Skip to main content
SpringerLink
Log in

Predicting Survival and Response to Treatment in Gastroesophageal Neuroendocrine Tumors: An Analysis of the National Cancer Database

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Neuroendocrine tumors (NETs) of the esophagus and stomach are rare neoplasms with variable behavior. We aim to describe their epidemiology and response to treatment.

Methods

NETs of the stomach and the esophagus were selected from the National Cancer Database (2004–2013) and classified by location. Survival analyses were performed with respect to tumor characteristics and treatment variables.

Results

NETs of the stomach (n = 2700; 92.8%) and esophagus (n = 210, 7.2%) were identified. Gastric cardia NETs had demographics and behavior similar to esophageal tumors and were associated with worse overall survival than NETs of the noncardia stomach independent of grade (p < 0.001). Poorly differentiated histology [hazard ratio (HR) 4.14, 95% confidence interval (CI) 2.26–7.57; p < 0.001] and distant metastases (HR 3.28, 95% CI 1.94–5.56; p < 0.001) were the greatest independent predictors of survival. For patients with poorly differentiated NETs, surgery was the only treatment to have benefit on overall survival (HR 0.38, 95% CI 0.27–0.54; p < 0.001) regardless of extent of disease. There was no additional benefit to adjuvant chemotherapy or radiation in patients undergoing resection (p = 0.39), even for patients with lymph node metastases (surgery alone versus surgery plus adjuvant therapy, p = 0.46), distant metastases (p = 0.19), or positive margins (p = 0.33).

Conclusions

Esophageal and gastric cardia NETs have worse survival than those of the noncardia stomach. Surgery offers the only survival benefit for poorly differentiated tumors, with no additional survival advantage to adjuvant chemotherapy or radiation.

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

Similar content being viewed by others

References

  1. Burkitt MD, Varro A, Pritchard DM. Importance of gastrin in the pathogenesis and treatment of gastric tumors. World J Gastroenterol. 2009;15(1):1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E. Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology. 1993;104(4):994–1006.

    Article  CAS  PubMed  Google Scholar 

  3. Burkitt MD, Pritchard DM. Review article: pathogenesis and management of gastric carcinoid tumours. Aliment Pharmacol Ther. 2006;24(9):1305–1320. https://doi.org/10.1111/j.1365-2036.2006.03130.x.

    Article  CAS  PubMed  Google Scholar 

  4. Borch K, Ahrén B, Ahlman H, Falkmer S, Granérus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005;242(1):64–73.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tustumi F, Takeda FR, Uema RH, Pereira GLS, Sallum RAA, Cecconello I. Primary neuroendocrine neoplasm of the esophagus–Report of 14 cases from a single institute and review of the literature. Arq Gastroenterol. 2017;54(1):4–10. https://doi.org/10.1590/s0004-2803.2017v54n1-01.

    Article  PubMed  Google Scholar 

  6. Deng H-Y, Ni P-Z, Wang Y-C, Wang W-P, Chen L-Q. Neuroendocrine carcinoma of the esophagus: clinical characteristics and prognostic evaluation of 49 cases with surgical resection. J Thorac Dis. 2016;8(6):1250–1256. https://doi.org/10.21037/jtd.2016.04.21.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Harmse JL, Carey FA, Baird AR, et al. Merkel cells in the human oesophagus. J Pathol. 1999;189(2):176–179. https://doi.org/10.1002/(SICI)1096-9896(199910)189:2<176::AID-PATH416>3.0.CO;2-U.

  8. Egashira A, Morita M, Kumagai R, et al. Neuroendocrine carcinoma of the esophagus: clinicopathological and immunohistochemical features of 14 cases. PLoS ONE. 2017;12(3):e0173501. https://doi.org/10.1371/journal.pone.0173501.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–3072. https://doi.org/10.1200/jco.2007.15.4377.

    Article  PubMed  Google Scholar 

  10. Mitry E, Baudin E, Ducreux M, et al. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer. 1999;81(8):1351–1355. https://doi.org/10.1038/sj.bjc.6690325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Moertel CG, Kvols LK, O’Connell MJ, Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer. 1991. Available at: http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19910715)68:2%3C227:AID-CNCR2820680202%3E3.0.CO;2-I/abstract.

  12. Kulke MH, Shah MH, Benson AB, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Canc Netw. 2015;13(1):78–108.

    Article  CAS  PubMed  Google Scholar 

  13. Xie JW, Sun YQ, Feng CY, et al. Evaluation of clinicopathological factors related to the prognosis of gastric neuroendocrine carcinoma. Eur J Surg Oncol. 2016;42(10):1464–1470. https://doi.org/10.1016/j.ejso.2016.08.004.

    Article  PubMed  Google Scholar 

  14. Sorbye H, Welin S, Langer SW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24(1):152–160. https://doi.org/10.1093/annonc/mds276.

    Article  CAS  PubMed  Google Scholar 

  15. Huang Q, Wu H, Nie L, et al. Primary high-grade neuroendocrine carcinoma of the esophagus: a clinicopathologic and immunohistochemical study of 42 resection cases. Am J Surg Pathol. 2013;37(4):467–483. https://doi.org/10.1097/pas.0b013e31826d2639.

    Article  PubMed  Google Scholar 

  16. Ku GY, Minsky BD, Rusch VW, Bains M, Kelsen DP, Ilson DH. Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the Memorial Sloan–Kettering experience. Ann Oncol. 2008;19(3):533–537. https://doi.org/10.1093/annonc/mdm476.

    Article  CAS  PubMed  Google Scholar 

  17. Strosberg JR, Coppola D, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010;39(6):799–800. https://doi.org/10.1097/mpa.0b013e3181ebb56f.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hentic O, Hammel P, Couvelard A, et al. FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3. Endocr Relat Cancer. 2012;19(6):751–757. https://doi.org/10.1530/erc-12-0002.

    Article  CAS  PubMed  Google Scholar 

  19. Ekeblad S, Sundin A, Janson ET, et al. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res. 2007;13(10):2986–2991. https://doi.org/10.1158/1078-0432.ccr-06-2053.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was internally funded.

Disclosure

The authors have no disclosures.

Author information

Authors and Affiliations

  1. Department of Surgery, New York Presbyterian Hospital—Weill Cornell Medicine, New York, NY, USA

    Katherine D. Gray MD, Maureen D. Moore MD, Suraj Panjwani MBBS, Adham Elmously MD, Cheguevara Afaneh MD, Thomas J. Fahey III MD & Rasa Zarnegar MD

Authors
  1. Katherine D. Gray MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maureen D. Moore MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suraj Panjwani MBBS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adham Elmously MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cheguevara Afaneh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas J. Fahey III MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rasa Zarnegar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rasa Zarnegar MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gray, K.D., Moore, M.D., Panjwani, S. et al. Predicting Survival and Response to Treatment in Gastroesophageal Neuroendocrine Tumors: An Analysis of the National Cancer Database. Ann Surg Oncol 25, 1418–1424 (2018). https://doi.org/10.1245/s10434-018-6389-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-018-6389-6

Keywords

Search

Navigation