Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2023; 15(4): 689-699
Published online Apr 15, 2023. doi: 10.4251/wjgo.v15.i4.689
Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma: A retrospective study
Jiang-Min Zhou, Hui-Fang Xiong, Xiao-Ping Chen, Zhi-Wei Zhang, Li-Ping Zhu, Biao Wu
Jiang-Min Zhou, Li-Ping Zhu, Biao Wu, Department of Hepatobiliary Surgery, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430030, Hubei Province, China
Hui-Fang Xiong, Department of Digestive Medicine, Dongxihu District People’s Hospital, Wuhan 430030, Hubei Province, China
Xiao-Ping Chen, Zhi-Wei Zhang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Zhou JM and Xiong HF analyzed the data and wrote the manuscript; Zhu LP, Zhang ZW, and Chen XP designed the research; Wu B modified the manuscript; and all authors read and approved the final manuscript.
Institutional review board statement: The study was approved by the Ethical Committee of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. All procedures performed in this study abided by the Declaration of Helsinki.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets (data) for this study can be found in the (figure) https://figshare.com/s/ee63fa5271448d51104e. The other datasets were available on request from the corresponding author at wuhanyywb@163.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Biao Wu, MD, Doctor, Department of Hepatobiliary Surgery, Wuhan Hospital of Traditional Chinese and Western Medicine, No. 215 Zhongshan Avenue, Qiaokou District, Wuhan 430030, Hubei Province, China. wuhanyywb@163.com
Received: October 26, 2022
Peer-review started: October 26, 2022
First decision: December 14, 2022
Revised: December 16, 2022
Accepted: March 23, 2023
Article in press: March 23, 2023
Published online: April 15, 2023
Processing time: 167 Days and 23.7 Hours
ARTICLE HIGHLIGHTS
Research background

Unresectable hepatocellular carcinoma (HCC).

Research motivation

Immune-related adverse events (irAEs) have a high incidence in immune checkpoint inhibitor (ICI) treatment of unresectable HCC. The relationship between irAEs and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.

Research objectives

A retrospective study was conducted to elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.

Research methods

A total of 190 unresectable HCC (Barcelona Clinic Liver Cancer stage C) patients receiving pembrolizumab treatment were retrospectively reviewed. All irAEs were reviewed and the relationship between irAEs and prognosis was analyzed.

Research results

In our study, we found that the overall incidence of irAEs was 72.6% (138/190) and 10.0% of them were severe irAEs (grade ≥ 3); elevated transaminase (> 3 times upper limit of normal) was the most common adverse reaction to ICIs. Patients who developed myocarditis or hypothyroidism tended to achieve partial response and have a more significant decrease in tumor burden. In addition, patients without irAEs were more likely to have progressive disease. It suggested that irAEs are indeed closely related to antitumor effects. In addition, hypothyroidism was the independent risk factors for time to progression and overall survival.

Research conclusions

irAEs, especially hypothyroidism, could be used as an indicator to evaluate the effect of immunotherapy.

Research perspectives

The study could help doctors in identifying patients who are responding to immunotherapy. In general, the response rate to both tyrosine kinase inhibitors and ICIs is less than 30%. Serious adverse events may put patients at risk of death. Therefore, timely identification of the right patients can not only reduce the side effects of immunotherapy but also improve the effectiveness of treatment.