Chemoembolization and Radioembolization in the Treatment of Primary Liver Cancers

  • Khairuddin Memon
  • Ahsun Riaz
  • Robert J. Lewandowski
  • Riad Salem
Reference work entry


The incidence of hepatocellular carcinoma is increasing worldwide. Chemoembolization and radioembolization represent two novel transarterial therapies which are primarily based on a similar basic concept of the direct delivery of toxic material to the tumor via the hepatic artery and its branches. This concept exploits the fact that normal hepatic parenchyma derives its blood supply primarily from portal vein, whereas hepatic tumors are hypervascular relying primarily on hepatic arterial blood. Chemoembolization involves the delivery of a combination of chemotherapeutic drugs directly to the vessel feeding the tumor. Another variety of this technique involves drug-eluting beads which are microspheres loaded with the chemotherapeutic drug. Radioembolization involves the delivery of micron-sized radioactive particles to the tumor. While both therapies seem similar upfront, there are distinct differences in the indications, patient selection, technique, patient monitoring, and complications. These therapies have led to an encouraging response in terms of tumor necrosis, progression-free and overall survival, quality of life, and incidence of complications; they are therefore gaining wide acceptance for treating appropriately selected patients with hepatocellular carcinoma.


Orthotopic Liver Transplantation Intrahepatic Cholangiocarcinoma Milan Criterion Locoregional Therapy Conventional Tace 


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127(5 Suppl 1):S5–16.CrossRefPubMedGoogle Scholar
  3. 3.
    Yao FY, Bass NM, Nikolai B, et al. A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy. Liver Transpl. 2003;9(7):684–92.CrossRefPubMedGoogle Scholar
  4. 4.
    Maddala YK, Stadheim L, Andrews JC, et al. Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization. Liver Transpl. 2004;10(3):449–55.CrossRefPubMedGoogle Scholar
  5. 5.
    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.CrossRefPubMedGoogle Scholar
  6. 6.
    Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34.CrossRefPubMedGoogle Scholar
  7. 7.
    Lewandowski RJ, Mulcahy MF, Kulik LM, et al. Chemoembolization for hepatocellular carcinoma: comprehensive imaging and survival analysis in a 172-patient cohort. Radiology. 2010;255(3):955–65.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140(2):497–507. e492.CrossRefPubMedGoogle Scholar
  9. 9.
    Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138(1):52–64.CrossRefPubMedGoogle Scholar
  10. 10.
    Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of Doxorubicin-Eluting-Bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010;33(1):41–52.CrossRefPubMedGoogle Scholar
  11. 11.
    Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35(5):1164–71.CrossRefPubMedGoogle Scholar
  13. 13.
    Liu DM, Salem R, Bui JT, et al. Angiographic considerations in patients undergoing liver-directed therapy. J Vasc Interv Radiol. 2005;16(7):911–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Lewandowski RJ, Sato KT, Atassi B, et al. Radioembolization with (90)y microspheres: angiographic and technical considerations. Cardiovasc Inter Rad. 2007;30(4):571–92.CrossRefGoogle Scholar
  15. 15.
    Salem R, Lewandowski RJ, Sato KT, et al. Technical aspects of radioembolization with 90Y microspheres. Tech Vasc Interv Radiol. 2007;10(1):12–29.CrossRefPubMedGoogle Scholar
  16. 16.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–36.CrossRefPubMedGoogle Scholar
  17. 17.
    Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35(3):421–430.CrossRefPubMedGoogle Scholar
  18. 18.
    Riaz A, Ryu RK, Kulik LM, et al. Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol. 2009;27(34):5734–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100(10):698–711.CrossRefPubMedGoogle Scholar
  20. 20.
    Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429–42.CrossRefPubMedGoogle Scholar
  22. 22.
    Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9(8):1920–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Chapman WC, Majella Doyle MB, Stuart JE, et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation. Ann Surg. 2008;248(4):617–25.PubMedGoogle Scholar
  24. 24.
    Ensminger W. Hepatic arterial chemotherapy for primary and metastatic liver cancers. Cancer Chemother Pharmacol. 1989;23(Suppl):S68–73.CrossRefPubMedGoogle Scholar
  25. 25.
    Eksborg S, Cedermark BJ, Strandler HS. Intrahepatic and intravenous administration of adriamycin–a comparative pharmacokinetic study in patients with malignant liver tumours. Med Oncol Tumor Pharmacother. 1985;2(1):47–54.PubMedGoogle Scholar
  26. 26.
    Solomon B, Soulen MC, Baum RA, Haskal ZJ, Shlansky-Goldberg RD, Cope C, et al. Chemoembolization of hepatocellular carcinoma with cisplatin, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol: prospective evaluation of response and survival in a U.S. population. J Vasc Interv Radiol. 1999;10(6):793–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Soulen MC. Chemoembolization of hepatic malignancies. Oncology (Williston Park). 1994;8(4):77–84; discussion 84, 89–90 passim.PubMedGoogle Scholar
  28. 28.
    Coldwell DM, Stokes KR, Yakes WF. Embolotherapy: agents, clinical applications, and techniques. Radiographics. 1994;14(3):623–43. quiz 645–26.CrossRefPubMedGoogle Scholar
  29. 29.
    Takayasu K, Arii S, Ikai I, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131(2):461–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Kiefer MV, Albert M, McNally M, et al. Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol. Cancer. 2011;117(7):1498–505.CrossRefPubMedGoogle Scholar
  31. 31.
    Murakami T, Ishimaru H, Sakamoto I, et al. Percutaneous radiofrequency ablation and transcatheter arterial chemoembolization for hypervascular hepatocellular carcinoma: rate and risk factors for local recurrence. Cardiovasc Intervent Radiol. 2007;30(4):696–704.CrossRefPubMedGoogle Scholar
  32. 32.
    Kagawa T, Koizumi J, Kojima S, et al. Transcatheter arterial chemoembolization plus radiofrequency ablation therapy for early stage hepatocellular carcinoma: comparison with surgical resection. Cancer. 2010;116(15):3638–44.CrossRefPubMedGoogle Scholar
  33. 33.
    Heckman JT, Devera MB, Marsh JW, et al. Bridging locoregional therapy for hepatocellular carcinoma prior to liver transplantation. Ann Surg Oncol. 2008;15(11):3169–77.CrossRefPubMedGoogle Scholar
  34. 34.
    Bartolozzi C, Lencioni R, Caramella D, et al. Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization. Radiology. 1995;197(3):812–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Xia J, Ren Z, Ye S, et al. Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. Eur J Radiol. 2006;59(3):407–12.CrossRefPubMedGoogle Scholar
  36. 36.
    Kim HK, Chung YH, Song BC, et al. Ischemic bile duct injury as a serious complication after transarterial chemoembolization in patients with hepatocellular carcinoma. J Clin Gastroenterol. 2001;32(5):423–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Belli L, Magistretti G, Puricelli GP, Damiani G, Colombo E, Cornalba GP. Arteritis following intra-arterial chemotherapy for liver tumors. Eur Radiol. 1997;7(3):323–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Lencioni R, Crocetti L, Petruzzi P, et al. Doxorubicin-eluting bead-enhanced radiofrequency ablation of hepatocellular carcinoma: a pilot clinical study. J Hepatol. 2008;49(2):217–22.CrossRefPubMedGoogle Scholar
  39. 39.
    Constantin M, Fundueanu G, Bortolotti F, Cortesi R, Ascenzi P, Menegatti E. Preparation and characterisation of poly(vinyl alcohol)/cyclodextrin microspheres as matrix for inclusion and separation of drugs. Int J Pharm. 2004;285(1–2):87–96.CrossRefPubMedGoogle Scholar
  40. 40.
    Gonzalez MV, Tang Y, Phillips GJ, et al. Doxorubicin eluting beads-2: methods for evaluating drug elution and in-vitro:in-vivo correlation. J Mater Sci Mater Med. 2008;19(2):767–75.CrossRefPubMedGoogle Scholar
  41. 41.
    Dhanasekaran RM. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocellular carcinoma (HCC). J Surg Oncol. 2010;101(6):476–80.PubMedGoogle Scholar
  42. 42.
    Taylor RR, Tang Y, Gonzalez MV, Stratford PW, Lewis AL. Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo evaluation of drug release properties. Eur J Pharm Sci. 2007;30(1):7–14.CrossRefPubMedGoogle Scholar
  43. 43.
    Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007;46(3):474–81.CrossRefPubMedGoogle Scholar
  44. 44.
    Reyes DK, Vossen JA, Kamel IR, et al. Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J. 2009;15(6):526–32.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Malagari K, Pomoni M, Kelekis A, et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2010;33(3):541–51.CrossRefPubMedGoogle Scholar
  46. 46.
    Ingold JA, Reed GB, Kaplan HS, Bagshaw MA. Radiation hepatitis. Am J Roentgenol Radium Ther Nucl Med. 1965;93:200–8.PubMedGoogle Scholar
  47. 47.
    Geschwind JF, Salem R, Carr BI, et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S194–205.CrossRefPubMedGoogle Scholar
  48. 48.
    Covey AM, Brody LA, Maluccio MA, Getrajdman GI, Brown KT. Variant hepatic arterial anatomy revisited: digital subtraction angiography performed in 600 patients. Radiology. 2002;224(2):542–7.CrossRefPubMedGoogle Scholar
  49. 49.
    TheraSphere Yttrium-90 microspheres package insert. Kanata, Canada: MDS Nordion; 2004.Google Scholar
  50. 50.
    Salem R, Thurston KG, Carr BI, Goin JE, Geschwind JF. Yttrium-90 microspheres: radiation therapy for unresectable liver cancer. J Vasc Interv Radiol. 2002;13(9 Pt 2):S223–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Kulik LM, Atassi B, van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere(R)) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol. 2006;94(7):572–86.CrossRefPubMedGoogle Scholar
  52. 52.
    Kulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of (90)Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2007;47(1):71–81.CrossRefGoogle Scholar
  53. 53.
    Hilgard P, Hamami M, Fouly AE, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52(5):1741–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Sangro B, Carpanese L, Cianni R, et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011;54(3):868–78.CrossRefPubMedGoogle Scholar
  55. 55.
    Ibrahim SM, Nikolaidis P, Miller FH, et al. Radiologic findings following Y90 radioembolization for primary liver malignancies. Abdom Imaging. 2009;34(5):566–81.CrossRefPubMedGoogle Scholar
  56. 56.
    Saxena A, Bester L, Chua TC, Chu FC, Morris DL. Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol. 2010;17(2):484–91.CrossRefPubMedGoogle Scholar
  57. 57.
    Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol. 2005;16(12):1627–39.CrossRefPubMedGoogle Scholar
  58. 58.
    Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys. 2006;65(2):412–25.CrossRefPubMedGoogle Scholar
  59. 59.
    Murthy R, Xiong H, Nunez R, et al. Yttrium 90 resin microspheres for the treatment of unresectable colorectal hepatic metastases after failure of multiple chemotherapy regimens: preliminary results. J Vasc Interv Radiol. 2005;16(7):937–45.CrossRefPubMedGoogle Scholar
  60. 60.
    Sangro B, Gil-Alzugaray B, Rodriguez J, et al. Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer. 2008;112(7):1538–46.CrossRefPubMedGoogle Scholar
  61. 61.
    Young JY, Rhee TK, Atassi B, et al. Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma. J Vasc Interv Radiol. 2007;18(11):1375–82.CrossRefPubMedGoogle Scholar
  62. 62.
    Jakobs TF, Saleem S, Atassi B, et al. Fibrosis, portal hypertension, and hepatic volume changes induced by intra-arterial radiotherapy with (90)yttrium microspheres. Dig Dis Sci. 2008;53(9):2556–63.CrossRefPubMedGoogle Scholar
  63. 63.
    Rhee TK, Naik NK, Deng J, et al. Tumor response after yttrium-90 radioembolization for hepatocellular carcinoma: comparison of diffusion-weighted functional MR imaging with anatomic MR imaging. J Vasc Interv Radiol. 2008;19(8):1180–6.CrossRefPubMedGoogle Scholar
  64. 64.
    Murthy R, Brown DB, Salem R, et al. Gastrointestinal complications associated with hepatic arterial yttrium-90 microsphere therapy. J Vasc Interv Radiol. 2007;18(4):553–61. quiz 562.CrossRefPubMedGoogle Scholar
  65. 65.
    Carretero C, Munoz-Navas M, Betes M, et al. Gastroduodenal injury after radioembolization of hepatic tumors. Am J Gastroenterol. 2007;102(6):1216–20.CrossRefPubMedGoogle Scholar
  66. 66.
    Murthy R, Eng C, Krishnan S, et al. Hepatic yttrium-90 radioembolotherapy in metastatic colorectal cancer treated with cetuximab or bevacizumab. J Vasc Interv Radiol. 2007;18(12):1588–91.CrossRefPubMedGoogle Scholar
  67. 67.
    WHO. WHO handbook for reporting results of cancer treatment. Geneva: WHO Offset Publication; 1979. No.48.Google Scholar
  68. 68.
    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.CrossRefGoogle Scholar
  69. 69.
    Forner A, Ayuso C, Varela M, et al. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable? Cancer. 2009;115(3):616–23.CrossRefPubMedGoogle Scholar
  70. 70.
    Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60.CrossRefPubMedGoogle Scholar
  71. 71.
    Riaz A, Miller FH, Kulik LM, et al. Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma. JAMA. 2010;303(11):1062–9.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Riaz A, Lewandowski RJ, Kulik L, et al. Radiologic-pathologic correlation of hepatocellular carcinoma treated with chemoembolization. Cardiovasc Intervent Radiol. 2010;33(6):1143–52.CrossRefPubMedGoogle Scholar
  73. 73.
    Riaz A, Kulik L, Lewandowski RJ, et al. Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres. Hepatology. 2009;49(4):1185–93.CrossRefPubMedGoogle Scholar
  74. 74.
    Riaz A, Memon K, Miller FH, et al. Role of the EASL, RECIST, and WHO response guidelines alone or in combination for hepatocellular carcinoma: radiologic–pathologic correlation. J Hepatol. 2011;54(4):695–704.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Khairuddin Memon
    • 1
  • Ahsun Riaz
    • 2
  • Robert J. Lewandowski
    • 2
  • Riad Salem
    • 2
  1. 1.Department of RadiologyNorthwestern Memorial HospitalChicagoUSA
  2. 2.Department of RadiologyNorthwestern UniversityChicagoUSA

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