Analyzing the impact of neoadjuvant radiation dose on pathologic response and survival outcomes in esophageal and gastroesophageal cancers

Background: The optimal neoadjuvant radiation therapy (RT) dose prior to esophagectomy is unknown. We compared patients receiving lower-dose RT (LD-RT) of 41.4–45 Gy versus those receiving higher-dose RT (HD-RT) of 50–54 Gy. Methods: Patients with non-metastatic esophageal or gastroesophageal cancer diagnosed from 2004 to 2015 who underwent neoadjuvant chemoradiation (CRT) followed by esophagectomy were identified using the National Cancer Database (NCDB) and divided into LD-RT and HD-RT groups. Logistic regression was used to evaluate predictors of HD-RT utilization and propensity score matching. Overall survival (OS) was compared between HD-RT and LD-RT groups using Cox regression. Logistic regression was performed with respect to pathologic complete response (pCR), positive surgical margins, postoperative mortality, and readmission rates. Results: We identified 7,996 patients meeting inclusion criteria, of which 5,732 (71.7%) received HD-RT. At median follow-up of 3.3 years, 3-year OS was 48.7% for HD-RT versus 48.4% for LD-RT (P=0.734). pCR rates were 20.3% with HD-RT versus 16.3% with LD-RT [odds ratio (OR) 1.24; 95% CI: 1.06–1.44; P=0.006]. There were no statistically significant differences between HD-RT and LD-RT with respect to positive margins, 90-day postoperative mortality, or readmission rates. In a separate analysis of patients treated with CRT alone and no subsequent esophagectomy, HD-RT was associated with improved OS (HR 0.83; 95% CI: 0.78–0.88; P<0.001). Conclusions: Our analysis suggests that 41.4–45 and 50–54 Gy dose regimens are similar in survival and postoperative outcomes. However, in cases of equivocal resectability, a higher RT dose of 50–54 Gy may be preferred.