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Is There a Role for Surgery in Patients with Neuroendocrine Tumors of the Esophagus? A Contemporary View from the NCDB

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

Abstract

Background

Esophageal neuroendocrine tumors (eNETs) are exceedingly rare, aggressive and have a poor prognosis. Treatment guidelines are ill-defined and mainly based on evidence from case reports and analogous experiences drawn from similar disease sites.

Methods

The NCDB was reviewed for histologically confirmed stage I–III, primary eNETs from 2006 to 2014. Patients were grouped into whether or not they underwent primary tumor resection. Univariate, multivariable, and full bipartite propensity score (PS) adjusted Cox regression analyses were used to assess overall and relative survival differences.

Results

A total of 250 patients were identified. Mean age was 65.0 (standard deviation [SD] 11.9) years, and 174 (69.6%) patients were male. Most patients had stage III disease (n = 136, 54.4%), and the most common type of NET was small cell eNET (n = 111, 44.4%). Chemotherapy was used in 186 (74.4%), radiation therapy in 178 (71.2%), and oncological resection was performed in 69 (27.6%) patients. Crude 2-year survival rates were higher in the operated (57.3%) compared with the nonoperated group (35.2%; p < 0.001). The survival benefit held true after multivariable adjustment (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.32–0.69, p < 0.001). After full bipartite PS adjustment analysis, survival was longer for patients who received a surgical resection compared with those who did not (HR 0.48, 95% CI 0.31–0.75, p = 0.003) with a corresponding 2-year overall survival rate of 63.3% (95% CI 52.0–77.2) versus 38.8% (95% CI 30.9–48.8), respectively.

Conclusions

Multimodal treatment that includes surgery is associated with better overall survival for eNETs. Additional research is needed to more definitively identify patients who benefit from esophagectomy and to establish an appropriate treatment algorithm.

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References

  1. Ilett E, Langer S, Olsen I, Federspiel B, Kjær A. Neuroendocrine carcinomas of the gastroenteropancreatic system: a comprehensive review. Diagnostics. 2015. http://www.mdpi.com/2075-4418/5/2/119/htm. Accessed 28 Aug 2017.

  2. Estrozi B, Bacchi CE. Neuroendocrine tumors involving the gastroenteropancreatic tract: a clinicopathological evaluation of 773 cases. Clinics (Sao Paulo). 2011;66(10):1671–5. https://doi.org/10.1590/s1807-59322011001000002.

    Article  PubMed Central  Google Scholar 

  3. Deng H, Ni P, Wang Y, Wang W. Neuroendocrine carcinoma of the esophagus: clinical characteristics and prognostic evaluation of 49 cases with surgical resection. J Thorac. 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886019/. Accessed 28 Aug 2017.

  4. Lee C, Lim Y, Park S, Jang B. The clinical features and treatment modality of esophageal neuroendocrine tumors: a multicenter study in Korea. BMC. 2014. https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-14-569. Accessed 28 Aug 2017.

  5. Schizas D, Mastoraki A, Kirkilesis GI, et al. Neuroendocrine tumors of the esophagus: state of the art in diagnostic and therapeutic management. J Gastrointest Cancer. 2017;48(4):299–304. https://doi.org/10.1007/s12029-017-9978-x.

    Article  PubMed  Google Scholar 

  6. Chin JL, O’Toole D. Diagnosis and management of upper gastrointestinal neuroendocrine tumors. Clin Endosc. 2017;50(6):520–9. https://doi.org/10.5946/ce.2017.181.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 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  CAS  PubMed  PubMed Central  Google Scholar 

  8. Caplin ME, Baudin E, Ferolla P, et al. Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Ann Oncol. 2015;26(8):1604–20. https://doi.org/10.1093/annonc/mdv041.

    Article  CAS  PubMed  Google Scholar 

  9. Kuo C, Hsieh C, Chan M, Li A. Small cell carcinoma of the esophagus: a report of 16 cases from a single institution and literature review. Ann Thorac. 2011. http://www.sciencedirect.com/science/article/pii/S0003497510021089. Accessed 28 Aug 2017.

  10. Hou X, Wei J-C, Wu J-X, et al. Multidisciplinary Modalities achieve encouraging long-term survival in resectable limited-disease esophageal small cell carcinoma. Ganti AK, editor. PLoS One. 2013;8(7):e69259. https://doi.org/10.1371/journal.pone.0069259.

    Article  CAS  Google Scholar 

  11. Nemoto K, Zhao H-J, Goto T, et al. Radiation therapy for limited-stage small-cell esophageal cancer. Am J Clin Oncol. 2002;25(4):404–7. http://www.ncbi.nlm.nih.gov/pubmed/12151974. Accessed 26 Oct 2018.

    Article  Google Scholar 

  12. Saddoughi SA, Taswell J, Harmsen WS, et al. Surgical resection of rare esophageal cancers. Ann Thorac Surg. 2016;101:311–5. https://doi.org/10.1016/j.athoracsur.2015.06.015.

    Article  PubMed  Google Scholar 

  13. Chen W-W, Wang F, Chen S, et al. Detailed analysis of prognostic factors in primary esophageal small cell carcinoma. Ann Thorac Surg. 2014;97(6):1975–81. https://doi.org/10.1016/j.athoracsur.2014.02.037.

    Article  PubMed  Google Scholar 

  14. Rindi G, Wiedenmann B. Neuroendocrine neoplasms of the gut and pancreas: new insights. Nat Rev Endocrinol. 2012;8(1):54–64. https://doi.org/10.1038/nrendo.2011.120.

    Article  CAS  Google Scholar 

  15. Luketich JD, Pennathur A, Awais O, et al. Outcomes after minimally invasive esophagectomy: review of over 1000 patients. Ann Surg. 2012;256(1):95–103. https://doi.org/10.1097/sla.0b013e3182590603.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hu Y, Mcmurry TL, Stukenborg GJ, Kozower BD. Readmission predicts 90-day mortality after esophagectomy: Analysis of Surveillance, Epidemiology, and End Results Registry linked to Medicare outcomes. J Thorac Cardiovasc Surg. 2015;150:1254–60. https://doi.org/10.1016/j.jtcvs.2015.08.071.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Soriano TT, Eslick G, Vanniasinkam T. Long-term nutritional outcome and health related quality of life of patients following esophageal cancer surgery: a meta-analysis. Nutr Cancer. 2017:1–12. https://doi.org/10.1080/01635581.2018.1412471.

    Article  Google Scholar 

  18. Brenner B, Tang LH, Klimstra DS, Kelsen DP. Small-cell carcinomas of the gastrointestinal tract: a review. J Clin Oncol. 2004;22(13):2730–9. https://doi.org/10.1200/jco.2004.09.075.

    Article  PubMed  Google Scholar 

  19. Hansen BB, Klopfer SO. Optimal full matching and related designs via network flows. J Comput Graph Stat. 2006;15(3):609–27. https://doi.org/10.1198/106186006x137047.

    Article  Google Scholar 

  20. Ho DE, Imai K, King G, Stuart EA. MatchIt: Nonparametric Preprocessing for Parametric Causal Inference. Vol. 42; 2011. http://www.jstatsoft.org/. Accessed 26 Oct 2018.

  21. Baiocchi M, Small DS, Yang L, Polsky D, Groeneveld PW. Near/far matching: a study design approach to instrumental variables. Heal Serv Outcomes Res Methodol. 2012;12(4):237–53. https://doi.org/10.1007/s10742-012-0091-0.

    Article  Google Scholar 

  22. Angrist JD, Imbens GW, Rubin DB. Identification of causal effects using instrumental variables. J Am Stat Assoc. 1996;91(434):444–55. https://doi.org/10.1080/01621459.1996.10476902.

    Article  Google Scholar 

  23. Series PH-ERR, 1988 undefined. Causal inference, path analysis and recursive structural equations models. Wiley Online Libr. http://onlinelibrary.wiley.com/doi/10.1002/j.2330-8516.1988.tb00270.x/full. Accessed 18 Feb 2018.

  24. Pohar M, Stare J. Making relative survival analysis relatively easy. Comput Biol Med. 2007;37(12):1741–9. https://doi.org/10.1016/j.compbiomed.2007.04.010.

    Article  PubMed  Google Scholar 

  25. Situ D, Lin Y, Long H, et al. Surgical treatment for limited-stage primary small cell cancer of the esophagus. Ann Thorac Surg. 2013;95(3):1057–62. https://doi.org/10.1016/j.athoracsur.2012.11.014.

    Article  PubMed  Google Scholar 

  26. Funakoshi S, Hashiguchi A, Teramoto K, et al. Second-line chemotherapy for refractory small cell neuroendocrine carcinoma of the esophagus that relapsed after complete remission with irinotecan plus cisplatin therapy: case report and review of the literature. Oncol Lett. 2013;5(1):117–22. https://doi.org/10.3892/ol.2012.1008.

    Article  CAS  PubMed  Google Scholar 

  27. Klöppel G. Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer. 2011;18(S1):S1–16. https://doi.org/10.1530/erc-11-0013.

    Article  PubMed  Google Scholar 

  28. Kuo CH, Hsieh CC, Chan ML, et al. Small cell carcinoma of the esophagus: a report of 16 cases from a single institution and literature review. Ann Thorac Surg. 2011. http://dx.doi.org/10.1016/j.athoracsur.2010.09.030.

    Article  PubMed  Google Scholar 

  29. Tanaka T, Matono S, Nagano T, et al. Original article: Surgical management for small cell carcinoma of the esophagus. Dis Esophagus. 2010;23(6):502–5. https://doi.org/10.1111/j.1442-2050.2009.01045.x.

    Article  CAS  PubMed  Google Scholar 

  30. Alese OB, Jiang R, Shaib W, et al. High-Grade Gastrointestinal Neuroendocrine Carcinoma Management and Outcomes: A National Cancer Database Study. Oncologist. November 2018:theoncologist.2018-0382. https://doi.org/10.1634/theoncologist.2018-0382.

    Article  Google Scholar 

  31. Chen S, Yang J, Yang W, Weng H. Treatment and prognosis of limited disease primary small cell carcinoma of esophagus. Dis. 2011. https://academic.oup.com/dote/article-abstract/24/2/114/2328443. Accessed 21 Sept 2017.

  32. Yau KK, Siu WT, Wong DCT, et al. Non-operative management of small cell carcinoma of esophagus. Dis Esophagus. 2007;20(6):487–90. https://doi.org/10.1111/j.1442-2050.2007.00635.x.

    Article  CAS  Google Scholar 

  33. Dhungel B, Diggs BS, Hunter JG, Sheppard BC, Vetto JT, Dolan JP. Patient and peri-operative predictors of morbidity and mortality after esophagectomy: American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), 2005-2008. J Gastrointest Surg. 2010;14(10):1492–501. https://doi.org/10.1007/s11605-010-1328-2.

    Article  PubMed  Google Scholar 

  34. Gurien LA, Tepas JJ, Lind DS, et al. How Safe Is the Safety Net? Comparison of Ivor-Lewis Esophagectomy at a Safety-Net Hospital Using the NSQIP Database. J Am Coll Surg. 2018;226(4):680–4. https://doi.org/10.1016/j.jamcollsurg.2017.12.036.

    Article  PubMed  Google Scholar 

  35. Zhang C, Wu Q-C, Hou P-Y, et al. Impact of the method of reconstruction after oncologic oesophagectomy on quality of life — a prospective, randomised study. Eur J Cardio-Thoracic Surg. 2010;39:109–14. https://doi.org/10.1016/j.ejcts.2010.04.032.

    Article  Google Scholar 

  36. Hsu P-K, Chen H-S, Wu S-C, et al. Impact of hospital volume on long-term survival after resection for oesophageal cancer: a population-based study in Taiwan†. Eur J Cardio-Thoracic Surg. 2014;46(6):e127–35. https://doi.org/10.1093/ejcts/ezu377.

    Article  Google Scholar 

  37. Dikken JL, van Sandick JW, Allum WH, et al. Differences in outcomes of oesophageal and gastric cancer surgery across Europe. Br J Surg. 2013;100(1):83–94. https://doi.org/10.1002/bjs.8966.

    Article  CAS  PubMed  Google Scholar 

  38. Munasinghe A, Markar SR, Mamidanna R, et al. Is it time to centralize high-risk cancer care in the united states? comparison of outcomes of esophagectomy between England and the United States. Ann Surg. 2015;262(1):79–85. https://doi.org/10.1097/sla.0000000000000805.

    Article  PubMed  Google Scholar 

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Acknowledgment

The authors thank the American College of Surgeons and the American Cancer Society for providing patient information through the NCDB used for this investigation. Furthermore, we thank the patients whose information through the NCDB allowed us to perform the investigation for this manuscript.

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Correspondence to Mathias Worni MD, MHS.

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Erdem, S., Troxler, E., Warschkow, R. et al. Is There a Role for Surgery in Patients with Neuroendocrine Tumors of the Esophagus? A Contemporary View from the NCDB. Ann Surg Oncol 27, 671–680 (2020). https://doi.org/10.1245/s10434-019-07847-1

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