Inclusion and Excluded Criteria

This study had 2 objectives. The first objective was to evaluate whether proton therapy was beneficial compared with photon therapy (including the dosimetric, prognosis, and toxic effects outcomes). The second objective was to assess the efficacy and safety of proton therapy using single-rate pooled analysis.

For the comparison of proton and photon therapy, inclusion criteria included for efficacy evaluation metrics were studies reporting objective response rate (ORR), OS, or progress-free survival (PFS). Safety metrics were cardiopulmonary toxic effects, myelotoxic effects, and esophageal toxic effects. For the dosimetric comparison analysis, the OARs were the lungs, heart (including substructures), spinal cord (SC), and bone marrow. If multiple proton techniques were available simultaneously in 1 study, the technique with the greatest comprehensive dose benefit to OARs was preferred. For the separate evaluation of proton therapy, the efficacy and safety evaluation metrics were same.

Finally, all studies had to include at least 10 patients. Studies with mixed-disease assessment were not included unless data related to esophageal cancer could be extracted separately. Additionally, studies among patients who had received radiotherapy previously were excluded, nor could patients receive proton and photon therapy simultaneously, except for salvage-therapy after recurrence. We only included the most recently published publications from the same cohort for the same metric. Editorials, letters, comments, case reports, reviews, meta-analyses, and conference abstracts were excluded (Figure 1).