Radiation Dose-Effect Relation in Patients with Esophageal Squamous Cell Carcinoma: A National Cancer Center Data and Literature-Based Analysis

INTRODUCTION: Despite receiving definitive chemoradiotherapy (dCRT) with radiation dose (RTD) of 50.4 Gy, survival of esophageal carcinoma was dismal. The effect of RTD in cancer control and radiotoxicity, and the extent to which local-regional control (LRC) influenced survival remain vague. This study aimed at evaluating RTD-effect relationship in esophageal squamous cell carcinoma (ESCC). METHODS: 1440 dRT/CRT-treated ESCC patients were enrolled. Restricted cubic spline regression model was applied to reveal nonlinear relationship between RTD and survival/radiotoxicity. Linear regression analysis (LRA) was performed to evaluate correlations between LRC and overall survival (OS) or progression-free survival (PFS). RESULTS: For 1440 dRT/CRT-treated ESCC patients, with RTD escalating, hazard ratios (HRs) of OS, PFS, LRC declined until RTD exceeded 60 Gy, then increased. HR of treatment-related mortality was stable until RTD exceeded 60 Gy, then increased. HR of LRC was lower for majority of patients treated with RTD≥60 Gy, except for those with KPS<80, T1-2 lesion, or without lymph node metastasis. LRA revealed strong correlations between LRC and OS/PFS. 45.5% and 44.9% of OS and PFS improvements were owing to improved LRC. CONCLUSIONS: RTD of 60 Gy was well tolerated, with favorable survival resulted of LRC improvement in local-advanced ESCC. Further stratification analyses based on radiation sensitivity will be helpful to determine potential beneficiaries of RTD escalation.