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Review

Systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors

, , , &
Pages 311-327 | Received 27 Feb 2016, Accepted 07 Jun 2016, Published online: 23 Jun 2016

References

  • Modlin IM, Shapiro MD, Kidd M. Siegfried oberndorfer: origins and perspectives of carcinoid tumors. Hum Pathol. 2004;35(12):1440–1451.
  • 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.
  • Hallet J, Law CH, Cukier M, et al. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer. 2015;121(4):589–597.
  • Tsai HJ, Wu CC, Tsai CR, et al. The epidemiology of neuroendocrine tumors in Taiwan: a nation-wide cancer registry-based study. PLoS One. 2013;8(4):e62487.
  • O’Connor JM, Marmissolle F, Bestani C, et al. Observational study of patients with gastroenteropancreatic and bronchial neuroendocrine tumors in Argentina: results from the large database of a multidisciplinary group clinical multicenter study. Mol Clin Oncol. 2014;2(5):673–684.
  • Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer (IARC); 2010.
  • Minnetti M, Grossman A. Somatic and germline mutations in NETs: implications for their diagnosis and management. Best Pract Res Clin Endocrinol Metabolism. 2016;30(1):115–127.
  • Karges W, Adler G. Clinical genetics of neuroendocrinetumors. Med Klin. 2003;98(12):712–716.
  • Thomas-Marques L, Murat A, Delemer B, et al. Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am J Gastroenterol. 2006;101(2):266–273.
  • Hough DM, Stephens DH, Johnson CD, et al. Pancreatic lesions in von Hippel-Lindau disease: prevalence, clinical significance, and CT findings. Ajr. 1994;162(5):1091–1094.
  • Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25(3):458–511.
  • Modlin IM, Kidd M, Latich I, et al. Current status of gastrointestinal carcinoids. Gastroenterology. 2005;128(6):1717–1751.
  • Sandler M, Karim SM, Williams ED. Prostaglandins in amine-peptide-secreting tumours. Lancet (London, England). 1968;2(7577):1053–1054.
  • Soga J, Yakuwa Y, Osaka M. Carcinoid syndrome: a statistical evaluation of 748 reported cases. J Exp Clin Cancer Res. 1999;18(2):133–141.
  • Shebani KO, Souba WW, Finkelstein DM, et al. Prognosis and survival in patients with gastrointestinal tract carcinoid tumors. Ann Surg. 1999;229(6):815.
  • Druce M, Rockall A, Grossman AB. Fibrosis and carcinoid syndrome: from causation to future therapy. Nat Rev. 2009;5(5):276–283.
  • Bernheim AM, Connolly HM, Hobday TJ, et al. Carcinoid heart disease. Prog Cardiovasc Dis. 2007;49(6):439–451.
  • Kanakis G, Kaltsas G. Biochemical markers for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Best Pract Res. 2012;26(6):791–802.
  • Oberg K. Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer. 2011;18(Suppl 1):S17–S25.
  • Modlin IM, Gustafsson BI, Moss SF, et al. Chromogranin A–biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol. 2010;17(9):2427–2443.
  • Yang X, Yang Y, Li Z, et al. Diagnostic value of circulating chromogranin a for neuroendocrine tumors: a systematic review and meta-analysis. PLoS One. 2015;10(4):e0124884.
  • Stridsberg M, Eriksson B, Oberg K, et al. A comparison between three commercial kits for chromogranin A measurements. J Endocrinol. 2003;177(2):337–341.
  • Nobels FRE, Kwekkeboom DJ, Coopmans W, et al. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the α-subunit of glycoprotein hormones. J Clin Endocrinol Metabolism. 1997;82(8):2622–2628.
  • Wang Y-H, Yang Q-C, Lin Y, et al. Chromogranin A as a marker for diagnosis, treatment, and survival in patients with gastroenteropancreatic neuroendocrine neoplasm. Medicine. 2014;93(27):e247.
  • Welin S, Stridsberg M, Cunningham J, et al. Elevated plasma chromogranin A is the first indication of recurrence in radically operated midgut carcinoid tumors. Neuroendocrinology. 2009;89(3):302–307.
  • Rossi RE, Garcia-Hernandez J, Meyer T, et al. Chromogranin A as a predictor of radiological disease progression in neuroendocrine tumours. Ann Transl Med. 2015;3(9):118.
  • Yao JC, Pavel M, Phan AT, et al. Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab. 2011;96(12):3741–3749.
  • Hijioka M, Ito T, Igarashi H, et al. Serum chromogranin A is a useful marker for Japanese patients with pancreatic neuroendocrine tumors. Cancer Sci. 2014;105(11):1464–1471.
  • Oberg K, Modlin IM, De Herder W, et al. Consensus on biomarkers for neuroendocrine tumour disease. Lancet. 2015;16(9):e435–e446.
  • Modlin IM, Oberg K, Taylor A, et al. Neuroendocrine tumor biomarkers: current status and perspectives. Neuroendocrinology. 2014;100(4):265–277.
  • Sherman SK, Maxwell JE, O’Dorisio MS, et al. Pancreastatin predicts survival in neuroendocrine tumors. Ann Surg Oncol. 2014;21(9):2971–2980.
  • Rustagi S, Warner RR, Divino CM. Serum pancreastatin: the next predictive neuroendocrine tumor marker. J Surg Oncol. 2013;108(2):126–128.
  • Alix-Panabieres C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016;6(5):479–491.
  • Khan MS, Kirkwood A, Tsigani T, et al. Circulating tumor cells as prognostic markers in neuroendocrine tumors. J Clin Oncol. 2012: JCO. 2013;31(3):365–372.
  • Childs A, Vesely C, Ensell L, et al. Detection of SSTR2 and 5 expression on circulating tumour cells in neuroendocrine tumours. Paper presented at: European neuroendocrine tumor society 2016; 2016 Mar 10; Barcelona.
  • Ćwikła JB, Bodei L, Kolasinska-Ćwikła A, et al. Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy. J Clin Endocrinol Metabolism. 2015;100(11):E1437–E1445.
  • Modlin IM, Frilling A, Salem RR, et al. Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies. Surgery. 2016;159(1):336–347.
  • Modlin IM, Aslanian H, Bodei L, et al. A PCR blood test outperforms chromogranin A in carcinoid detection and is unaffected by proton pump inhibitors. Endocr Connect. 2014;3(4):215–223.
  • Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–297.
  • Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol Med. 2014;20(8):460–469.
  • Ruebel K, Leontovich AA, Stilling GA, et al. MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression. Mod Pathol. 2010;23(3):367–375.
  • Li SC, Essaghir A, Martijn C, et al. Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors. Mod Pathol. 2013;26(5):685–696.
  • Tan EH, Tan CH. Imaging of gastroenteropancreatic neuroendocrine tumors. World J Clin Oncol. 2011;2(1):28–43.
  • Semelka RC, Custodio CM, Cem Balci N, et al. Neuroendocrine tumors of the pancreas: spectrum of appearances on MRI. Jmri. 2000;11(2):141–148.
  • Vossen JA, Buijs M, Liapi E, et al. Receiver operating characteristic analysis of diffusion-weighted magnetic resonance imaging in differentiating hepatic hemangioma from other hypervascular liver lesions. J Comput Assist Tomogr. 2008;32(5):750–756.
  • Dromain C, de Baere T, Lumbroso J, et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J clin oncol: official journal of the American Society of Clinical Oncology. 2005;23(1):70–78.
  • Puli SR, Kalva N, Bechtold ML, et al. Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: a systematic review and meta analysis. World J Gastroenterol. 2013;19(23):3678–3684.
  • Yang J, Kan Y, Ge BH, et al. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol (Stockholm, Sweden: 1987). 2014;55(4):389–398.
  • Adams S, Baum R, Rink T, et al. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med. 1998;25(1):79–83.
  • Squires MH III, Adsay NV, Schuster DM, et al. Octreoscan versus FDG-PET for neuroendocrine tumor staging: a biological approach. Ann Surg Oncol. 2015;22(7):2295–2301.
  • Binderup T, Knigge U, Loft A, et al. 18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16(3):978–985.
  • Hofman MS, Hicks RJ. Changing paradigms with molecular imaging of neuroendocrine tumors. Discov Med. 2012;14(74):71–81.
  • Pavel M, O’Toole D, Costa F, et al. ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 2016;103(2):172–185.
  • Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 2012;61(1):6–32.
  • Kulke MH, Anthony LB, Bushnell DL, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39(6):735–752.
  • Kulke MH, Shah MH, Benson AB 3rd, et al. Neuroendocrine tumors, version 1.2015. Jnccn. 2015;13(1):78–108.
  • Starker LF, Carling T. Molecular genetics of gastroenteropancreatic neuroendocrine tumors. Curr Opin Oncol. 2009;21(1):29–33.
  • Jiao Y, Shi C, Edil BH, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science (New York, NY). 2011;331(6021):1199–1203.
  • Yao JC, Hainsworth JD, Wolin EM, et al. Multivariate analysis including biomarkers in the phase III RADIANT-2 study of octreotide LAR plus everolimus (E+ O) or placebo (P+ O) among patients with advanced neuroendocrine tumors (NET). J Clin Oncol. 2012;30(Suppl 4):A157.
  • 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 (London, England). 2016;387(10022):968–977.
  • Waldherr C, Pless M, Maecke HR, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002;43(5):610–616.
  • Modlin IM, Lye KD, Kidd M. A 5‐decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–959.
  • Steinmüller T, Kianmanesh R, Falconi M, et al. Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2008;87(1):47–62.
  • McEntee GP, Nagorney DM, Kvols LK, et al. Cytoreductive hepatic surgery for neuroendocrine tumors. Surgery. 1990;108(6):1091–1096.
  • Sarmiento JM, 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(1):29–37.
  • Que FG, Nagorney DM, Batts KP, et al. Hepatic resection for metastatic neuroendocrine carcinomas. Am J Surg. 1995;169(1):36–42; discussion 42–33.
  • Soreide O, Berstad T, Bakka A, et al. Surgical treatment as a principle in patients with advanced abdominal carcinoid tumors. Surgery. 1992;111(1):48–54.
  • Mayo SC, de Jong MC, Pulitano C, et al. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol. 2010;17(12):3129–3136.
  • Glazer ES, Tseng JF, Al-Refaie W, et al. Long-term survival after surgical management of neuroendocrine hepatic metastases. Hpb. 2010;12(6):427–433.
  • Ahmed A, Turner G, King B, et al. Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study. Endocr Relat Cancer. 2009;16(3):885–894.
  • De Baere T, Deschamps F, Tselikas L, et al. GEP-NETS UPDATE: interventional radiology: role in the treatment of liver metastases from GEP-NETs. Eur J Endocrinol. 2015;172(4):R151–R166.
  • de Herder WW, Rehfeld JF, Kidd M, et al. A short history of neuroendocrine tumours and their peptide hormones. Best Pract Res Clin Endocrinol Metabol. 2016;30(1):3–17.
  • Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol. 1999;20(3):157–198.
  • Larsson LI, Goltermann N, De Magistris L, et al. Somatostatin cell processes as pathways for paracrine secretion. Science (New York, NY). 1979;205(4413):1393–1395.
  • Reichlin S. Somatostatin. N Engl J Med. 1983;309(24):1495–1501.
  • Jonas S, John M, Boese-Landgraf J, et al. Somatostatin receptor subtypes in neuroendocrine tumor cell lines and tumor tissues. Langenbecks Arch Chir. 1995;380(2):90–95.
  • Srirajaskanthan R, Watkins J, Marelli L, et al. Expression of somatostatin and dopamine 2 receptors in neuroendocrine tumours and the potential role for new biotherapies. Neuroendocrinology. 2009;89(3):308–314.
  • de Herder WW, Hofland LJ, van der Lely AJ, et al. Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer. 2003;10(4):451–458.
  • Barnett P. Somatostatin and somatostatin receptor physiology. Endocrine. 2003;20(3):255–264.
  • Modlin IM, Pavel M, Kidd M, et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010;31(2):169–188.
  • Zhang J, Jia Z, Li Q, et al. Elevated expression of vascular endothelial growth factor correlates with increased angiogenesis and decreased progression-free survival among patients with low-grade neuroendocrine tumors. Cancer. 2007;109(8):1478–1486.
  • Susini C, Buscail L. Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol. 2006;17(12):1733–1742.
  • Ferone D, Boschetti M, Resmini E, et al. Neuroendocrine‐immune interactions. Ann N Y Acad Sci. 2006;1069(1):129–144.
  • Bauer W, Briner U, Doepfner W, et al. SMS 201-995: a very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci. 1982;31(11):1133–1140.
  • Harris AG. Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects. Gut. 1994;35(3 Suppl):S1–S4.
  • Saif MW. Lanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors. Expert Opin Pharmacother. 2016;17(3):443–456.
  • Wolin EM, Jarzab B, Eriksson B, et al. Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. Drug Des Devel Ther. 2015;9:5075–5086.
  • Anthony L, Freda PU. From somatostatin to octreotide LAR: evolution of a somatostatin analogue. Curr Med Res Opin. 2009;25(12):2989–2999.
  • Kvols LK, Moertel CG, O’Connell MJ, et al. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986;315(11):663–666.
  • Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol. 1999;17(2):600.
  • 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.
  • Rinke A, Wittenberg M, 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 (PROMID): results on long term survival. Neuroendocrinology. 2016. doi:10.1159/000443612. [Epub ahead of print].
  • O’Toole D, Kianmanesh R, Caplin M. ENETS 2016 consensus guidelines for the management of patients with digestive neuroendocrine tumors: an update. Neuroendocrinology. 2016;103(2):117–118.
  • Oberg K, Akerstrom G, Rindi G, et al. Neuroendocrine gastroenteropancreatic tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v223–v227.
  • Vinik A, Wolin EM, Audry H, et al.; Group ES. ELECT: a phase 3 study of efficacy and safety of lanreotide autogel/depot (LAN) treatment for carcinoid syndrome in patients with neuroendocrine tumors (NETs). J Clin Oncol. 2014;32(Suppl 3; abstr 268). Paper presented at: ASCO Annual Meeting Proceedings 2014.
  • Oberg K, Kvols L, Caplin M, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004;15(6):966–973.
  • Caplin ME, Pavel M, Ćwikła JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224–233.
  • Bruns C, Lewis I, Briner U, et al. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol. 2002;146(5):707–716.
  • Kulke M, Ruszniewski P, Van Cutsem E, et al. A randomized open-label phase II study of Everolimus alone or in combination with Pasireotide LAR in advanced, progressive pancreatic neuroendocrine tumors (pNET): COOPERATE-2 trial. Neuroendocrinology. 2015.;102(42036):131–131.
  • Suleiman Y, Mahipal A, Shibata D, et al. Phase I study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2015;76(3):481–487.
  • Strosberg JR, Benson AB, Huynh L, et al. Clinical benefits of above-standard dose of octreotide LAR in patients with neuroendocrine tumors for control of carcinoid syndrome symptoms: a multicenter retrospective chart review study. Oncologist. 2014;19(9):930–936.
  • Engelman K, Lovenberg W, Sjoerdsma A. Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with the carcinoid syndrome. N Engl J Med. 1967;277(21):1103–1108.
  • Lapuerta P, Zambrowicz B, Fleming D, et al. Telotristat etiprate, a novel inhibitor of serotonin synthesis for the treatment of carcinoid syndrome. Clin Investig. 2015;5(5):447–456.
  • Kulke MH, Hörsch D, Caplin M, et al. Telotristat etiprate shows benefit in treating patients with carcinoid syndrome that is inadequately controlled by somatostatin analog therapy in the phase 3 TELESTAR clinical trial. Abstracts Presented at the 8th annual meeting of the North American NeuroEndocrine Tumor Society; 2015 Oct 14–18; Austin, TX. Pancreas. 2016;45(3):466–448.
  • Horsch D, Kulke M, Caplin M, et al. Efficacy and safety of telotristat etiprate in patients with carcinoid syndrome not adequately controlled by somatostatin analog therapy: analysis of the ongoing TELESTAR extension period. Paper presented at: the 13th Annual ENETS Conference; 2016 Mar 11; Barcelona.
  • Moertel CG, Kvols LK, O’Connell MJ, et al. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer. 1991;68(2):227–232.
  • Sorbye H, Strosberg J, Baudin E, et al. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014;120(18):2814–2823.
  • 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.
  • Ramanathan RK, Cnaan A, Hahn RG, et al. Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol. 2001;12(8):1139–1143.
  • Ekeblad S, Sundin A, Janson ET, et al. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res. 2007;13(10):2986–2991.
  • Fine RL, Gulati AP, Tsushima D, et al. Prospective phase II study of capecitabine and temozolomide (CAPTEM) for progressive, moderately, and well-differentiated metastatic neuroendocrine tumors. Paper presented at: ASCO Annual Meeting Proceedings 2014; 2014 Jan 17. Abstract 179.
  • Koumarianou A, Kaltsas G, Kulke MH, et al. Temozolomide in advanced neuroendocrine neoplasms: pharmacological and clinical aspects. Neuroendocrinology. 2015;101(4):274–288.
  • Wick W, Meisner C, Hentschel B, et al. Prognostic or predictive value of MGMT promoter methylation in gliomas depends on IDH1 mutation. Neurology. 2013;81(17):1515–1522.
  • Cives M, Ghayouri M, Brelsford M, et al. Identification of response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. Paper presented at: Neuroendocrine Tumor Symposium 2015.
  • Kulke M, Frauenhoffer C, Hooshmand S, et al. Prediction of response to temozolomide (TMZ)-based therapy by loss of MGMT expression in patients with advanced neuroendocrine tumors (NET). Paper presented at: ASCO Annual Meeting Proceedings 2007.
  • Mitry E, Baudin E, Ducreux M, et al. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer. 1999;81(8):1351–1355.
  • Sorbye H, Welin S, Langer SW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24(1):152–160.
  • Cassier PA, Walter T, Eymard B, et al. Gemcitabine and oxaliplatin combination chemotherapy for metastatic well-differentiated neuroendocrine carcinomas: a single-center experience. Cancer. 2009;115(15):3392–3399.
  • 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.
  • Pape U, Tiling N, Bartel C, et al. Oxaliplatin plus 5-fluorouracil/folinic acid as palliative treatment for progressive malignant gastrointestinal neuroendocrine carcinomas. J clin Oncol. 2006;24(Suppl 18):14074. Paper presented at: ASCO Annual Meeting Proceedings; Chicago, IL.
  • Venook A, Ko A, Tempero M, et al. Phase II trial of FOLFOX plus bevacizumab in advanced, progressive neuroendocrine tumors. J Clin Oncol. 2008;26(Suppl 15):15545. Paper presented at: ASCO Annual Meeting Proceedings; Chicago, IL.
  • Kunz P, Kuo T, Zahn J, et al. A phase II study of capecitabine, oxaliplatin, and bevacizumab for metastatic or unresectable neuroendocrine tumors. J Clin Oncol. 2010;28(Suppl 15):4104. Paper presented at: ASCO Annual Meeting Proceedings; Chicago, IL..
  • Hanna N, Bunn PA Jr., Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006;24(13):2038–2043.
  • Jin S, Wang T, Chen X, et al. Phase II study of weekly irinotecan plus cisplatin in patients with previously untreated extensive-stage extrapulmonary small cell carcinoma. Onkologie. 2011;34(7):378–381.
  • Yamaguchi T, Machida N, Morizane C, et al. Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system. Cancer Sci. 2014;105(9):1176–1181.
  • Hentic O, Hammel P, Couvelard A, et al. FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3. Endocr Relat Cancer. 2012;19(6):751–757.
  • Strosberg JR, Coppola D, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010;39(6):799–800.
  • O’Brien ME, Ciuleanu T-E, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006;24(34):5441–5447.
  • Olsen IH, Knigge U, Federspiel B, et al. Topotecan monotherapy in heavily pretreated patients with progressive advanced stage neuroendocrine carcinomas. J Cancer. 2014;5(8):628–632.
  • Oberg K. Interferon in the management of neuroendocrine GEP-tumors: a review. Digestion. 2000;62(Suppl 1):92–97.
  • Arnold R, Rinke A, Klose K-J, et al. Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial. Clin Gastroenterol Hepatol. 2005;3(8):761–771.
  • Oberg K, Eriksson B. The role of interferons in the management of carcinoid tumours. Br J Haematol. 1991;79(Suppl 1):74–77.
  • Sleijfer S, Bannink M, Gool AR, et al. Side effects of interferon-α therapy. Pharm World Sci. 2005;27(6):423–431.
  • Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev. 2009;10(5):307–318.
  • Shida T, Kishimoto T, Furuya M, et al. Expression of an activated mammalian target of rapamycin (mTOR) in gastroenteropancreatic neuroendocrine tumors. Cancer Chemother Pharmacol. 2010;65(5):889–893.
  • 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 (London, England). 2011;378(9808):2005–2012.
  • Castellano D, Bajetta E, Panneerselvam A, et al. Everolimus plus octreotide long-acting repeatable in patients with colorectal neuroendocrine tumors: a subgroup analysis of the phase III RADIANT-2 study. Oncologist. 2013;18(1):46–53.
  • Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–523.
  • Terris B, Scoazec JY, Rubbia L, et al. Expression of vascular endothelial growth factor in digestive neuroendocrine tumours. Histopathology. 1998;32(2):133–138.
  • Couvelard A, O’Toole D, Turley H, et al. Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression. Br J Cancer. 2005;92(1):94–101.
  • Raymond E, Dahan L, Raoul J-L, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):501–513.
  • Raymond E, Niccoli P, Castellano D, et al. Sunitinib (SU) in patients with advanced, progressive pancreatic neuroendocrine tumors (pNET): final overall survival (OS) results from a phase III randomized study including adjustment for crossover. J Clin Oncol. 2016;34(Suppl 4):309. Paper presented at: ASCO Annual Meeting Proceedings;Chicago, IL.
  • A study of sunitinib versus placebo in combination with lanreotide in patients with progressive advanced/metastatic midgut carcinoid tumors (SUNLAND) [Internet]. clinicaltrials.gov. [cited 2016 Jan 20] Available from: https://clinicaltrials.gov/ct2/show/NCT01731925.
  • Yao JC, Guthrie K, Moran C, et al. SWOG S0518: phase III 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 15):4004. Paper presented at: ASCO Annual Meeting Proceedings; Chicago, IL.
  • Kulke MH, Niedzwiecki D, Foster NR, et al. Randomized phase II study of everolimus (E) versus everolimus plus bevacizumab (E+ B) in patients (Pts) with locally advanced or metastatic pancreatic neuroendocrine tumors (pNET), CALGB 80701 (Alliance). J Clin Oncol. 2015;33(Suppl 15):4005. Paper presented at: ASCO Annual Meeting Proceedings; Chicago, IL.
  • Chan JA, Stuart K, Earle CC, et al. Prospective study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors. J Clin Oncol. 2012;30:2963–2968.
  • Uronis HE, Bendell JC, Altomare I, et al. A phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. Oncologist. 2013;18(3):271–272.
  • 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 (Oxford, England: 1990). 2013;49(18):3780–3787.
  • Cummins M, Pavlakis N. The use of targeted therapies in pancreatic neuroendocrine tumours: patient assessment, treatment administration, and management of adverse events. Ther Adv Med Oncol. 2013;5(5):286–300.
  • Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev. 2003;24(4):389–427.
  • Baum RP, Puranik AD, Kulkarni HR. Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors: current state and future perspectives. Int J Endocr Oncol. 2015;2(2):151–158.
  • Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26(13):2124–2130.
  • Bodei L, Kidd M, Paganelli G, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging. 2015;42(1):5–19.
  • Teunissen JJ, Kwekkeboom DJ, Krenning EP. Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Clin Oncol. 2004;22(13):2724–2729.
  • Strosberg JR, Wolin EM, Chasen B, et al. NETTER-1 phase III: progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate. J Clin Oncol. 2016;34(Suppl 4):194. Paper presented at: ASCO Annual Meeting Proceedings; Chicago, IL.
  • van Essen M, Krenning EP, Kam BL, et al. Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2008;35(4):743–748.
  • Kashyap R, Hofman MS, Michael M, et al. Favourable outcomes of (177)Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2015;42(2):176–185.
  • Kong G, Lau E, Ramdave S, et al. High-dose In-111 octreotide therapy in combination with radiosensitizing 5-FU chemotherapy for treatment of SSR-expressing neuroendocrine tumors. J Nucl Med. 2005;46(Suppl 2):151P.
  • Patel D, Lawrie J, Cehic J, et al. Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced neuroendocrine tumours (NET): South Australian sub study of the SIGNETURe registry. European Cancer Congress 2015; 2015; Vienna.
  • Sabet A, Haslerud T, Pape U-F, et al. Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014;41(2):205–210.
  • Tamagno G, McGowan L, King R, et al. Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor. Pancreas. 2010;39(2):281.
  • Metz DC, Choi J, Strosberg J, et al. A rationale for multidisciplinary care in treating neuroendocrine tumours. Curr Opin Endocrinol Diabetes Obes. 2012;19(4):306–313.
  • Singh S, Law C. Multidisciplinary reference centers: the care of neuroendocrine tumors. J Oncol Pract. 2010;6(6):e11–e16.
  • Beaumont JL, Cella D, Phan AT, et al. Comparison of health-related quality of life in patients with neuroendocrine tumors with quality of life in the general US population. Pancreas. 2012;41(3):461–466.
  • Prasad V, Ambrosini V, Hommann M, et al. Detection of unknown primary neuroendocrine tumours (CUP-NET) using 68Ga-DOTA-NOC receptor PET/CT. Eur J Nucl Med Mol Imaging. 2010;37(1):67–77.
  • Kayani I, Bomanji JB, Groves A, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112(11):2447–2455.
  • Raj NP, Soumerai T, Valentino E, et al. Next-generation sequencing (NGS) in advanced well differentiated pancreatic neuroendocrine tumors (WD pNETs): a study using MSK-IMPACT. J Clin Oncol. 2016;34(Suppl 4S; abstr 246). Paper presented at 2016 Gastrointestinal Cancers Symposium; San Francisco, CA.
  • Nasi G, Cucciniello M, Guerrazzi C. The role of mobile technologies in health care processes: the case of cancer supportive care. J Med Internet Res. 2015;17(2):e26.

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