Skip to main content

Advertisement

SpringerLink
Log in

Influence of Neoadjuvant Radiation Dose on Patients Undergoing Esophagectomy and Survival in Locally Advanced Esophageal Cancer

  • 2018 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Neoadjuvant chemoradiotherapy followed by resection is standard of care for patients with locally advanced esophageal cancer, however, a significant portion of these patients do not undergo surgical intervention. This study evaluates radiation dose and other factors associated with undergoing esophageal resection and their impact on outcomes including survival.

Methods

Patients diagnosed with esophageal cancer between 2010 and 15 were queried from the National Cancer Database and stratified into low-dose radiation (41.4 Gy) (LDR) or high-dose radiation (50.0 or 50.4 Gy) (HDR) groups. Multivariable Logistic and Cox Regression analyses were performed to investigate the effect of multiple variables on the likelihood of undergoing esophagectomy and overall survival, respectively. Propensity score matching was performed to reduce bias between groups.

Results

A total of 3633 patients met study criteria with 3005 (82.7%) undergoing esophagectomy. A greater proportion received HDR (3163 (87.1%)) than LDR (470 (12.9%)). The use of LDR increased from 4.7% (n = 22) in 2010 to 20.7% (n = 154) in 2015. Factors associated with undergoing esophagectomy included LDR, adenocarcinoma histology, and younger age. Radiation dosage did not impact overall survival, but undergoing esophagectomy was associated with improved survival. After propensity matching, a greater portion of the LDR group underwent esophagectomy (87.0 vs 81.1%, p = 0.013). There was no difference in R0 3 resection (93.2 vs 92.4%, p = 0.678) or complete pathologic response (19.3 vs 21.5%, p = 0.442) between LDR and HDR groups.

Conclusion

The use of LDR is increasing but still underutilized. LDR is associated with increased rates of esophagectomy without negatively impacting overall survival, R0 resection, or complete pathologic response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ferlay, J., I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D.M. Parkin, D. Forman, and F. Bray, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer, 2015. 136(5).

  2. Noone AM, H.N., Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2015. Available from: https://seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site, April 2018.

  3. Arnold, M., M. Laversanne, L.M. Brown, S.S. Devesa, and F. Bray, Predicting the future burden of esophageal cancer by histological subtype: international trends in incidence up to 2030. The American journal of gastroenterology, 2017. 112(8): p. 1247.

    Article  PubMed  Google Scholar 

  4. Little, A.G., A.E. Lerut, D.H. Harpole, W.L. Hofstetter, J.D. Mitchell, N.K. Altorki, and M.J. Krasna, The Society of Thoracic Surgeons practice guidelines on the role of multimodality treatment for cancer of the esophagus and gastroesophageal junction. The Annals of Thoracic Surgery, 2014. 98(5): p. 1880–1885.

    Article  PubMed  Google Scholar 

  5. Tepper, J., M.J. Krasna, D. Niedzwiecki, D. Hollis, C.E. Reed, R. Goldberg, K. Kiel, C. Willett, D. Sugarbaker, and R. Mayer, Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 2008. 26(7): p. 1086.

    Article  CAS  Google Scholar 

  6. Khushalani, N.I., C.G. Leichman, G. Proulx, H. Nava, L. Bodnar, D. Klippenstein, A. Litwin, J. Smith, E. Nava, and L. Pendyala, Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer. Journal of Clinical Oncology, 2002. 20(12): p. 2844–2850.

    Article  CAS  PubMed  Google Scholar 

  7. Buckstein, M., R. Rhome, M. Ru, and E. Moshier, Neoadjuvant chemoradiation radiation dose levels for surgically resectable esophageal cancer: predictors of use and outcomes. Diseases of the Esophagus, 2017.

  8. Herskovic, A., K. Martz, M. Al-Sarraf, L. Leichman, J. Brindle, V. Vaitkevicius, J. Cooper, R. Byhardt, L. Davis, and B. Emami, Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. New England Journal of Medicine, 1992. 326(24): p. 1593–1598.

    Article  CAS  PubMed  Google Scholar 

  9. Minsky, B.D., T.F. Pajak, R.J. Ginsberg, T.M. Pisansky, J. Martenson, R. Komaki, G. Okawara, S.A. Rosenthal, and D.P. Kelsen, INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. Journal of clinical oncology, 2002. 20(5): p. 1167–1174.

    Article  CAS  PubMed  Google Scholar 

  10. van Hagen, P., M. Hulshof, J. Van Lanschot, E. Steyerberg, M.V.B. Henegouwen, B. Wijnhoven, D. Richel, G. Nieuwenhuijzen, G. Hospers, and J. Bonenkamp, Preoperative chemoradiotherapy for esophageal or junctional cancer. New England Journal of Medicine, 2012. 366(22): p. 2074–2084.

    Article  PubMed  Google Scholar 

  11. Cox, J.D. and K.K. Ang, Radiation Oncology E-Book: Rationale, Technique, Results. 2009: Elsevier Health Sciences.

  12. Gunderson, L.L. and J.E. Tepper, Clinical Radiation Oncology, Fourth Edition. 2016, Philadelphia, PA: Elsevier.

    Google Scholar 

  13. Lin, S.H., K.W. Merrell, J. Shen, V. Verma, A.M. Correa, L. Wang, P.F. Thall, N. Bhooshan, S.E. James, and M.G. Haddock, Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer. Radiotherapy and Oncology, 2017. 123(3): p. 376–381.

    Article  PubMed  Google Scholar 

  14. Network, N.C.C., NCCN Esophageal Cancer Guidelines. 2016. 2017.

  15. Haque, W., V. Verma, E.B. Butler, and B.S. Teh, Radiation dose in neoadjuvant chemoradiation therapy for esophageal cancer: patterns of care and outcomes from the National Cancer Data Base. Journal of gastrointestinal oncology, 2018. 9(1): p. 80.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kelsen, D.P., K.A. Winter, L.L. Gunderson, J. Mortimer, N.C. Estes, D.G. Haller, J.A. Ajani, W. Kocha, B.D. Minsky, and J.A. Roth, Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. Journal of Clinical Oncology, 2007. 25(24): p. 3719–3725.

    Article  PubMed  Google Scholar 

  17. Whited, W.M., J.R. Trivedi, E.R. Bond, V.H. van Berkel, and M.P. Fox, Optimal Therapy in Locally Advanced Esophageal Cancer: a National Cancer Database Analysis. Journal of Gastrointestinal Surgery, 2018. 22(2): p. 187–193.

    Article  PubMed  Google Scholar 

  18. Reid, T., I.L. Davies, J. Mason, S. Roberts, T. Crosby, and W. Lewis, Stage for stage comparison of recurrence patterns after definitive chemoradiotherapy or surgery for oesophageal carcinoma. Clinical Oncology, 2012. 24(9): p. 617–624.

    Article  CAS  PubMed  Google Scholar 

  19. Hategan, M., N. Cook, S. Prewett, A. Hindmarsh, W. Qian, and D. Gilligan, Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a single-center experience and review of the literature. Diseases of the Esophagus, 2015. 28(7): p. 612–618.

    Article  CAS  PubMed  Google Scholar 

  20. Bedenne, L., P. Michel, O. Bouché, C. Milan, C. Mariette, T. Conroy, D. Pezet, B. Roullet, J.-F. Seitz, and J.-P. Herr, Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. Journal of clinical oncology, 2007. 25(10): p. 1160–1168.

    Article  CAS  PubMed  Google Scholar 

  21. Stahl, M., M. Stuschke, N. Lehmann, H.-J. Meyer, M.K. Walz, S. Seeber, B. Klump, W. Budach, R. Teichmann, and M. Schmitt, Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. Journal of clinical oncology, 2005. 23(10): p. 2310–2317.

    Article  PubMed  Google Scholar 

  22. Brower, J.V., S. Chen, M.F. Bassetti, M. Yu, P.M. Harari, M.A. Ritter, and A.M. Baschnagel, Radiation dose escalation in esophageal cancer revisited: a contemporary analysis of the National Cancer Data Base, 2004 to 2012. International Journal of Radiation Oncology• Biology• Physics, 2016. 96(5): p. 985–993.

    Article  Google Scholar 

  23. Kachnic, L.A., K. Winter, T. Wasserman, D. Kelsen, R. Ginsberg, T.M. Pisansky, J. Martenson, R. Komaki, G. Okawara, and S.A. Rosenthal, Longitudinal quality-of-life analysis of RTOG 94–05 (Int 0123): A Phase III trial of definitive chemoradiotherapy for esophageal cancer. Gastrointestinal cancer research: GCR, 2011. 4(2): p. 45.

    PubMed  Google Scholar 

  24. Lee, H.K., A.A. Vaporciyan, J.D. Cox, S.L. Tucker, J.B. Putnam, J.A. Ajani, Z. Liao, S.G. Swisher, J.A. Roth, and W.R. Smythe, Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose–volume histogram parameters. International Journal of Radiation Oncology• Biology• Physics, 2003. 57(5): p. 1317–1322.

    Article  Google Scholar 

  25. Tucker, S.L., H.H. Liu, S. Wang, X. Wei, Z. Liao, R. Komaki, J.D. Cox, and R. Mohan, Dose–volume modeling of the risk of postoperative pulmonary complications among esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery. International Journal of Radiation Oncology• Biology• Physics, 2006. 66(3): p. 754–761.

    Article  Google Scholar 

Download references

Acknowledgments

Presented at Digestive Disease Week 2018, June 5, 2018, Washington DC.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Louisville School of Medicine, 201 Abraham Flexner Way, Ste 1200, Louisville, KY, 40202, USA

    Mickey S. Ising

  2. Department of Cardiovascular and Thoracic Surgery, University of Louisville School of Medicine, Louisville, KY, USA

    Mickey S. Ising, Katy Marino, Jaimin R. Trivedi, Victor van Berkel & Matthew P. Fox

  3. Division of Medical Oncology and Hematology, Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA

    Adam A. Rojan

  4. Department of Radiation Oncology, Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA

    Neal E. Dunlap

Authors
  1. Mickey S. Ising
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katy Marino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jaimin R. Trivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adam A. Rojan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Neal E. Dunlap
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Victor van Berkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Matthew P. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Per the guidelines of the International Committee of Medical Journal Editors (ICMJE), all persons listed as authors meet all of the following criteria:

- Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work.

- Drafting the work or revising it critically for important intellectual content.

- Final approval of the version to be published.

- Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Matthew P. Fox.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ising, M.S., Marino, K., Trivedi, J.R. et al. Influence of Neoadjuvant Radiation Dose on Patients Undergoing Esophagectomy and Survival in Locally Advanced Esophageal Cancer. J Gastrointest Surg 23, 670–678 (2019). https://doi.org/10.1007/s11605-019-04141-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-019-04141-z

Keywords

Search

Navigation