Objective To investigate the effects of different treatment modalities on prognosis and safety in hepatocellular carcinoma(HCC) patients with portal vein tumor thrombus(PVTT).

Methods The retrospective cohort study was conducted. The clinicopathological data of 269 HCC patients with PVTT who were admitted to 19 medical centers in China, including Third Affiliated Hospital of Naval Medical University et al, from September 2021 to December 2023 were collected. There were 237 males and 32 females, aged (53±11) years. Among the 269 patients, 75 cases undergoing systemic therapy alone were assigned to the systemic therapy group, 155 cases undergoing systemic therapy combined with interventional therapy were assigned to the combined therapy group, and 39 cases undergoing radiotherapy combined with systemic therapy and interventional therapy were assigned to the radiotherapy plus combined therapy group. Observation indicators: (1) propensity score matching (PSM) and comparison of clinicopathological characteristics after matching; (2) patient prognosis; (3) prognostic factors analysis of patients; (4) treatment safety analysis. Comparison of measurement data with normal distribution among groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among groups was conducted using the Kruskal‑Wallis H test. Comparison of count data among groups was conducted using the chi‑square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rates and plot survival curves, and survival analysis was performed using the Log‑rank test. Pairwise comparison was adjusted using the Bonferroni method. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. PSM was performed using a 1:2:3 optimal full matching method with a caliper of 0.30.

Results (1) PSM and comparison of clinicopathological characteristics after matching: among the 269 patients, 216 cases were successfully matched, with 72 cases in the systemic therapy group, 108 cases in the combined therapy group, and 36 cases in the radiotherapy plus combined therapy group. After PSM, the elimination of body mass index, platelet and disease progression confounding bias ensured comparability. (2) Patient prognosis: the follow‑up time of patients after PSM was 20.1(range, 0.6-43.2) months. The 1‑, 2‑, and 3‑year overall survival and progression‑free survival rates were 97.0%, 61.5%, 43.9% and 57.6%, 31.5%, 25.2% for the radiotherapy plus combined therapy group, 80.7%, 64.4%, 61.9% and 50.1%, 29.2%, 22.4% for the combined therapy group, 66.8%, 47.4%, 34.6% and 43.3%, 35.3%, 19.6% for the systemic therapy group, respectively. Significant difference was observed in overall survival rate among the 3 groups (χ²=11.10, P<0.05), whereas no significant difference was found in progression‑free survival rate (χ²=3.32, P>0.05). Further pairwise comparisons showed no significant difference in overall survival rate between the radiotherapy plus combined therapy group and combined therapy group (χ²=0.04, P>0.05). There was a significant difference in overall survival rate between the radiotherapy plus combined therapy group and systemic therapy group, between the combined therapy group and systemic therapy group (χ²=5.75, 8.52, P<0.05). (3) Prognostic factors analysis of patients: after PSM, multivariate analysis showed that the neutrophil-to-lymphocyte ratio ≥2.5, the number of tumors ≥3, and disease progression were independent risk factors for overall survival rate in HCC patients with PVTT (hazard ratio=1.81, 1.82, 4.66, 95% confidence interval as 1.09-3.01, 1.05-3.15, 2.74-7.92, P<0.05). Combined therapy was identified as a protective factor for overall survival rate compared with systemic therapy alone (hazard ratio=0.58, 95% confidence interval as 0.34-0.99, P<0.05). Alpha‑fetoprotein ≥400 μg/L and disease progression were risk factors for progression‑free survival rate in HCC patients with PVTT (hazard ratio=1.52, 7.39, 95% confidence interval as 1.06-2.18, 4.70-11.6, P<0.05). (4) Treatment safety analysis: among the 269 patients, 251 cases had adverse reactions, of which 96 cases were classified as grade 3-4. There were 70, 145, and 36 patients with adverse reactions in the systemic therapy group, combined therapy group, and radiotherapy plus combined therapy group, respectively, showing no significant difference among the 3 groups (χ²=0.08, P>0.05). There were significant differences in the fatigue, radiation dermatitis, neutropenia, thrombocytopernia, proteinuria among the 3 groups (P<0.05). There were 22, 51, and 23 patients with grade 3-4 adverse reactions in the systemic therapy group, combined therapy group, and radiotherapy plus combined therapy group, respectively, showing a significant difference among the 3 groups (χ²=11.04, P<0.05).

Conclusions Compared with systemic therapy, systemic therapy combined with interventional, radiotherapy plus both systemic therapy and interventional can improve prognosis of HCC patients with PVTT. However, the addition of radiotherapy to the systemic combined with interventional therapy does not further improve patient prognosis, and increases the incidence and severity of certain adverse reactions.