Neuroendocrine tumors (NETs; syn. carcinoid tumors) are highly or moderately differentiated neoplasms. They comprise a large variety of rare and heterogeneous tumors with an estimated incidence of 3-5/100,000/year. They can arise in virtually every internal organ, but mainly occur in the gastroenteropancreatic and bronchopulmonary systems. Around 25% of the NETs are localized in the bronchopulmonary system. Approximately 2% of all lung tumors are NETs. According to the World Health Organization (WHO) classification of lung tumors, bronchopulmonary NETs are subdivided into typical carcinoids (TCs) and atypical carcinoids (ACs). The parameter with the highest impact on NET behavior and prognosis is the histological classification and staging according to the tumor/node/metastasis (TNM) system. The diagnosis of NETs is established by histological examination and the immunohistochemical detection of general neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. Serum markers and the use of functional imaging techniques are important additive tools to establish the diagnosis of a NET. The only curative option for lung NETs is complete surgical resection. Beyond that, the currently available interdisciplinary therapeutic options are local ablation, biotherapy (somatostatin analogues), or chemotherapy. New therapeutic options such as peptide receptor radionuclide therapy (PRRT) and molecularly targeted therapies achieve promising results and are under further evaluation. This report is a consensus summary of the interdisciplinary symposium ‘Neuroendocrine Tumors of the Lung and of the Gastroenteropancreatic System (GEP NET) - Expert Dialogue' held on February 25-26, 2011 in Weimar, Germany. At this conference, a panel of 23 German experts shared their knowledge and exchanged their thoughts about research, diagnosis, and clinical management of NETs, whereby special attention was paid to NETs of the respiratory tract.

1.
Klöppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, Scarpa A, Scoazec JY, Wiedenmann B, Papotti M, Rindi G, Plöckinger U; Mallorca Consensus Conference participants; European Neuroendocrine Tumor Society: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology 2009;90:162-166.
[PubMed]
2.
Sobin LH, Gospodarowicz MK, Wittekind C: TNM Classification of Malignant Tumours, ed 7. Chichester, Wiley-Blackwell, 2009.
3.
Rindi G: The ENETS guidelines: the new TNM classification system. Tumori 2010;96:806-809.
[PubMed]
4.
Rindi G, Arnold R, Bosman FT, Capella C, Klimstra DS, Klöppel G, Komminoth P, Solcia E: Nomenclature and classification of neuroendocrine neoplasms of the digestive system; in Bosman FT, Carniero F, Hruban RH, Theise ND (eds): WHO Classification of Tumours of the Digestive System, ed 4. Lyon, IARC, 2010, pp 13-14.
5.
Anlauf M: Neuroendocrine neoplasms of the gastroenteropancreatic system: pathology and classification. Horm Metab Res 2011;43:825-831.
[PubMed]
6.
Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB: 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;26:3063-3072.
[PubMed]
7.
Öberg K, Hellman P, Kwekkeboom D, Jelic S; ESMO Guidelines Working Group: Neuroendocrine bronchial and thymic tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(suppl 5):v220-v222.
[PubMed]
8.
Grohe C, data on file.
9.
Gosney J, Travis WD: Pathology and genetics: tumors of the lung, pleura, thymus and heart; in Travis W, Brambilla E, Müller-Hermelink H, Harris C (eds): World Health Organization classification of tumors. Lyon, IARC, 2004, pp 76-77.
10.
Presselt N, data on file.
11.
Naalsund A, Rostad H, Strøm EH, Lund MB, Strand TE: Carcinoid lung tumors - incidence, treatment and outcomes: a population-based study. Eur J Cardiothorac Surg 2011;39:565-569.
[PubMed]
12.
Cardillo G, Sera F, Di Martino M, Graziano P, Giunti R, Carbone L, Facciolo F, Martelli M: Bronchial carcinoid tumors: nodal status and long-term survival after resection. Ann Thorac Surg 2004;77:1781-1785.
[PubMed]
13.
Travis WD, Rush W, Flieder DB, Falk R, Fleming MV, Gal AA, Koss MN: Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 1998;22:934-944.
[PubMed]
14.
Phan AT, Oberg K, Choi J, Harrison LH Jr, Hassan MM, Strosberg JR, Krenning EP, Kocha W, Woltering EA, Maples WJ; North American Neuroendocrine Tumor Society (NANETS): NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the thorax (includes lung and thymus). Pancreas 2010;39:784-798.
[PubMed]
15.
Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D: International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011;6:244-248.
[PubMed]
16.
Vinik AI, Woltering EA, Warner RR, Caplin M, O'Dorisio TM, Wiseman GA, Coppola D, Go VL; North American Neuroendocrine Tumor Society (NANETS): NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas 2010;39:713-734.
[PubMed]
17.
Öberg K, Astrup L, Eriksson B, Falkmer SE, Falkmer UG, Gustafsen J, Haglund C, Knigge U, Vatn MH, Välimäki M; Nordic NE Tumour Group: Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Acta Oncol 2004;617-636.
[PubMed]
18.
Baum RP, Prasad V, Hommann M, Hörsch D: Receptor PET/CT imaging of neuroendocrine tumors. Recent Results Cancer Res 2008;170:225-42.
[PubMed]
19.
Kaemmerer D, Khatib-Chahidi K, Baum RP, Hörsch D, Presselt N, Sänger J, Kunze A, Hommann M: Concomitant lung and gastroenteropancreatic neuroendocrine tumors and the value of gallium-68 PET/CT. Cancer Imaging 2011;11: 179-183.
[PubMed]
20.
Baum RP, Kulkarni HR, Carreras C: Peptides and receptors in image-guided therapy: theranostics for neuroendocrine neoplasms. Semin Nucl Med 2012;42:190-207.
[PubMed]
21.
Yendamuri S, Gold D, Jayaprakash V, Dexter E, Nwogu C, Demmy T: Is sublobar resection sufficient for carcinoid tumors? Ann Thorac Surg 2011;92:1774-1778.
[PubMed]
22.
Machuca TN, Cardoso PF, Camargo SM, Signori L, Andrade CF, Moreira AL, Moreira Jda S, Felicetti JC, Camargo JJ: Surgical treatment of bronchial carcinoid tumors: a single-center experience. Lung Cancer 2010;70:158-162.
[PubMed]
23.
Stamatis G, Freitag L, Greschuchna D: Limited and radical resection for tracheal and bronchopulmonary carcinoid tumour. Report on 227 cases. Eur J Cardiothorac Surg 1990;4:527-532.
[PubMed]
24.
Van Boxem TJ, Venmans BJ, van Mourik JC, Postmus PE, Sutedja TG: Bronchoscopic treatment of intraluminal typical carcinoid: a pilot study. J Thorac Cardiovasc Surg 1998;116:402-406.
[PubMed]
25.
Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R; PROMID Study Group: Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009;27: 4656-4663.
[PubMed]
26.
Kvols LK, Oberg KE, O'Dorisio TM, Mohideen P, de Herder WW, Arnold R, Hu K, Zhang Y, Hughes G, Anthony L, Wiedenmann B: Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. Endocr Relat Cancer 2012;19:657-666.
[PubMed]
27.
Van Essen M, Krenning EP, De Jong M, Valkema R, Kwekkeboom DJ: Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol 2007;46:723-734.
[PubMed]
28.
Kvols LK, Brendtro KL; North American Neuroendocrine Tumor Society (NANETS): The North American Neuroendocrine Tumor Society (NANETS) guidelines: mission, goals, and process. Pancreas 2010;39:705-706.
[PubMed]
29.
Goeckenjan G, Sitter H, Thomas M, Branscheid D, Flentje M, Griesinger F, Niederle N, Stuschke M, Blum T, Deppermann KM, Ficker JH, Freitag L, Lübbe AS, Reinhold T, Späth-Schwalbe E, Ukena D, Wickert M, Wolf M, Andreas S, Auberger T, Baum RP, Baysal B, Beuth J, Bickeböller H, Böcking A, Bohle RM, Brüske I, Burghuber O, Dickgreber N, Diederich S, Dienemann H, Eberhardt W, Eggeling S, Fink T, Fischer B, Franke M, Friedel G, Gauler T, Gütz S, Hautmann H, Hellmann A, Hellwig D, Herth F, Heussel CP, Hilbe W, Hoffmeyer F, Horneber M, Huber RM, Hübner J, Kauczor HU, Kirchbacher K, Kirsten D, Kraus T, Lang SM, Martens U, Mohn-Staudner A, Müller KM, Müller-Nordhorn J, Nowak D, Ochmann U, Passlick B, Petersen I, Pirker R, Pokrajac B, Reck M, Riha S, Rübe C, Schmittel A, Schönfeld N, Schütte W, Serke M, Stamatis G, Steingräber M, Steins M, Stoelben E, Swoboda L, Teschler H, Tessen HW, Weber M, Werner A, Wichmann HE, Irlinger Wimmer E, Witt C, Worth H; German Respiratory Society; German Cancer Society: Prevention, diagnosis, therapy, and follow-up of lung cancer: interdisciplinary guideline of the German Respiratory Society and the German Cancer Society. Pneumologie 2011;65:39-59.
[PubMed]
30.
Granberg D, Eriksson B, Wilander E, Grimfjärd P, Fjällskog ML, Oberg K, Skogseid B: Experience in treatment of metastatic pulmonary carcinoid tumors. Ann Oncol 2001;12:1383-1391.
[PubMed]
31.
Fjällskog ML, Granberg DP, Welin SL, Eriksson C, Oberg KE, Janson ET, Eriksson BK: Treatment with cisplatin and etoposide in patients with neuroendocrine tumors. Cancer 2001;92:1101-1107.
[PubMed]
32.
Modlin IM, Pavel M, Kidd M, Gustafsson BI: Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther 2010;31:169-188.
[PubMed]
33.
Yamazaki S, Sekine I, Matsuno Y, Takei H, Y amamoto N, Kunitoh H, Ohe Y, Tamura T, Kodama T, Asamura H, Tsuchiya R, Saijo N: Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy. Lung Cancer 2005;49:217-223.
[PubMed]
34.
Ekeblad S, Sundin A, Janson ET, Welin S, Granberg D, Kindmark H, Dunder K, Kozlovacki G, Orlefors H, Sigurd M, Oberg K, Eriksson B, Skogseid B: Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res 2007;13: 2986-2991.
[PubMed]
35.
Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P: Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011;364: 501-513.
[PubMed]
36.
Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K; RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group: Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011;364:514-523.
[PubMed]
37.
Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group: Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet 2011;378:2005-2012.
[PubMed]
38.
Fazio N, Granberg D, Grossman A, Saletan S, Klimovsky J, Panneerselvam A, Wolin EM: Everolimus plus octreotide LAR in patients with advanced lung neuroendocrine tumors: analysis of the phase III, randomized, placebo-controlled RADIANT-2 study. Chest 2013;143:955-962.
[PubMed]
39.
Pavel ME, Wiedenmann B, Capdevila J, Reed N, Valle JW, Caglio S, May C, Comis S, Castellana R, de Herder WW, Metzner C, Salazar R, Hörsch D, Oberg K: RAMSETE: a single-arm, multicenter, single-stage phase II trial of RAD001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in Europe. J Clin Oncol 2012;30(suppl): abstr 4122.
40.
ClinicalTrials.gov: Everolimus plus best supportive care vs placebo plus best supportive care in the treatment of patients with advanced neuroendocrine tumors (GI or lung origin) (RADIANT-4). ClinicalTrials.gov Identifier: NCT01524783; other Study ID Numbers: CRAD001T2302, 2011-002887-26; last updated January 30, 2014. www.clinicaltrials.gov/ct2/show/NCT01524783 (last accessed February 12, 2014).
41.
ClinicalTrials.gov: 3-Arm trial to evaluate pasireotide LAR/everolimus alone/in combination in patients with lung/thymus NET - LUNA Trial. ClinicalTrials.gov Identifier: NCT01563354; other Study ID Numbers: CSOM230DIC03, 2011-002872-17; last updated February 3, 2014. www.clinicaltrials.gov/show/NCT01563354 (last accessed February 12, 2014).
42.
ClinicalTrials.gov: RAD001 with paclitaxel and carboplatin in first line treatment of patients with advanced large cell lung cancer with neuroendocrine differentiation (MACS1419). ClinicalTrials. gov Identifier: NCT01317615; other Study ID Numbers: CRAD001KDE37, EudraCT 2010-022273-34, 2010-022273-34; last updated December 15, 2013. www.clinicaltrials.gov/ct2/show/NCT01317615 (last accessed February 12, 2014).
43.
Yao JC, Phan A, Hoff PM, Chen HX, Charnsangavej C, Yeung SC, Hess K, Ng C, Abbruzzese JL, Ajani JA: Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol 2008;26:1316-1323.
[PubMed]
You do not currently have access to this content.