Radiation-emitting metallic stent for unresectable Bismuth type III or IV perihilar cholangiocarcinoma: a multicenter randomized trial

Abstract

Background and aims: Self-expandable metallic stents (SEMSs) have been recommended for patients with unresectable malignant biliary obstruction, while radiation-emitting metallic stents (REMSs) loaded with 125 I seeds have recently been approved to provide longer patency and overall survival in malignant biliary tract obstruction. This trial is to evaluate the efficacy and safety of REMS plus hepatic arterial infusion chemotherapy (REMS-HAIC) versus SEMS plus HAIC (SEMS-HAIC) for unresectable perihilar cholangiocarcinoma (pCCA).

Materials and methods: This multicenter randomized controlled trial recruited patients with unresectable Bismuth type III or IV pCCA between March 2021 and January 2023. Patients were randomly assigned (1:1 ratio) to receive either REMS-HAIC or SEMS-HAIC using permuted block randomization, with a block size of six. The primary endpoint was overall survival (OS). The secondary endpoints were time to symptomatic progression (TTSP), stent patency, relief of jaundice, quality of life, and safety.

Results: A total of 126 patients were included in the intent-to-treat population, with 63 in each group. The median OS was 10.2 months versus 6.7 months ( P =0.002). The median TTSP was 8.6 months versus 5.4 months ( P =0.003). The median stent patency was longer in the REMS-HAIC group than in the SEMS-HAIC group ( P =0.001). The REMS-HAIC group showed better improvement in physical functioning scale ( P <0.05) and fatigue symptoms ( P <0.05) when compared to the SEMS-HAIC group. No significant differences were observed in relief of jaundice (85.7% vs. 84.1%; P =0.803) or the incidence of grade 3 or 4 adverse events (9.8% vs. 11.9%; P =0.721).

Conclusion: REMS plus HAIC showed better OS, TTSP, and stent patency compared with SEMS plus HAIC in patients with unresectable Bismuth type III or IV pCCA with an acceptable safety profile.

Graphical abstract

Figure 1

Representative images of a 75-year-old male patient who received a radiation-emitting metallic stent for unresectable perihilar cholangiocarcinoma. (A) Cholangiogram showing tumor involving the common hepatic duct, bifurcation, left primary branch, and right primary branch opening (Bismuth type IV). (B) The balloon catheter was used for coaxial dilation of the passage. (C) The outer seed-loaded stent was implanted and released to cover the stricture. (D) The inner stent was immediately deployed to overlap the outer one, and then the cholangiogram showed the successful flow of contrast medium into the intestine through the stent. pCCA, perihilar cholangiocarcinoma; REMS, radiation-emitting metallic stent.

Figure 2

Trial profile. HAIC, hepatic arterial infusion chemotherapy; REMS, radiation-emitting metallic stent; SEMS, self-expandable metallic stent.

Figure 3

Kaplan–Meier estimate of overall survival.

Figure 4

Subgroup analysis of overall survival. CI, confidence interval; HAIC, hepatic arterial infusion chemotherapy; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; REMS, radiation-emitting metallic stent; SEMS, self-expandable metallic stent.

Figure 5

Kaplan–Meier estimate of time to symptomatic progression. HAIC, hepatic arterial infusion chemotherapy; REMS, radiation-emitting metallic stent; SEMS, self-expandable metallic stent.

Figure 6

Kaplan–Meier estimate of stent patency. HAIC, hepatic arterial infusion chemotherapy; REMS, radiation-emitting metallic stent; SEMS, self-expandable metallic stent.

Figure 7

Correlation of stent patency with survival time.

Figure 8

Waterfall plot for total bilirubin changes visualization. (A) REMS-HAIC group. (B) SEMS-HAIC group. HAIC, hepatic arterial infusion chemotherapy; REMS, radiation-emitting metallic stent; SEMS, self-expandable metallic stent; TB, total bilirubin.