# Combination of locoregional and systemic therapy for hepatocellular carcinoma with portal vein tumor thrombus: a real-world retrospective study

## TL;DR

Combining local and systemic treatments for advanced liver cancer with vein tumor blockage improves survival, but balancing effectiveness and side effects is crucial.

## Contribution

This study compares real-world outcomes of different combined therapies for HCC with PVTT, highlighting efficacy and safety trade-offs.

## Key findings

- Combination therapies improved survival compared to TACE alone.
- HAIC-TP showed a better efficacy-safety balance than TACE-HAIC-TP.
- TACE-TP and HAIC-TP had comparable survival outcomes.

## Abstract

The optimal treatment strategy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains undefined. Although combinations of locoregional therapies—such as transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC)—with systemic agents (tyrosine kinase inhibitors [TKIs] and PD-1 inhibitors) show promise, direct comparative evidence among different regimens remains limited.

In this single-center retrospective study, we included 347 patients with unresectable HCC and PVTT treated between January 2020 and December 2022. Patients were categorized into four groups based on initial therapy: TACE-HAIC-TP (n = 79), TACE-TP (n = 90), HAIC-TP (n = 98), and TACE alone (n = 80). The primary endpoints were overall survival (OS) and progression-free survival (PFS).

All combination regimens significantly improved OS and PFS compared with TACE alone (median OS: 11.4 months; median PFS: 5.8 months; all p < 0.001). The TACE-HAIC-TP group had the longest median OS (21.0 months) and PFS (15.3 months). However, after propensity score matching, no significant difference in survival outcomes was observed between the TACE-HAIC-TP and HAIC-TP groups. The HAIC-TP and TACE-TP regimens demonstrated comparable efficacy. Regarding safety, TACE-HAIC-TP was associated with the highest incidence of adverse events, including appetite loss, fatigue, nausea/vomiting, bleeding, and immune-related pneumonia. HAIC-TP carried a higher risk of gastrointestinal reactions and bleeding, whereas hand-foot syndrome was more frequent with TACE-TP.

In patients with unresectable HCC and PVTT, combining TKIs and PD-1 inhibitors with locoregional therapy (TACE or HAIC) confers superior survival benefits over TACE monotherapy. The HAIC-TP regimen was associated with a more favorable balance of efficacy and tolerability compared with the more intensive TACE-HAIC-TP strategy, suggesting it may represent a promising therapeutic option pending prospective validation. Treatment selection should be individualized based on efficacy–safety trade-offs.