Skip to main content
SpringerLink
Log in

Hepatic intra-arterial therapies in metastatic neuroendocrine tumors: lessons from clinical practice

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Background

Liver metastases are common in patients with neuroendocrine tumors (NETs), having a negative impact on disease prognosis. The options for selective therapy in patients with unresectable multiple liver metastases are limited to TACE (transarterial chemoembolization), TAE (transarterial embolization), or SIRT (selective internal radiation therapy).

Aim

To explore the clinical outcome, survival and safety of these therapies in NETs patients.

Methods

Retrospective case series of consecutive patients (mean age 56.6 years, 59% male) treated at two tertiary university medical centers from 2005 to 2015.

Results

Fifty-seven patients with G1, G2, and low G3 NETs with liver metastases were investigated (pancreatic NET (pNET), 24; small bowel, 16; unknown origin (UKO), 9; rectal, 3; lung, 3; and gastric, 2). Fifty-three patients underwent TACE, three patients underwent TAE, and one patient underwent SIRT. Clinical improvement and tumor response were observed in 54/57 patients (95%), together with marked decreased in tumor markers. The median time to tumor progression following the first treatment was 14 ± 16 months. The median overall survival was 22 ± 18 months, more pronounced in the pNET, followed by small bowel and UKO subgroups. There was a trend for a better survival in patients with disease limited to the liver and in whom the primary tumor was resected.

Conclusion

Hepatic intra-arterial therapies are well tolerated in the majority of patients with NETs and liver metastases and associated with both clinical improvement and tumor stabilization for prolonged periods. These therapies should be always considered, irrespective of the presence of extrahepatic metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. S. Grozinsky-Glasberg, D.J. Gross, New drugs in the therapy of neuroendocrine tumors. J. Endocrinol. Invest. 35, 930–936 (2012)

    CAS  PubMed  Google Scholar 

  2. I.M. Modlin, K.D. Lye, M. Kidd, A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97, 934–959 (2003)

    Article  PubMed  Google Scholar 

  3. G. Rindi, The ENETS guidelines: the new TNM classification system. Tumori 96, 806–809 (2010)

    Article  PubMed  Google Scholar 

  4. M. Pavel, D. O’Toole, F. Costa et al. Vienna Consensus Conference 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 103, 172–185 (2016)

    Article  CAS  PubMed  Google Scholar 

  5. T. de Baere, F. Deschamps, L. Tselikas et al. Interventional radiology: role in the treatment of liver metastases from GEP-NETs. Eur. J. Endocrinol. 172, R151–166 (2015)

    Article  PubMed  Google Scholar 

  6. B. Lawrence, B.I. Gustafsson, A. Chan et al. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol. Metab. Clin. North Am. 40, 1–18 (2011)

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. A.K. Clift, A. Frilling, Management of patients with hepatic metastases from neuroendocrine tumors. Ann. Saudi Med. 34, 279–290 (2014)

    Article  PubMed  Google Scholar 

  9. A. Frilling, A.K. Clift, Therapeutic strategies for neuroendocrine liver metastases. Cancer 121, 1172–1186 (2015)

    Article  CAS  PubMed  Google Scholar 

  10. A. Kennedy, L. Bester, R. Salem et al., Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB 17, 29–37 (2015)

    Article  PubMed  Google Scholar 

  11. S. Gupta, Intra-arterial liver-directed therapies for neuroendocrine hepatic metastases. Semin. Interv. Radiol. 30, 28–38 (2013)

    Article  Google Scholar 

  12. F. Yinglu, L. Changquan, Z. Xiaofeng et al. A new way: alleviating postembolization syndrome following transcatheter arterial chemoembolization. J. Altern. Complement. Med. 15, 175–181 (2009)

    Article  PubMed  Google Scholar 

  13. E. Moon, M.D. Tam, R.N. Kikano et al. Prophylactic antibiotic guidelines in modern interventional radiology practice. Semin. Interv. Radiol. 27, 327–337 (2010)

    Article  Google Scholar 

  14. G. Rindi, W.W. de Herder, D. O’Toole et al., Consensus guidelines for the management of patients with digestive neuroendocrine tumors: the second event and some final considerations. Neuroendocrinology 87, 5–7 (2008)

    Article  CAS  PubMed  Google Scholar 

  15. T.J. Vogl, N.N. Naguib, S. Zangos et al. Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur. J. Radiol. 72, 517–528 (2009)

    Article  PubMed  Google Scholar 

  16. L.M. Wang, A.R. Jani, E.J. Hill et al. Anatomical basis and histopathological changes resulting from selective internal radiotherapy for liver metastases. J. Clin. Pathol. 66, 205–211 (2013)

    Article  CAS  PubMed  Google Scholar 

  17. S.C. Pitt, J. Knuth, J.M. Keily et al. Hepatic neuroendocrine metastases: chemo- or bland embolization? J. Gastrointest. Surg. 12, 1951–1960 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  18. H. Martensson, A. Nobin, S. Bengmark et al. Embolization of the liver in the management of metastatic carcinoid tumors. J. Surg. Oncol. 27, 152–158 (1984)

    Article  CAS  PubMed  Google Scholar 

  19. M. Del Prete, F. Fiore, R. Modica et al., Multidisciplinary group for neuroendocrine tumors. hepatic arterial embolization in patients with neuroendocrine tumors. J. Exp. Clin. Cancer Res. 33, 33–43 (2014)

    Article  Google Scholar 

  20. M. Pericleous, M.E. Caplin, E. Tsochatzis et al. Hepatic artery embolization in advanced neuroendocrine tumors: Efficacy and long-term outcomes. Asia Pac. J. Clin. Oncol. 12, 61–69 (2016)

    Google Scholar 

  21. C. Loewe, M. Schindl, M. Cejna et al. Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: assessment of mid- and long-term results. Am. J. Roentgenol. 180, 1379–1384 (2003)

    Article  Google Scholar 

  22. C.H. Carrasco, C. Charnsangavej, J. Ajani et al. The carcinoid syndrome: palliation by hepatic artery embolization. Am. J. Roentgenol. 147, 149–154 (1986)

    Article  CAS  Google Scholar 

  23. C.H. Carrasco, S. Wallace, C. Charnsangavej et al. Treatment of hepatic metastases in ocular melanoma. Embolization of the hepatic artery with polyvinyl sponge and cisplatin. JAMA 255, 3152–3154 (1986)

    Article  CAS  PubMed  Google Scholar 

  24. J.R. Strosberg, J. Choi, A.B. Cantor et al. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control. 13, 72–78 (2006)

    Article  PubMed  Google Scholar 

  25. B.K. Eriksson, E.G. Larsson, B.M. Skogseid et al. Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer 83, 2293–2301 (1998)

    Article  CAS  PubMed  Google Scholar 

  26. F. Fiore, M. Del Prete, R. Franco et al. Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors. Endocrine 47, 177–182 (2014)

    Article  CAS  PubMed  Google Scholar 

  27. C. Sward, V. Johanson, E. Nieveen van Dijkum et al., Prolonged survival after hepatic artery embolization in patients with midgut carcinoid syndrome. Br. J. Surg. 96, 517–521 (2009)

    Article  CAS  PubMed  Google Scholar 

  28. S. Dominguez, A. Denys, I. Madeira et al. Hepatic arterial chemoembolization with streptozotocin in patients with metastatic digestive endocrine tumours. Eur. J. Gastroenterol. Hepatol. 12, 151–157 (2000)

    Article  CAS  PubMed  Google Scholar 

  29. P. Ruszniewski, P. Rougier, A. RocheA et al., Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients. Cancer 71, 2624–2630 (1993)

    Article  CAS  PubMed  Google Scholar 

  30. J.D. Drougas, L.B. Anthony, T.K. Blair et al., Hepatic artery chemoembolization for management of patients with advanced metastatic carcinoid tumors. Am. J. Surg. 175, 408–412 (1998)

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  32. S. Gupta, M.M. Johnson, R. Murthy et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 104, 1590–1602 (2005)

    Article  PubMed  Google Scholar 

  33. R. Caprotti, C. Angelini, C. Mussi et al. Gastrointestinal carcinoids. Prognosis and survival. Minerva Chir. 58, 523–532 (2003)

    CAS  PubMed  Google Scholar 

  34. E.W. McDermott, B. Guduric, M.F. Brennan, Prognostic variables in patients with gastrointestinal carcinoid tumours. Br. J. Surg. 81, 1007–1009 (1994)

    Article  CAS  PubMed  Google Scholar 

  35. C.T. Sofocleous, E.N. Petre, M. Gonen et al., Factors affecting periprocedural morbidity and mortality and long-term patient survival after arterial embolization of hepatic neuroendocrine metastases. J. Vasc. Interv. Radiol. 25, 22–30 (2014)

    Article  PubMed  Google Scholar 

  36. J.A. Ajani, C.H. Carrasco, C. Charnsangavej et al. Islet cell tumors metastatic to the liver: effective palliation by sequential hepatic artery embolization. Ann. Intern. Med. 108, 340–344 (1988)

    Article  CAS  PubMed  Google Scholar 

  37. A. Nobin, B. Mansson, A. Lunderquist, Evaluation of temporary liver dearterialization and embolization in patients with metastatic carcinoid tumour. Acta Oncol. 28, 419–424 (1989)

    Article  CAS  PubMed  Google Scholar 

  38. E. Therasse, F. Breittmayer, A. Roche et al. Transcatheter chemoembolization of progressive carcinoid liver metastasis. Radiology 189, 541–547 (1993)

    Article  CAS  PubMed  Google Scholar 

  39. M.E. Clouse, L. Perry, K. Stuart et al. Hepatic arterial chemoembolization for metastatic neuroendocrine tumors. Digestion 55, 92–97 (1994)

    Article  PubMed  Google Scholar 

  40. L.J. Perry, K. Stuart, K.R. Stokes et al., Hepatic arterial chemoembolization for metastatic neuroendocrine tumors. Surgery 116, 1111–1116 (1994)

    CAS  PubMed  Google Scholar 

  41. B. Wangberg, G. Westberg, U. Tylen et al. Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction. World J. Surg. 20, 892–899 (1996)

    Article  CAS  PubMed  Google Scholar 

  42. E. Diamandidou, J.A. Ajani, D.J. Yang et al., Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors. Am. J. Roentgenol. 170, 339–344 (1998)

    Article  CAS  Google Scholar 

  43. K.T. Brown, B.Y. Koh, L.A. Brody et al. Particle embolization of hepatic neuroendocrine metastases for control of pain and hormonal symptoms. J. Vasc. Interv. Radiol. 10, 397–403 (1999)

    Article  CAS  PubMed  Google Scholar 

  44. Y.H. Kim, J.A. Ajani, C.H. Carrasco et al. Selective hepatic arterial chemoembolization for liver metastases in patients with carcinoid tumor or islet cell carcinoma. Cancer Invest. 17, 474–478 (1999)

    Article  CAS  PubMed  Google Scholar 

  45. A. Roche, B.V. Girish, T. de Baere et al. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur. Radiol. 13, 136–140 (2003)

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  47. O. Kress, H.J. Wagner, M. Wied et al. Transarterial chemoembolization of advanced liver metastases of neuroendocrine tumors--a retrospective single-center analysis. Digestion 68, 94–101 (2003)

    Article  CAS  PubMed  Google Scholar 

  48. A.T. Ruutiainen, M.C. Soulen, C.M. Tuite et al. Chemoembolization and bland embolization of neuroendocrine tumor metastases to the liver. J. Vasc. Interv. Radiol. 18, 847–855 (2007)

    Article  PubMed  Google Scholar 

  49. A.S. Ho, J. Picus, M.D. Darcy et al. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. Am. J. Roentgenol. 188, 1201–1207 (2007)

    Article  Google Scholar 

  50. T. de Baere, F. Deschamps, C. Teriitheau et al., Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J. Vasc. Interv. Radiol. 19, 855–861 (2008)

    Article  PubMed  Google Scholar 

  51. A. Frilling, I.M. Modlin, M. Kidd, et al., Working Group on Neuroendocrine Liver Metastases, Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol. 15, 8–21 (2014).

  52. X.D. Dong, B.I. Carr, Hepatic artery chemoembolization for the treatment of liver metastases from neuroendocrine tumors: a long-term follow-up in 123 patients. Med. Oncol. 28, 286–290 (2011)

    Article  Google Scholar 

Download references

Author information

Author notes

  1. S. Grozinsky-Glasberg and G. Kaltsas contributed equally to this work.

  2. A. I. Bloom and D. J. Gross jointly supervised this work.

Authors and Affiliations

  1. Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    S. Grozinsky-Glasberg, I. Uri & D. J. Gross

  2. Department of Pathophysiology, Division of Endocrinology, National University of Athens, Athens, Greece

    G. Kaltsas & M. Kaltsatou

  3. Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    N. Lev-Cohain, A. Klimov & A. I. Bloom

  4. Department of Radiology, Laiko General Hospital, Athens, Greece

    V. Vergadis

Authors
  1. S. Grozinsky-Glasberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Kaltsas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Kaltsatou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Lev-Cohain
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Klimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Vergadis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I. Uri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. I. Bloom
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D. J. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Grozinsky-Glasberg.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grozinsky-Glasberg, S., Kaltsas, G., Kaltsatou, M. et al. Hepatic intra-arterial therapies in metastatic neuroendocrine tumors: lessons from clinical practice. Endocrine 60, 499–509 (2018). https://doi.org/10.1007/s12020-018-1537-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-018-1537-0

Keywords

Search

Navigation