Abstract
BACKGROUND: Radiotherapy for locally advanced esophageal cancer can induce lymphopenia, potentially worsening outcomes. This study examines the association between clinical outcomes and the effective dose to the immune cells (EDIC), a measure of lymphocyte radiation exposure. METHODS: We retrospectively analyzed 107 patients with locally advanced esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy (CCRT). The EDIC was calculated based on the mean lung dose, mean heart dose, and integral total body dose using established models. Patients were stratified into high (n = 42) and low (n = 65) effective dose to the immune cells (EDIC) groups using a cut-off value of 4.28 Gy. Survival outcomes, including overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS), were assessed. RESULTS: The 5-year OS and PFS rates were significantly lower in the high EDIC group than in the low EDIC group (51.9% vs. 66.6%, p = 0.043; 20.8% vs. 31.8%, p = 0.002, respectively). Multivariate analysis identified high EDIC as an independent predictor of poorer OS (hazard ratio (HR): 2.06, 95% confidence interval (CI): 1.1-3.86, p = 0.024) and PFS (HR: 1.7, 95% CI: 1.04-2.78, p = 0.034). Similarly, the 5-year LRFS and DMFS rates were significantly lower in the high EDIC group than in the low EDIC group (24.1% vs. 34.9%, p = 0.003; 29.0% vs. 44.0%, p = 0.018, respectively). CONCLUSION: A higher EDIC is an independent predictor of poor survival in patients with esophageal squamous cell carcinoma undergoing CCRT. Reducing radiation exposure to the immune system through optimized radiation planning and lymphocyte-sparing techniques may improve patient outcomes.