Background: Traditional neoadjuvant therapy for esophageal cancer has used chemoradiation doses greater than 45 Gy. This study aimed to examine the dose of preoperative radiation in relation to the pathologic complete response (pCR) rate and overall survival (OS) for patients with resectable esophageal cancer. Methods: The National Cancer Database was queried for all patients with esophageal or gastroesophageal junction cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy between 2006 and 2015. The radiation doses were divided into four ranges based on Grays (Gy) received: less than 39.6 Gy, 39.60–44.99 Gy, 45–49.99 Gy, and 50 Gy or more. Results: The inclusion criteria were met by 10,293 patients. All patients received neoadjuvant CRT, with 689 patients (6.7%) receiving less than 39.6 Gy, 973 patients (9.5%) receiving 39.6–44.9 Gy, 3837 patients (37.3%) receiving 45–49.9 Gy, and 4794 patients (46.6%) receiving 50 Gy or more. The overall pCR rate was 17.2% (1769/10,293) and was significantly lower for those who received less than 39.6 Gy of radiation than for those who received 39.6 Gy or more (13.9% [96/689] vs. 17.4% [1673/9604]; p = 0.017). The median OS of 37.2 months was significantly better for those who received 39.6 Gy or more than for those who received less than 39.6 Gy (38 vs. 29.6 months (p < 0.0001). The pCR and OS did not differ between the three higher radiation doses (39.6–44.9 vs. 45–49.9 Gy vs. ≥ 50 Gy; pCR [p = 0.1] vs. OS [p = 0.097]). The patients who received 39.6–44.9 Gy were propensity matched with those who received 45 Gy or more of radiation. There remained no difference in pCR (p = 0.375) or OS (p = 0.957). Conclusions: In the United States, the heterogeneity in neoadjuvant CRT dosing is significant, with 84% of patients receiving more than 45 Gy. The benefit of neoadjuvant CRT in terms of pCR and overall survival is seen with doses of 39.6 Gy or more, but not with doses higher than 45 Gy.
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