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

Richard Li, Ashwin Shinde, Scott Glaser, Joseph Chao, Jae Kim, Sana D. Karam, Karyn Goodman, Yi-Jen Chen, Arya Amini


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.