High versus standard radiation dose of definitive concurrent chemoradiotherapy for esophageal cancer: A systematic review and meta-analysis of randomized clinical trials

Objectives: Compare the efficacy and safety of high vs standard radiation dose of definitive concurrent chemoradiotherapy (dCCRT) for esophageal cancer (EC). Methods and materials: This meta-analysis is registered in PROSPERO, and it was followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Eligible randomized clinical trials (RCTs) comparing high dose (HD;≥59.4 Gy/1.8 Gy) and standard doses (SD; 50 Gy/2Gy or 50.4 Gy/1.8 Gy) were identified on electronic databases. STATA16.0 was used for statistical analysis. A meta-analysis was performed to compare treatment effect and toxicity. Results: Four articles with a total of 1014 patients were finally included. The results showed that the two groups had similar 1-, 2-, and 3-year OS rates (RR = 1.08, 95 % CI = 0.90–1.30, P = 0.395; RR = 1.07, 95 % CI = 0.95–1.20, P = 0.272; RR = 1.06, 95 % CI = 0.97–1.17, P = 0.184; respectively) and 2-, and 3-year locoregional progression-free survival (LRPFS) (RR = 0.95, 95 % CI = 0.81–1.10, P = 0.478; RR = 0.97, 95 % CI = 0.85–1.11, P = 0.674; respectively). The HD-RT group had higher grade ≥ 3 treatment-related toxicities (OR = 1.35, 95 % CI = 1.03–1.77, P = 0.029) and treatment-related deaths rates (OR = 1.85, 95 % CI = 1.04–3.28, P = 0.036) compared with the SD-RT group. Results of subgroup analysis also indicated that HD could not bring benefit compared to SD, even with modern radiotherapy techniques. Conclusion: SD-RT had similar treatment effect but lower Grade ≥ 3 treatment-related toxicities rates compared with the HD-RT. Therefore, SD (50 Gy/2Gy or 50.4 Gy/1.8 Gy) should be considered as the recommended dose in dCCRT for EC. Further RCTs are needed to verify our conclusions.