放射治疗在食管癌的治疗中发挥着重要作用。质子治疗具有独特的物理性质和较高的相对生物学效应。然而，质子治疗是否比光子治疗具有更大的益处仍然不清楚。为评估质子治疗是否与光子治疗相比，具有更好的疗效和安全性结果，包括剂量学、预后和毒副作用结果，并评估质子治疗的疗效和安全性。通过系统搜索PubMed、Embase、Cochrane图书馆、Web of Science、SinoMed和中国国家知识基础设施数据库，检索到2021年11月25日至2023年3月25日期间发表的文章。比较质子和光子治疗的研究包括剂量学、预后和相关毒副作用的结果。对质子治疗的单独评估评估了相同的指标。提取研究设计、个体特征和结果的数据。如果I2大于50%，则选择随机效应模型。此次荟萃分析按照系统评价和荟萃分析偏好报告项目（PRISMA）报告指南进行报告。主要结果包括风险器官（OARs）剂量学结果、预后（总生存率[OS]、无进展生存率[PFS]和客观缓解率[ORR]）和与放射相关的毒副作用。共纳入45个研究进行荟萃分析。剂量学分析显示，质子治疗与显著降低的OARs剂量相关。荟萃分析显示，光子治疗与较差的OS（风险比[HR]，1.31；95%可信区间[CI]，1.07-1.61；I2 = 11%）相关，但PFS无差异。亚组分析显示，在野蛮治疗组中，光子治疗与较差的OS（HR，1.42；95%CI，1.14-1.78；I2 = 34%）和PFS（HR，1.48；95%CI，1.06-2.08；I2 = 7%）相关。质子治疗组与光子治疗组在病理完全缓解率方面相似。质子治疗与明显减少的2级或更高放射性肺炎和心包积液以及4级或更高的淋巴细胞减少相关。质子治疗的单终点分析显示，在1年时，OS为89%，PFS为65%；在2年时，OS为71%，PFS为56%；在3年时，OS为63%，PFS为48%；在5年时，OS为56%，PFS为42%。2级或更高放射性食管炎的发生率为50%，2级或更高放射性肺炎的发生率为2%，2级或更高胸腔积液的发生率为4%，2级或更高心包积液的发生率为3%，3级或更高放射性食管炎的发生率为8%，4级或更高淋巴细胞减少的发生率为17%。在这个荟萃分析中，质子治疗与光子治疗相比，与食管癌的OARs剂量和毒副作用减少以及预后改善相关，但需要谨慎使用。将来应在随机临床试验中进一步验证这些发现。

Radiotherapy plays an important role in the treatment of esophageal cancer. Proton therapy has unique physical properties and higher relative biological effectiveness. However, whether proton therapy has greater benefit than photon therapy is still unclear.To evaluate whether proton was associated with better efficacy and safety outcomes, including dosimetric, prognosis, and toxic effects outcomes, compared with photon therapy and to evaluate the efficacy and safety of proton therapy singly.A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, and China National Knowledge Infrastructure databases was conducted for articles published through November 25, 2021, and updated to March 25, 2023.For the comparison of proton and photon therapy, studies including dosimetric, prognosis, and associated toxic effects outcomes were included. The separate evaluation of proton therapy evaluated the same metrics.Data on study design, individual characteristics, and outcomes were extracted. If I2 was greater than 50%, the random-effects model was selected. This meta-analysis is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.The main outcomes were organs at risk (OARs) dosimetric outcomes, prognosis (overall survival [OS], progression-free survival [PFS], and objective response rate [ORR]), and radiation-related toxic effects.A total of 45 studies were included in the meta-analysis. For dosimetric analysis, proton therapy was associated with significantly reduced OARs dose. Meta-analysis showed that photon therapy was associated with poor OS (hazard ratio [HR], 1.31; 95% CI, 1.07-1.61; I2 = 11%), but no difference in PFS was observed. Subgroup analysis showed worse OS (HR, 1.42; 95% CI, 1.14-1.78; I2 = 34%) and PFS (HR, 1.48; 95% CI, 1.06-2.08; I2 = 7%) in the radical therapy group with photon therapy. The pathological complete response rate was similar between groups. Proton therapy was associated with significantly decreased grade 2 or higher radiation pneumonitis and pericardial effusion, and grade 4 or higher lymphocytopenia. Single-rate analysis of proton therapy found 89% OS and 65% PFS at 1 year, 71% OS and 56% PFS at 2 years, 63% OS and 48% PFS at 3 years, and 56% OS and 42% PFS at 5 years. The incidence of grade 2 or higher radiation esophagitis was 50%, grade 2 or higher radiation pneumonitis was 2%, grade 2 or higher pleural effusion was 4%, grade 2 or higher pericardial effusion was 3%, grade 3 or higher radiation esophagitis was 8%, and grade 4 or higher lymphocytopenia was 17%.In this meta-analysis, proton therapy was associated with reduced OARs doses and toxic effects and improved prognosis compared with photon therapy for esophageal cancer, but caution is warranted. In the future, these findings should be further validated in randomized clinical trials.