125I stent plus combination therapy for HCC and portal vein tumor thrombosis: a nationwide target trial emulation

Patients with hepatocellular carcinoma (HCC) and Vp4 portal vein tumor thrombosis (PVTT) have a poor prognosis and limited effective treatment options.

To evaluate the safety and efficacy of irradiation stent placement (ISP) followed by transcatheter arterial chemoembolization (TACE) plus immune checkpoint inhibitors (ICIs) and targeted therapy (TT, ISP-TACE) versus ICIs plus TT alone (ICIs-TT) in patients with HCC and Vp4 PVTT.

Retrospective cohort study using a target trial emulation framework was conducted in thirty-one centers across China. Patients with HCC and Vp4 PVTT between January 2020 and May 2023 were screened. The clone-censor-weighting approach was used as the primary analysis; overlap propensity score weighting, multiregional cluster propensity score matching, landmark analyses, Cox proportional hazards models, and traditional propensity score matching were used as sensitivity analyses. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and safety.

Among the 444 participants (mean [SD] age, 57.0 [10.8] years; 396 (89.2%) male), 131 were included in the ISP-TACE group and 313 were included in the ICIs-TT group. The ISP-TACE group demonstrated a median OS of 356 days (95% CI: 309-420) versus 258 days (95% CI: 235-287) in the ICIs-TT group (log-rank P <.0001). The ISP-TACE group demonstrated longer PFS when compared with the ICIs-TT group (150 vs 96 days when using RECIST 1.1, log-rank P = .0075). Sensitivity analyses confirmed the robustness of these findings. Grade ≥3 treatment-related adverse events were reported in 55 (42.0%) patients in the ISP-TACE group and in 105 (33.5%) patients in the ICIs-TT group (P = .091).

The findings of this target trial emulation suggest that ISP followed by TACE in combination with ICIs and TT may be a promising and well-tolerated therapeutic strategy for patients with HCC and Vp4 PVTT.