Long-Term Outcomes of Concurrent Chemoradiotherapy With S-1 in Older Patients With Esophageal Cancer
Year: 2026
Type: article
Abstract: Importance: Most older patients with esophageal cancer (EC) are unable to complete standard platinum-based concurrent chemoradiotherapy (CCRT) due to reduced organ reserve, comorbidities, and malnutrition. A new treatment option-CCRT with S-1-has been found to have high efficacy and fewer toxic effects for this population, yet long-term data supporting its use remain limited. Objective: To evaluate the long-term outcomes of CCRT with S-1 vs radiotherapy (RT) alone in older patients with EC. Design, Setting, and Participants: This secondary analysis of a phase 3 randomized clinical trial conducted at 23 centers in China was not prespecified in the trial protocol. Patients aged 70 to 85 years with histologically confirmed EC were enrolled between June 1, 2016, and August 31, 2018. Data cutoff date was February 1, 2025, with an additional follow-up of 54 months beyond the primary analysis. Data were analyzed from February 1 to April 1, 2025. Interventions: Patients were randomly assigned 1:1 to receive CCRT with S-1 consisting of 54 Gy in 30 fractions with S-1, 70 mg/m2 per day on days 1 to 14 and 29 to 42, or RT alone consisting of 60 Gy in 30 fractions, 2.0 Gy per day 5 days per week. Main Outcomes and Measures: The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), cause-specific mortality, cumulative incidence of death from EC or other reasons, and cumulative incidences of locoregional or distant metastasis during treatment or relapse after treatment. Results: A total of 298 patients (median [IQR] age, 77 [74-79] years; 180 males [60.4%]) were enrolled. There were 151 patients (50.7%) clinically diagnosed with stage III to IV disease. With a median (IQR) follow-up of 87 (85-92) months, the median OS was 24.7 (95% CI, 21.2-37.6) months in the CCRT group and 15.1 (95% CI, 12.4-18.6) months in the RT group (hazard ratio [HR], 0.69; 95% CI, 0.53-0.90; P = .005). The 5-year OS rates were 33.5% (95% CI, 26.7%-42.1%) and 24.4% (95% CI, 18.3%-32.4%) for the CCRT and RT groups, respectively; the 8-year OS rates were 26.2% and 16.1%, respectively. The median PFS was 18.7 (95% CI, 13.1-25.8) months in the CCRT group and 9.2 (95% CI, 7.9-12.7) months in the RT group (HR, 0.69; 95% CI, 0.54-0.90; P = .005). Cause-specific analyses showed reduced EC-related mortality with CCRT (HR, 0.67; 95% CI, 0.50-0.89; P = .005), with 8-year absolute risks of 58.5% vs 72.9%, respectively, and no excess noncancer-related mortality. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, long-term results showed that CCRT with S-1 was associated with a sustained survival benefit compared with RT alone, without increased noncancer-related mortality. This finding supports CCRT with S-1 as the preferred regimen for patients aged 70 to 85 years with EC. Trial Registration: ClinicalTrials.gov Identifier: NCT02813967.
Source: JAMA Network Open
Authors: Yongling Ji, Min Fang, Weiguo Zhu, Yanguang Yang, Jun Ma, Li Zhang, Jiancheng Li, Hua Tao, Jianhong Xia, Haihua Yang, Jin Huang, Yong Bao, Dexi Du, Degan Liu, Xiusheng Wang, Chaoming Li, Xinmei Yang, Ming Zeng, Zhigang Liu, Wen Zheng, Juan Pu, Jun Chen, Wangyuan Hu, Xinyi Wang, Peijing Li, Jin Wang, Yujin Xu, Xiao Zheng, Keying Chen, Wanwei Wang, Guangzhou Tao, Jing Cai, Jizhong Zhao, Jun Zhu, Ming Jiang, Yan Yan, Guoping Xu, Wenjing Xu, Shanshan Bu, Binbin Song, Ke Xie, Shan Huang, Yuanda Zheng, Liming Sheng, Xiaojing Lai, Ying Chen, Lei Cheng, Xiao Hu, Wenhao Ji, Yue Kong, Xiaofu Yu, Huizhang Li, Runhua Li, Rong Huang, Han He, Xianghui Du, Ming Chen
Institutions: Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Huaian First People’s Hospital, Nanjing Medical University, Nantong University, Nantong Tumor Hospital, University of Science and Technology of China, Fujian Provincial Cancer Hospital, Jiangsu Cancer Hospital, Second People’s Hospital of Huai’an, Zhejiang Taizhou Hospital, The First People's Hospital of Changzhou, The First Affiliated Hospital, Sun Yat-sen University, Lishui Central Hospital, Henan Cancer Hospital, First Hospital of Jiaxing, University of Electronic Science and Technology of China, Dongguan People’s Hospital, Southern Medical University, Duke University, First People's Hospital of Foshan, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
OpenAlex ID: W7141193845