CardioVascular and Interventional Radiology

, Volume 35, Issue 5, pp 1109–1118

Hepatic Toxicity After Radioembolization of the Liver Using 90Y-Microspheres: Sequential Lobar Versus Whole Liver Approach

  • Ricarda Seidensticker
  • Max Seidensticker
  • Robert Damm
  • Konrad Mohnike
  • Kerstin Schütte
  • Peter Malfertheiner
  • Mark Van Buskirk
  • Maciej Pech
  • Holger Amthauer
  • Jens Ricke
Clinical Investigation



90Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus “whole liver” 90Y-radioembolization.


Thirty-four patients with liver malignancy in noncirrhotic livers were included; 90Y-radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed.


Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P < 0.05). Three patients treated with whole liver RE suffered from radioembolization-induced liver disease (REILD). Pathological increases in bilirubin at 3 months were observed for the whole liver group only (52.3 vs. 18.7 μmol/l, P = 0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P < 0.05). Portal vein diameter increased significantly in whole liver-treated patients only (+17% vs. +6.6%, P = 0.043).


Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy.


Yttrium-90 Hepatic toxicity Radiation induced liver disease RILD REILD Hepatic metastases Local ablation 


  1. 1.
    Wallace S, Carrasco CH, Charnsangavej C et al (1990) Hepatic artery infusion and chemoembolization in the management of liver metastases. Cardiovasc Intervent Radiol 13(3):153–160PubMedCrossRefGoogle Scholar
  2. 2.
    Cosimelli M, Golfieri R, Cagol PP et al (2010) Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. Br J Cancer 103(3):324–331PubMedCrossRefGoogle Scholar
  3. 3.
    Gray B, Van Hazel G, Hope M et al (2001) Randomised trial of SIR-Spheres plus chemotherapy vs chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol 12(12):1711–1720PubMedCrossRefGoogle Scholar
  4. 4.
    Mulcahy MF, Lewandowski RJ, Ibrahim SM et al (2009) Radioembolization of colorectal hepatic metastases using yttrium-90 microspheres. Cancer 115(9):1849–1858PubMedCrossRefGoogle Scholar
  5. 5.
    Hilgard P, Hamami M, Fouly AE et al (2010) Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 52(5):1741–1749PubMedCrossRefGoogle Scholar
  6. 6.
    Kennedy A, Nag S, Salem R et al (2007) 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 68(1):13–23PubMedCrossRefGoogle Scholar
  7. 7.
    Nicolay NH, Berry DP, Sharma RA (2009) Liver metastases from colorectal cancer: radioembolization with systemic therapy. Nat Rev Clin Oncol 6(12):687–697PubMedCrossRefGoogle Scholar
  8. 8.
    Sharma RA, van Hazel GA, Morgan B et al (2007) Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 25(9):1099–1106PubMedCrossRefGoogle Scholar
  9. 9.
    van Hazel GA, Pavlakis N, Goldstein D et al (2009) Treatment of fluorouracil-refractory patients with liver metastases from colorectal cancer by using yttrium-90 resin microspheres plus concomitant systemic irinotecan chemotherapy. J Clin Oncol 27(25):4089–4095PubMedCrossRefGoogle Scholar
  10. 10.
    Salem R, Lewandowski RJ, Kulik L et al (2011) Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 140(2):497–507PubMedCrossRefGoogle Scholar
  11. 11.
    Leung TW, Lau WY, Ho SK et al (1995) Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors. Int J Radiat Oncol Biol Phys 33(4):919–924PubMedCrossRefGoogle Scholar
  12. 12.
    Sangro B, Gil-Alzugaray B, Rodriguez J et al (2008) Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer 112(7):1538–1546PubMedCrossRefGoogle Scholar
  13. 13.
    Bianco JA, Appelbaum FR, Nemunaitis J et al (1991) Phase I–II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Blood 78(5):1205–1211PubMedGoogle Scholar
  14. 14.
    Essell JH, Schroeder MT, Harman GS et al (1998) Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128(12 Pt 1):975–981Google Scholar
  15. 15.
    Forrest DL, Thompson K, Dorcas VG et al (2003) Low molecular weight heparin for the prevention of hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplantation: a prospective phase II study. Bone Marrow Trans 31(12):1143–1149CrossRefGoogle Scholar
  16. 16.
    Ricke J, Seidensticker M, Ludemann L et al (2005) In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation. Int J Radiat Oncol Biol Phys 62(3):776–784PubMedCrossRefGoogle Scholar
  17. 17.
    Seidensticker M, Seidensticker R, Mohnike K et al (2011) Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes. Radiat Oncol 6:40PubMedCrossRefGoogle Scholar
  18. 18.
    Field KM, Dow C, Michael M (2008) Part I: liver function in oncology: biochemistry and beyond. Lancet Oncol 9(11):1092–1101PubMedCrossRefGoogle Scholar
  19. 19.
    Deleporte A, Flamen P, Hendlisz A (2010) State of the art: radiolabeled microspheres treatment for liver malignancies. Expert Opin Pharmacother 11(4):579–586PubMedCrossRefGoogle Scholar
  20. 20.
    Hermann RM, Rave-Frank M, Pradier O (2008) Combining radiation with oxaliplatin: a review of experimental results. Cancer Radiother 12(1):61–67PubMedCrossRefGoogle Scholar
  21. 21.
    Rubbia-Brandt L, Audard V, Sartoretti P et al (2004) Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 15(3):460–466PubMedCrossRefGoogle Scholar
  22. 22.
    Denecke T, Ruhl R, Hildebrandt B et al (2008) Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques. Eur Radiol 18(5):892–902PubMedCrossRefGoogle Scholar
  23. 23.
    Seidensticker R, Denecke T, Kraus P et al (2011) Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases. Cardiovasc Intervent Radiol (in press)Google Scholar
  24. 24.
    Salem R, Lewandowski RJ, Gates VL et al (2011) Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol 22(3):265–278PubMedCrossRefGoogle Scholar
  25. 25.
    Fajardo LF, Colby TV (1980) Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med 104(11):584–588PubMedGoogle Scholar
  26. 26.
    Bayraktar UD, Seren S, Bayraktar Y (2007) Hepatic venous outflow obstruction: three similar syndromes. World J Gastroenterol 13(13):1912–1927PubMedGoogle Scholar
  27. 27.
    DeLeve LD, Shulman HM, McDonald GB (2002) Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis 22(1):27–42PubMedCrossRefGoogle Scholar
  28. 28.
    Jakobs TF, Saleem S, Atassi B et al (2008) Fibrosis, portal hypertension, and hepatic volume changes induced by intra-arterial radiotherapy with 90yttrium microspheres. Dig Dis Sci 53(9):2556–2563PubMedCrossRefGoogle Scholar
  29. 29.
    Dawson LA, Normolle D, Balter JM et al (2002) Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53(4):810–821PubMedCrossRefGoogle Scholar
  30. 30.
    Lawrence TS, Robertson JM, Anscher MS et al (1995) Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 31(5):1237–1248PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2011

Authors and Affiliations

  • Ricarda Seidensticker
    • 1
  • Max Seidensticker
    • 1
  • Robert Damm
    • 1
  • Konrad Mohnike
    • 1
  • Kerstin Schütte
    • 2
  • Peter Malfertheiner
    • 2
  • Mark Van Buskirk
    • 3
  • Maciej Pech
    • 1
  • Holger Amthauer
    • 1
  • Jens Ricke
    • 1
  1. 1.Universitätsklinikum Magdeburg, Klinik für Radiologie & NuklearmedizinMagdeburgGermany
  2. 2.Universitätsklinikum Magdeburg, Klinik für Gastroenterologie, Hepatologie und InfektiologieMagdeburgGermany
  3. 3.Data ReductionChesterUSA

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