PMID- 36811662 OWN - NLM STAT- MEDLINE DCOM- 20230615 LR - 20240426 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 72 IP - 7 DP - 2023 Jul TI - Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients. PG - 1957-1969 LID - 10.1007/s00262-023-03390-x [doi] AB - BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades >/= 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Han, Cheng-Long AU - Han CL AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Tian, Bao-Wen AU - Tian BW AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Yan, Lun-Jie AU - Yan LJ AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Ding, Zi-Niu AU - Ding ZN AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Liu, Hui AU - Liu H AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Mao, Xin-Cheng AU - Mao XC AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Tian, Jin-Cheng AU - Tian JC AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Xue, Jun-Shuai AU - Xue JS AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Tan, Si-Yu AU - Tan SY AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Dong, Zhao-Ru AU - Dong ZR AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Yan, Yu-Chuan AU - Yan YC AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Hong, Jian-Guo AU - Hong JG AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Chen, Zhi-Qiang AU - Chen ZQ AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Wang, Dong-Xu AU - Wang DX AD - Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China. FAU - Li, Tao AU - Li T AD - Department of General Surgery, Qilu Hospital, The Second Hospital of Shandong University, 107 West Wen Hua Road, Jinan, 250012, People's Republic of China. litao7706@163.com. LA - eng GR - 82073200/National Natural Science Foundation of China/ GR - ZR2021ZD26/Major basic research of Shandong Provincial Natural Science Foundation/ GR - 2020GXRC023/funds for Independent Cultivation of Innovative Team from Universities in Jinan/ PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20230222 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Immune Checkpoint Inhibitors) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/pathology MH - Immune Checkpoint Inhibitors/adverse effects MH - *Liver Neoplasms/pathology MH - Prognosis PMC - PMC10991272 OTO - NOTNLM OT - Adverse events OT - Extrahepatic metastasis OT - Immune therapy OT - Immune-related adverse events OT - Meta-analyses OT - Objective response rate OT - Overall survival OT - Primary liver cancer OT - Progression-free survival OT - Vascular invasion COIS- There are no conflicts of interest to declare. EDAT- 2023/02/23 06:00 MHDA- 2023/06/15 06:42 PMCR- 2023/02/22 CRDT- 2023/02/22 15:52 PHST- 2022/12/07 00:00 [received] PHST- 2023/01/27 00:00 [accepted] PHST- 2023/06/15 06:42 [medline] PHST- 2023/02/23 06:00 [pubmed] PHST- 2023/02/22 15:52 [entrez] PHST- 2023/02/22 00:00 [pmc-release] AID - 10.1007/s00262-023-03390-x [pii] AID - 3390 [pii] AID - 10.1007/s00262-023-03390-x [doi] PST - ppublish SO - Cancer Immunol Immunother. 2023 Jul;72(7):1957-1969. doi: 10.1007/s00262-023-03390-x. Epub 2023 Feb 22.