A phase II randomized trial comparing radiation doses in concurrent chemoradiotherapy with TS-1/nedaplatin for curative treatment of newly diagnosed or recurrent esophageal cancer.

Abstract

To evaluate and compare progression-free survival (PFS) between 50.4-Gy and 60-Gy radiation doses in definitive chemoradiotherapy (CRT) for patients with esophageal cancer, and to confirm that the 50.4-Gy is non-inferior to the 60-Gy irradiation method in terms of PFS. Patients with medically inoperable (including patient refusal), unresectable, and/or recurrent esophageal carcinoma referred for definitive CRT were randomly assigned to either the group receiving a total dose of 50.4 Gy in 28 fractions (1.8 Gy/day) for 5.5 weeks or the group receiving a total dose of 60 Gy in 30 fractions (2.0 Gy/day) using involved-field radiation therapy. Chemotherapy consisted of two courses of concurrent nedaplatin (80 mg/m²) and tegafur, gimeracil, and oteracil potassium (S-1) (80 mg/m²) in both arms every four weeks. The primary end point was PFS. Between December 2015 and February 2025, 97 patients with squamous cell carcinoma were included. Radiation treatment was completed in 98% of patients. The median follow-up time for surviving patients was 33.2 months. The 3-year PFS was 45% in the 50.4-Gy group versus 26% in the 60-Gy group (p = 0.017). The 3-year cumulative local control rate was 65% and 46% for the 50.4-Gy and 60-Gy groups, respectively (p = 0.047). The 3-year overall survival was 73% and 42% for the 50.4-Gy and 60-Gy groups, respectively (p = 0.018). Overall, grade 3-4 toxicities were observed in 53% of the 50.4-Gy group versus 51% of the 60-Gy group. The PFS and overall survival differences between the 50.4-Gy and 60-Gy groups were no longer statistically significant after adjustment for key covariates using multivariable analysis. A radiation dose of 50.4 Gy remains the standard dose in concurrent CRT for esophageal squamous cell carcinoma.