The impact of radiation dose on the efficacy of definitive chemoradiotherapy in patients with locally advanced esophageal carcinoma: a systematic review and meta-analysis

To investigate the impact of radiation dose on the efficacy of definitive chemoradiotherapy(dCCRT) in patients with locally advanced esophageal carcinoma. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Wanfang, and Chinese National Knowledge Infrastructure(CNKI) were searched for eligible studies. Studies that compared high-dose radiation(HD-RT) group with low-dose radiation(LD-RT) group using modern radiotherapy techniques for locally advanced esophageal carcinoma patients in dCCRT were identified. The hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and the odds ratios (OR) for clinical complete response (cCR), local–regional failure (LRF), distant metastasis (DM), and grade≥3 AEs. Meta-analysis was performed when relevant data were available. Eleven studies involving 1943 patients were included for analyses. The results showed that the HD-RT group had better OS (pooled HR 0.78 [0.70, 0.87], p < .00001), PFS (pooled HR 0.72 [0.55, 0.94], p = .01), cCR (OR 1.52 [1.13, 2.05], p = .005), and LRF (OR 0.60 [0.45, 0.80], p = .0004). In addition, there were no significant differences between the two groups in terms of DM (OR 1.43 [1.00, 2.04], p = .05), grade 3–5 radiation pneumonitis (OR 1.38 [0.71, 2.68], p = .35), grade 3–5 radiation esophagitis (OR 1.36 [0.88, 2.10], p = .17), grade 3–5 other esophageal toxicities(stenosis/fistula/hemorrhage) (OR 1.22 [0.75, 2.00], p = .43), and treatment-related death (OR 1.40 [0.73, 2.68], p = .31). High-dose radiotherapy in definitive CCRT for patients with locally advanced esophageal carcinoma is associated with improved PFS, OS, cCR, and LC with no increase of grade≥3AEs. Simultaneously, we await the preliminary and final results of several ongoing dose-escalation randomized trials. Furthermore, future studies should provide personalized radiotherapy doses for these patients.