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CardioVascular and Interventional Radiology

, Volume 40, Issue 1, pp 69–80 | Cite as

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

  • James X. Chen
  • Steven Rose
  • Sarah B. White
  • Ghassan El-Haddad
  • Nicholas Fidelman
  • Hooman Yarmohammadi
  • Winifred Hwang
  • Daniel Y. Sze
  • Nishita Kothary
  • Kristen Stashek
  • E. Paul Wileyto
  • Riad Salem
  • David C. Metz
  • Michael C. Soulen
Clinical Investigation

Abstract

Purpose

The purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.

Materials and Methods

This was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.

Results

Median HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.

Conclusion

Higher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

Keywords

Neuroendocrine tumor Liver metastases Embolization 

Notes

Compliance with Ethical Standards

Conflict of Interest

Steven C. Rose: consultant—SIRTeX; scientific advisory board—Surefire Medical. Sarah B. White: consultant—Guerbet, IO-rad, Grants—RSNA, SIR foundation, research support—Siemens. Nicholas Fidelman: Grants: BTG, GE Healthcare, Nordion. Daniel Y. Sze: consultant—Amgen, BTG, SirTeX Medical, W.L. Gore & Associates, Covidien, Guerbet, Cook, Codman; scientific advisory board—SureFire Medical, KoliMedical, Northwind Medical, TreusMedical, RadiAction Medical, EmboIX, Lunar Design, Jennerex Biotherapeutics. Riad Salem: consultant: BTG. David C. Metz MD: grants—Ipsen, Lexicon, AAA; consultant—Novartis, Takeda. Michael C. Soulen: grants—BTG, Guerbet; consultant—Guerbet, Merit. James X. Chen, Ghassan El-Haddad, Hooman Yarmohammadi, Winifred Hwang, Nishita Kothary, Kristen Stashek, E. Paul Wileyto, No disclosures.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

References

  1. 1.
    Barbier CE, Garske-Roman U, Sandstrom M, Nyman R, Granberg D. Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases. Eur J Nucl Med Mol Imaging. 2016;43(8):1425–31.CrossRefPubMedGoogle Scholar
  2. 2.
    Dong XD, Carr BI. Hepatic artery chemoembolization for the treatment of liver metastases from neuroendocrine tumors: a long-term follow-up in 123 patients. Med Oncol. 2011;28(Suppl 1):S286–90.CrossRefPubMedGoogle Scholar
  3. 3.
    Fiore F, Del Prete M, Franco R, et al. Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. Endocrine. 2014;47(1):177–82.CrossRefPubMedGoogle Scholar
  4. 4.
    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(8):1590–602.CrossRefPubMedGoogle Scholar
  5. 5.
    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(3):403–15.CrossRefPubMedGoogle Scholar
  6. 6.
    Pericleous M, Caplin ME, Tsochatzis E, Yu D, Morgan-Rowe L, Toumpanakis C. Hepatic artery embolization in advanced neuroendocrine tumors: efficacy and long-term outcomes. Asia Pac J Clin Oncol. 2016;12(1):61–9.CrossRefPubMedGoogle Scholar
  7. 7.
    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(7):847–55.CrossRefPubMedGoogle Scholar
  8. 8.
    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(1):22–30 quiz 31.CrossRefPubMedGoogle Scholar
  9. 9.
    Sommer WH, Ceelen F, Garcia-Albeniz X, et al. Defining predictors for long progression-free survival after radioembolisation of hepatic metastases of neuroendocrine origin. Eur Radiol. 2013;23(11):3094–103.CrossRefPubMedGoogle Scholar
  10. 10.
    Strosberg JR, Choi J, Cantor AB, Kvols LK. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control. 2006;13(1):72–8.PubMedGoogle Scholar
  11. 11.
    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(2):449–59.CrossRefPubMedGoogle Scholar
  12. 12.
    Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum. Pancreas. 2010;39(6):753–66.CrossRefPubMedGoogle Scholar
  13. 13.
    Kennedy A, Bester L, Salem R, et al. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB (Oxford). 2015;17(1):29–37.CrossRefGoogle Scholar
  14. 14.
    Kulke MH, Anthony LB, Bushnell DL, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39(6):735–52.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kulke MH, Shah MH, Benson AB 3rd, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Canc Netw. 2015;13(1):78–108.PubMedGoogle Scholar
  16. 16.
    Pavel M, Baudin E, Couvelard A, et al. 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(2):157–76.CrossRefPubMedGoogle Scholar
  17. 17.
    Pitt SC, Knuth J, Keily JM, et al. Hepatic neuroendocrine metastases: chemo- or bland embolization? J Gastrointest Surg. 2008;12(11):1951–60.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Maire F, Lombard-Bohas C, O’Toole D, et al. Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumors: a prospective randomized study. Neuroendocrinology. 2012;96(4):294–300.CrossRefPubMedGoogle Scholar
  19. 19.
    Ho AS, Picus J, Darcy MD, et al. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol. 2007;188(5):1201–7.CrossRefPubMedGoogle Scholar
  20. 20.
    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):4656–63.CrossRefPubMedGoogle Scholar
  21. 21.
    Caplin ME, Pavel M, Cwikla JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224–33.CrossRefPubMedGoogle Scholar
  22. 22.
    Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514–23.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):501–13.CrossRefPubMedGoogle Scholar
  24. 24.
    Van Essen M, Krenning EP, De Jong M, Valkema R, Kwekkeboom DJ. Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol. 2007;46(6):723–34.CrossRefPubMedGoogle Scholar
  25. 25.
    Gaba RC. Chemoembolization practice patterns and technical methods among interventional radiologists: results of an online survey. AJR Am J Roentgenol. 2012;198(3):692–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Memon K, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for neuroendocrine liver metastases: safety, imaging, and long-term outcomes. Int J Radiat Oncol Biol Phys. 2012;83(3):887–94.CrossRefPubMedGoogle Scholar
  27. 27.
    de Baere T, Arai Y, Lencioni R, et al. Treatment of liver tumors with lipiodol TACE: technical recommendations from experts opinion. Cardiovasc Intervent Radiol. 2016;39(3):334–43.CrossRefPubMedGoogle Scholar
  28. 28.
    Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRefPubMedGoogle Scholar
  29. 29.
    National Cancer Institute NIoH. Common terminology criteria for adverse events v4.03. 2010.Google Scholar
  30. 30.
    Lepage C, Rachet B, Coleman MP. Survival from malignant digestive endocrine tumors in England and Wales: a population-based study. Gastroenterology. 2007;132(3):899–904.CrossRefPubMedGoogle Scholar
  31. 31.
    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):3063–72.CrossRefPubMedGoogle Scholar
  32. 32.
    Whitney R, Valek V, Fages JF, et al. Transarterial chemoembolization and selective internal radiation for the treatment of patients with metastatic neuroendocrine tumors: a comparison of efficacy and cost. Oncologist. 2011;16(5):594–601.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Rhee TK, Lewandowski RJ, Liu DM, et al. 90Y Radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience. Ann Surg. 2008;247(6):1029–35.CrossRefPubMedGoogle Scholar
  34. 34.
    Moertel CG, Johnson CM, McKusick MA, et al. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med. 1994;120(4):302–9.CrossRefPubMedGoogle Scholar
  35. 35.
    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(3):271–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2016

Authors and Affiliations

  • James X. Chen
    • 1
  • Steven Rose
    • 2
  • Sarah B. White
    • 3
  • Ghassan El-Haddad
    • 4
  • Nicholas Fidelman
    • 5
  • Hooman Yarmohammadi
    • 6
  • Winifred Hwang
    • 7
  • Daniel Y. Sze
    • 7
  • Nishita Kothary
    • 7
  • Kristen Stashek
    • 8
  • E. Paul Wileyto
    • 9
  • Riad Salem
    • 10
  • David C. Metz
    • 11
  • Michael C. Soulen
    • 1
  1. 1.Division of Interventional Radiology, Department of RadiologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Division of Interventional Radiology, Department of RadiologyUniversity of San Diego Medical CenterSan DiegoUSA
  3. 3.Division of Interventional Radiology, Department of RadiologyMedical College of WisconsinMilwaukeeUSA
  4. 4.Division of Interventional Radiology, Department of RadiologyMoffitt Cancer CenterTampaUSA
  5. 5.Division of Interventional Radiology, Department of RadiologyUniversity of San Francisco Medical CenterSan FranciscoUSA
  6. 6.Division of Interventional Radiology, Department of RadiologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  7. 7.Division of Interventional Radiology, Department of RadiologyStanford University Medical CenterStanfordUSA
  8. 8.Department of PathologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  9. 9.Department of Biostatistics and EpidemiologyUniversity of PennsylvaniaPhiladelphiaUSA
  10. 10.Division of Interventional Radiology, Department of RadiologyNorthwestern Memorial HospitalChicagoUSA
  11. 11.Division of Gastroenterology, Department of MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA

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