S. Ji3, S. Thomas5,7, K. Anderson3, J. Frakes2, S. Roman4,7,8, J. A. Sosa4,6,7,8, T. Robinson2 3Duke University Medical Center,School Of Medicine,Durham, NC, USA 4Duke University Medical Center,Department Of Surgery,Durham, NC, USA 5Duke University Medical Center,Department Of Biostatistics And Bioinformatics,Durham, NC, USA 6Duke University Medical Center,Department Of Medicine,Durham, NC, USA 7Duke Cancer Institute,Durham, NC, USA 8Duke Clinical Research Institute,Durham, NC, USA 1Duke University Medical Center,Durham, NC, USA 2Moffitt Cancer Center And Research Institute,Tampa, FL, USA
Introduction:
The addition of neoadjuvant chemoradiation prior to resection of locally advanced esophageal cancer has been shown to improve disease-free and overall survival. However, the optimal radiation dose remains unknown, and conventional U.S. practice has been to use a higher dose (50.4 Gy) than that used in recent European trials (41.4 Gy). Our objective was to characterize current U.S. practice patterns and compare primary tumor and nodal down-staging, perioperative mortality, and overall survival as a function of total radiation dose.
Methods:
We performed a retrospective analysis of adult patients with non-metastatic esophageal cancer diagnosed between 2004 and 2013 within the National Cancer Data Base treated with neoadjuvant chemoradiotherapy followed by resection. The primary outcome was overall survival. Secondary outcomes included 30- and 90-day mortality and pathologic down-staging. Univariate and multivariate analyses were used to assess the association between selected outcomes and total radiation dose (41.4, 45.0 or 50.4 Gy) after controlling for patient demographic and clinical factors.
Results:
A total of 5,835 patients met inclusion criteria: 154 (2.6%) received 41.4 Gy, 1,696 (29.1%) 45 Gy and 3,985 (68.3%) 50.4 Gy. Patient demographic characteristics and comorbidities were balanced among groups. The use of 41.4 and 50.4 Gy both increased substantially (2.1% to 6.3% and 45.1% to 75.4%, respectively), while use of 45 Gy decreased (52.9% to 18.3%) during the study period (p<0.001). Compared with the 41.4 Gy group, patients receiving 45 and 50.4 Gy had higher rates of nodal down-staging (49% and 48% vs. 38%, respectively; p=0.05). Survival outcomes including 30-day, 90-day and overall survival did not vary significantly by radiation dose; however, patients receiving 41.4 Gy had numerically lower rates of 30-day and 90-day (0.0% and 1.3%) mortality compared to those with 45.0 Gy (2.8% and 7.0%) or 50.4 Gy (2.7% and 6.1%; p=0.21 for 30-day; p=0.16 for 90-day mortality, respectively).
Conclusion:
To our knowledge, this study provides the first nationally representative assessment of neoadjuvant chemoradiation dose escalation practice patterns in the treatment of locally advanced esophageal cancer in the U.S. We observed no statistically significant differences in overall or short-term survival as a function of radiation dose. Although higher radiation doses were significantly associated with improved nodal down-staging, lower dose radiation exhibited a non-significant trend towards lower 30- and 90-day mortality rates. Our study lends support to neoadjuvant approaches that balance lower elective doses (41.4 Gy) to minimize toxicity while maintaining higher doses (50.4 Gy) to gross disease to maximize locoregional control. Further research is warranted to assess the impact of neoadjuvant radiation dose escalation on locoregional disease control, perioperative complications, and overall survival.