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Neuroendocrine Cancers

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Gastrointestinal Oncology

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Abstract

Neuroendocrine tumors (NETs) originate from neuroendocrine cells which are located throughout the body. This chapter focuses on low- to intermediate-grade NETs of the gastrointestinal tract, though the term “neuroendocrine tumor” can also denote other diseases such as small-cell carcinoma of pulmonary and extrapulmonary origins, thyroid medullar carcinoma, neuroblastoma, and Merkel cell tumors. Islet cell carcinomas, also known as pancreatic endocrine tumors, pancreatic NETs, or pancreatic carcinoid, arise from the islets of Langerhans. Low- to intermediate-grade NETs arising from other sites are generally called carcinoids and are most commonly localized in the gastrointestinal tract and bronchopulmonary tree. Both of these tumor groups share the capacity for hormone production and usually have indolent clinical courses. Presenting symptoms, when present, are caused by excess hormones, local tumor growth, and metastasis. Surgical resection is the curative approach for localized disease. In unresectable, metastatic disease, the introduction of somatostatin analogs such as octreotide have significantly improved quality of life, and the potential tumor stabilization properties of newer, targeted agents are the subject of ongoing phase III trials. Nonetheless, advanced NETs remain largely incurable and often require the concerted efforts of a multidisciplinary team for effective palliation.

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Abbreviations

5-HIAA:

5-Hydroxyindoleacetic acid

5-HT:

5-Hydroxytryptophan

5-HTP:

5-Hydroxytryptamine

ACTH:

Adrenocorticotropic hormone

CGA:

Chromogranin A

CGH:

Comparative genomic hybridization

CHD:

Carcinoid heart disease

CT:

Computed tomography

DOTA:

Tetraazacyclo-dodecanetetra-acetic acid

DTPA:

Diethylenetriamine pentaacetic acid

EGF:

Epidermal growth factor

FAS:

5-Fluorouracil, doxorubicin, and streptozocin

FDG:

2-Fluoro-2-deoxy-D-glucose

HACE:

Hepatic artery chemoembolization

HAE:

Hepatic artery embolization

IFN α:

Interferon α

LOH:

Loss of heterozygosity

MEN1:

Multiple endocrine neoplasia type 1

MRI:

Magnetic resonance imaging

mTOR:

Mammalian target of rapamycin

NCCN:

National comprehensive cancer network

NET:

Neuroendocrine tumor

NF1:

Neurofibromatosis type 1

NSE:

Neuron-specific enolase

NYHA:

New York Heart Association

PDGF:

Platelet-derived growth factor

PET:

Positron emission tomography

PFS:

Progression-free survival

RFA:

Radiofrequency ablation

SEER:

Surveillance, Epidemiology, End Results

SNP:

Single nucleotide polymorphism

TGF β:

Transforming growth factor β

TSC2:

Tuberous sclerosis complex 2

TTP:

Time to progression

VEGF:

Vascular endothelial growth factor

VHL:

von Hippel–Lindau syndrome

VIP:

Vasoactive intestinal peptide

ZES:

Zollinger-Ellison syndrome

References

  • Anlauf M, Garbrecht N, Bauersfeld J et al (2007) Hereditary neuroendocrine tumors of the gastroenteropancreatic system. Virchows Arch 451(Suppl 1):S29–S38

    Article  PubMed  Google Scholar 

  • Arnnold R, Muller H, Schage-Brittinger C et al (2009) Placebo-controlled, double-blind, prospective, randomized study of 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 27(28):4656–4663

    Google Scholar 

  • Arnold R, Benning R, Neuhaus C et al (1993) Gastroenteropancreatic endocrine tumours: effect of Sandostatin on tumour growth. The German Sandostatin Study Group. Digestion 54:72–75

    Article  PubMed  Google Scholar 

  • Berge T, Linell F (1976) Carcinoid tumours. Frequency in a defined population during a 12-year period. Acta Pathol Microbiol Scand A 84:322–330

    CAS  PubMed  Google Scholar 

  • Bernick P, Klimstra D, Shia J et al (2004) Neuroendocrine carcinomas of the colon and rectum. Dis Colon Rectum 47:163–169

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharyya S, Toumpanakis C, Caplin ME et al (2008) Analysis of 150 patients with carcinoid syndrome seen in a single year at one institution in the first decade of the twenty-first century. Am J Cardiol 101:378–381

    Article  PubMed  Google Scholar 

  • Bloomston M, Al-Saif O, Klemanski D et al (2007) Hepatic artery chemoembolization in 122 patients with metastatic carcinoid tumor: lessons learned. J Gastrointest Surg 11:264–271

    Article  PubMed  Google Scholar 

  • Chamberlain R, Canes D, Brown K et al (2000) Hepatic neuroendocrine metastases: does intervention alter outcomes? J Am Coll Surg 190:432–445

    Article  CAS  PubMed  Google Scholar 

  • Chaudhry A, Papanicolaou V, Oberg K et al (1992) Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. Cancer Res 52:1006–1012

    CAS  PubMed  Google Scholar 

  • Cho C, Labow M, Tang L et al (2008) Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms. Cancer 113:126–134

    Article  PubMed  Google Scholar 

  • Clincaltrials.gov (2006a) Phase III, randomised, double-blind, stratified comparative, placebo controlled, parallel group, multi-centre study to assess the effect of deep subcutaneous injections of lanreotide autogel 120 mg administered every 28 days on tumour progression free survival in patients with non-functioning entero-pancreatic endocrine tumour. http://www.clinicaltrials.gov/ct2/show/NCT00353496. Accessed 9 Jan 2009

  • Clincaltrials.gov (2006b) A randomized, double-blind placebo-controlled, multicenter phase III study in patients with advanced carcinoid tumor receiving octreotide depot and everolimus 10 mg/day or octreotide depot and placebo. http://clinicaltrials.gov/ct2/show/NCT00412061. Accessed 29 May 2009

  • Clincaltrials.gov (2007a) Phase III prospective, randomized comparison of depot octreotide plus interferon alpha versus depot octreotide plus bevacizumab (NSC #704865) in advanced, poor prognosis carcinoid patients. http://clinicaltrials.gov/ct2/show/NCT00569127. Accessed 29 May 2009

  • Clincaltrials.gov (2007b) A phase III randomized, double-blind study of sunitinib (SU011248, sutent) versus placebo in patients with progressive advanced/metastatic well-differentiated pancreatic islet cell tumors. http://clinicaltrials.gov/ct2/show/NCT00428597. Accessed 14 May 2009

  • Clincaltrials.gov (2007c) A randomized double-blind phase III study of RAD001 10 mg/d plus best supportive care versus placebo plus best supportive care in the treatment of patients with advanced pancreatic neuroendocrine tumor (NET). http://clinicaltrials.gov/ct2/show/NCT00510068. Accessed 29 May 2009

  • Dierdorf SF (2003) Carcinoid tumor and carcinoid syndrome. Curr Opin Anaesthesiol 16:343–347

    Article  PubMed  Google Scholar 

  • Doherty GM (2005) Rare endocrine tumours of the GI tract. Best Pract Res Clin Gastroenterol 19:807–817

    Article  PubMed  Google Scholar 

  • Duran I, Kortmansky J, Singh D et al (2006) A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer 95:1148–1154

    Article  CAS  PubMed  Google Scholar 

  • Eriksson B, Bergstrom M, Lilja A et al (1993) Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors. Acta Oncol 32:189–196

    Article  CAS  PubMed  Google Scholar 

  • Eriksson B, Bergstrom M, Sundin A et al (2002) The role of PET in localization of neuroendocrine and adrenocortical tumors. Ann N Y Acad Sci 970:159–169

    Article  CAS  PubMed  Google Scholar 

  • Feldman JM (1989) Carcinoid tumors and the carcinoid syndrome. Curr Probl Surg 26:835–885

    Article  CAS  PubMed  Google Scholar 

  • Feldman J, Lee E (1985) Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid. Am J Clin Nutr 42:639–643

    CAS  PubMed  Google Scholar 

  • Fendrich V, Langer P, Waldmann J et al (2007) Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas. Br J Surg 94:1331–1341

    Article  CAS  PubMed  Google Scholar 

  • Frank M, Klose KJ, Wied M et al (1999) Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol 94:1381–1387

    CAS  PubMed  Google Scholar 

  • Gupta S, Yao JC, Ahrar K et al (2003) Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience. Cancer J 9:261–267

    Article  PubMed  Google Scholar 

  • Gupta S, Johnson MM, Murthy R et al (2005) Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors. Cancer 104:1590–1602

    Article  PubMed  Google Scholar 

  • Hanson MW, Feldman JM, Blinder RA et al (1989) Carcinoid tumors: Iodine-131 MIBG scintigraphy. Radiology 172:699–703

    CAS  PubMed  Google Scholar 

  • Hellman P, Ladjevardi S, Skogseid B et al (2002) Radiofrequency tissue ablation using cooled tip for liver metastases of endocrine tumors. World J Surg 26:1052–1056

    Article  PubMed  Google Scholar 

  • Ho AS, Picus J, Darcy MD et al (2007) Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol 188:1201–1207

    Article  PubMed  Google Scholar 

  • Hobday T, Holen K, Donehower R et al (2006) A phase II trial of gefitinib in patients (pts) with progressive metastatic neuroendocrine tumors (NET): a phase ii consortium (P2C) study. J Clin Oncol [ASCO Annual Meeting Proceedings] 24:189s

    Google Scholar 

  • Janson EM, Ahlstrom H, Andersson T et al (1992a) Octreotide and interferon alfa: a new combination for the treatment of malignant carcinoid tumours. Eur J Cancer 10:1647–1650

    Article  Google Scholar 

  • Janson ET, Ronnblom L, Ahlstrom H et al (1992b) Treatment with alpha-interferon versus alpha-interferon in combination with streptozocin and doxorubicin in patients with malignant carcinoid tumors: a randomized trial. Ann Oncol 3:635–638

    CAS  PubMed  Google Scholar 

  • Janson ET, Kauppinen HL, Oberg K (1993) Combined alpha- and gamma-interferon therapy for malignant midgut carcinoid tumors. A phase I-II trial. Acta Oncol 32:231–233

    Article  CAS  PubMed  Google Scholar 

  • Kim DH, Nagano Y, Choi IS et al (2008) Allelic alterations in well-differentiated neuroendocrine tumors (carcinoid tumors) identified by genome-wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors. Genes Chromosomes Cancer 47:84–92

    Article  PubMed  Google Scholar 

  • Kouvaraki MA, Ajani JA, Hoff P et al (2004) Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 22:4762–4771

    Article  CAS  PubMed  Google Scholar 

  • Krenning EP, Kooij PPM, Bakker WH et al (1994) Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D-Phe1]-octreotide. Ann N Y Acad Sci 733:496–506

    Article  CAS  PubMed  Google Scholar 

  • Krishnamurthy S, Dayal Y (1997) Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids. Am J Surg Pathol 21:327–333

    Article  CAS  PubMed  Google Scholar 

  • Kulke MH, Lenz HJ, Meropol NJ et al (2008) Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 26:3403–3410

    Article  CAS  PubMed  Google Scholar 

  • Kulke MH, Bergsland EK, Yao JC (2009) Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med 360:195–197

    Article  CAS  PubMed  Google Scholar 

  • Kwaan M, Goldberg J, Bleday R et al (2008) Rectal carcinoid tumors: review of results after endoscopic and surgical therapy. Arch Surg 143:471–475

    Article  PubMed  Google Scholar 

  • Kwekkeboom DJ, de Herder WW, Kam BL et al (2008) Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 26:2124–2130

    Article  CAS  PubMed  Google Scholar 

  • Kytola S, Hoog A, Nord B et al (2001) Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids. Am J Pathol 158:1803–1808

    CAS  PubMed  Google Scholar 

  • Memon M, Nelson H (1997) Gastrointestinal carcinoid tumors: current management strategies. Dis Colon Rectum 40:1101–1118

    Article  CAS  PubMed  Google Scholar 

  • Modlin IM, Lye KD, Kidd M (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97:934–959

    Article  PubMed  Google Scholar 

  • Moertel CG, Sauer WG, Docherty MB et al (1961) Life history of the carcinoid tumor of the small intestine. Cancer 14:291–293

    Google Scholar 

  • NCCN (2009) Neuroendocrine tumors. http://www.nccn.org/professionals/physician_gls/PDF/neuroendocrine. Accessed 12 Dec 2009

  • Nilsson O (1996) Gastrointestinal carcinoids – aspects of diagnosis and classification. APMIS 104:481–492

    Article  CAS  PubMed  Google Scholar 

  • Que F, Nagorney D, Batts KP et al (1995) Hepatic resection for metastatic neuroendocrine tumors. Am J Surg 169:36–42

    Article  CAS  PubMed  Google Scholar 

  • Rubin J, Ajani J, Schirmer W et al (1999) Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol 17:600–606

    CAS  PubMed  Google Scholar 

  • Sakai H, Kodaira S, Ono K et al (1993) Disseminated pancreatic polypeptidioma. Intern Med 32:737–741

    Article  CAS  PubMed  Google Scholar 

  • Saltz L, Trochanowski B, Buckley M et al (1993) Octreotide as an antineoplastic agent in the treatment of functional and nonfunctional neuroendocrine tumors. Cancer 72:244–248

    Article  CAS  PubMed  Google Scholar 

  • Saltz L, Kemeny N, Schwartz G et al (1994) A phase II trial of alpha-interferon and 5-fluorouracil in patients with advanced carcinoid and islet cell tumors. Cancer 74:958–961

    Article  CAS  PubMed  Google Scholar 

  • Schnirer II, Yao JC, Ajani JA (2003) Carcinoid – a comprehensive review. Acta Oncol 42:672–692

    Article  PubMed  Google Scholar 

  • Schonfeld WH, Eikin EP, Woltering EA et al (1998) The cost-effectiveness of octreotide acetate in the treatment of carcinoid syndrome and VIPoma. Int J Technol Assess Health Care 14:514–525

    Article  CAS  PubMed  Google Scholar 

  • Shah MH, Young D, Kindler HL et al (2004) Phase II study of the proteasome inhibitor bortezomib (PS-341) in patients with metastatic neuroendocrine tumors. Clin Cancer Res 10:6111–6118

    Article  CAS  PubMed  Google Scholar 

  • Stinner B, Rothmund M (2005) Neuroendocrine tumours (carcinoids) of the appendix. Best Pract Res Clin Gastroenterol 19:729–738

    Article  CAS  PubMed  Google Scholar 

  • Strosberg JR, Nasir A, Hodul P et al (2008) Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res 2:113–125

    PubMed  Google Scholar 

  • Talamonti M, Stuart K, Yao J (2004) Neuroendocrine tumors of the gastrointestinal tract: how aggressive should we be? In: Perry M (ed) American society of clinical oncology 2004 education book. American Society of Clinical Oncology, Alexandria, pp 206–215

    Google Scholar 

  • Tamm EP, Kim EE, Ng CS (2007) Imaging of neuroendocrine tumors. Hematol Oncol Clin North Am 21:409–432, vii

    Google Scholar 

  • Terris B, Scoazec JY, Rubbia L et al (1998) Expression of vascular endothelial growth factor in digestive neuroendocrine tumours. Histopathology 32:133–138

    Article  CAS  PubMed  Google Scholar 

  • Tonnies H, Toliat MR, Ramel C et al (2001) Analysis of sporadic neuroendocrine tumours of the enteropancreatic system by comparative genomic hybridisation. Gut 48:536–541

    Article  CAS  PubMed  Google Scholar 

  • Toumpanakis CG, Caplin ME (2008) Molecular genetics of gastroenteropancreatic neuroendocrine tumors. Am J Gastroenterol 103:729–732

    Article  CAS  PubMed  Google Scholar 

  • Tucker ON, Crotty PL, Conlon KC (2006) The management of insulinoma. Br J Surg 93:264–275

    Article  CAS  PubMed  Google Scholar 

  • Vinik AI, Thompson N, Eckhauser F et al (1989) Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management. Acta Oncol 28:389–402

    Article  CAS  PubMed  Google Scholar 

  • Wang AY, Ahmad NA (2006) Rectal carcinoids. Curr Opin Gastroenterol 22:529–535

    Article  PubMed  Google Scholar 

  • Wang L, Ignat A, Axiotis C (2002) Differential expression of the PTEN tumor suppressor protein in fetal and adult neuroendocrine tissues and tumors: progressive loss of PTEN expression in poorly differentiated neuroendocrine neoplasms. Appl Immunohistochem Mol Morphol 10:139–146

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Hua X (2007) In search of tumor suppressing functions of menin. Mol Cell Endocrinol 265–266:34–41

    Article  PubMed  Google Scholar 

  • Yao JC, Zhang JX, Rashid A et al (2007) Clinical and in vitro studies of imatinib in advanced carcinoid tumors. Clin Cancer Res 13:234–240

    Article  CAS  PubMed  Google Scholar 

  • Yao JC, Hassan M, Phan A et al (2008a) One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26:3063–3072

    Article  PubMed  Google Scholar 

  • Yao JC, Phan A, Hoff PM et al (2008b) 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 26:1316–1323

    Article  CAS  PubMed  Google Scholar 

  • Yao JC, Phan AT, Chang DZ et al (2008c) Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 26:4311–4318

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    John A. Jakob, Alexandria Phan & James C. Yao

  2. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Carlo Mario Contreras & Eddie K. Abdalla

Authors
  1. John A. Jakob
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  2. Carlo Mario Contreras
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  3. Eddie K. Abdalla
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  4. Alexandria Phan
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  5. James C. Yao
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Correspondence to James C. Yao .

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Editors and Affiliations

  1. Div. Medical Oncology, University of British Columbia, West 10th Avenue 600, Vancouver, V5Z 4E6, British Columbia, Canada

    Charles D. Blanke

  2. FB 19 Zentrum der Radiologie, Klinik f. Strahlentherapie, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany

    Claus Rödel

  3. Evanston Northwestern Healthcare, Northwestern University, Ridge Ave. 2650, Evanston, 60201, Illinois, USA

    Mark S. Talamonti

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Jakob, J.A., Contreras, C.M., Abdalla, E.K., Phan, A., Yao, J.C. (2011). Neuroendocrine Cancers. In: Blanke, C., Rödel, C., Talamonti, M. (eds) Gastrointestinal Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13306-0_11

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