Yttrium-90 Radioembolotherapy for Hepatocellular Cancer

  • Ravi Murthy
  • Pritesh Mutha
  • Sanjay Gupta


Hepatocellular carcinoma (HCC) accounts for between 85 and 90% of primary liver cancers. Over a million cases of hepatocellular cancer occur annually making it the fifth most common cancer worldwide and the third most common cause of cancer mortality. In the United States, the incidence of HCC has steadily increased over the past two decades, with an estimated 21,370 new cases having occurred in 2008 [1]. HCC-related mortality has increased in parallel with 18,410 estimated deaths during the same time period [1]. In addition, the incidence of HCC in patients with both known risks such as hepatitis C and unknown risk factors is increasing [2].


Hepatocellular cancer Yttrium-90 


  1. 1.
    Jemal A, Siegel R, Ward E et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96CrossRefPubMedGoogle Scholar
  2. 2.
    El-Serag HB (2007) Epidemiology of hepatocellular carcinoma in USA. Hepatol Res 37(Suppl 2):S88–S94Google Scholar
  3. 3.
    Mazzaferro V, Regalia E, Doci R et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699CrossRefPubMedGoogle Scholar
  4. 4.
    Dawson LA (2005) Hepatic arterial yttrium 90 microspheres: another treatment option for hepatocellular carcinoma. J Vasc Interv Radiol 16:161–164PubMedGoogle Scholar
  5. 5.
    Kloop CT, Alford TC, Bateman J, Berry GN, Winship T (1950) Fractionated Intraarterial cancer; chemotherapy with methyl bis amine hydrochloride; a preliminary report. Ann Surg 132:811–832CrossRefGoogle Scholar
  6. 6.
    Muller JH, Rossier PH (1951) A new method for the treatment of cancer of the lung by means of artificial radioactivity. Act Radiol 35:449–468CrossRefGoogle Scholar
  7. 7.
    Pochin EE CG, Cunningham RM, Hollman A, Hudswell F, Payne BR (1954) Localization of colloidal gold in the lungs. Proceedings of the Radioisotope Conference 1:30Google Scholar
  8. 8.
    Ya PM, Guzman T, Loken MK, Perry JF Jr (1961) Isotope localization with tagged microspheres. Surgery 49:644–650PubMedGoogle Scholar
  9. 9.
    Kim YS LaFave JW, MacLean LD (1962) The use of radiating microspheres in the treatment of experimental and human malignancy. Surgery 52:220–231Google Scholar
  10. 10.
    Blanchard RJ, Grotenhuis I, LaFave JW et al (1964) Treatment of experimental tumors: Utilization of radioactive microspheres. Arch Surg 89:406–410PubMedGoogle Scholar
  11. 11.
    Blanchard RJ, LaFave JW, Kim YS et al (1964) Treatment of patients with advanced cancer utilizing Y90 microspheres. Cancer 18:375–380CrossRefGoogle Scholar
  12. 12.
    Ariel I, Pack G (1967) Treatment of inoperable cancer of the liver by intra-arterial radioactive isotopes and chemotherapy. Cancer 20:793–804CrossRefPubMedGoogle Scholar
  13. 13.
    Grady E (1979) Internal radiation therapy of hepatic cancer. Dis Colon Rectum 22:371–375CrossRefPubMedGoogle Scholar
  14. 14.
    Mantravadi R, Spigos D, Tan W, Felix E (1982) Intraarterial yttrium 90 in the treatment of hepatic malignancy. Radiology 142:783–786PubMedGoogle Scholar
  15. 15.
    Wollner I, Knutsen C, Smith P et al (1988) Effects of hepatic arterial yttrium 90 glass microspheres in dogs. Cancer 61:1336–1344CrossRefPubMedGoogle Scholar
  16. 16.
    Yan ZP, Lin G, Zhao HY, Dong YH (1993) Yttrium-90 glass microspheres injected via the portal vein. An experimental study. Acta Radiol 34:395–398PubMedGoogle Scholar
  17. 17.
    Yan ZP, Lin G, Zhao HY, Dong YH (1993) An experimental study and clinical pilot trials on yttrium-90 glass microspheres through the hepatic artery for treatment of primary liver cancer. Cancer 72:3210–3215CrossRefPubMedGoogle Scholar
  18. 18.
    Shen S, DeNardo GL, Yuan A, DeNardo DA, DeNardo SJ (1994) Planar gamma camera imaging and quantitation of yttrium-90 bremsstrahlung. J Nucl Med 35:1381–1389PubMedGoogle Scholar
  19. 19.
    Shen S, DeNardo GL, DeNardo SJ (1994) Quantitative bremsstrahlung imaging of yttrium-90 using a Wiener filter. Med Phys 21:1409–1417CrossRefPubMedGoogle Scholar
  20. 20.
    Stabin MG, Eckerman KF, Ryman JC, Williams LE (1994) Bremsstrahlung radiation dose in yttrium-90 therapy applications. J Nucl Med 35:1377–1380PubMedGoogle Scholar
  21. 21.
    Shepherd F, Rotstein L, Houle S, Yip T, Paul K, Sniderman K (1992) A phase I dose escalation trial of yttrium-90 microspheres in the treatment of primary hepatocellular carcinoma. Cancer 70:2250–2254CrossRefPubMedGoogle Scholar
  22. 22.
    Andrews J, Walker S, Ackermann R, Cotton L, Ensminger W, Shapiro B (1994) Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up. J Nucl Med 35:1637–1644PubMedGoogle Scholar
  23. 23.
    Murthy R, Nunez R, Szklaruk J et al (2005) Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications. Radiographics 25(Suppl 1):S41–S55Google Scholar
  24. 24.
    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 68:13–23CrossRefPubMedGoogle Scholar
  25. 25.
    Liu DM, Salem R, Bui JT et al (2005) Angiographic considerations in patients undergoing liver-directed therapy. J Vasc Interv Radiol 16:911–935PubMedGoogle Scholar
  26. 26.
    Murthy R, Brown DB, Salem R et al (2007) Gastrointestinal complications associated with hepatic arterial Yttrium-90 microsphere therapy. J Vasc Interv Radiol 18:553–561; quiz 562Google Scholar
  27. 27.
    Sato K, Lewandowski RJ, Bui JT et al (2006) Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization. Cardiovasc Intervent Radiol 29:522–529CrossRefPubMedGoogle Scholar
  28. 28.
    Murthy R, Xiong H, Nunez R, et al (2005) Yttrium 90 resin microspheres for the treatment of unresectable colorectal hepatic metastases after failure of multiple chemotherapy regimens: preliminary results. J Vasc Interv Radiol 16:937–945PubMedGoogle Scholar
  29. 29.
    Leung T, Lau W, Ho S et al (1995) Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors. Int J Radiat Oncol Biol Phys 33:919–924CrossRefPubMedGoogle Scholar
  30. 30.
    Salem R, Parikh P, Atassi B et al (2008) Incidence of radiation pneumonitis after hepatic intra-arterial radiotherapy with yttrium-90 microspheres assuming uniform lung distribution. Am J Clin Oncol 31:431–438CrossRefPubMedGoogle Scholar
  31. 31.
    Murthy R, Kennedy A, Line B, Lund G, Stainken B, Van Echo D (2002) Augmentation of hepatopulmonary shunting following trans-arterial hepatic brachytherapy (TAHB) with yttrium 90 25micron spheres: therasphere – Therapeutic implications. Radiology 225:307Google Scholar
  32. 32.
    Kamel IR, Reyes DK, Liapi E, Bluemke DA, Geschwind JF (2007) Functional MR imaging assessment of tumor response after 90Y microsphere treatment in patients with unresectable hepatocellular carcinoma. J Vasc Interv Radiol 18:49–56CrossRefPubMedGoogle Scholar
  33. 33.
    Keppke AL, Salem R, Reddy D et al (2007) Imaging of hepatocellular carcinoma after treatment with yttrium-90 microspheres. AJR Am J Roentgenol 188:768–775CrossRefPubMedGoogle Scholar
  34. 34.
    Salem R, Lewandowski R, Atassi B et al (2005) Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 16:1627–1639PubMedGoogle Scholar
  35. 35.
    Kennedy A, Nutting C, Coldwell D, Gaiser J, Drachenberg C (2004) Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers. Int J Radiat Oncol Biol Phys 60:1552–1563CrossRefPubMedGoogle Scholar
  36. 36.
    Riaz A, Kulik L, Lewandowski RJ et al (2009) Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres. Hepatology 49:1185–1193CrossRefPubMedGoogle Scholar
  37. 37.
    Goin J, Dancey JE, Roberts C et al (2004) Comparison of post-embolization syndrome in the treatment of patients with unresectable hepatocellular carcinoma: Trans-catheter arterial chemo-embolization versus yttrium-90 glass microspheres. World J Nucl Med 3:49–56Google Scholar
  38. 38.
    Gulec SA, Mesoloras G, Dezarn WA, McNeillie P, Kennedy AS (2007) Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: The tumor selectivity of the treatment as a function of tumor to liver flow ratio. J Transl Med 5:15CrossRefPubMedGoogle Scholar
  39. 39.
    Young JY, Rhee TK, Atassi B et al (2007) Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma. J Vasc Interv Radiol 18:1375–1382CrossRefPubMedGoogle Scholar
  40. 40.
    Goin J, Salem R, Carr B et al (2005) Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol 16:205–213PubMedGoogle Scholar
  41. 41.
    Carr B (2004) Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl 10:S107–S110Google Scholar
  42. 42.
    Atassi B, Bangash AK, Lewandowski RJ et al (2008) Biliary sequelae following radioembolization with Yttrium-90 microspheres. J Vasc Interv Radiol 19:691–697CrossRefPubMedGoogle Scholar
  43. 43.
    Ng SS, Yu SC, Lai PB, Lau WY (2008) Biliary complications associated with selective internal radiation (SIR) therapy for unresectable liver malignancies. Dig Dis Sci 53:2813–2817CrossRefPubMedGoogle Scholar
  44. 44.
    Dancey J, Shepherd F, Paul K et al (2000) Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres. J Nucl Med 41:1673–1681PubMedGoogle Scholar
  45. 45.
    Lau W, Leung W, Ho S et al (1994) Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study. Br J Cancer 70:994–999PubMedGoogle Scholar
  46. 46.
    Lau W, Ho S, Leung W, Chan M, Lee W, Johnson P (2001) What determines survival duration in hepatocellular carcinoma treated with intraarterial Yttrium-90 microspheres? Hepatogastroenterology 48:338–340PubMedGoogle Scholar
  47. 47.
    Geschwind J, Salem R, Carr B et al (2004) Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology 127:S194–S205Google Scholar
  48. 48.
    Liu MD, Uaje MB, Al-Ghazi MS et al (2004) Use of yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma. Am Surg 70:947–953PubMedGoogle Scholar
  49. 49.
    Salem R, Lewandowski R, Roberts C et al (2004) Use of yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis. J Vasc Interv Radiol 15:335–345PubMedGoogle Scholar
  50. 50.
    Kulik LM, Carr BI, Mulcahy MF et al (2008) Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology 47:71–81CrossRefPubMedGoogle Scholar
  51. 51.
    Sangro B, Bilbao JI, Boan J et al (2006) Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 66:792–800CrossRefPubMedGoogle Scholar
  52. 52.
    Ertle J, Antoch G, Hamami M, Bockisch A, Ferken G, Hilgard P (2008) Radioembolization with therasphere yttrium-90 glass microspheres for advanced hepatocellular carcinoma: a European pilot phase II study. Presented at the Second Annual Meeting of the International Liver Cancer Association, Chicago, IL, September 2008, O-035Google Scholar
  53. 53.
    Romito R, Mazzaferro V, Spreafico C et al (2008) Intra-hepatic arterial radioembolization with 90Y-glass microspheres for hepatocellular carcinoma with macrovascular invasion: preliminary results. Presented at the Second Annual Meeting of the International Liver Cancer Association (ILCA), Chicago, IL, September 2008, p 142Google Scholar
  54. 54.
    Iñarrairaegui M, Thurston KG, Martinez-Cuesta A et al (2008) Radioembolization of hepatocellular carcinoma in patients presenting with portal vein occlusion: a safety analysis. Presented at the Second Annual Meeting of the International Liver Cancer Association (ILCA), Chicago, IL, September 2008, p 140Google Scholar
  55. 55.
    D’Avola DD, Iñarrairaegui M, Bilbao JI et al (2008) Extended survival in patients with unresectable advanced hepatocellular carcinoma treated using radioembolization. Presented at the Second Annual Meeting of the International Liver Cancer Association (ILCA), Chicago, IL, September 2008, p 139Google Scholar
  56. 56.
    Carpanese LPG, Vallati G et al (2008) Selective internal radiation therapy 90Y (SIRT) in multifocal HCC: clinical preliminary results in one year follow-up. World Conference on Interventional Oncology 2008, Poster P69Google Scholar
  57. 57.
    Rhee T, Omary R, Gates V et al (2005) The effect of catheter-directed CT angiography on yttrium-90 radioembolization treatment of hepatocellular carcinoma. J Vasc Interv Radiol 16:1085–1091PubMedGoogle Scholar
  58. 58.
    Kulik LM, Atassi B, van Holsbeeck L et al (2006) Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol 94:572–586CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ravi Murthy
    • 1
  • Pritesh Mutha
    • 1
  • Sanjay Gupta
    • 1
  1. 1.Section of Interventional Radiology, Division of Diagnostic ImagingThe University of Texas MD Anderson Cancer CenterHoustonUSA

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