Yongling Ji1, Xianghui Du1, Weiguo Zhu2, Yanguang Yang3, Jun Ma4, Li Zhang5, Jiancheng Li6, Hua Tao7, Jianhong Xia8, Haihua Yang9, Jin Huang10, Yong Bao11, Dexi Du12, Degan Liu13, Xiusheng Wang14, Chaoming Li15, Xinmei Yang16, Ming Zeng17, Zhigang Liu18, Wen Zheng19, Juan Pu20, Jun Chen21, Wangyuan Hu22, Peijing Li1, Jin Wang1, Yujin Xu1, Xiao Zheng1, Jianxiang Chen1, Wanwei Wang2, Guangzhou Tao2, Jing Cai3, Jizhong Zhao3, Jun Zhu7, Ming Jiang7, Yan Yan8, Guoping Xu10, Shanshan Bu14, Binbin Song16, Ke Xie17, Shan Huang17, Yuanda Zheng1, Liming Sheng1, Xiaojing Lai1, Ying Chen1, Lei Cheng1, Xiao Hu1, Wenhao Ji1, Min Fang1, Yue Kong1, Xiaofu Yu1, Huizhang Li1, Runhua Li1, Lei Shi23, Wei Shen23, Chaonan Zhu23, Junwei Lv23, Rong Huang24, Han He24, Ming Chen1,25. 1. Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Science/Institute of Cancer and Basic Medicine, Chinese Academy of Science, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China. 2. The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Nanjing, China. 3. Nantong Tumor Hospital, Nantong, China. 4. Anhui Provincial Hospital, Hefei, China. 5. Chongqing Sanxia Central Hospital, Chongqing, China. 6. Fujian Provincial Cancer Hospital, Fuzhou, China. 7. Jiangsu Cancer Hospital, Nanjing, China. 8. Huaian Second People's Hospital, Huaian, China. 9. Taizhou Hospital of Zhejiang Province, Taizhou, China. 10. The First People's Hospital of Changzhou, Changzhou, China. 11. The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 12. Lishui Municipal Central Hospital, Lishui, China. 13. Xinghua City People's Hospital, Xinghua, China. 14. Henan Cancer Hospital, Zhengzhou, China. 15. Maoming People's Hospital, Maoming, China. 16. The First Hospital of Jiaxing, Jiaxing, China. 17. Sichuan Provincial People's Hospital, Chengdu, China. 18. The Fifth Affiliated Hospital Sun Yat-sen University, Guangzhou, China. 19. Shangrao People's Hospital, Shangrao, China. 20. Lianshui County People's Hospital, Lianshui, China. 21. Yinzhou People's Hospital, Ningbo, China. 22. Jinhua Municipal Central Hospital, Jinhua, China. 23. Shanghai Key Laboratory of Artificial Intelligence for Medical Image and Knowledge Graph, Shanghai, China. 24. The First People's Hospital of Foshan, Foshan, China. 25. Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Abstract
IMPORTANCE: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. OBJECTIVE: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. INTERVENTIONS: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. RESULTS: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02813967.
IMPORTANCE: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. OBJECTIVE: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. INTERVENTIONS: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. RESULTS: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02813967.