Efficacy and safety of immune checkpoint inhibitors plus chemotherapy in esophageal cancer patients with liver metastases

doi:10.4251/wjgo.v18.i1.113440

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Gastrointest Oncol. Jan 15, 2026; 18(1): 113440
Published online Jan 15, 2026. doi: 10.4251/wjgo.v18.i1.113440

Efficacy and safety of immune checkpoint inhibitors plus chemotherapy in esophageal cancer patients with liver metastases

En-Hui Dai, Shu-Hao Que, Huan Xu, Guo-Qiang Zhong, Zhen Zhang, Xu Liang, Shu-Wei Zhai, Yue-Tong Li, Jing-Jing Wang, Wei Feng

En-Hui Dai, The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China

Shu-Hao Que, Department of Radiotherapy, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310006, Zhejiang Province, China

Huan Xu, Guo-Qiang Zhong, Department of Clinical Medicine, Hebei University of Engineering, Handan 056300, Hebei Province, China

Zhen Zhang, Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht 6229 HX, Netherlands

Zhen Zhang, Wei Feng, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou 310022, Zhejiang Province, China

Xu Liang, Department of Radiotherapy, The Sixth Affiliated Hospital of Nantong University, Yancheng Third People's Hospital, Yancheng 224002, Jiangsu Province, China

Shu-Wei Zhai, Department of Radiation Oncology, Changzhou Jintan First People's Hospital, Changzhou 213000, Jiangsu Province, China

Yue-Tong Li, Department of Oncology, The First Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang 050000, Hebei Province, China

Jing-Jing Wang, Wei Feng, Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China

Author contributions: Conception and design were performed by Feng W and Dai EH; administrative support was performed by Feng W; provision of study materials or patients were performed by Feng W; collection and assembly of data were performed by Dai EH; data analysis and interpretation were performed by Dai EH, Que SH, and Wang JJ; all authors were responsible for manuscript writing and final approval of manuscript.

Supported by National Natural Science Foundation of China, No. 82303672; Zhejiang Provincial Health Commission and Zhejiang Provincial Administration of Traditional Chinese Medicine through the Targeted Project for Medical and Health Research, No. 2025ZL017; and China Primary Health Care Foundation, No. ZLMY20240311001ZJ.

Institutional review board statement: All procedures were performed in compliance with relevant laws and institutional guidelines. The study was reviewed and approved by the Zhejiang Cancer Hospital Institutional Review Board, Approval No. IRB-2025-980(IIT).

Informed consent statement: The necessity of consent for this retrospective analysis was waived.

Conflict-of-interest statement: The authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence this study.

STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.

Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

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: Wei Feng, MD, Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Gongshu District, Hangzhou 310022, Zhejiang Province, China. fengwei@zjcc.org.cn

Received: August 27, 2025
Revised: October 11, 2025
Accepted: November 18, 2025
Published online: January 15, 2026
Processing time: 139 Days and 2.1 Hours

Abstract

BACKGROUND

The liver represents a common site of distant metastasis in patients with esophageal cancer (EC). Conventional chemotherapy (CMT) presents limited efficacy for EC, and EC patients with liver metastases typically experience a poor prognosis, highlighting an urgent need to explore novel treatment approaches. This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors (ICIs) in the treatment of EC patients with liver metastases. Furthermore, prognostic factors influencing outcomes in this patient population were identified.

AIM

To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.

METHODS

This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024. Patients receiving CMT were compared with those receiving CMT + ICI. Analyzed variables included clinicopathological features, treatment history, characteristics of metastasis, systemic and local treatments, overall survival (OS), and treatment-related adverse events (TRAEs). Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models. Finally, efficacy outcomes and TRAE profiles were compared between the two groups.

RESULTS

A significant difference in median OS was identified between the two groups (10.8 months in the CMT group vs 20.8 months in the CMT + ICI group, P = 0.004). The CMT + ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months (P < 0.001). Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate. Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases: Karnofsky Performance Status score ≥ 70, receipt of local therapy for liver metastases, and the number of cycles of CMT and immunotherapy received. Furthermore, the incidence of TRAEs did not significantly differ between the CMT + ICI and CMT groups.

CONCLUSION

For EC patients with liver metastases, the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone, while maintaining manageable TRAEs.

Keywords: Esophageal cancer; Liver metastasis; Chemotherapy; Immunotherapy; Local liver-directed therapy

Core Tip: Although chemoimmunotherapy is the standard first-line treatment for metastatic esophageal cancer, its efficacy in the subgroup with liver metastases remains poorly characterized. This study demonstrated that chemoimmunotherapy significantly improved overall survival in this population, with a manageable safety profile. Key prognostic factors were identified, and the addition of local therapy to liver metastases may provide a rational approach to further optimize treatment outcomes.