuridine between 2000 and 2022. The primary outcome was BS, intractable hyperbilirubinemia, and/or biliary stricture not caused by cancer progression requiring percutaneous or endoscopic stenting or drainage. BS was analyzed using competing risk methods where death was the competing event. Between 2000 and 2022, a total of 2239 patients received HAIC for CRLM, 48% (n=1067) received adjuvant HAIC and 52% (n=1172) were unresectable. There were 128 (6% at 60 months) BS events, and rates did not differ between adjuvant (n=66) and unresectable (n=62) groups (60-month estimate: 6% [95% confidence interval (CI) 5-8] vs 6% [95% CI 4-7]; p=0.362). Operative variables, variant hepatic arterial anatomy, non-gastroduodenal artery cannulation, and extrahepatic perfusion were not associated with BS. In adjuvant cases, BS risk increased with each cycle (hazard ratio [HR] 1.123, p=0.003) and every 100 mg of cumulative floxuridine (HR 1.087, p<0.001) controlling for concurrent colorectal resection and variant vessel ligation. Among unresectable patients, each cycle (HR 1.087, p<0.001) and every 100 mg of cumulative floxuridine (HR 1.054, p<0.001) increased BS risk, controlling for race and concurrent colorectal resection. The incidence of BS after HAIC for CRLM is 6% after 60 months and does not differ in the adjuvant and unresectable setting due to meaningful differences in survival. Cumulative floxuridine dose and number of HAIC cycles were independently associated with increased BS risk.