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Journal of Gastrointestinal Surgery

, Volume 23, Issue 5, pp 885–894 | Cite as

Low- vs. High-Dose Neoadjuvant Radiation in Trimodality Treatment of Locally Advanced Esophageal Cancer

  • Keven S. Y. Ji
  • Samantha M. Thomas
  • Sanziana A. Roman
  • Brian Czito
  • Kevin L. AndersonJr.
  • Jessica Frakes
  • Mohamed A. Adam
  • Julie A. Sosa
  • Timothy J. RobinsonEmail author
Original Article
  • 120 Downloads

Abstract

Background

The optimal dose of neoadjuvant radiation for locally advanced, resectable esophageal cancer remains controversial in the absence of randomized clinical trials, with conventional practice favoring the use of 50.4 vs. 41.4 Gy.

Methods

Retrospective analysis of adults with non-metastatic esophageal cancer in the National Cancer Database (2004–2015) treated with neoadjuvant chemoradiotherapy. Outcomes were compared between patients undergoing 41.4, 45, or 50.4 Gy. Primary outcome was overall survival. Secondary outcomes included T and N downstaging and perioperative mortality adjusted for demographics, clinicopathologic factors, and facility volume.

Results

Eight thousand eight hundred eighty-one patients were included: 439 (4.9%) received low-dose (41.4 Gy), 2194 (24.7%) received moderate-dose (45 Gy), and 6248 (70.4%) received high-dose (50.4 Gy) neoadjuvant radiation. Compared to high-dose, low-dose radiation was associated with superior median overall survival (52.6 vs. 40.7 months) and 5-year survival (48.3% vs. 40.2%), and lower unadjusted 90-day mortality (2.3% vs. 6.5%, all p ≤ 0.01). Multivariable proportional hazards models confirmed an increased hazard of death associated with high-dose radiation therapy (HR = 1.38, 95% CI 1.10–1.72, p = 0.005). There was no significant difference in T and/or N downstaging between low-dose vs. high-dose therapy (p > 0.1 for both). Patients receiving 45 Gy exhibited the lowest median overall survival (37.2 months) and 5-year survival (38.7%, log-rank p = 0.04).

Conclusions

Compared to 50.4 Gy, 41.4 Gy is associated with reduced perioperative mortality and superior overall survival with similar downstaging in locally advanced esophageal cancer. In the absence of randomized clinical data, our findings support the use of 41.4 Gy in patients with chemoradiation followed by esophagectomy. Prospective trials are warranted to further validate these results.

Keywords

Esophageal neoplasms Chemoradiotherapy Neoadjuvant therapy 

Notes

Compliance with Ethical Standards

Conflict of Interest

Julie A. Sosa, M.D., M.A., is a member of the Data Monitoring Committee for the Medullary Thyroid Cancer Consortium Registry supported by Novo Nordisk, GlaxoSmithKline, Astra Zeneca, and Eli Lilly. The other authors declare that they have no competing interests.

Supplementary material

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Supplementary Figure 1 (PDF 10 kb)
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Supplementary Figure 2 (PDF 91 kb)
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Supplementary Table 1 (DOCX 24 kb)
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Supplementary Table 2 (DOCX 16 kb)
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Supplementary Table 7 (DOCX 15 kb)

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Copyright information

© The Society for Surgery of the Alimentary Tract 2018

Authors and Affiliations

  • Keven S. Y. Ji
    • 1
  • Samantha M. Thomas
    • 2
    • 3
  • Sanziana A. Roman
    • 4
  • Brian Czito
    • 5
  • Kevin L. AndersonJr.
    • 1
  • Jessica Frakes
    • 6
  • Mohamed A. Adam
    • 7
  • Julie A. Sosa
    • 4
  • Timothy J. Robinson
    • 6
    Email author
  1. 1.Duke University School of MedicineDurhamUSA
  2. 2.Duke Cancer InstituteDurhamUSA
  3. 3.Department of Biostatistics & BioinformaticsDuke UniversityDurhamUSA
  4. 4.Department of SurgeryUniversity of California at San Francisco-UCSFSan FranciscoUSA
  5. 5.Department of Radiation OncologyDuke University Medical CenterDurhamUSA
  6. 6.Department of Radiation OncologyMoffitt Cancer CenterTampa BayUSA
  7. 7.Department of SurgeryDuke University Medical CenterDurhamUSA

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