Skip to main content
SpringerLink
Log in

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers

  • Review
  • Published:
Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Radioembolization using 90Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope 90Y is a β-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of 90Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12 weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.

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

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    CAS  Google Scholar 

  2. Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D, et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008;248:84–96.

    PubMed  Google Scholar 

  3. Grandhi MS, Kim AK, Ronnekleiv-Kelly SM, Kamel IR, Ghasebeh MA, Pawlik TM. Hepatocellular carcinoma: from diagnosis to treatment. Surg Oncol. 2016;25:74–85.

    PubMed  Google Scholar 

  4. Doherty B, Nambudiri VE, Palmer WC. Update on the diagnosis and treatment of cholangiocarcinoma. Curr Gastroenterol Rep. 2017;19(2):017–0542-4.

    Google Scholar 

  5. Hickey R, Lewandowski RJ, Prudhomme T, Ehrenwald E, Baigorri B, Critchfield J, et al. 90Y radioembolization of colorectal hepatic metastases using glass microspheres: safety and survival outcomes from a 531-patient multicenter study. J Nucl Med. 2016;57:665–71.

    CAS  PubMed  Google Scholar 

  6. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25:4575–80.

    PubMed  Google Scholar 

  7. Voutsinas N, Lekperic S, Barazani S, Titano JJ, Heiba SI, Kim E. Treatment of primary liver tumors and liver metastases, part 1: nuclear medicine techniques. J Nucl Med. 2018;59:1649–54.

    CAS  PubMed  Google Scholar 

  8. Giammarile F, Bodei L, Chiesa C, Flux G, Forrer F, Kraeber-Bodere F, et al. EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. Eur J Nucl Med Mol Imaging. 2011;38:1393–406.

    CAS  PubMed  Google Scholar 

  9. Kim YC, Kim YH, Uhm SH, Seo YS, Park EK, Oh SY, et al. Radiation safety issues in y-90 microsphere selective hepatic radioembolization therapy: possible radiation exposure from the patients. Nucl Med Mol Imaging. 2010;44:252–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Carr BI. Hepatic arterial 90Yttrium glass microspheres (therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl. 2004;10:S107–10.

    PubMed  Google Scholar 

  11. Coldwell D, Sangro B, Wasan H, Salem R, Kennedy A. General selection criteria of patients for radioembolization of liver tumors: an international working group report. Am J Clin Oncol. 2011;34:337–41.

    PubMed  Google Scholar 

  12. Lin KH, Chen YW, Lee RC, Wang LW, Chou FI, Chang CW, et al. Nuclear theranostics in Taiwan. Nucl Med Mol Imaging. 2019;53:86–91.

    CAS  PubMed  Google Scholar 

  13. Herba MJ, Illescas FF, Thirlwell MP, Boos GJ, Rosenthall L, Atri M, et al. Hepatic malignancies: improved treatment with intraarterial Y-90. Radiology. 1988;169:311–4.

    CAS  PubMed  Google Scholar 

  14. Wollner I, Knutsen C, Smith P, Prieskorn D, Chrisp C, Andrews J, et al. Effects of hepatic arterial yttrium 90 glass microspheres in dogs. Cancer. 1988;61:1336–44.

    CAS  PubMed  Google Scholar 

  15. Gray BN, Burton MA, Kelleher DK, Anderson J, Klemp P. Selective internal radiation (SIR) therapy for treatment of liver metastases: measurement of response rate. J Surg Oncol. 1989;42:192–6.

    CAS  PubMed  Google Scholar 

  16. Andrews JC, Walker SC, Ackermann RJ, Cotton LA, Ensminger WD, Shapiro B. Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up. J Nucl Med. 1994;35:1637–44.

    CAS  PubMed  Google Scholar 

  17. Dancey JE, Shepherd FA, Paul K, Sniderman KW, Houle S, Gabrys J, et al. Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres. J Nucl Med. 2000;41:1673–81.

    CAS  PubMed  Google Scholar 

  18. Van Hazel G, Blackwell A, Anderson J, Price D, Moroz P, Bower G, et al. Randomised phase 2 trial of SIR-spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol. 2004;88:78–85.

    PubMed  Google Scholar 

  19. Saini A, Wallace A, Alzubaidi S, Knuttinen MG, Naidu S, Sheth R, et al. History and evolution of yttrium-90 radioembolization for hepatocellular carcinoma. J Clin Med. 2019;8. https://doi.org/10.3390/jcm8010055.

    PubMed Central  Google Scholar 

  20. Murthy R, Nunez R, Szklaruk J, Erwin W, Madoff DC, Gupta S, et al. Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications. Radiographics. 2005;25(Suppl 1):S41–55.

    PubMed  Google Scholar 

  21. Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: technical and methodologic considerations. J Vasc Interv Radiol. 2006;17:1251–78.

    PubMed  Google Scholar 

  22. Inarrairaegui M, Pardo F, Bilbao JI, Rotellar F, Benito A, D'Avola D, et al. Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma. Eur J Surg Oncol. 2012;38:594–601.

    CAS  PubMed  Google Scholar 

  23. Cremonesi M, Chiesa C, Strigari L, Ferrari M, Botta F, Guerriero F, et al. Radioembolization of hepatic lesions from a radiobiology and dosimetric perspective. Front Oncol. 2014;4:210.

    PubMed  PubMed Central  Google Scholar 

  24. Sato K, Lewandowski RJ, Bui JT, Omary R, Hunter RD, Kulik L, et al. Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization. Cardiovasc Intervent Radiol. 2006;29:522–9.

    PubMed  Google Scholar 

  25. Spreafico C, Maccauro M, Mazzaferro V, Chiesa C. The dosimetric importance of the number of 90Y microspheres in liver transarterial radioembolization (TARE). Eur J Nucl Med Mol Imaging. 2014;41:634–8.

    PubMed  Google Scholar 

  26. Sofocleous CT, Violari EG, Sotirchos VS, Shady W, Gonen M, Pandit-Taskar N, et al. Radioembolization as a salvage therapy for heavily pretreated patients with colorectal cancer liver metastases: factors that affect outcomes. Clin Colorectal Cancer. 2015;14:296–305.

    PubMed  PubMed Central  Google Scholar 

  27. Nezami N, Kokabi N, Camacho JC, Schuster DM, Xing M, Kim HS. (90)Y radioembolization dosimetry using a simple semi-quantitative method in intrahepatic cholangiocarcinoma: glass versus resin microspheres. Nucl Med Biol. 2018;59:22–8.

    CAS  PubMed  Google Scholar 

  28. Piana PM, Bar V, Doyle L, Anne R, Sato T, Eschelman DJ, et al. Early arterial stasis during resin-based yttrium-90 radioembolization: incidence and preliminary outcomes. HPB (Oxford). 2014;16:336–41.

    Google Scholar 

  29. Kennedy AS, Ball D, Cohen SJ, Cohn M, Coldwell DM, Drooz A, et al. Multicenter evaluation of the safety and efficacy of radioembolization in patients with unresectable colorectal liver metastases selected as candidates for (90)Y resin microspheres. J Gastrointest Oncol. 2015;6:134–42.

    PubMed  PubMed Central  Google Scholar 

  30. Bishay VL, Biederman DM, Ward TJ, van der Bom IM, Patel RS, Kim E, et al. Transradial approach for hepatic radioembolization: initial results and technique. AJR Am J Roentgenol. 2016;207:1112–21.

    PubMed  Google Scholar 

  31. Lambert B, Mertens J, Sturm EJ, Stienaers S, Defreyne L, D'Asseler Y. 99mTc-labelled macroaggregated albumin (MAA) scintigraphy for planning treatment with 90Y microspheres. Eur J Nucl Med Mol Imaging. 2010;37:2328–33.

    CAS  PubMed  Google Scholar 

  32. Leung TW, Lau WY, Ho SK, Ward SC, Chow JH, Chan MS, et al. Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors. Int J Radiat Oncol Biol Phys. 1995;33:919–24.

    CAS  PubMed  Google Scholar 

  33. Ho S, Lau WY, Leung TW, Chan M, Johnson PJ, Li AK. Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J Nucl Med. 1997;24:293–8.

    CAS  PubMed  Google Scholar 

  34. Zarva A, Mohnike K, Damm R, Ruf J, Seidensticker R, Ulrich G, et al. Safety of repeated radioembolizations in patients with advanced primary and secondary liver tumors and progressive disease after first selective internal radiotherapy. J Nucl Med. 2014;55:360–6.

    PubMed  Google Scholar 

  35. Lam MG, Louie JD, Iagaru AH, Goris ML, Sze DY. Safety of repeated yttrium-90 radioembolization. Cardiovasc Intervent Radiol. 2013;36:1320–8.

    PubMed  Google Scholar 

  36. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–14.

    PubMed  Google Scholar 

  37. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985;56:918–28.

    CAS  PubMed  Google Scholar 

  38. Schafer DF, Sorrell MF. Hepatocellular carcinoma. Lancet. 1999;353:1253–7.

    CAS  PubMed  Google Scholar 

  39. Novell JR, Hilson A, Hobbs KE. Therapeutic aspects of radio-isotopes in hepatobiliary malignancy. Br J Surg. 1991;78:901–6.

    CAS  PubMed  Google Scholar 

  40. Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.

    PubMed  Google Scholar 

  41. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–71.

    CAS  PubMed  Google Scholar 

  42. Hu HT, Kim JH, Lee LS, Kim KA, Ko GY, Yoon HK, et al. Chemoembolization for hepatocellular carcinoma: multivariate analysis of predicting factors for tumor response and survival in a 362-patient cohort. J Vasc Interv Radiol. 2011;22:917–23.

    PubMed  Google Scholar 

  43. Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2016;151:1155,1163.e2.

    Google Scholar 

  44. Silva JP, Berger NG, Tsai S, Christians KK, Clarke CN, Mogal H, et al. Transarterial chemoembolization in hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis. HPB (Oxford). 2017;19:659–66.

    Google Scholar 

  45. Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017;18:1624–36.

    CAS  PubMed  Google Scholar 

  46. Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol. 2018;36:1913–21.

    CAS  PubMed  Google Scholar 

  47. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.

    Google Scholar 

  48. Benson AB,3rd, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Saenz DA, et al. NCCN guidelines insights: hepatobiliary cancers, version 1.2017. J Natl Compr Cancer Netw. 2017;15:563–73.

    PubMed  PubMed Central  Google Scholar 

  49. Morise Z, Sugioka A, Tokoro T, Tanahashi Y, Okabe Y, Kagawa T, et al. Surgery and chemotherapy for intrahepatic cholangiocarcinoma. World J Hepatol. 2010;2:58–64.

    PubMed  PubMed Central  Google Scholar 

  50. Lee Y, Yoo IR, Boo SH, Kim H, Park HL, Hyun OJ. The role of F-18 FDG PET/CT in intrahepatic cholangiocarcinoma. Nucl Med Mol Imaging. 2017;51:69–78.

    CAS  PubMed  Google Scholar 

  51. Kuhlmann JB, Euringer W, Spangenberg HC, Breidert M, Blum HE, Harder J, et al. Treatment of unresectable cholangiocarcinoma: conventional transarterial chemoembolization compared with drug eluting bead-transarterial chemoembolization and systemic chemotherapy. Eur J Gastroenterol Hepatol. 2012;24:437–43.

    CAS  PubMed  Google Scholar 

  52. Currie BM, Soulen MC. Decision making: intra-arterial therapies for cholangiocarcinoma-TACE and TARE. Semin Intervent Radiol. 2017;34:92–100.

    PubMed  PubMed Central  Google Scholar 

  53. Scheuermann U, Kaths JM, Heise M, Pitton MB, Weinmann A, Hoppe-Lotichius M, et al. Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma—a single-center experience. Eur J Surg Oncol. 2013;39:593–600.

    CAS  PubMed  Google Scholar 

  54. Ibrahim SM, Mulcahy MF, Lewandowski RJ, Sato KT, Ryu RK, Masterson EJ, et al. Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer. 2008;113:2119–28.

    CAS  PubMed  Google Scholar 

  55. Hoffmann RT, Paprottka PM, Schon A, Bamberg F, Haug A, Durr EM, et al. Transarterial hepatic yttrium-90 radioembolization in patients with unresectable intrahepatic cholangiocarcinoma: factors associated with prolonged survival. Cardiovasc Intervent Radiol. 2012;35:105–16.

    PubMed  Google Scholar 

  56. Reimer P, Virarkar MK, Binnenhei M, Justinger M, Schon MR, Tatsch K. Prognostic factors in overall survival of patients with unresectable intrahepatic cholangiocarcinoma treated by means of yttrium-90 radioembolization: results in therapy-naive patients. Cardiovasc Intervent Radiol. 2018;41:744–52.

    CAS  PubMed  Google Scholar 

  57. Boas FE, Brody LA, Erinjeri JP, Yarmohammadi H, Shady W, Kishore S, et al. Quantitative measurements of enhancement on preprocedure triphasic CT can predict response of colorectal liver metastases to radioembolization. AJR Am J Roentgenol. 2016;207:671–5.

    PubMed  PubMed Central  Google Scholar 

  58. Hendlisz A, Van den Eynde M, Peeters M, Maleux G, Lambert B, Vannoote J, et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. J Clin Oncol. 2010;28:3687–94.

    CAS  PubMed  Google Scholar 

  59. Seidensticker R, Denecke T, Kraus P, Seidensticker M, Mohnike K, Fahlke J, et al. Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases. Cardiovasc Intervent Radiol. 2012;35:1066–73.

    PubMed  Google Scholar 

  60. Gray B, Van Hazel G, Hope M, Burton M, Moroz P, Anderson J, et al. Randomised trial of SIR-spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol. 2001;12:1711–20.

    CAS  PubMed  Google Scholar 

  61. Gibbs P, Gebski V, Van Buskirk M, Thurston K, Cade DN, Van Hazel GA, et al. Selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study. BMC Cancer. 2014;14:897,2407–14-897.

    Google Scholar 

  62. Dutton SJ, Kenealy N, Love SB, Wasan HS, Sharma RA, FOXFIRE Protocol Development Group and the NCRI Colorectal Clinical Study Group. FOXFIRE protocol: an open-label, randomised, phase III trial of 5-fluorouracil, oxaliplatin and folinic acid (OxMdG) with or without interventional selective internal radiation therapy (SIRT) as first-line treatment for patients with unresectable liver-only or liver-dominant metastatic colorectal cancer. BMC Cancer. 2014;14(497):2407–14-497.

    Google Scholar 

  63. van Hazel GA, Heinemann V, Sharma NK, Findlay MP, Ricke J, Peeters M, et al. SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 (plus or minus bevacizumab) versus mFOLFOX6 (plus or minus bevacizumab) plus selective internal radiation therapy in patients with metastatic colorectal cancer. J Clin Oncol. 2016;34:1723–31.

    PubMed  Google Scholar 

  64. Virdee PS, Moschandreas J, Gebski V, Love SB, Francis EA, Wasan HS, et al. Protocol for combined analysis of FOXFIRE, SIRFLOX, and FOXFIRE-global randomized phase III trials of chemotherapy +/- selective internal radiation therapy as first-line treatment for patients with metastatic colorectal cancer. JMIR Res Protoc. 2017;6:e43.

    PubMed  PubMed Central  Google Scholar 

  65. Wasan HS, Gibbs P, Sharma NK, Taieb J, Heinemann V, Ricke J, et al. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol. 2017;18:1159–71.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This paper was written as part of Konkuk University's research support program for its faculty on sabbatical leave in 2019.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Seoul Medical Center, 156 Sinnae-ro, Jungnang-gu, Seoul, South Korea

    Eun Jeong Lee

  2. Departments of Nuclear Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul, South Korea

    Hyun Woo Chung, Joon-Hyung Jo & Young So

Authors
  1. Eun Jeong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyun Woo Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joon-Hyung Jo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young So
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hyun Woo Chung.

Ethics declarations

Conflict of Interest

Eun Jeong Lee, Hyun Woo Chung, Joon Hyung Jo, and Young So declare that they have no conflicts of interest.

Ethical Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

Informed Consent

For this type of study, formal consent is not required and informed consent is not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, E.J., Chung, H.W., Jo, JH. et al. Radioembolization for the Treatment of Primary and Metastatic Liver Cancers. Nucl Med Mol Imaging 53, 367–373 (2019). https://doi.org/10.1007/s13139-019-00615-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13139-019-00615-9

Keywords

Search

Navigation