Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial

Abstract

Background and aim: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients.

Methods: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety.

Results: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73).

Conclusion: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.

Trial registration: ClinicalTrials.gov NCT03730675.

Graphical abstract

Figure 1

Representative images of irradiation stent placement for portal vein tumor thrombosis (PVTT). Representative images of a 50-year-old male patient who underwent irradiation portal vein stent placement for PVTT. (A) Portography showed a filling defect at the right branch of the portal vein and proximal main portal trunk (Vp4). (B) The self-expandable ¹²⁵I radioactive seed-loaded stent was first inserted under fluoroscopic guidance. (C) A self-expandable nitinol stent was introduced and overlapped the outer stent within. (D) Portography showed immediate recanalization of the portal vein.

Figure 2

Trial profile. ISP-TACE, irradiation stent placement plus transcatheter arterial chemoembolization; TACE, transcatheter arterial chemoembolization.

Figure 3

Kaplan–Meier estimate of overall survival (OS). Kaplan–Meier curves show the median OS as the primary endpoint of this study was 9.9 months (95% CI: 7.6–12.2) in the ISP-TACE group compared with 6.3 months (95% CI: 5.4–7.2) in the Sora-TACE group (P=0.016). The survival rates at 3, 6, and 12 months in the ISP-TACE group versus the Sora-TACE group were 84, 73, and 22% versus 81, 41, and 9%, respectively (P=0.016). ISP-TACE group, irradiation stent placement plus transcatheter arterial chemoembolization group; Sora-TACE group, sorafenib plus transcatheter arterial chemoembolization group; TACE, transcatheter arterial chemoembolization.

Figure 4

Overall survival of select subgroups according to baseline prognostic factors. The forest plot shows that the risk of death for participants in the ISP-TACE group was reduced by 44% when compared with the Sora-TACE group. OS for participants in all the subgroups benefited from ISP-TACE treatment. AFP, alpha fetoprotein; ECOG PS, Eastern Cooperative Oncology Group performance status; HCC, hepatocellular carcinoma; ISP-TACE, irradiation stent placement plus transcatheter arterial chemoembolization; PVTT, portal vein tumor thrombosis; Sora-TACE, sorafenib plus transcatheter arterial chemoembolization; TACE, transcatheter arterial chemoembolization.

Figure 5

Kaplan–Meier estimate of time to symptomatic progression. Kaplan–Meier curves show the median time to symptomatic progression was 6.6 months (95% CI: 5.1–8.1) in the ISP-TACE group and 4.2 months (95% CI: 3.6–4.8) in the Sora-TACE group (P=0.04). ISP-TACE group, irradiation stent placement plus transcatheter arterial chemoembolization group; Sora-TACE group, sorafenib plus transcatheter arterial chemoembolization group; TACE, transcatheter arterial chemoembolization.