Progress in diagnosis and therapy of advanced pulmonary carcinoid_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Xuebin ,  LI Shanqing

Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, 100730, P.R.China;

Corresponding author：

LI Shanqing, Email: lidanqing@pumch.cn

Keywords：

Pulmonary carcinoid; histopathology; diagnosis; therapy

DOI：

10.7507/1007-4848.201703049

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Pulmonary carcinoid (PC) is a rare low-grade malignant neuroendocrine tumor. Unlike other neuroendocrine tumors of the digestive tract, PC seldom causes hormone-related neuroendocrine symptoms, and the diagnosis mainly depends on the biopsy of the lesion. Besides, the immunohistochemical staining technique is an important supplement and a grading standard for pathological diagnosis. Surgery is the first choice for the treatment of early PC. However, the therapy of advanced PC which is the main problem perplexing most of clinicians is controversial and still facing severe challenges. Therefore, we will discuss the current progress of the diagnosis and therapy of advanced PC.

Citation： WANG Xuebin, LI Shanqing. Progress in diagnosis and therapy of advanced pulmonary carcinoid. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2017, 24(7): 551-557. doi: 10.7507/1007-4848.201703049 Copy

1.	Hauso O, Gustafsson BI, Kidd M, et al. Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer, 2008, 113(10): 2655-2664.
2.	Modlin IM, Lye KDKidd M. A 5-decade analysis of 13, 715 carcinoid tumors. Cancer, 2003, 97(4): 934-959.
3.	Yao JC, 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(18): 3063-3072.
4.	Cao C, Yan TD, Kennedy C, et al. Bronchopulmonary carcinoid tumors: long-term outcomes after resection. Ann Thorac Surg, 2011, 91(2): 339-343.
5.	Ferolla P, Daddi N, Urbani M, et al. Tumorlets, multicentric carcinoids, lymph-nodal metastases, and long-term behavior in bronchial carcinoids. J Thorac Oncol, 2009, 4(3): 383-387.
6.	Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of lung tumors: impact of genetic, vlinical and tadiologic advances since the 2004 classification. J Thorac Oncol, 2015, 10(9): 1243-1260.
7.	Travis WD. Advances in neuroendocrine lung tumors. Ann Oncol, 2010, 21(Suppl 7): vii65-vii71.
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): 1604-1620.
9.	Lim E, Goldstraw P, Nicholson AG, et al. Proceedings of the IASLC International Workshop on Advances in Pulmonary Neuroendocrine Tumors 2007. J Thorac Oncol, 2008, 3(10): 1194-1201.
10.	Filosso PL, Oliaro A, Ruffini E, et al. Outcome and prognostic factors in bronchial carcinoids: a single-center experience. J Thorac Oncol, 2013, 8(10): 1282-1288.
11.	Jeung MY, Gasser B, Gangi A, et al. Bronchial carcinoid tumors of the thorax: spectrum of radiologic findings. Radiographics, 2002, 22(2): 351-365.
12.	Oberg K, Hellman P, Ferolla P, et al. Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2012, 23 Suppl 7: vii120-123.
13.	Meisinger QC, Klein JS, Butnor KJ, et al. CT features of peripheral pulmonary carcinoid tumors. AJR Am J Roentgenol, 2011, 197(5): 1073-1080.
14.	Phan AT, Oberg K, Choi J, et al. 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(6): 784-798.
15.	Kayani I, Conry BG, Groves AM, et al. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med, 2009, 50(12): 1927-1932.
16.	Daniels CE, Lowe VJ, Aubry MC, et al. The utility of fluorodeoxyglucose positron emission tomography in the evaluation of carcinoid tumors presenting as pulmonary nodules. Chest, 2007, 131(1): 255-260.
17.	Pattenden HA, Leung M, Beddow E, et al. Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. Thorax, 2015, 70(4): 379-381.
18.	Filosso PL, Ferolla P, Guerrera F, et al. Multidisciplinary management of advanced lung neuroendocrine tumors. J Thorac Dis, 2015, 7(Suppl 2): S163-S171.
19.	Rinke A, Muller HH, Schade-Brittinger C, et al. 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(28): 4656-4663.
20.	Caplin ME, Pavel M, Cwikla JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med, 2014, 371(3): 224-233.
21.	Kvols LK, Brendtro KL, North American Neuroendocrine Tumor Society. The North American Neuroendocrine Tumor Society (NANETS) guidelines: mission, goals, and process. Pancreas, 2010, 39(6): 705-706.
22.	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(22): 4897-4904.
23.	Bajetta E, Catena L, Procopio G, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? Cancer Chemother Pharmacol, 2007, 59(5): 637-642.
24.	Brizzi MP, Berruti A, Ferrero A, et al. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer, 2009, 9: 388.
25.	Crona J, Fanola I, Lindholm DP, et al. Effect of temozolomide in patients with metastatic bronchial carcinoids. Neuroendocrinology, 2013, 98(2): 151-155.
26.	Ettinger DS, Wood DE, Akerley W, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4. 2016. J Natl Compr Canc Netw, 2016, 14(3): 255-264.
27.	Van Essen M, Krenning EP, De Jong M, et al. Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol, 2007, 46(6): 723-734.
28.	Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol, 2011, 29(17): 2416-2423.
29.	Pfeifer AK, Gregersen T, Gronbaek H, et al. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland. Neuroendocrinology, 2011, 93(3): 189-196.
30.	Kim SJ, Pak K, Koo PJ, et al. The efficacy of (177)Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis. Eur J Nucl Med Mol Imaging, 2015, 42(13): 1964-1970.
31.	Khan S, Krenning EP, van Essen M, et al. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0, Tyr3] octreotate. J Nucl Med, 2011, 52(9): 1361-1368.
32.	Kwekkeboom DJ, Krenning EP. Peptide receptor radionuclide therapy in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am, 2016, 30(1): 179-191.
33.	Sabet A, Biersack HJ, Ezziddin S. Advances in peptide receptor radionuclide therapy. Semin Nucl Med, 2016, 46(1): 40-46.
34.	Bodei L, Cremonesi M, Kidd M, et al. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors. Thorac Surg Clin, 2014, 24(3): 333-349.
35.	Valkema R, Pauwels SA, Kvols LK, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0), Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med, 2005, 46 Suppl 1: 83S-91S.
36.	Kwekkeboom DJ, Krenning EP, Lebtahi R, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology, 2009, 90(2): 220-226.
37.	Ferolla P. Medical treatment of advanced thoracic neuroendocrine tumors. Thorac Surg Clin, 2014, 24(3): 351-355.
38.	Kulke MH, Lenz HJ, Meropol NJ, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol, 2008, 26(20): 3403-3410.
39.	Yao JC, Phan A, Hoff PM, 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(8): 1316-1323.
40.	Castellano D, Capdevila J, Sastre J, et al. Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumour: a phase II study of Spanish Neuroendocrine Tumour Group (GETNE0801). Eur J Cancer, 2013, 49(18): 3780-3787.
41.	Yao JC Guthrie K, Moran C, et al. Prospective randomized comparison of depot octreotide plus interferon alpha-2b versus depot octreotide plus bevacizumab (NSC #704865) in advanced, poor prognosis carcinoid patients (NCT00569127). J Clin Oncol, 2015, 33: (suppl; abstr 4004).
42.	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(3): 548-555.
43.	Righi L, Volante M, Rapa I, et al. Mammalian target of rapamycin signaling activation patterns in neuroendocrine tumors of the lung. Endocr Relat Cancer, 2010, 17(4): 977-987.
44.	Pavel ME, Hainsworth JD, 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(9808): 2005-2012.
45.	Fazio N, Granberg D, Grossman A, et al. Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study. Chest, 2013, 143(4): 955-962.
46.	Pavel ME, Wiedenman B, Capdevila J, et al. 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).
47.	Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet, 2016, 387(10022): 968-977.

1. Hauso O, Gustafsson BI, Kidd M, et al. Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer, 2008, 113(10): 2655-2664.
2. Modlin IM, Lye KDKidd M. A 5-decade analysis of 13, 715 carcinoid tumors. Cancer, 2003, 97(4): 934-959.
3. Yao JC, 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(18): 3063-3072.
4. Cao C, Yan TD, Kennedy C, et al. Bronchopulmonary carcinoid tumors: long-term outcomes after resection. Ann Thorac Surg, 2011, 91(2): 339-343.
5. Ferolla P, Daddi N, Urbani M, et al. Tumorlets, multicentric carcinoids, lymph-nodal metastases, and long-term behavior in bronchial carcinoids. J Thorac Oncol, 2009, 4(3): 383-387.
6. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of lung tumors: impact of genetic, vlinical and tadiologic advances since the 2004 classification. J Thorac Oncol, 2015, 10(9): 1243-1260.
7. Travis WD. Advances in neuroendocrine lung tumors. Ann Oncol, 2010, 21(Suppl 7): vii65-vii71.
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): 1604-1620.
9. Lim E, Goldstraw P, Nicholson AG, et al. Proceedings of the IASLC International Workshop on Advances in Pulmonary Neuroendocrine Tumors 2007. J Thorac Oncol, 2008, 3(10): 1194-1201.
10. Filosso PL, Oliaro A, Ruffini E, et al. Outcome and prognostic factors in bronchial carcinoids: a single-center experience. J Thorac Oncol, 2013, 8(10): 1282-1288.
11. Jeung MY, Gasser B, Gangi A, et al. Bronchial carcinoid tumors of the thorax: spectrum of radiologic findings. Radiographics, 2002, 22(2): 351-365.
12. Oberg K, Hellman P, Ferolla P, et al. Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2012, 23 Suppl 7: vii120-123.
13. Meisinger QC, Klein JS, Butnor KJ, et al. CT features of peripheral pulmonary carcinoid tumors. AJR Am J Roentgenol, 2011, 197(5): 1073-1080.
14. Phan AT, Oberg K, Choi J, et al. 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(6): 784-798.
15. Kayani I, Conry BG, Groves AM, et al. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med, 2009, 50(12): 1927-1932.
16. Daniels CE, Lowe VJ, Aubry MC, et al. The utility of fluorodeoxyglucose positron emission tomography in the evaluation of carcinoid tumors presenting as pulmonary nodules. Chest, 2007, 131(1): 255-260.
17. Pattenden HA, Leung M, Beddow E, et al. Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. Thorax, 2015, 70(4): 379-381.
18. Filosso PL, Ferolla P, Guerrera F, et al. Multidisciplinary management of advanced lung neuroendocrine tumors. J Thorac Dis, 2015, 7(Suppl 2): S163-S171.
19. Rinke A, Muller HH, Schade-Brittinger C, et al. 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(28): 4656-4663.
20. Caplin ME, Pavel M, Cwikla JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med, 2014, 371(3): 224-233.
21. Kvols LK, Brendtro KL, North American Neuroendocrine Tumor Society. The North American Neuroendocrine Tumor Society (NANETS) guidelines: mission, goals, and process. Pancreas, 2010, 39(6): 705-706.
22. 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(22): 4897-4904.
23. Bajetta E, Catena L, Procopio G, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? Cancer Chemother Pharmacol, 2007, 59(5): 637-642.
24. Brizzi MP, Berruti A, Ferrero A, et al. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer, 2009, 9: 388.
25. Crona J, Fanola I, Lindholm DP, et al. Effect of temozolomide in patients with metastatic bronchial carcinoids. Neuroendocrinology, 2013, 98(2): 151-155.
26. Ettinger DS, Wood DE, Akerley W, et al. NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4. 2016. J Natl Compr Canc Netw, 2016, 14(3): 255-264.
27. Van Essen M, Krenning EP, De Jong M, et al. Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol, 2007, 46(6): 723-734.
28. Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol, 2011, 29(17): 2416-2423.
29. Pfeifer AK, Gregersen T, Gronbaek H, et al. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland. Neuroendocrinology, 2011, 93(3): 189-196.
30. Kim SJ, Pak K, Koo PJ, et al. The efficacy of (177)Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis. Eur J Nucl Med Mol Imaging, 2015, 42(13): 1964-1970.
31. Khan S, Krenning EP, van Essen M, et al. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0, Tyr3] octreotate. J Nucl Med, 2011, 52(9): 1361-1368.
32. Kwekkeboom DJ, Krenning EP. Peptide receptor radionuclide therapy in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am, 2016, 30(1): 179-191.
33. Sabet A, Biersack HJ, Ezziddin S. Advances in peptide receptor radionuclide therapy. Semin Nucl Med, 2016, 46(1): 40-46.
34. Bodei L, Cremonesi M, Kidd M, et al. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors. Thorac Surg Clin, 2014, 24(3): 333-349.
35. Valkema R, Pauwels SA, Kvols LK, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with (90)Y-DOTA(0), Tyr(3)-octreotide and (177)Lu-DOTA(0), Tyr(3)-octreotate. J Nucl Med, 2005, 46 Suppl 1: 83S-91S.
36. Kwekkeboom DJ, Krenning EP, Lebtahi R, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology, 2009, 90(2): 220-226.
37. Ferolla P. Medical treatment of advanced thoracic neuroendocrine tumors. Thorac Surg Clin, 2014, 24(3): 351-355.
38. Kulke MH, Lenz HJ, Meropol NJ, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol, 2008, 26(20): 3403-3410.
39. Yao JC, Phan A, Hoff PM, 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(8): 1316-1323.
40. Castellano D, Capdevila J, Sastre J, et al. Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine tumour: a phase II study of Spanish Neuroendocrine Tumour Group (GETNE0801). Eur J Cancer, 2013, 49(18): 3780-3787.
41. Yao JC Guthrie K, Moran C, et al. Prospective randomized comparison of depot octreotide plus interferon alpha-2b versus depot octreotide plus bevacizumab (NSC #704865) in advanced, poor prognosis carcinoid patients (NCT00569127). J Clin Oncol, 2015, 33: (suppl; abstr 4004).
42. 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(3): 548-555.
43. Righi L, Volante M, Rapa I, et al. Mammalian target of rapamycin signaling activation patterns in neuroendocrine tumors of the lung. Endocr Relat Cancer, 2010, 17(4): 977-987.
44. Pavel ME, Hainsworth JD, 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(9808): 2005-2012.
45. Fazio N, Granberg D, Grossman A, et al. Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study. Chest, 2013, 143(4): 955-962.
46. Pavel ME, Wiedenman B, Capdevila J, et al. 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).
47. Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet, 2016, 387(10022): 968-977.

Previous Article
Minimally invasive multi-vessel coronary artery bypass grafting through a small incision in left chest
Next Article
Imaging diagnosis progress of chronic aortic dissection

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Progress in diagnosis and therapy of advanced pulmonary carcinoid

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content