Skip to main content

Advertisement

SpringerLink
Log in

Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection

  • Original Scientific Report
  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies.

Methods

We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage.

Results

Median follow-up was 47 (95%CI 41–79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3–70.9) and 47.4% (95%CI 32.3–61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01–1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6–93.6) and 38.2% (95%CI 20.6–55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1–78.8) and 54.2% (95%CI 32.6–71.6) (p = 0.31), respectively.

Conclusions

A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.

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

Similar content being viewed by others

References

  1. Fasano M, Della Corte CM, Papaccio F et al (2015) Pulmonary large-cell neuroendocrine carcinoma: from epidemiology to therapy. J Thorac Oncol 10:1133–1141

    Article  PubMed  PubMed Central  Google Scholar 

  2. Detterbeck FC (2010) Management of carcinoid tumors. Ann Thorac Surg 89:998–1005

    Article  PubMed  Google Scholar 

  3. Veronesi G, Morandi U, Alloisio M et al (2006) Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer 53:111–115

    Article  PubMed  Google Scholar 

  4. Roesel C, Terjung S, Weinreich G et al (2016) A single-institution analysis of the surgical management of pulmonary large cell neuroendocrine carcinomas. Ann Thorac Surg 101:1909–1914

    Article  PubMed  Google Scholar 

  5. Filosso PL, Rena O, Guerrera F et al (2015) Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group. Eur J Cardiothorac Surg 48:55–64

    Article  PubMed  Google Scholar 

  6. Sarkaria IS, Iyoda A, Roh MS et al (2011) Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience. Ann Thorac Surg 92:1180–1186

    Article  PubMed  Google Scholar 

  7. Asamura H, Kameya T, Matsuno Y et al (2006) Neuroendocrine neoplasms of the lung: a prognostic spectrum. J Clin Oncol 24:70–76

    Article  PubMed  Google Scholar 

  8. Paci M, Cavazza A, Annessi V et al (2004) Large cell neuroendocrine carcinoma of the lung: a 10-year clinicopathologic retrospective study. Ann Thorac Surg 77:1163–1167

    Article  PubMed  Google Scholar 

  9. Takei H, Asamura H, Maeshima A et al (2002) Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg 124:285–292

    Article  PubMed  Google Scholar 

  10. Eichhorn F, Dienemann H, Muley T et al (2015) Predictors of survival after operation among patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 99:983–989

    Article  PubMed  Google Scholar 

  11. Fournel L, Falcoz PE, Alifano M et al (2013) Surgical management of pulmonary large cell neuroendocrine carcinomas: a 10-year experience. Eur J Cardiothorac Surg 43:111–114

    Article  PubMed  Google Scholar 

  12. Iyoda A, Hiroshima K, Toyozaki T et al (2001) Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. Cancer 92:1108–1112

    Article  CAS  PubMed  Google Scholar 

  13. Rossi G, Cavazza A, Marchioni A et al (2005) Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol 23:8774–8785

    Article  CAS  PubMed  Google Scholar 

  14. Dresler CM, Ritter JH, Patterson GA et al (1997) Clinical-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 63:180–185

    Article  CAS  PubMed  Google Scholar 

  15. RieberJ SJ, Warth A et al (2015) Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas. Eur J Med Res 20:64–71

    Article  CAS  Google Scholar 

  16. Kujtan L, Muthukumar V, Kennedy KF et al (2018) The role of systemic therapy in the management of stage i large cell neuroendocrine carcinoma of the lung. J Thorac Oncol 13:707–714

    Article  PubMed  Google Scholar 

  17. NCCN Clinical Practice Guidelines in Oncology. Small cell lung cancer. Version 1.2016. https://www.NCCN.org

  18. Filosso PL, Guerrera F, Evangelista A et al (2017) Adjuvant chemotherapy for large-cell neuroendocrine lung carcinoma: results from the European Society for Thoracic Surgeons Lung Neuroendocrine Tumours retrospective Database. Eur J Cardiothorac Surg 52:339–345

    PubMed  Google Scholar 

  19. Kozuky T, Fujimoto N, Ueoka H et al (2005) Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma. J Cancer Res Clin Oncol 131:147–151

    Article  Google Scholar 

  20. Yamazaki S, Sekine I, Matsuno Y et al (2005) Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy. Lung Cancer 49:217–223

    Article  PubMed  Google Scholar 

  21. Ramirez RA, Chauhan A, Gimenez J et al (2017) Management of pulmonary neuroendocrine tumors. Rev Endocr Metab Disord 18:433–442

    Article  PubMed  Google Scholar 

  22. Mazières J, Daste G, Molinier L et al (2002) Large cell neuroendocrine carcinoma of the lung: pathological study and clinical outcome of 18 resected cases. Lung Cancer 37:287–292

    Article  PubMed  Google Scholar 

  23. Saji H, Tsuboi M, Matsubayashi J et al (2010) Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy. Anticancer Drugs 21:89–93

    Article  CAS  PubMed  Google Scholar 

  24. Battafarano RJ, Fernandez FG, Ritter J et al (2005) Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer. J Thorac Cardiovasc Surg 130:166–172

    Article  PubMed  Google Scholar 

  25. Zacharias J, Nicholson AG, Ladas GP et al (2003) Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection. Ann Thorac Surg 75:348–352

    Article  PubMed  Google Scholar 

  26. García-Yuste M, Matilla JM, Alvarez-Gago T et al (2000) Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study. Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR). Ann Thorac Surg 70:258–263

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the contribution of Ms. Sandra Blitz for her statistical input and advice.

Author information

Authors and Affiliations

  1. Division of Thoracic Surgery, Swedish Cancer Institute, 1101 Madison Street, Suite 900, Seattle, WA, 98105, USA

    Maria Cattoni, Eric Vallières, Catherine Mann, Alexander S. Farivar, Ralph W. Aye & Brian E. Louie

  2. Center for Thoracic Surgery, Department of Medicine and Surgery, University of Insubria, Ospedale di Circolo, 9 Via Guicciardini, 21100, Varese, Italy

    Maria Cattoni, Andrea Imperatori & Nicola Rotolo

  3. Section of General Thoracic Surgery, Department of Surgery, UC Davis Health, 2221 Stockton Boulevard, Room 2115, Sacramento, CA, 95817, USA

    Lisa M. Brown & Amir A. Sarkeshik

  4. Unit of Thoracic Surgery, Catholic University ‘Sacred Heart’, 1 Largo Francesco Vito, 00168, Rome, Italy

    Stefano Margaritora & Alessandra Siciliani

  5. Department of Thoracic Surgery, San Giovanni Battista Hospital, 3 Via Genova, 10126, Turin, Italy

    Pier Luigi Filosso & Francesco Guerrera

  6. Division of Cardiothoracic Surgery, University of Washington Medical Center, 1959 NE Pacific Street, 3rd Floor, Seattle, WA, 98195, USA

    Farhood Farjah & Grace Wandell

  7. Division of Thoracic Surgery, Providence Regional Medical Center, 1330 Rockefeller Avenue, Suite 400, Everett, WA, 98201, USA

    Kimberly Costas

  8. Division of Thoracic Surgery, Virginia Mason Hospital & Seattle Medical Center, 1100 9th Avenue, Seattle, WA, 98101, USA

    Michal Hubka & Stephen Kaplan

Authors
  1. Maria Cattoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric Vallières
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lisa M. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amir A. Sarkeshik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stefano Margaritora
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessandra Siciliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pier Luigi Filosso
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Francesco Guerrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrea Imperatori
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nicola Rotolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Farhood Farjah
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Grace Wandell
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kimberly Costas
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Catherine Mann
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Michal Hubka
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Stephen Kaplan
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Alexander S. Farivar
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ralph W. Aye
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Brian E. Louie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian E. Louie.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

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

Cattoni, M., Vallières, E., Brown, L.M. et al. Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection. World J Surg 43, 1712–1720 (2019). https://doi.org/10.1007/s00268-019-04951-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-019-04951-x

Search

Navigation