Re-evaluating the Optimal Radiation Dose for Definitive Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Background: The optimal radiation dose for treating esophageal squamous cell carcinoma (ESCC) has long been debated. We evaluated if doses greater than 50.4 Gy delivered with modern techniques are beneficial in terms of tumor control, survival, and toxicity. Methods: We included 193 consecutive patients with ESCC treated with definitive concurrent chemoradiotherapy from 1998 to 2012. Patients were treated to a dose of <= 50.4 Gy (low-dose, n = 137) or greater than 50.4 Gy (high-dose, n = 56). Tumor response, local-regional control, survival, and treatment toxicity were compared between groups. Results: High-dose group had a significantly lower local failure rate (17.9% versus 34.3%, p = 0.024) and a marginal better 5-year local-regional failure-free survival (68.7% versus 55.9%, p = 0.052) than the low-dose group. No significant differences were found between high-and low-dose groups in tumor complete response rate (p = 0.975), regional failure rate (p = 0.336), distant metastasis rate (p = 0.390), or 5-year overall survival (p = 0.617). No difference in the incidence of toxic effects was observed between the two groups except for grade 3 skin reaction (12.5% [high] versus 2.2% [low], p < 0.001) and grade greater than or equal to 3 esophageal stricture (32.1% [high] versus 18.2% [low], p = 0.037). Conclusions: Local tumor control might be improved by higher dose of greater than 50.4 Gy, when delivered with modern techniques and concurrent chemotherapy, at the consequence of increased toxicity without impact on overall survival.