Chang Liu,1,2,* Weixing Jiang,3,* Juxian Sun,1,* Jingwei Cui,4 Dandan He,1 Shuqun Cheng,1 Jie Shi1 

1Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, People’s Republic of China; 2Yangzhou Clinical Medical College, Xuzhou Medical University, Yangzhou, People’s Republic of China; 3Department of General Surgery, Nantong Haimen People’s Hospital, Nantong, People’s Republic of China; 4Department of General Surgery, Yancheng Clinical College of Xuzhou Medical University & The First People’s Hospital of Yancheng, Yancheng, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jie Shi; Shuqun Cheng, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200433, People’s Republic of China, Tel +86 13816768296; +86 13901746139, Email docshijie@aliyun.com; chengshuqun@aliyun.com

Background: Hepatocellular carcinoma (HCC) with pulmonary metastasis (PM) significantly worsens prognosis, and current treatment options remain limited.
Methods: A retrospective study was conducted on HCC patients treated with sintilimab combined with lenvatinib at three hospitals in China between 2020 and 2021. Progression-free survival (PFS), overall survival (OS), and tumor response based on RECIST 1.1 were compared. Treatment safety was assessed by analyzing treatment-related adverse events (TRAEs).
Results: Among 144 patients, 105 received sintilimab combined with lenvatinib (S+L), while 39 were treated with radiotherapy combined with sintilimab and lenvatinib (RT+S+L). The RT+S+L group showed superior outcomes in OS (25 months vs 16 months, HR = 0.58, 95% CI = 0.35– 0.94, P=0.025) and PFS (14 months vs 6 months, HR = 0.61, 95% CI = 0.40– 0.94, P=0.022) compared to the S+L group. Similarly, the RT+S+L group exhibited significantly higher objective response rate (ORR) and disease control rate (DCR) compared to the S+L group (61.5% vs 27.6%, P< 0.001; 94.9% vs 76.2%, P=0.011). The most common grade 3/4 TRAEs in the RT+S+L group were hypertension, decreased platelet count, elevated total bilirubin, and proteinuria.
Conclusion: Radiotherapy combined with sintilimab and lenvatinib is an effective strategy for treating HCC with pulmonary metastasis. These findings highlight the critical role of radiotherapy in the management of HCC.

Keywords: hepatocellular carcinoma, pulmonary metastasis, radiotherapy, targeted therapy, immunotherapy