ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1646568
This article is part of the Research TopicAdvances in Esophageal Cancer: Treatment Updates and Future ChallengesView all 24 articles
Immunotherapy Combined with Definitive Chemoradiotherapy for Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
Provisionally accepted
Yidan Hong1Qishu Tan1Yixin Li1Bo Yang2Yinan Wu3Lijun Zhao1
Yang Zhao4Yu Chen1Zihao Zhu1
XIANG ZHI ZHU1*
Lingling Gu2*
Ning Jiang1*- 1Department of Radiation Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, nanjing, China
- 2Department of Medical Imaging Center, The Affiliated Cancer Hospital of Nanjing Medical University, nanjing, China
- 3Department of Pathology, The Affiliated Cancer Hospital of Nanjing Medical University, nanjing, China
- 4Department of Information, The Affiliated Cancer Hospital of Nanjing Medical University, nanjing, China
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Background: The clinical value of immune checkpoint inhibitors (ICIs) in the treatment of unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains under investigation in large-scale randomized clinical trials. In this study, we aimed to assess the efficacy and safety of concurrent ICIs in combination with definitive chemoradiotherapy (dCRT) in a relatively large cohort of patients with unresectable LA-ESCC. Methods: Between January 2019 and December 2023, this retrospective study included patients with LA-ESCC who received ICIs concurrently with dCRT at Jiangsu Cancer Hospital. The primary endpoints were overall survival (OS) and progression-free survival (PFS), while secondary endpoints included clinical response and safety. Results: A total of 165 patients with LA-ESCC were included in this study, with a median age of 66 years (IQR 60–70 years), and 163 (98.8%) had stage III or IVA disease. After a median follow-up of 24 months (IQR 16–33 months), the 2-year OS was 64.3% (95%CI 57.2%-72.3%), and the 2-year PFS was 50.2% (95%CI 42.9%-58.8%). It is noteworthy that induction therapy before dCRT did not improve OS (HR = 1.09, 95% CI: 0.61–1.93, P = 0.770) or PFS (HR = 1.00, 95% CI: 0.59–1.72, P = 1.000). The objective response rate (ORR) was 70.9% and disease control rate (DCR) was 86.7%. The most common adverse event was grade 3 or worse lymphopenia, observed in 60.0% of the patients (90/165). Conclusion: ICIs combined with concurrent dCRT demonstrated promising efficacy and manageable safety in patients with unresectable LA-ESCC.
Keywords: esophageal squamous cell carcinoma, Immunotherapy, Chemoradiotherapy (CRT), survival analysis, Toxicicity
Received: 13 Jun 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Hong, Tan, Li, Yang, Wu, Zhao, Zhao, Chen, Zhu, ZHU, Gu and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
XIANG ZHI ZHU, 13182948068@163.com
Lingling Gu, 13851706157@163.com
Ning Jiang, njiang117@njmu.edu.cn
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