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Original Investigation
August 5, 2021

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial

Author Affiliations
  • 1Department 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
  • 2The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Nanjing, China
  • 3Nantong Tumor Hospital, Nantong, China
  • 4Anhui Provincial Hospital, Hefei, China
  • 5Chongqing Sanxia Central Hospital, Chongqing, China
  • 6Fujian Provincial Cancer Hospital, Fuzhou, China
  • 7Jiangsu Cancer Hospital, Nanjing, China
  • 8Huaian Second People's Hospital, Huaian, China
  • 9Taizhou Hospital of Zhejiang Province, Taizhou, China
  • 10The First People's Hospital of Changzhou, Changzhou, China
  • 11The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  • 12Lishui Municipal Central Hospital, Lishui, China
  • 13Xinghua City People's Hospital, Xinghua, China
  • 14Henan Cancer Hospital, Zhengzhou, China
  • 15Maoming People's Hospital, Maoming, China
  • 16The First Hospital of Jiaxing, Jiaxing, China
  • 17Sichuan Provincial People's Hospital, Chengdu, China
  • 18The Fifth Affiliated Hospital Sun Yat-sen University, Guangzhou, China
  • 19Shangrao People's Hospital, Shangrao, China
  • 20Lianshui County People's Hospital, Lianshui, China
  • 21Yinzhou People's Hospital, Ningbo, China
  • 22Jinhua Municipal Central Hospital, Jinhua, China
  • 23Shanghai Key Laboratory of Artificial Intelligence for Medical Image and Knowledge Graph, Shanghai, China
  • 24The First People's Hospital of Foshan, Foshan, China
  • 25Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
JAMA Oncol. Published online August 5, 2021. doi:10.1001/jamaoncol.2021.2705
Key Points

Question  Is concurrent chemoradiotherapy with S-1 an effective and tolerable treatment for older patients with esophageal cancer?

Findings  In this randomized phase 3 clinical trial that included 298 older patients with esophageal cancer, concurrent chemoradiotherapy with S-1 significantly improved 2-year overall survival compared with radiotherapy alone (53.2% vs 35.8%). The incidence of grade 3 or higher toxic effects was not significantly higher except for leukopenia (9.5% vs 2.7%).

Meaning  The findings of this trial indicate that concurrent chemoradiotherapy with S-1 is an effective and tolerable treatment for older patients with esophageal cancer.


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

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