Transarterial Chemoembolization, Molecular Targeted Treatments, and Programmed Death-(Ligand)1 Inhibitors, for Hepatocellular Carcinoma with Lung Metastasis: A Retrospective Cohort Study

Junjie Lu1,2 *, Xiang Chen1,2 *, Yongfa Liu,1,2 Yi Ding,1,2 Bo Li,1,2 Jin Yang,1,2 Wei Peng,3 Xiaoli Yang1,2 1Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2NuclearMedicine and Molecular Imaging Key Laboratory of Sichuan Province, Academician(Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Peng, Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email [email protected] Xiaoli Yang, Department of General Surgery(Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email [email protected]: Treatment options for patients with hepatocellular carcinoma (HCC) and lung metastases are diverse, requiring a personalized approach. Current CNLC guidelines recommend systemic therapy and focal radiation, emphasizing the roles of molecular targeted treatments (MTT) and programmed death-(ligand)1 (PD-[L]1) inhibitors. However, the efficacy of combining TACE with these treatments remains uncertain.Purpose: To compare the efficacy and adverse reactions of TACE combined with MTT and PD-(L)1 versus MTT and (PD-[L]1) in patients with HCC and lung metastasis.Materials and Methods: We retrospectively analyzed data from patients treated between January 2019 and May 2024 at the Affiliated Hospital of Southwest Medical University and West China Hospital of Sichuan University. Stabilized inverse probability weighting was employed to reduce bias. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS) and objective response rate (ORR).Results: Among 167 patients, 141 received TACE, MTT, and PD-(L)1, while 26 received MTT and PD-(L)1. The median follow-up times were 28 and 29 months, respectively. After weighting, baseline characteristics were well balanced. The median OS was significantly longer in the TACE group (15 months) compared to the MTT group (8 months; p=0.023), and PFS was also longer (8 months vs 5 months; p=0.038). For liver lesions, ORR was 42.6% in the TACE group and 46.2% in the MTT group (p=0.73); for lung lesions, ORR was 26.2% and 19.2%, respectively (p=0.449). Safety profiles were similar, except for a higher incidence of rash in the MTT group.Conclusion: TACE combined with MTT and PD-(L)1 demonstrated better outcomes for patients with liver cancer and lung metastases compared to MTT and PD-(L)1 alone, without increasing complication rates, suggesting a promising first-line treatment option.Keywords: hepatocellular carcinoma, transarterial chemoembolization, molecular targeted treatments, tyrosine kinase inhibitor, programmed death-(ligand)1 inhibitors