Results in Hepatocellular Carcinoma

  • Mercedes Iñarrairaegui
  • Bruno Sangro
Part of the Medical Radiology book series (MEDRAD)


In the last years, new locoregional and systemic therapies have been developed for the management of hepatocellular carcinoma. Among the novel therapeutic procedures, yttrium-90 radioembolization has produced encouraging results across the whole spectrum of HCC, from early to advanced stages. All the evidence that support the use of radioembolization in HCC is based on retrospective series or non-controlled prospective studies, However, reliable data can be obtained from the literature, particularly since the recent publication of large series accounting for nearly 700 patients. Radioembolization achieves intense tumor response in targeted lesions and produces average disease control rates above 80 %. This effect supports its use for the treatment of early tumors with a curative intent, as a bridge to liver transplantation, and for unresectable HCC who exceed the transplant criteria or are not suitable for liver resection, with a downstaging intention. When compared to the standard of care for the intermediate and advanced stages (transarterial embolization and sorafenib), radioembolization consistently provides similar survival rates. It can be considered as a treatment option for those patients who are not considered good candidates for or have failed to transarterial embolization. It can also be a true alternative to sorafenib for the treatment of advanced tumors without extrahepatic metastases. The toxicity profile of radioembolization is favorable. Rarely, complications may result from irradiation of nontarget tissues including the liver and liver toxicity is the most challenging adverse event in HCC patients arising in a cirrhotic liver.


National Comprehensive Cancer Network Portal Vein Thrombosis Liver Toxicity Barcelona Clinic Liver Cancer Locoregional Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ben-Josef E, Normolle D, Ensminger WD et al (2005) Phase II trial of highdose conformal radiation therapy with concurrent hepatic artery floxu-ridine for unresectable intrahepatic malignancies. J Clin Oncol 23:8739–8747PubMedCrossRefGoogle Scholar
  2. Benson AB, Abrams TA, Ben-Josef E (2009) NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw 7:350–391PubMedGoogle Scholar
  3. Bilbao JI, de Martino A, de Luis E et al (2009) Biocompatibility, inflammatory response, and recannalization characteristics of nonradioactive resin microspheres: histological findings. Cardiovasc Intervent Radiol 32:727–736Google Scholar
  4. Bolondi L, Piscaglia F (2013) Yttrium 90 radioembolization: the horizon is changing for patients with intermediate and advanced hepatocellular carcinoma Hepatology. doi: 10.1002/hep.26154
  5. Bosch FX, Ribes J, Diaz M et al (2004) Primary liver cancer: wroldwide incidence and trends. Gastroenterology 127:S5–S16PubMedCrossRefGoogle Scholar
  6. Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022PubMedCentralPubMedCrossRefGoogle Scholar
  7. Bruix J, Raoul JL, Sherman M et al (2012) Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 57:821–829PubMedCrossRefGoogle Scholar
  8. Brunello F, Veltri A, Carucci P et al (2008) Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: a randomized controlled trial. Scand J Gastroenterol 43:727–735PubMedCrossRefGoogle Scholar
  9. Burrel M, Reig M, Forner A (2012) Surivial of patients with hepatocelllular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads. Implications for clinical practice and trial design. J Hepatol 56:1330–1335PubMedCrossRefGoogle Scholar
  10. Cammà C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224:47–54PubMedCrossRefGoogle Scholar
  11. Carr BI (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
  12. Carr BI, Kondragunta V, Buch SC et al (2010) Therapeutic equivalence in survival for hepatic arterial chemoembolization and yttrium-90 microsphere treatments in unresectable hepatocellular carcinoma: a twocohort study. Cancer 116:1305–1314PubMedCentralPubMedCrossRefGoogle Scholar
  13. Chen CH, Hu FC, Huang GT et al (2009) Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method analysis of 2010 Taiwanese patients. Eur J Cancer 45:1630–1639PubMedCrossRefGoogle Scholar
  14. Cheng AL, Kang YK, Chen Z et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomized, double-blind, placebo-controlled trial. Lancet Oncol 10:25–34Google Scholar
  15. Dancey JE, Shepherd FA, Paul K et al (2000) Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres. J Nucl Med 41:1673–1681PubMedGoogle Scholar
  16. Dawson LA, McGinn CJ, Normolle D et al (2000) Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies. J Clin Oncol 18:2210–2218PubMedGoogle Scholar
  17. European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943Google Scholar
  18. Fernandez-Ros N, Silva N, Bilbao JI et al (2013) Partial liver volume radioembolization induces hypertrophy in the spared lobe without inducing major signs of portal hypertension. HPB doi:10.1111/hpb.12095Google Scholar
  19. Furuse J, Ishii H, Nagase M et al (2005) Adverse hepatic events caused by radiotherapy for advanced hepatocellular carcinoma. J Gastroenterol Hepatol 20:1512–1518PubMedCrossRefGoogle Scholar
  20. Gaba RC, Lewandowski RJ, Kulik LM et al (2009) Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization. Ann Surg Oncol 16:1587–1596PubMedCrossRefGoogle Scholar
  21. Garin E, Lenoir L, Rolland Y et al (2012) Dosimetry based on 99mTc-Macroaggregated albumin SPECT/CT accurately predicts tumor response and survival in hepatocellular carcinomapatietns treated with 90Y-loaded glass microspheres: preliminary results. J Nucl Med 53:255–263PubMedCrossRefGoogle Scholar
  22. Geschwind JF, Salem R, Carr BI et al (2004) Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology127(Suppl 1):S194–S205Google Scholar
  23. Gil-Alzugaray B, Chopitea A, Iñarrairaegui M et al (2012) Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology. doi:  10.1002/hep.26191
  24. Golfieri R, Cappelli A, Cucchetti A et al (2011) Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5 cm) hepatocellular carcinomas. Hepatology 53:1580–1589PubMedCrossRefGoogle Scholar
  25. Heckman JT, Devera MB, Marsh JW et al (2008) Bridging locoregional therapy for hepatocellular carcinoma prior to liver transplantation. Ann Surg Oncol 15:3169–3177PubMedCrossRefGoogle Scholar
  26. 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 52:1741–1749PubMedCrossRefGoogle Scholar
  27. Ho MC, Huang GT, Tsang YM et al (2009) Liver resection improves survival of patients with multiple hepatocellular carcinomas. Ann Surg Oncol 16:848–855PubMedCrossRefGoogle Scholar
  28. Hsu KF, Chu CH, Chan DC et al (2011) Superselective transarterial chemoembolization vs hepatic resection for resectable early-stage hepatocellular carcinoma in patients with Child-Pugh class a liver function. Eur J Radiol 81:466–471PubMedCrossRefGoogle Scholar
  29. Iñarrairaegui M, Thurston KG, Bilbao JI et al (2010a) Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 21:1205–1212PubMedCrossRefGoogle Scholar
  30. Iñarrairaegui M, Martinez-Cuesta A, Rodríguez M et al (2010b) Analysis of prognostic factors after yttrium-90 radioembolization of advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 77:1441–1448PubMedCrossRefGoogle Scholar
  31. Iñarrairaegui M, Pardo F, Bilbao JI (2012) 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 38:594–601PubMedCrossRefGoogle Scholar
  32. 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 53:2556–2563PubMedCrossRefGoogle Scholar
  33. Jelic S, Sotiropoulos GC; ESMO Guidelines Working Group (2010) Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(suppl 5):59–64Google Scholar
  34. Kennedy A, Nag S, Salem R et al (2007) Recommendations for radioembolization of hepatic malignancies using yttrium-90 micorsphere brachiterapy: a consensus panel report from the radioembolization brachyterapy oncology conssortium. Int J Radiat Oncol Biol Ohys 68:13–23CrossRefGoogle Scholar
  35. Kooby DA, Egnatashvili V, Srinivasan S et al (2010) Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol 21:224–230PubMedCrossRefGoogle Scholar
  36. 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 94:572–586PubMedCrossRefGoogle Scholar
  37. 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 47:71–81PubMedCrossRefGoogle Scholar
  38. Kulik L (2010) Is radioembolization ready for the barcelona clinic liver cancer staging system? Hepatology 52:1528–1530PubMedCrossRefGoogle Scholar
  39. Lance C, Mc Lennan G, Obuchowski N et al (2011) Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma. J Vasc Interv Radiol 22:1697–1705Google Scholar
  40. Lau W, Leung W, Ho S, Leung NW et al (1994) Treatment of hepatocellular carcinoma with intra-hepatic arterial yttrium-90 microspheres: a phase I and II study. Br J Cancer 70:994–999PubMedCentralPubMedCrossRefGoogle Scholar
  41. Lau W, Ho S, Leung T et al (1998) Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90_yttrium microspheres. Int J Radiat Oncol Biol Phys 40:583–592PubMedCrossRefGoogle Scholar
  42. Lau W-Y, Kennedy AS, Kim YH et al (2012) Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys 82:401–407PubMedCrossRefGoogle Scholar
  43. Lawrence TS, Robertson JM, Anscher MS et al (1995) Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 31:1237–1248PubMedCrossRefGoogle Scholar
  44. Lencioni RA, Allgaier HP, Cioni D et al (2003) Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228:235–240PubMedCrossRefGoogle Scholar
  45. Lewandowski RJ, Kulik LM, Riaz A et al (2009) A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant 9:1920–1928PubMedCrossRefGoogle Scholar
  46. Lewandowski RJ, Mulcahy MF, Kulik LM et al (2010) Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort. Radiology 255:955–965PubMedCentralPubMedCrossRefGoogle Scholar
  47. Lin SM, Lin CJ, Lin CC et al (2004) Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma Bor _4 cm. Gastroenterology 127:1714–1723PubMedCrossRefGoogle Scholar
  48. Lin SM, Lin CJ, Lin CC et al (2005) Randomized controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 54:1151–1156PubMedCentralPubMedCrossRefGoogle Scholar
  49. Llovet JM, Real MI, Montaña X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359:1734–1739PubMedCrossRefGoogle Scholar
  50. Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171PubMedCrossRefGoogle Scholar
  51. Marelli L, Stigliano R, Triantos C et al (2007) Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 30:6–25PubMedCrossRefGoogle Scholar
  52. Mazzaferro V, Sposito C, Bhoori S et al (2013) Yttrium90 radioembolization for intermediate-advanced hepatocarcinoma: a phase II study. Hepatology. doi: 10.1002/hep.26014
  53. McGinn CJ, Ten Haken RK, Ensminger WD et al (1998) Treatment of intrahepatic cancers with radiation doses based on a normal tissue complication probability model. J Clin Oncol 16:2246–2252PubMedGoogle Scholar
  54. Memon K, Kulik K, Lewandowski J et al (2011) Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times. Gastroenterology 141:526–535PubMedCentralPubMedCrossRefGoogle Scholar
  55. Moreno-Luna LE, Yang JD, Sanchez W et al (2012) Efficacy and Safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol 24 (epub ahead of print)Google Scholar
  56. Mornex F, Girard N, Beziat C et al (2006) Feasibility and efficacy of high-dose three-dimensional-conformal radiotherapy in cirrhotic patients with small-size hepatocellular carcinoma non-eligible for curative therapies—mature results of the French phase II RTF-1 trial. Int J Radiat Oncol Biol Phys 66:1152–1158PubMedCrossRefGoogle Scholar
  57. Nosher J, Ohman-Strickland PA, Jabbour S et al (2011) Changes in liver and spleen volumes and liver function after radioembolization with yttrium-90 resin microspheres. Vasc Interv Radiol 22:1706–1713Google Scholar
  58. Raoul JL, Sangro B, Forner A et al (2011) Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev 37:212–220PubMedCrossRefGoogle Scholar
  59. Riaz A, Kulik L, Lewandowski RJ et al (2009) Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium- 90 microspheres. Hepatology 49:1185–1193PubMedCrossRefGoogle Scholar
  60. Riaz A, Miller F, Kulik L et al (2010a) Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma. JAMA 303:1062–1069PubMedCentralPubMedCrossRefGoogle Scholar
  61. Riaz A, Lewandowski RJ, Kulik L et al (2010b) Radiologic-pathologic correlation of hepatocellular carcinoma treated with chemoembolization. Cardiovasc Intervent Radiol 33:1143–1152PubMedCentralPubMedCrossRefGoogle Scholar
  62. Riaz A, Gates VL, Atassi B et al (2011) Radiation segmentectomy: a novel approach to increase safety and efficacy of radioembolization. Int J Radiat Oncol Biol Phys 79:163–171PubMedCrossRefGoogle Scholar
  63. Robertson JM, McGinn CJ, Walker S et al (1997) A phase I trial of hepatic arterial bromodeoxyuridine and conformal radiation therapy for patients with primary hepatobiliary cancers or colorectal liver metastases. Int J Radiat Oncol Biol Phys 39:1087–1092PubMedCrossRefGoogle Scholar
  64. Salem R, Lewandowski RJ, 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 16:1627–1639PubMedCrossRefGoogle Scholar
  65. Salem R, Lewandowski RJ, Mulcahy MF et al (2010) Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 138:52–64PubMedCrossRefGoogle Scholar
  66. 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 140:497–507PubMedCentralPubMedCrossRefGoogle Scholar
  67. 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 66:792–780Google Scholar
  68. Sangro B, Gil-Alzugaray B, Rodriguez J et al (2008) Liver disease induced by radioembolization of liver tumors. Cancer 112:1538–1546PubMedCrossRefGoogle Scholar
  69. Sangro B, Carpanese L, Cianni R (2011) On behalf of the European network on radioembolization with Yttrium-90 resin microspheres (ENRY). Survival after Yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology 54:868–878PubMedCrossRefGoogle Scholar
  70. 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 29:522–529PubMedCrossRefGoogle Scholar
  71. Sherman M (2010) The resurrection of alphafetoprotein. Hepatology 52:939–940CrossRefGoogle Scholar
  72. Shiina S, Teratani T, Obi S et al (2005) A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 129:122–130PubMedCrossRefGoogle Scholar
  73. Uchino K, Tateishi R, Shiina S et al (2011) Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors. Cancer 117:4475–4483PubMedCrossRefGoogle Scholar
  74. Wang JH, Chang chien CS, Hu TH et al (2008) The efficacy of treatment schedules according to Barcelona clinic liver cancer staging for hepatocellular carcinoma—survival analysis of 3892 patients. Eur J Cancer 44:1000–1006Google Scholar
  75. Woodall CE, Scoggins CR, Ellis SF et al (2009) Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis? J Am Coll Surg 208:375–382PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Liver UnitClinica Universidad de NavarraPamplonaSpain
  2. 2.Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD)PamplonaSpain

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