Chlorotrianisene

The introduction of immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) has spurred interest in evaluating their use in earlier lines of therapy, including in combination with locoregional therapy for patients with intermediate-stage disease. Transarterial chemoembolisation (TACE) is believed to increase neoantigen release and local tumour PD-L1 expression, suggesting the potential for enhanced antitumour responses if combined with ICIs. The EMERALD-1 trial randomised 616 patients with Child-Pugh A-B7 and localised HCC (including 6-8% with Vp1-Vp2 vascular invasion) to durvalumab plus bevacizumab plus TACE, durvalumab plus placebo plus TACE, and placebo plus TACE. The primary endpoint, progression-free survival, was significantly longer with durvalumab plus bevacizumab plus TACE vs. TACE alone (hazard ratio [HR] 0.77, 95% CI 0.61-0.98) but not durvalumab plus TACE vs. TACE alone (HR 0.94, 95% CI 0.75-1.19). The LEAP-012 trial randomised 480 patients with Child-Pugh A and liver-localised HCC to lenvatinib plus pembrolizumab plus TACE vs. placebos plus TACE. Progression-free survival was significantly longer with lenvatinib plus pembrolizumab plus TACE vs. TACE alone (HR 0.66, 95% CI 0.51-0.84). Both trials demonstrated increased grade 3-4 treatment-related adverse events in the combination vs. TACE alone arms, including those resulting in treatment discontinuation. Early data from LEAP-012 suggested a trend toward overall survival benefit (HR 0.80, 95% CI 0.57-1.11), although this failed to achieve statistical significance on follow-up analyses. Neither trial has yet reported on other outcomes, including quality of life. Clinicians should emphasise individualised patient selection when deciding between TACE plus ICI vs. TACE alone in patients with HCC eligible for locoregional therapy.

The management of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) remains challenging because of its heterogeneous clinical behavior. Various treatment strategies have been introduced, including transarterial chemoembolization (TACE), tyrosine kinase inhibitors (TKIs) combined with radiotherapy (RT), and atezolizumab/bevacizumab (AB) with or without RT. This study evaluated the efficacy and safety of these approaches by using a previously proposed MVI risk stratification model.

We retrospectively analyzed 526 treatment-naïve patients with HCC and MVI. Patients were categorized into very low/low-risk (n = 259) and intermediate/high-risk (n = 267) groups based on the MVI sub-classification. They were treated with TACE + RT (n = 417), TKI + RT (n = 67), AB alone (n = 25), or AB + RT (n = 17). Survival outcomes, including intrahepatic progression-free survival (IPFS), extrahepatic PFS (EPFS), PFS, and overall survival (OS), were assessed using Kaplan-Meier and multivariate Cox regression analyses.

With a median follow-up of 11.6 months, the median IPFS, EPFS, PFS, and OS were 6.3, 7.4, 4.2, and 12.4 months, respectively. The MVI risk group subclassification was significantly correlated with all survival outcomes (p < 0.05). In the very low/low-risk groups, TACE + RT showed superior outcomes compared with TKI + RT. In the intermediate/high-risk group, AB + RT revealed improved survival compared with TACE + RT or AB alone. Liver function deterioration was most frequent in the TKI + RT group.

The proposed MVI risk stratification effectively differentiated prognosis and may guide optimal treatment selection for HCC with MVI. Prospective validation is required to confirm the clinical utility.