Treatment of pulmonary neuroendocrine tumours: State of the art and future developments

Cancer Treatment Reviews

Volumn 39, Issue 5, 2013, Pages 466-472

  Gridelli, Cesare ^a   Rossi, Antonio ^a   Airoma, Giuseppe ^b   Bianco, Roberto ^c   Costanzo, Raffaele ^d   Daniele, Bruno ^e   Chiara, Giovanni De ^a   Grimaldi, Giuseppe ^f   Irtelli, Luciana ^g   Maione, Paolo ^a   Morabito, Alessandro ^d   Piantedosi, Franco Vito ^h   Riccardi, Ferdinando ⁱ  

^a S G MOSCATI HOSPITAL   (Italy)

^b ASL NA 1   (Italy)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^d NATIONAL CANCER INSTITUTE   (Italy)

^e G RUMMO HOSPITAL   (Italy)

^f Umberto i Hospital   (Italy)

^g SS Annunziata Hospital   (Italy)

^h MONALDI HOSPITAL   (Italy)

ⁱ CARDARELLI HOSPITAL   (Italy)

Author keywords

Carcinoids; Large cell neuroendocrine carcinoma; Lung cancer; Pulmonary neuroendocrine tumours; Somatostatin analogues therapy; Targeted therapy

Indexed keywords

5 HYDROXYINDOLEACETIC ACID; ANGIOPEPTIN; CAPECITABINE; CHROMOGRANIN A; CISPLATIN; CORTICOTROPIN; DOXORUBICIN; ETOPOSIDE; FLUOROURACIL; G PROTEIN COUPLED RECEPTOR; GALLIUM 68; MITOMYCIN; NEURON SPECIFIC ENOLASE; OCTREOTIDE; OXALIPLATIN; PENTETREOTIDE; PENTETREOTIDE IN 111; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; SEROTONIN; SOMATOMEDIN C; SOMATOSTATIN RECEPTOR; STREPTOZOCIN; SUNITINIB; SYNAPTOPHYSIN; TEMOZOLOMIDE; UNINDEXED DRUG; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3; VINDESINE;

ANGIOGENESIS; CANCER ADJUVANT THERAPY; CANCER CLASSIFICATION; CANCER DIAGNOSIS; CANCER RADIOTHERAPY; CANCER STAGING; CANCER SURGERY; CANCER SURVIVAL; CARCINOID SYNDROME; CELL ADHESION; CELL DIFFERENTIATION; CELL PROLIFERATION; CHROMOSOME 17P; COUGHING; DIARRHEA; DIFFERENTIAL DIAGNOSIS; DRUG HALF LIFE; HEMOPTYSIS; HETEROZYGOSITY LOSS; HUMAN; INTRACELLULAR SIGNALING; LARGE CELL NEUROENDOCRINE CARCINOMA; LUNG NON SMALL CELL CANCER; LUNG TUMOR; LYMPH NODE METASTASIS; NEUROENDOCRINE TUMOR; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POINT MUTATION; PROTEIN EXPRESSION; PULMONARY NEUROENDOCRINE TUMOR; RADIATION EXPOSURE; REVIEW; SENSITIVITY AND SPECIFICITY; SIGNAL TRANSDUCTION; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; SMOKING; SURVIVAL RATE; UPREGULATION; WHEEZING;

CARCINOMA, SMALL CELL; HUMANS; LUNG NEOPLASMS; NEOPLASM STAGING; NEUROENDOCRINE TUMORS; SOMATOSTATIN;

EID: 84876991156     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2012.06.012     Document Type: Review

References (88)

1. Oberg K., Hellman P., Kwekkeboom D., Jelic S. Neuroendocrine bronchial and thymic tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010, 21(Suppl. 5):v220-v222.
2. Yao J.C., 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, 26:3063-3072.
3. Leotlela P.D., Jauch A., Holtgreve-Grez H., Thakker R.V. Genetics of neuroendocrine and carcinoid tumours. Endocr Relat Cancer 2003, 10:437-450.
4. Oberg K. Carcinoid tumors: molecular genetics, tumor biology, and update of diagnosis and treatment. Curr Opin Oncol 2002, 14:38-45.
5. Beasley M.B., Brambilla E., Travis W.D. The 2004 World Health Organization classification of lung tumors. Semin Roentgenol 2005, 40:90-97.
6. Govindan R., Page N., Morgensztern D., et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30years: analysis of the Surveillance, Epidemiologic, and End Results database. J Clin Oncol 2006, 24:4539-4544.
7. Volante M., Bozzalla-Cassione F., Papotti M. Somatostatin receptors and their interest in diagnostic pathology. Endocr Pathol 2004, 15:275-291.
8. Patel Y.C., Srikant C.B. Subtype selectivity of peptide analogs for all five cloned human somatostatin receptors (hsstr 1-5). Endocrinology 1994, 135:2814-2817.
9. Righi L., Volante M., Tavaglione V., et al. Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 'clinically aggressive' cases. Ann Oncol 2010, 21:548-555.
10. Muscarella L.A., D'Alessandro V., La Torre A., et al. Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patients. Cell Oncol (Dordr) 2011, 34:435-441.
11. Onuki N., Wistuba I.I., Travis W.D., et al. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 1999, 85:600-607.
12. Murakami I., Fujiwara Y., Yamaoka N., Hiyama K., Ishioka S., Yamakido M. Detection of p53 gene mutations in cytopathology and biopsy specimens from patients with lung cancer. Am J Respir Crit Care Med 1996, 154:1117-1123.
13. Sampietro G., Tomasic G., Collini P., et al. Gene product immunophenotyping of neuroendocrine lung tumors. No linking evidence between carcinoids and small-cell lung carcinomas suggested by multivariate statistical analysis. Appl Immunohistochem Mol Morphol 2000, 8:49-56.
14. Sugio K., Osaki T., Oyama T., et al. Genetic alteration in carcinoid tumors of the lung. Ann Thorac Cardiovasc Surg 2003, 9:149-154.
15. Kobayashi Y., Tokuchi Y., Hashimoto T., et al. Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors. Cancer Sci 2004, 95:334-341.
16. Zaffaroni N., De Polo D., Villa R., et al. Differential expression of telomerase activity in neuroendocrine lung tumours: correlation with gene product immunophenotyping. J Pathol 2003, 201:127-133.
17. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991, 251:1451-1455.
18. Travis W.D. Lung tumours with neuroendocrine differentiation. Eur J Cancer 2009, 45(Suppl. 1):251-266.
19. Sachithanandan N., Harle R.A., Burgess J.R. Bronchopulmonary carcinoid in multiple endocrine neoplasia type 1. Cancer 2005, 103:509-515.
20. Fink G., Krelbaum T., Yellin A., et al. Pulmonary carcinoid: presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest 2001, 119:1647-1651.
21. Travis W.D., Giroux D.J., Chansky K., et al. The IASLC lung cancer staging project: proposals for the inclusion of broncho-pulmonary carcinoid tumors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol 2008, 3:1213-1223.
22. Filosso P.L., Rena O., Donati G., et al. Bronchial carcinoid tumors: surgical management and long-term outcome. J Thorac Cardiovasc Surg 2002, 123:303-309.
23. McCaughan B.C., Martini N., Bains M.S. Bronchial carcinoids: review of 124 cases. J Thorac Cardiovasc Surg 1985, 89:8-17.
24. Davila D., Dunn W., Tazelaar H., Pairolero P. Bronchial carcinoid tumors. Mayo Clin Proc 1993, 68:795-803.
25. Soga J., Yakuwa Y. Bronchopulmonary carcinoids: an analysis of 1875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg 1999, 5:211-219.
26. Marty-Ané C.H., Costes V., Pujol J.L., Alauzen M., Baldet P., Mary H. Carcinoid tumors of the lung: do atypical features require aggressive management?. Ann Thorac Surg 1995, 59:78-83.
27. Oshiro Y., Kusumoto M., Matsuno Y., et al. CT findings of surgically resected large cell neuroendocrine carcinoma of the lung in 38 patients. AJR Am J Roentgenol 2004, 182:87-91.
28. Kruger S., Buck A.K., Blumstein N.M., et al. Use of integrated FDG PET/CT imaging in pulmonary carcinoid tumours. J Intern Med 2006, 260:545-550.
29. Erasmus J., McAdams H., Patz E., et al. Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 1998, 170:1369-1373.
30. Daniels C.E., Lowe V.J., Aubry M.C., Allen M.S., Jett J.R. The utility of fluorodeoxyglucose positron emission tomography in the evaluation of carcinoid tumors presenting as pulmonary nodules. Chest 2007, 131:255-260.
31. Binderup T., Knigge U., Loft A., et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med 2010, 51:704-712.
32. Bruns C., Weckbecker G., Raulf F., et al. Molecular pharmacology of somatostatin-receptor subtypes. Ann N Y Acad Sci 1994, 733:138-146.
33. Granberg D., Sundin A., Janson E.T., Oberg K., Skogseid B., Westlin J.E. Octreoscan in patients with bronchial carcinoid tumours. Clin Endocrinol (Oxf) 2003, 59:793-799.
34. Rodrigues M., Traub-Weidinger T., Li S., Ibi B., Virgolini I. Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTAlanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2006, 33:532-540.
35. Papotti M., Croce S., Bello M., et al. Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy. Virchows Arch 2001, 439:787-797.
36. Binderup T., Knigge U., Loft A., et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med 2010, 51:704-712.
37. Virgolini I.J., Gabriel M., von Guggenberg E., Putzer D., Kendler D., Decristoforo C. Role of radiopharmaceuticals in the diagnosis and treatment of neuroendocrine tumours. Eur J Cancer 2009, 45(Suppl. 1):274-291.
38. Antunes P., Ginji M., Zhang H., et al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?. Eur J Nucl Med Mol Imaging 2007, 34:982-993.
39. Ducrocq X., Thomas P., Massard G., et al. Operative risk and prognostic factors of typical bronchial carcinoid tumors. Ann Thorac Surg 1998, 65:1410-1414.
40. Escalon J., Detterbeck F. Carcinoid tumors. General thoracic surgery 2009, 1539-1554. Lippincott Williams & Wilkins, Philadelphia. 7th ed. T. Shields, J.I. LoCicero, C. Reed, R. Feins (Eds.).
41. 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, 4:527-533.
42. Mezzetti M., Raveglia F., Panigalli T., et al. Assessment of outcomes in typical and atypical carcinoids according to latest WHO classification. Ann Thorac Surg 2003, 76:1838-1842.
43. Ferguson M.K., Landreneau R.J., Hazelrigg S.R., et al. Long-term outcome after resection for bronchial carcinoid tumors. Eur J Cardiothorac Surg 2000, 18:156-161.
44. Åberg T., Blöndal T., Nõu E., Malmaeus J. The choice of operation for bronchial carcinoids. Ann Thorac Surg 1981, 32:19-22.
45. Luckraz H., Amer K., Thomas L., Gibbs A., Butchart E.G. Long-term outcome of bronchoscopically resected endobronchial typical carcinoid tumors. J Thorac Cardiovasc Surg 2006, 132:113-115.
46. Brokx H.A., Risse E.K., Paul M.A., et al. Initial bronchoscopic treatment for patients with intraluminal bronchial carcinoids. J Thorac Cardiovasc Surg 2007, 133:973-978.
47. Garcia-Yuste M., Matilla J.M., Cueto A., et al. Typical and atypical carcinoid tumours: analysis of the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung. Eur J Cardiothorac Surg 2007, 31:192-197.
48. Zacharias J., Nicholson A.G., Ladas G.P., Goldstraw P. 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 2003, 75:348-352.
49. Thomas C.F., Tazelaar H.D., Jett J.R. Typical and atypical pulmonary carcinoids: outcome in patients presenting with regional lymph node involvement. Chest 2001, 119:1143-1150.
50. Mackley H.B., Videtic G.M. Primary carcinoid tumors of the lung: a role for radiotherapy. Oncology (Williston Park) 2006, 20:1537-1543.
51. Righi L., Volante M., Rapa I., et al. Neuroendocrine tumors of the lung: a review of relevant pathological and molecular data. Virchows Arch 2007, 451:S51-S59.
52. Cooper W.A., Thourani V.H., Gal A.A., et al. The surgical spectrum of pulmonary neuroendocrine neoplasm. Chest 2001, 119:14-18.
53. Veronesi G., Morandi U., Alloisio M., et al. Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer 2006, 53:111-115.
54. Saji H., Tsuboi M., Matsubayashi J., et al. Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy. Anticancer Drugs 2010, 21:89-93.
55. Iyoda A., Hiroshima K., Moriya Y., et al. Postoperative recurrence and the role of adjuvant chemotherapy in patients with pulmonary large cell carcinoma. J Thorac Cardiovasc Surg 2009, 132:446-453.
56. Rossi G., Cavazza A., Marchioni A., et al. Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and MET in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol 2005, 23:8774-8785.
57. Skov B.G., Holm B., Erreboe A., Skov T., Mellemgaard A. ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: distribution and impact on serviva. J Thorac Oncol 2010, 5:453-459.
58. Beasley M.B., Thunnissen F.B., Brambilla E., et al. Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol 2000, 31:1255-1265.
59. Sun W., Lipsitz S., Catalano P., et al. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol 2005, 23:4897-4904.
60. Granberg D., Eriksson B., Wilander E., et al. Experience in treatment of metastatic pulmonary carcinoid tumors. Ann Oncol 2001, 12:1383-1391.
61. De Dosso S., Bajetta E., Procopio G., et al. Pulmonary carcinoid tumours: indolent but not benign. Oncology 2007, 73:162-168.
62. Ekeblad S., Sundin A., Janson E.T., et al. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res 2007, 13:2986-2991.
63. Sarmiento J.M., Heywood G., Rubin J., et al. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 2003, 197:29-37.
64. Gupta S., Johnson M.M., Murthy R., et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 2005, 104:1590-1602.
65. Ahlman H., Wangberg B., Nilsson O., et al. Aspects on diagnosis and treatment of the foregut carcinoid syndrome. Scand J Gastroenterol 1992, 27:459-471.
66. Igawa S., Watanabe R., Ito I., et al. Comparison of chemotherapy for unresectable pulmonary high grade non-small cell neuroendocrine carcinoma and small-cell lung cancer. Lung Cancer 2010, 68:438-445.
67. Yamazaki S., Sekine I., Matsuno Y., et al. Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin based chemotherapy. Lung Cancer 2005, 49:217-223.
68. National Cancer Comprehensive Center - Clinical Practice Guidelines in Oncology - Small cell lung cancer. Version v2. 2012. Available from: [accessed on February 25, 2012]. http://www.nccn.org.
69. Srirajaskanthan R., Toumpanakis C., Karpathakis A., et al. Surgical management and palliative treatment in bronchial neuroendocrine tumours: a clinical study of 45 patients. Lung Cancer 2009, 65:68-73.
70. Filosso P.L., Ruffini E., Oliaro A., Papalia E., Donati G., Rena O. Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide. Eur J Cardiothorac Surg 2002, 21:913-917.
71. de Jong M., Breeman W.A., Bernard B.F., et al. Tumor response after [(90)Y-DOTA(0), Tyr(3)]octreotide radionuclide therapy in a transplantable rat tumor model is dependent on tumor size. J Nucl Med 2001, 42:1841-1846.
72. Waldherr C., Pless M., Maecke H.R., et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med 2002, 43:610-616.
73. 90Y-endotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol 2010, 28:1652-1659.
74. Kwekkeboom D.J., de Herder W.W., Kam B.L., et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008, 26:2124-2130.
75. O'Reilly K.E., Rojo F., She Q.B., et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006, 66:1500-1508.
76. Pollak M.N., Polychronakos C., Guyda H. Somatostatin analogue SMS 201-995 reduces serum IGF-I levels in patients with neoplasms potentially dependent on IGF-I. Anticancer Res 1989, 9:889-891.
77. Yao J.C., Phan A.T., Chang D.Z., et al. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 2008, 26:4311-4318.
78. Pavel M.E., Hainsworth J.D., Baudin E., et al. 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.
79. Turner H.E., Harris A.L., Melmed S., Wass J.A. Angiogenesis in endocrine tumors. Endocr Rev 2003, 24:600-632.
80. La Rosa S., Uccella S., Finzi G., Albarello L., Sessa F., Capella C. Localization of vascular endothelial growth factor and its receptors in digestive endocrine tumors: Correlation with microvessel density and clinicopathologic features. Hum Pathol 2003, 34:18-27.
81. Chaudhry A., Papanicolaou V., Oberg K., Heldin C.H., Funa K. Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. Cancer Res 1992, 52:1006-1012.
82. Van Gompel J.J., Chen H. Insulin-like growth factor 1 signaling in human gastrointestinal carcinoid tumor cells. Surgery 2004, 136:1297-1302.
83. Mendel D.B., Laird A.D., Xin X., et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: Determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003, 9:327-337.
84. Kulke M.H., Lenz H.J., Meropol N.J., et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 2008, 26:3403-3410.
85. Faiss S., Pape U.F., Bohmig M., et al. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors: The International Lanreotide and Interferon Alfa Study Group. J Clin Oncol 2003, 21:2689-2696.
86. Kolby L., Persson G., Franzen S., Ahren B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg 2003, 90:687-693.
87. Yao J.C., Phan A., Hoff P.M., et al. 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.
88. Rickman O.B., Vohra P.K., Sanyal B., et al. Analysis of ErbB receptors in pulmonary carcinoid tumors. Clin Cancer Res 2009, 15:3315-3324.