AUTHOR=Hong Yidan , Tan Qishu , Li Yixin , Yang Bo , Wu Yinan , Zhao Lijun , Zhao Yang , Chen Yu , Zhu Zihao , Zhu Xiangzhi , Gu Lingling , Jiang Ning 

TITLE=Immunotherapy combined with definitive chemoradiotherapy for locally advanced unresectable esophageal squamous cell carcinoma

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1646568

DOI=10.3389/fimmu.2025.1646568

ISSN=1664-3224

ABSTRACT=BackgroundThe 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.MethodsBetween 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.ResultsA 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).ConclusionICIs combined with concurrent dCRT demonstrated promising efficacy and manageable safety in patients with unresectable LA-ESCC.