Digestive Disease Interventions 2019; 03(01): 046-051
DOI: 10.1055/s-0039-1688517
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Embolotherapy for Neuroendocrine Tumors

Gregory J. Nadolski
2   Division of Interventional Radiology, Department of Radiology, Penn Image-Guided Interventional Laboratory, University of Pennsylvania, Philadelphia
,
Michael C. Soulen
1   Division of Interventional Oncology, Department of Radiology and Surgery, Abramson Cancer Center, University of Pennsylvania, Philadelphia
› Author Affiliations
Further Information

Publication History

10 November 2018

10 February 2019

Publication Date:
22 April 2019 (online)

Abstract

The most frequent solid organ involved in metastatic neuroendocrine tumors (NET) is the liver. Hepatic metastases occur during the lifetime of 46% to 93% of patients with NETs. Intra-arterial embolotherapies are palliative and should be used for patients with unresectable disease not amenable to resection or ablation. The most widely accepted indications for liver embololization for NET metastases are progression of unresectable hepatic metastases threatening liver function and palliation of hormone-related symptoms uncontrolled by somatostatin analogues. This article will discuss patient selection and administration of all embolotherapies currently used for palliation of neuroendocrine liver metastases.

 
  • References

  • 1 Frilling A, Li J, Malamutmann E, Schmid KW, Bockisch A, Broelsch CE. Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease. Br J Surg 2009; 96 (02) 175-184
  • 2 Chamberlain RS, Canes D, Brown KT. , et al. Hepatic neuroendocrine metastases: does intervention alter outcomes?. J Am Coll Surg 2000; 190 (04) 432-445
  • 3 Knox CD, Anderson CD, Lamps LW, Adkins RB, Pinson CW. Long-term survival after resection for primary hepatic carcinoid tumor. Ann Surg Oncol 2003; 10 (10) 1171-1175
  • 4 Touzios JG, Kiely JM, Pitt SC. , et al. Neuroendocrine hepatic metastases: does aggressive management improve survival?. Ann Surg 2005; 241 (05) 776-783 , discussion 783–785
  • 5 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
  • 6 Frilling A, Clift AK. Therapeutic strategies for neuroendocrine liver metastases. Cancer 2015; 121 (08) 1172-1186
  • 7 Roche A, Girish BV, de Baère T. , et al. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur Radiol 2003; 13 (01) 136-140
  • 8 Engstrom PF, Lavin PT, Moertel CG, Folsch E, Douglass Jr HO. Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor. J Clin Oncol 1984; 2 (11) 1255-1259
  • 9 Schell SR, Camp ER, Caridi JG, Hawkins Jr IF. Hepatic artery embolization for control of symptoms, octreotide requirements, and tumor progression in metastatic carcinoid tumors. J Gastrointest Surg 2002; 6 (05) 664-670
  • 10 Pueyo I, Jiménez JR, Hernández J. , et al. Carcinoid syndrome treated by hepatic embolization. AJR Am J Roentgenol 1978; 131 (03) 511-513
  • 11 Lunderquist A, Ericsson M, Nobin A, Sandén G. Gelfoam powder embolization of the hepatic artery in liver metastases of carcinoid tumors. Radiologe 1982; 22 (02) 65-70
  • 12 Ajani JA, Carrasco CH, Charnsangavej C, Samaan NA, Levin B, Wallace S. Islet cell tumors metastatic to the liver: effective palliation by sequential hepatic artery embolization. Ann Intern Med 1988; 108 (03) 340-344
  • 13 Burns WR, Edil BH. Neuroendocrine pancreatic tumors: guidelines for management and update. Curr Treat Options Oncol 2012; 13 (01) 24-34
  • 14 Madoff DC, Gupta S, Ahrar K, Murthy R, Yao JC. Update on the management of neuroendocrine hepatic metastases. J Vasc Interv Radiol 2006; 17 (08) 1235-1249 , quiz 1250
  • 15 de Baere T, Dufaux J, Roche A. , et al. Circulatory alterations induced by intra-arterial injection of iodized oil and emulsions of iodized oil and doxorubicin: experimental study. Radiology 1995; 194 (01) 165-170
  • 16 de Baère T, Denys A, Briquet R, Chevallier P, Dufaux J, Roche A. Modification of arterial and portal hemodynamics after injection of iodized oils and different emulsions of iodized oils in the hepatic artery: an experimental study. J Vasc Interv Radiol 1998; 9 (02) 305-310
  • 17 Imaeda T, Yamawaki Y, Seki M. , et al. Lipiodol retention and massive necrosis after lipiodol-chemoembolization of hepatocellular carcinoma: correlation between computed tomography and histopathology. Cardiovasc Intervent Radiol 1993; 16 (04) 209-213
  • 18 Dominguez S, Denys A, Madeira I. , et al. Hepatic arterial chemoembolization with streptozotocin in patients with metastatic digestive endocrine tumours. Eur J Gastroenterol Hepatol 2000; 12 (02) 151-157
  • 19 Taylor RR, Tang Y, Gonzalez MV, Stratford PW, Lewis AL. Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo evaluation of drug release properties. Eur J Pharm Sci 2007; 30 (01) 7-14
  • 20 Gaur SK, Friese JL, Sadow CA. , et al. Hepatic arterial chemoembolization using drug-eluting beads in gastrointestinal neuroendocrine tumor metastatic to the liver. Cardiovasc Intervent Radiol 2011; 34 (03) 566-572
  • 21 Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, Geschwind JF. New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res 2006; 12 (08) 2563-2567
  • 22 Carter S, Martin Ii RCG. Drug-eluting bead therapy in primary and metastatic disease of the liver. HPB (Oxford) 2009; 11 (07) 541-550
  • 23 Varela M, Real MI, Burrel M. , et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 2007; 46 (03) 474-481
  • 24 Bhagat N, Reyes DK, Lin M. , et al. Phase II study of chemoembolization with drug-eluting beads in patients with hepatic neuroendocrine metastases: high incidence of biliary injury. Cardiovasc Intervent Radiol 2013; 36 (02) 449-459
  • 25 Guiu B, Deschamps F, Aho S. , et al. Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. J Hepatol 2012; 56 (03) 609-617
  • 26 de Baère T, Roche A, Amenabar JM. , et al. Liver abscess formation after local treatment of liver tumors. Hepatology 1996; 23 (06) 1436-1440
  • 27 Khan W, Sullivan KL, McCann JW. , et al. Moxifloxacin prophylaxis for chemoembolization or embolization in patients with previous biliary interventions: a pilot study. AJR Am J Roentgenol 2011; 197 (02) W343-5
  • 28 Patel S, Tuite CM, Mondschein JI, Soulen MC. Effectiveness of an aggressive antibiotic regimen for chemoembolization in patients with previous biliary intervention. J Vasc Interv Radiol 2006; 17 (12) 1931-1934
  • 29 Sofocleous CT, Petre EN, Gonen M. , et al. Factors affecting periprocedural morbidity and mortality and long-term patient survival after arterial embolization of hepatic neuroendocrine metastases. J Vasc Interv Radiol 2014; 25 (01) 22-30 , quiz 31
  • 30 Memon K, Lewandowski RJ, Riaz A, Salem R. Chemoembolization and radioembolization for metastatic disease to the liver: available data and future studies. Curr Treat Options Oncol 2012; 13 (03) 403-415
  • 31 Vogl TJ, Naguib NN, Zangos S, Eichler K, Hedayati A, Nour-Eldin NE. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur J Radiol 2009; 72 (03) 517-528
  • 32 Pitt SC, Knuth J, Keily JM. , et al. Hepatic neuroendocrine metastases: chemo- or bland embolization?. J Gastrointest Surg 2008; 12 (11) 1951-1960
  • 33 Frilling A, Modlin IM, Kidd M. , et al; Working Group on Neuroendocrine Liver Metastases. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol 2014; 15 (01) e8-e21
  • 34 Kennedy AS. Hepatic-directed Therapies in Patients with Neuroendocrine Tumors. Hematol Oncol Clin North Am 2016; 30 (01) 193-207
  • 35 Gupta S, Johnson MM, Murthy R. , et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 2005; 104 (08) 1590-1602
  • 36 Chen JX, Rose S, White SB. , et al. Embolotherapy for neuroendocrine tumor liver metastases: prognostic factors for hepatic progression-free survival and overall survival. Cardiovasc Intervent Radiol 2017; 40 (01) 69-80
  • 37 Kennedy A, Nag S, Salem R. , et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys 2007; 68 (01) 13-23
  • 38 Peterson JL, Vallow LA, Johnson DW. , et al. Complications after 90Y microsphere radioembolization for unresectable hepatic tumors: An evaluation of 112 patients. Brachytherapy 2013; 12 (06) 573-579
  • 39 Riaz A, Awais R, Salem R. Side effects of yttrium-90 radioembolization. Front Oncol 2014; 4: 198
  • 40 Gil-Alzugaray B, Chopitea A, Iñarrairaegui M. , et al. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology 2013; 57 (03) 1078-1087
  • 41 Su Y-K, Mackey RV, Riaz A. , et al. Long-term hepatotoxicity of yttrium-90 radioembolization as treatment of metastatic neuroendocrine tumor to the liver. J Vasc Interv Radiol 2017; 28 (11) 1520-1526
  • 42 Kennedy A, Coldwell D, Sangro B, Wasan H, Salem R. Integrating radioembolization into the treatment paradigm for metastatic neuroendocrine tumors in the liver. Am J Clin Oncol 2012; 35 (04) 393-398
  • 43 Kennedy AS, Dezarn WA, McNeillie P. , et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol 2008; 31 (03) 271-279
  • 44 Saxena A, Chua TC, Bester L, Kokandi A, Morris DL. Factors predicting response and survival after yttrium-90 radioembolization of unresectable neuroendocrine tumor liver metastases: a critical appraisal of 48 cases. Ann Surg 2010; 251 (05) 910-916
  • 45 Strosberg JR, Choi J, Cantor AB, Kvols LK. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Contr 2006; 13 (01) 72-78
  • 46 Ruutiainen AT, Soulen MC, Tuite CM. , et al. Chemoembolization and bland embolization of neuroendocrine tumor metastases to the liver. J Vasc Interv Radiol 2007; 18 (07) 847-855