Comparison of radiation esophagitis associated with daytime versus evening radiotherapy in patients with esophageal carcinoma

Purpose: Based on the demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G2/M phase in the afternoon and at night, the present study evaluated the severity of acute radiation esophagitis and treatment outcomes in esophageal squamous cell carcinoma patients receiving radiotherapy (RT) in the daytime versus in the evening.

Methods: From the 488 eligible patients of esophageal squamous cell carcinoma receiving concurrent chemoradiotherapy (CCRT), 369 patients received RT in the daytime (before 19:00) and 119 patients received RT in the evening (after 19:00). The grades of radiation esophagitis (Common Terminology Criteria for Adverse Events version 5.0) and survival outcomes were compared in the two groups. Analyses were performed by using ordinal logistic regression and Cox proportional hazard regression.

Results: The median follow-up was 27 months. In multivariate logistic regression models, evening treatment (after 19:00) (odds ratio, 1.660 [95% CI 1.094-2.518]), tumor length ≥ 5 cm (odds ratio, 1.632 [95% CI 1.102-2.416]), PGTV dose ≥ 59.34 Gy (odds ratio, 1.702 [95% CI 1.099-2.635]), female sex (odds ratio, 2.241 [95% CI 1.475-3.405]), and tumor location in cervical segment and upper thoracic (odds ratio, 1.665 [95% CI 1.043-2.658]) were associated with higher odds of radiation esophagitis. There was no difference in the overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) (all p > 0.05) between the daytime treatment group and evening treatment group. The results of the subgroup analysis showed that no significant difference was found in radiation esophagitis between the two groups with PGTV dose < 59.34 Gy, while there was a higher odds for the Grade 2 or higher radiation esophagitis in the evening treatment group than the daytime treatment group (odds ratio, 1.675 [95% CI 1.062-2.643]) with PGTV dose ≥ 59.34 Gy.

Conclusion: RT in the evening (after 19:00) was associated with higher odds to present esophagitis for esophageal squamous cell carcinoma patients, especially with higher radiation doses, but treatment outcomes did not differ according to the time of RT.