title: 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†.
abstract: OBJECTIVE
  In 2012, the European Society of Thoracic Surgeons (ESTS) created the Lung Neuroendocrine Tumors Working Group (NETs-WG) with the aim to develop scientific knowledge on clinical management of such rare neoplasms. This paper outlines the outcome and prognostic factors of two aggressive NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs).
  
  
  METHODS
  Using the ESTS NETs-WG database, we retrospectively collected data on 261 patients in seven institutions in Europe, between 1994 and 2011. We used a Cox regression model to evaluate variables affecting patient survival and disease-free survival. Univariate and multivariate analysis were also carried out.
  
  
  RESULTS
  Five-year overall survival rates for ACs and LCNCs were 77 vs 28% (P < 0.001), respectively. We found that for ACs, age (P < 0.001), tumour size (P = 0.015) and sub-lobar surgical resection (P = 0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumours (P = 0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases developed in 93 patients and were statistically more frequent in LCNCs (P = 0.02).
  
  
  CONCLUSIONS
  The biological aggressiveness of ACs and LCNCs has been demonstrated with this study. Our aim is to confirm these results with enhanced data collection through the ESTS NETs database.
authors.affiliation: Department of Thoracic Surgery, University of Torino, Turin, Italy pierluigi.filosso@unito.it.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Filosso
authors.affiliation: Unit of Thoracic Surgery, 'Amedeo Avogadro' University of Eastern Piedmont, Novara, Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Rena
authors.affiliation: Department of Thoracic Surgery, University of Torino, Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Guerrera
authors.affiliation: Department of Thoracic Surgery, University Hospital 'Reina Sofia', Cordoba, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Moreno Casado
authors.affiliation: Unit of Thoracic Surgery, Medical University of Lublin, Lublin, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Sagan
authors.affiliation: Unit of Thoracic Surgery, 'Ospedaliera San Paolo', Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Raveglia
authors.affiliation: Department of Thoracic Surgery, St James's University Hospital, Leeds, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Brunelli
authors.affiliation: Division of Thoracic Surgery, Ruhrlandklinik Essen, Essen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Welter
authors.affiliation: Department of Thoracic Surgery, Lung Transplantation and Diseases of the Esophagus, Aix-Marseille University and Hospitals System of Marseille (AP-HM), Marseille, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Gust
authors.affiliation: Department of Thoracic Surgery, St James's University Hospital, Leeds, UK.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Pompili
authors.affiliation: Unit of Thoracic Surgery, 'Amedeo Avogadro' University of Eastern Piedmont, Novara, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Casadio
authors.affiliation: Department of Thoracic Surgery, University of Torino, Turin, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bora
authors.affiliation: Department of Thoracic Surgery, University Hospital 'Reina Sofia', Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alvarez
authors.affiliation: Department of Nephrology, Medical University of Lublin, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zaluska
authors.affiliation: Unit of Thoracic Surgery, 'Ospedaliera San Paolo', Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Baisi
authors.affiliation: Division of Thoracic Surgery, Ruhrlandklinik Essen, Essen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Roesel
authors.affiliation: Department of Thoracic Surgery, Lung Transplantation and Diseases of the Esophagus, Aix-Marseille University and Hospitals System of Marseille (AP-HM), Marseille, France.
authors.forename: Pascal Alexandre
authors.initials: PA
authors.lastname: Thomas
mesh_terms: D000368:Aged; D002276:Carcinoid Tumor / Q000175:diagnosis / Q000401:mortality / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D018287:Carcinoma, Large Cell / Q000175:diagnosis / Q000401:mortality / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis / Q000401:mortality / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
keywords: Atypical carcinoid; Large-cell neuroendocrine carcinoma; Lung; Metastasis; Neuroendocrine tumour; Recurrence; Surgery; Survival