S-1 Chemoradiation vs Radiotherapy Alone in Patients Aged 70 to 85 With Esophageal Cancer

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In a Chinese phase III trial reported in JAMA Oncology, Ji et al found that concurrent chemoradiation with S-1 was associated with improved overall survival and acceptable toxicity vs radiotherapy alone in older patients with esophageal cancer.  

As stated by the investigators, “Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy. An effective and tolerable chemoradiotherapy regimen for older patients is needed.”

Study Details

The multicenter open-label trial included 298 patients with stage IB to IVB (including only metastasis to the supraclavicular/celiac lymph nodes) disease and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned between June 2016 and August 2018 to receive radiotherapy at 54 Gy in 30 fractions with concurrent S-1 at 70 mg/m2 per day on days 1 to 14 and 29 to 42 (n = 149) or radiotherapy alone at 60 Gy in 30 fractions (n = 149).

Patients in both groups had a median age of 77 years. Stage III or IV disease was present in 51% of patients. The primary endpoint was 2-year overall survival in the intention-to-treat population.


  • Chemoradiation with S-1 was associated with improved overall survival vs radiotherapy alone.
  • Overall survival at 2 years was 53.2% vs 35.8% and median overall survival was 24.9 vs 15.4 months.

Overall Survival

At the time of analysis (August 2020), median follow-up was 33.9 months (interquartile range = 28.5–38.2 months) among surviving patients. Overall survival at 2 years was 53.2% in the chemoradiation group vs 35.8% in the radiotherapy alone group (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47–0.85, P = .002). Overall survival rates at 1 and 3 years were 74.3% vs 59.7% and 43.4% vs 28.4%, respectively. Median overall survival was 24.9 months vs 15.4 months.

Complete response was observed in 41.6% vs 26.8% of patients (P = .007). Locoregional progression was observed in 28.2% vs 40.9% (P = .02). Median progression-free survival was 18.7 months vs 9.5 months (HR = 0.66, 95% CI = 0.50–0.87, P = .003).

Adverse Events

The chemoradiation group had higher rates of any-grade neutropenia (33.8% vs 22.1%, P = .04), thrombocytopenia (25.7% vs 12.8%, P = .007), and constipation (15.5% vs 7.4%, P = .04). The most common grade ≥ 3 adverse events in the chemoradiation group were leukopenia (9.5% vs 2.7% in radiotherapy group, P = .01), esophagitis (8.8% vs 6.0%), and infection (4.7% vs 4.0); no significant differences in the incidence of grade ≥ 3 adverse events were observed between groups, apart from leukopenia.

Treatment-related death occurred in three patients (2.0%) in the chemoradiation group—all due to radiotherapy-associated pneumonitis—and in four patients (2.7%) in the radiotherapy group, with causes consisting of radiotherapy-associated pneumonitis in two and pneumonia in two. Six of the seven treatment-related deaths occurred in patients aged 75 or older, including three aged 80 or older.

The investigators concluded, “In this phase III randomized clinical trial, concurrent chemoradiation therapy with S-1 was tolerable and provided significant benefits over radiotherapy alone in older patients with esophageal cancer.”

Ming Chen, MD, of the Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by a Zhejiang Basic Public Welfare Research Project and National Natural Science Foundation of China. For full disclosures of the study authors, visit

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