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01-10-2012 | Review Article

Treatment of Liver Metastases in Patients with Digestive Neuroendocrine Tumors

Authors: Roberta Elisa Rossi, Sara Massironi, Matilde Pia Spampatti, Dario Conte, Clorinda Ciafardini, Federica Cavalcoli, Maddalena Peracchi

Published in: Journal of Gastrointestinal Surgery | Issue 10/2012

Abstract

Background

Liver metastases are a strong prognostic indicator in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Therapeutic options for metastatic NETs are expanding and not mutually exclusive.

Aims

This paper reviews the literature relating to multidisciplinary approach towards GEP-NET metastases, to highlight advances in knowledge regarding these tumors, and to understand the interdisciplinary management of individual patients.

Methods

A PubMed search was performed for English-language publications from 1995 through 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for GEP-NET-related liver metastases were selected.

Results

There is considerable controversy regarding the optimal management of GEP-NET metastases. Although radical surgery still remains the gold standard, a variety of other therapeutic options are available for metastatic GEP-NETs, including loco-regional chemotherapy/radiotherapy, radioembolization, systemic peptide receptor radionuclide therapy, biotherapy, and chemotherapy. In selected patients, liver transplantation should also be considered. Systemic somatostatin analogues and/or interferon show anti-proliferative effects, representing an appropriate first-line treatment for most patients. In advanced metastatic NETs, recent options include targeted therapies (i.e., everolimus and sunitinib).

Conclusions

It is evident that multidisciplinary care and multimodality treatments remain the cornerstone of management of NET patients. Since NETs often show a more indolent behavior compared to other malignancies, physicians should aim to preserve a satisfactory quality of life for the patient by personalizing the therapeutic approach according to the tumor’s features and prognostic factors.

Steinmüller T, Kianmanesh R, Falconi M, Scarpa A, Taal B, Kwekkeboom DJ, Lopes JM, Perren A, Nikou G, Yao J, Delle Fave GF, O’Toole D; Frascati Consensus Conference participants. Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 2008;87:47-62.CrossRefPubMed

Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmüller T, Anlauf M, Wiedenmann B, Salazar R. ENETS Consensus Guidelines for the Management of Patients with Liver and Other Distant Metastases from Neuroendocrine Neoplasms of Foregut, Midgut, Hindgut, and Unknown Primary. Neuroendocrinology 2012;95:157-176CrossRefPubMed

Ramage JK, Ahmed A, Ardill J, Bax N, Breen DJ, Caplin ME, Corrie P, Davar J, Davies AH, Lewington V, Meyer T, Newell-Price J, Poston G, Reed N, Rockall A, Steward W, Thakker RV, Toubanakis C, Valle J, Verbeke C, Grossman AB; UK and Ireland Neuroendocrine Tumour Society. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012;61:6–32CrossRefPubMed

Klöppel G, Rindi G, Perren A, Komminoth P, Klimstra DS. The ENETS and AJCC/UICC TNM classification of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. Virchows Arch 2010;456:595-7CrossRefPubMed

Rindi G, Arnold R, Bosman FT, Capella C, Klimstra DS, Klöppel G, Komminoth P and Solcia E. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: Bosman FT, Carneiro F, Hruban RH and Theise ND eds. WHO classification of tumors of the digestive system. Lyon: International Agency for Research on Cancer (IRAC), 2010:13–14

Panzuto F, Nasoni S, Falconi M, Corleto VD, Capurso G, Cassetta S, Di Fonzo M, Tornatore V, Milione M, Angeletti S, Cattaruzza MS, Ziparo V, Bordi C, Pederzoli P, Delle Fave G. Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization. Endocr Relat Cancer 2005;12:1083-1092.CrossRefPubMed

Tomassetti P, Campana D, Piscitelli L, Casadei R, Santini D, Nori F, Morselli-Labate AM, Pezzilli R, Corinaldesi R. Endocrine pancreatic tumors: factors correlated with survival. Ann Oncol 2005;16:1806–1810.CrossRefPubMed

Saxena A Chua TC, Chu F, Al-Zahrani A, Morris DL. Optimizing the surgical effort in patients with advanced neuroendocrine neoplasm hepatic metastases: a critical analysis of 40 patients treated by hepatic resection and cryoablation. Am J Clin Oncol 2011 Jun 4. [Epub ahead of print]

Moertel CG. Karnofsky memorial lecture: An odyssey in the land of small tumors. J Clin Oncol 1987;5:1502–1522PubMed

10.

Shebani KO, Souba WW, Finkelstein DM, Stark PC, Elgadi KM, Tanabe KK, Ott MJ. Prognosis and survival in patients with gastrointestinal tract carcinoid tumors. Ann Surg 1999;229:815-821CrossRefPubMed

11.

Atwell TD, Charboneau JW, Que FG, Rubin J, Lewis BD, Nagorney DM, Callstrom MR, Farrell MA, Pitot HC, Hobday TJ. Treatment of neuroendocrine cancer metastatic to the liver: the role of ablative techniques. Cardiovasc Intervent Radiol 2005;28:409–21CrossRefPubMed

12.

Strosberg JR, Cheema A, Kvols LK. A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract. Cancer Control 2011;18:127–37.PubMed

13.

Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009;27:4656–63CrossRefPubMed

14.

Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K; RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for Advanced Pancreatic Neuroendocrine Tumors. N Engl J Med 2011;364:514–523CrossRefPubMed

15.

Raymond E, Dahan L, Raoul J-L, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski. Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors. N Engl J Med 2011;364:501-513CrossRefPubMed

16.

Oberg K. Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors). Curr Opin Endocrinol Diabetes Obes. 2009;16:72-8CrossRefPubMed

17.

Capurso G, Lattimore S, Crnogorac-Jurcevic T, Panzuto F, Milione M, Bhakta V, Campanini N, Swift SM, Bordi C, Delle Fave G, Lemoine NR. Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets.Endocr Relat Cancer. 2006; 13:541-58.CrossRefPubMed

18.

Centre for Evidence Based Medicine. Levels of Evidence. http://www.cebm.net/index.aspx?o¼1025 (accessed Jun 2011).

19.

Cwikla JB, Sankowski A, Seklecka N, Buscombe JR, Nasierowska-Guttmejer A, Jeziorski KG, Mikolajczak R, Pawlak D, Stepien K, Walecki J. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010;21:787-794CrossRefPubMed

20.

Capurso G, Bettini R, Rinzivillo M, Boninsegna L, Delle Fave G, Falconi M. Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review. Neuroendocrinology 2011;93:223–9.CrossRefPubMed

21.

Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-76CrossRefPubMed

22.

Davies AH, Larsson G, Ardill J, Friend E, Jones L, Falconi M, Bettini R, Koller M, Sezer O, Fleissner C, Taal B, Blazeby JM, Ramage JK; EORTC Quality of Life Group. Development of a disease-specific quality of life questionnaire module for patients with gastrointestinal neuroendocrine tumours.Eur J Cancer 2006;42:477–84CrossRefPubMed

23.

Sarmiento J, Que F. Hepatic surgery for metastases from neuroendocrine tumors. Surg Oncol Clin N Am 2003;12:231-242.CrossRefPubMed

24.

Elias D, Lasser P, Ducreux M, Duvillard P, Ouellet JF, Dromain C, Schlumberger M, Pocard M, Boige V, Miquel C, Baudin E. Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: a 15-year single center prospective study. Surgery 2003;133:375-382.CrossRefPubMed

25.

Que FG, Nagorney DM, Batts KP, Linz LJ, Kvols LK. Hepatic resection for metastatic neuroendocrine carcinomas. Am J Surg 1995;169:36–42CrossRefPubMed

26.

Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 2003;197:29–37CrossRefPubMed

27.

Chamberlain RS, Canes D, Brown KT, Saltz L, Jarnagin W, Fong Y, Blumgart LH. Hepatic neuroendocrine metastases: Does intervention alter outcomes? J Am Coll Surg 2000;190:432–445.CrossRefPubMed

28.

Carty SE, Jensen RT, Norton JA. Prospective study of aggressive resection of metastatic pancreatic endocrine tumors. Surgery 1992;112:1024–1031.PubMed

29.

Dousset B, Saint-Marc O, Pitre J, Soubrane O, Houssin D, Chapuis Y. Metastatic endocrine tumors: Medical treatment, surgical resection, or liver transplantation. World J Surg 1996;20:908–914.CrossRefPubMed

30.

Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 2004;15:966–973.CrossRefPubMed

31.

Jaeck D, Oussoultzoglou E, Bachellier P. Hepatic metastases of gastroenteropancreatic neuroendocrine tumors: safe hepatic surgery.World J Surg 2001;25:689–692.CrossRefPubMed

32.

Adam R, Bismuth H, Castaing D. Repeat hepatectomy for colorectal liver metastases. Ann Surg 1997;225:51CrossRefPubMed

33.

Ahlman H, Wängberg B, Jansson S, Friman S, Olausson M, Tylén U, Nilsson O. Interventional treatment of gastrointestinal neuroendocrine tumours. Digestion 2000;62(suppl 1):59-68.CrossRefPubMed

34.

Ruszniewski P, O’Toole D. Ablative therapies for liver metastases of gastroenteropancreatic endocrine tumors. Neuroendocrinology 2004;80(suppl 1):74-78.CrossRefPubMed

35.

Hellman P, Ladjevardi S, Skogseid B, Akerström G, Elvin A. Radiofrequency tissue ablation using cooled tip for liver metastases of endocrine tumors. World J Surg 2002;26:1052–1056.CrossRefPubMed

36.

Kvols LK, Turaga KK, Strosberg J, Choi J. Role of interventional radiology in the treatment of patients with neuroendocrine metastases in the liver. J Natl Compr Canc Netw 2009;7:765–772.PubMed

37.

Siperstein A, Berber E. Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases. World J Surg 2001;25:693–696.CrossRefPubMed

38.

Nave H, Mossinger E, Feist H. Surgery as primary treatment in patients with liver metastases from carcinoid tumors: a retrospective, unicentric study over 13 years. Surgery 2001;129:170-175.CrossRefPubMed

39.

Pawlik T, Izzo F, Cohen D, Morris J, Curley M. Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 2003;10:1059–1069CrossRefPubMed

40.

Fioole B, Jansen M, van Duijnhoven F, van Hillegersberg R, van Gulik T, Borel Rinkes I. Combining partial liver resection and local ablation of liver tumours: a preliminary Dutch experience. World J Surg Oncol 2006;4:46.CrossRefPubMed

41.

Cozzi PJ, Englund R, Morris DL. Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors. Cancer 1995;76:501-509.CrossRefPubMed

42.

Anthuber M, Jauch K-W, Briegel J. Results of liver transplantation for gastroenteropancreatic tumor metastases. World J Surg 1996;20:73–76.CrossRefPubMed

43.

Livraghi T, Vettori C, Lazzaroni S. Liver metastases: results of percutaneous ethanol injection in 14 patients. Radiology 1991;179:709–712.PubMed

44.

Ruszniewski P, Rougier P, Roche A, Legmann P, Sibert A, Hochlaf S, Ychou M, Mignon M. Hepatic arterial hemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients. Cancer 1993;71:2624–2630CrossRefPubMed

45.

Marrache F, Vullierme MP, Roy C, El Assoued Y, Couvelard A, O’Toole D, Mitry E, Hentic O, Hammel P, Lévy P, Ravaud P, Rougier P, Ruszniewski P. Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours.Br J Cancer 2007;96:49–55.CrossRefPubMed

46.

Ricke J, Wust P, Wieners G, Beck A, Cho C, Seidensticker M, Pech M, Werk M, Rosner C, Hänninen EL, Freund T, Felix R. Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation. J Vasc Interv Radiol 2004;15:1279–1286.CrossRefPubMed

47.

Mitty HA, Warner RR, Newman LH, Train JS, Parnes IH. Control of carcinoid syndrome with hepatic artery embolization. Radiology 1985;155:623–626.PubMed

48.

Roche A, Girish BV, de Baere T, Baudin E, Boige V, Elias D, Lasser P, Schlumberger M, Ducreux M. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur Radiol 2003;13:136–140.PubMed

49.

Baere T, Indushekar S, Ducreux M, Lasser P, Elias D, Rougier P. Transcatheter chemoembolization of progressive carcinoid liver metastasis. Radiology 1993;189:541-547.PubMed

50.

Perry L, Stuart K, Stokes K, Clouse M. Hepatic arterial chemoembolization for metastatic neuroendocrine tumors. Surgery 1994;16:1111-1117.

51.

Diaco DS, Hajarizadeh H, Mueller CR, Fletcher WS, Pommier RF, Woltering EA. Treatment of metastatic carcinoid tumors using multimodality therapy of octreotide acetate, intra-arterial chemotherapy, and hepatic arterial chemoembolization. Am J Surg 1995;169:523–528.CrossRefPubMed

52.

Khasraw M, Gill A, Harrington T, Pavlakis N, Modlin I. Management of advanced neuroendocrine tumors with hepatic metastasis.J Clin Gastroenterol 2009;43:838–47.CrossRefPubMed

53.

Grossman EJ, Millis JM. Liver transplantation for non-hepatocellular carcinoma malignancy: Indications, limitations, and analysis of the current literature.Liver Transpl 2010;16:930–42.CrossRefPubMed

54.

van Vilsteren FG, Baskin-Bey ES, Nagorney DM, Sanderson SO, Kremers WK, Rosen CB, et al. Liver transplantation for gastroenteropancreatic neuroendocrine cancers: defining selection criteria to improve survival. Liver Transpl 2006;12:448–456.CrossRefPubMed

55.

Yao KA, Talamonti MS, Nemcek A, Angelos P, Chrisma H, Skarda J, Benson AB, Rao S, Joehl RJ. Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors. Surgery 2001;130:677–682.CrossRefPubMed

56.

Blonski WC, Reddy KR, Shaked A, Siegelman E, Metz DC. Liver transplantation for metastatic neuroendocrine tumor: a case report and review of the literature. World J Gastroenterol 2005;48:7676-7683.

57.

Sutcliffe R, Maguire D, Ramage J, Rela M, Heaton N. Management of neuroendocrine liver metastases. Am J Surg 2004;187:39–46.CrossRefPubMed

58.

Pascher A, Steinmuller T, Radke C, Hosten N, Wiedenmann B, Neuhaus P, Bechstein WO. Primary and secondary hepatic manifestation of neuroendocrine tumors. Langenbecks Arch Surg 2000;385:265-270.CrossRefPubMed

59.

Penn I. Hepatic transplantation for primary and metastatic cancers of the liver. Surgery 1991;110:726–734.PubMed

60.

Bechstein WO, Neuhaus P. Liver transplantation for hepatic metastases of neuroendocrine tumors. Ann N Y Ac Sci 1994;733:507–514CrossRef

61.

Le Treut YP, Delpero JR, Dousset B, Cherqui D, Segol P, Mantion G, Hannoun L, Benhamou G, Launois B, Boillot O, Domergue J, Bismuth H. Results of liver transplantation in the treatment of metastatic neuroendocrine tumors. A 31-case French multicenter report. Ann Surg 1997; 225:355-364.CrossRefPubMed

62.

Lehnert T. Liver transplantation for metastatic neuroendocrine carcinoma: an analysis of 103 patients. Transplantation 1998;66:1307-1312.CrossRefPubMed

63.

Mazzaferro V, Pulvirenti A, Coppa J. Neuroendocrine tumors metastatic to the liver: how to select patients for liver transplantation? J Hepatol 2007;47:460-6.CrossRefPubMed

64.

Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, O’dorisio TM, Valkema R, Bodei L, Chinol M, Maecke HR, Krenning EP. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med 2005;46(suppl 1):62S-66S.PubMed

65.

Valkema R, Pauwels S, Kvols LK, Barone R, Jamar F, Bakker WH, Kwekkeboom DJ, Bouterfa H, Krenning EP. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0,Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2006;36:147-156.CrossRefPubMed

66.

Bushnell DL Jr, O’Dorisio TM, O’Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, Baulieu JL, Borson-Chazot F, Anthony L, Benson AB, Oberg K, Grossman AB, Connolly M, Bouterfa H, Li Y, Kacena KA, LaFrance N, Pauwels SA.. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol 2010;28:1652-165.CrossRefPubMed

67.

Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, Feelders RA, van Aken MO, Krenning EP. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124-2130.CrossRefPubMed

68.

Massironi S, Conte D, Sciola V, Spampatti MP, Ciafardini C, Valenti L, Rossi RE, Peracchi M. Plasma chromogranin A response to octreotide test: prognostic value for clinical outcome in endocrine digestive tumors. Am J Gastroenterol 2010;105:2072-8.CrossRefPubMed

69.

Kulke M. Clinical presentation and management of carcinoid tumors. Hematol Oncol Clin N Am 2007;21:433-55.CrossRef

70.

Garland J, Buscombe JR, Bouvier C, Bouloux P, Chapman MH, Chow AC, Reynolds N, Caplin ME. Sandostatin LAR (long-acting octreotide acetate) for malignant carcinoid syndrome: a 3-year experience. Aliment Pharmacol Ther 2003;17:437-44.CrossRefPubMed

71.

Kolby L, Persson G, Franzen S, Ahrén B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg 2003;90:687-93.CrossRefPubMed

72.

Welin SV, Janson ET, Sundin A, Stridsberg M, Lavenius E, Granberg D, Skogseid B, Oberg KE, Eriksson BK. High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours. Eur J Endocrinol 2004;151:107-12.CrossRefPubMed

73.

Saltz L, Trochanowski B, Buckley M, Heffernan B, Niedzwiecki D, Tao Y, Kelsen D. Octreotide as an antineoplastic agent in the treatment of functional and nonfunctional neuroendocrine tumors. Cancer 1993;72:244CrossRefPubMed

74.

Oberg K, Norheim I, Theodorsson E. Treatment of malignant midgut carcinoid tumours with a long-acting somatostatin analogue octreotide. Acta Oncol 1991;30:503-7.CrossRefPubMed

75.

Walter T, Brixi-Benmansour H, Lombard-Bohas C, Cadiot G. New treatment strategies in advanced neuroendocrine tumours. Dig Liver Dis. 2012;44:95-105CrossRefPubMed

76.

Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, Yao JC. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 2004;22:4762-71.CrossRefPubMed

77.

Delaunoit T, Ducreux M, Boige V, Dromain C, Sabourin JC, Duvillard P, Schlumberger M, de Baere T, Rougier P, Ruffie P, Elias D, Lasser P, Baudin E. The doxorubicin-streptozotocin combination for the treatment of advanced well-differentiated pancreatic endocrine arcinoma; a judicious option? Eur J Cancer 2004;40:515–20CrossRefPubMed

78.

Plöckinger U, Rindi G, Arnold R, Eriksson B, Krenning E, de Herder WW, Goede A, Caplin M, Oberg K, Reubi JC, Nilsson O, Delle Fave G, Ruszniewski P, Ahlman H, Wiedenmann B; European Neuroendocrine Tumour Society. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. Neuroendocrinology 2004;80:395–424.

79.

Kulke MH, Hornick JL, Frauenhoffer C, Hooshmand S, Ryan DP, Enzinger PC, Meyerhardt JA, Clark JW, Stuart K, Fuchs CS, Redston MS. O6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clin Cancer Res 2009;15:338-45.CrossRefPubMed

80.

Vignot S, Faivre S, Aguirre D, Raymond E. mTOR-targeted therapy of cancer with rapamycin derivatives. Ann Oncol 2005;16:525-537CrossRefPubMed

81.

Verhoef S, van Diemen-Steenvoorde R, Akkersdijk WL, Bax NM, Ariyurek Y, Hermans CJ, van Nieuwenhuizen O, Nikkels PG, Lindhout D, Halley DJ, Lips K, van den Ouweland AM. Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in childhood. Eur J Pediatr 1999;158:284-287.CrossRefPubMed

82.

Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, Helm J, Kvols L. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 2011;117:268-75CrossRefPubMed

83.

Missiaglia E, Dalai I, Barbi S, Beghelli S, Falconi M, della Peruta M, Piemonti L, Capurso G, Di Florio A, delle Fave G, Pederzoli P, Croce CM, Scarpa A. Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway.J Clin Oncol. 2010;28:245-55CrossRefPubMed

84.

Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F. 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;26:4311–8CrossRefPubMed

85.

Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, O’Dorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 2010;28:69-76.CrossRefPubMed

86.

Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378:2005-12.CrossRefPubMed

87.

Duran I, Kortmansky J, Singh D, Hirte H, Kocha W, Goss G, Le L, Oza A, Nicklee T, Ho J, Birle D, Pond GR, Arboine D, Dancey J, Aviel-Ronen S, Tsao MS, Hedley D, Siu LL. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas.Br J Cancer 2006;95:1148-1154CrossRefPubMed

88.

Ramanathan RK, Cnaan A, Hahn RG, Carbone PP, Haller DG. Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol 2001;12:1139-1143.CrossRefPubMed

89.

Mitry E, Baudin E, Ducreux M, Sabourin JC, Rufié P, Aparicio T, Lasser P, Elias D, Duvillard P, Schlumberger M, Rougier P. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer 1999;81:1351-1355CrossRefPubMed

90.

Kulke MH, Lenz HJ, Meropol NJ, Posey J, Ryan DP, Picus J, Bergsland E, Stuart K, Tye L, Huang X, Li JZ, Baum CM, Fuchs CS. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 2008;26:3403-3410.CrossRefPubMed

91.

Boudreaux JP, Klimstra DS, Hassan MM, Woltering EA, Jensen RT, Goldsmith SJ, Nutting C, Bushnell DL, Caplin ME, Yao JC; North American Neuroendocrine Tumor Society (NANETS). The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: welldifferentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum. Pancreas 2010;39:753-66.CrossRefPubMed

92.

Bettini R, Mantovani W, Boninsegna L, Crippa S, Capelli P, Bassi C, Scarpa A, Pederzoli P, Falconi M. Primary tumour resection in metastatic nonfunctioning pancreatic endocrine carcinomas. Dig Liver Dis 2009;41:49-55.CrossRefPubMed

Title: Treatment of Liver Metastases in Patients with Digestive Neuroendocrine Tumors
Authors: Roberta Elisa Rossi
Sara Massironi
Matilde Pia Spampatti
Dario Conte
Clorinda Ciafardini
Federica Cavalcoli
Maddalena Peracchi
Publication date: 01-10-2012
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 10/2012
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-012-1951-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Treatment of Liver Metastases in Patients with Digestive Neuroendocrine Tumors

Abstract

Background

Aims

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Aims

Methods

Results

Conclusions

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Meta-analysis of the Results of Randomized Controlled Trials that Compared Laparoscopic and Open Surgery for Acute Appendicitis

Damage Control Surgery with Abdominal Vacuum and Delayed Bowel Reconstruction in Patients with Perforated Diverticulitis Hinchey III/IV

Extramammary Paget Disease in Peristomal Skin: Report of a Unique Case