Current Hepatology Reports

, Volume 17, Issue 4, pp 399–411 | Cite as

Indications and Best Practices for Intra-arterial Therapies to Treat Hepatocellular Carcinoma

  • Michael Hsu
  • Muneeb Ahmed
  • Ammar SarwarEmail author
Hepatic Cancer (A Singal and A Mufti, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Hepatic Cancer


Purpose of Review

The purpose of this review is to re-evaluate the role of intra-arterial therapies for hepatocellular carcinoma (HCC) recommended by contemporary staging systems.

Recent Findings

Currently, intra-arterial therapies are recommended by the Barcelona Clinic Liver Cancer (BCLC) staging system only for patients with BCLC B HCC in the form of trans-arterial chemoembolization. Recently, randomized controlled trials in patients with BCLC C HCC without metastatic disease have suggested a potential role for trans-arterial radioembolization (TARE) with fewer adverse events and better quality of life compared to sorafenib. Randomized controlled trials have also demonstrated the benefit of using combination therapy of trans-arterial chemoembolization (TACE) with ablation for patients with BCLC A HCC [single tumors (3–7 cm)] compared to ablation alone. Finally, promising results from single-center studies indicate that TARE using a radiation segmentectomy technique may be a potentially curative therapy for tumors less than 3 cm, supporting its use in patients with BCLC A HCC that are not amenable to surgical or ablative therapies.


Recent randomized clinical trials have demonstrated the benefit of intra-arterial therapies in subpopulations of BCLC stages A, B, and C. These studies highlight the need for careful patient assessment, staging, and multidisciplinary discussion to consider treatments that are not currently included in guidelines but can improve patient outcomes for HCC.


Trans-arterial Chemoembolization Radioembolization Hepatocellular carcinoma 


Compliance with Ethical Standards

Conflict of Interest

Michael Hsu, Muneeb Ahmed, and Ammar Sarwar each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

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


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Wang H, Naghavi M, Allen C, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1459–544.Google Scholar
  2. 2.
    Petrick JL, Braunlin M, Laversanne M, Valery PC, Bray F, McGlynn KA. International trends in liver cancer incidence, overall and by histologic subtype, 1978–2007. Int J Cancer. 2016;139(7):1534–45.PubMedPubMedCentralGoogle Scholar
  3. 3.
    • Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38 This is the original description of BCLC classification, which is very helpful in stratifying patients with HCC by prognosis and optimal treatment modality.PubMedGoogle Scholar
  4. 4.
    Marrero JA, Kulik LM, Sirlin C, et al. Diagnosis, staging and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatol Baltim Md 2018;Google Scholar
  5. 5.
    Kim BK, Kim SU, Park JY, et al. Applicability of BCLC stage for prognostic stratification in comparison with other staging systems: single centre experience from long-term clinical outcomes of 1717 treatment-naïve patients with hepatocellular carcinoma. Liver Int. 2012;32(7):1120–7.PubMedGoogle Scholar
  6. 6.
    Marrero JA, Kudo M, Bronowicki J-P. The challenge of prognosis and staging for hepatocellular carcinoma. Oncologist. 2010;15(Suppl 4):23–33.PubMedGoogle Scholar
  7. 7.
    Sangiovanni A, Colombo M. Treatment of hepatocellular carcinoma: beyond international guidelines. Liver Int. 2016;36(S1):124–9.PubMedGoogle Scholar
  8. 8.
    Kalyan A, Kulik L. Multidisciplinary care in hepatocellular carcinoma: where do we go from here? Gastroenterology. 2017;152(8):1823–5.PubMedGoogle Scholar
  9. 9.
    • Serper M, Taddei TH, Mehta R, et al. Association of provider specialty and multidisciplinary care with hepatocellular carcinoma treatment and mortality. Gastroenterology. 2017;152(8):1954–64 This study highlights the value of multi-disciplinary care for HCC treatment.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Holliday EB, Allen PK, Elhalawani H, Abdel-Rahman O. Treatment at a high-volume centre is associated with improved survival among patients with non-metastatic hepatocellular carcinoma. Liver Int Off J Int Assoc Study Liver. 2018;38(4):665–75.Google Scholar
  11. 11.
    Song MJ. Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma. World J Gastroenterol WJG. 2015;21(13):3843–9.PubMedGoogle Scholar
  12. 12.
    Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–42.PubMedGoogle Scholar
  13. 13.
    Facciorusso A, Bellanti F, Villani R, et al. Transarterial chemoembolization vs bland embolization in hepatocellular carcinoma: a meta-analysis of randomized trials. United Eur Gastroenterol J. 2017;5(4):511–8.Google Scholar
  14. 14.
    Park J-W, Chen M, Colombo M, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015;35(9):2155–66.PubMedPubMedCentralGoogle Scholar
  15. 15.
    de Baere T, Arai Y, Lencioni R, et al. Treatment of liver tumors with lipiodol TACE: technical recommendations from experts opinion. Cardiovasc Intervent Radiol. 2016;39(3):334–43.PubMedGoogle Scholar
  16. 16.
    Ji SK, Cho YK, Ahn YS, et al. Multivariate analysis of the predictors of survival for patients with hepatocellular carcinoma undergoing transarterial chemoembolization: focusing on superselective chemoembolization. Korean J Radiol. 2008;9(6):534–40.PubMedPubMedCentralGoogle Scholar
  17. 17.
    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;115:616–23.PubMedGoogle Scholar
  18. 18.
    Gillmore R, Stuart S, Kirkwood A, et al. EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J Hepatol. 2011;55(6):1309–16.PubMedGoogle Scholar
  19. 19.
    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.PubMedPubMedCentralGoogle Scholar
  20. 20.
    • Johnson PJ, Berhane S, Kagebayashi C, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33:550–8 This study demonstrates the use of the ALBI grade to prognosticate patients with HCC.PubMedGoogle Scholar
  21. 21.
    Hickey R, Mouli S, Kulik L, et al. Independent analysis of albumin-bilirubin grade in a 765-patient cohort treated with transarterial locoregional therapy for hepatocellular carcinoma. J Vasc Interv Radiol. 2016;27:795–802.PubMedGoogle Scholar
  22. 22.
    Roayaie S. PALBI-an objective score based on platelets, albumin & bilirubin stratifies HCC patients undergoing resection & ablation better than child’s classification. 2015.Google Scholar
  23. 23.
    Liu PH, Hsu CY, Hsia CY, et al. ALBI and PALBI grade predict survival for HCC across treatment modalities and BCLC stages in the MELD Era. J Gastroenterol Hepatol. 2017;32:879–86.PubMedGoogle Scholar
  24. 24.
    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649–55.PubMedGoogle Scholar
  25. 25.
    Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatol Baltim Md. 2010;52(2):762–73.Google Scholar
  26. 26.
    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;359:1734–9.PubMedGoogle Scholar
  27. 27.
    Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–71.PubMedGoogle Scholar
  28. 28.
    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.PubMedGoogle Scholar
  29. 29.
    Lencioni R, de Baere T, Burrel M, et al. Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Interv Radiol. 2012;35:980–5.Google Scholar
  30. 30.
    • 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 Interv Radiol. 2010;33:41–52 This study is one of the seminal RCT of conventional vs. DEB TACE, which demonstrated no survival benefit of DEB-TACE compared to conventional TACE.Google Scholar
  31. 31.
    Golfieri R, Giampalma E, Renzulli M, et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014;111:255–64.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Facciorusso A, Di Maso M, Muscatiello N. Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma: a meta-analysis. Dig Liver Dis. 2016;48:571–7.PubMedGoogle Scholar
  33. 33.
    Lee KH, Liapi E, Vossen JA, et al. Distribution of iron oxide-containing embosphere particles after transcatheter arterial embolization in an animal model of liver cancer: evaluation with MR imaging and implication for therapy. J Vasc Interv Radiol. 2008;19:1490–6.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Dreher MR, Sharma KV, Woods DL, et al. Radiopaque drug-eluting beads for transcatheter embolotherapy: experimental study of drug penetration and coverage in swine. J Vasc Interv Radiol 2012;23:257–64 e4.Google Scholar
  35. 35.
    Malagari K, Pomoni M, Moschouris H, et al. Chemoembolization of hepatocellular carcinoma with HepaSphere 30-60 mum. Safety and efficacy study. Cardiovasc Interv Radiol. 2014;37:165–75.Google Scholar
  36. 36.
    Aliberti C, Carandina R, Lonardi S, et al. Transarterial chemoembolization with small drug-eluting beads in patients with hepatocellular carcinoma: experience from a cohort of 421 patients at an Italian center. J Vasc Interv Radiol. 2017;28:1495–502.PubMedGoogle Scholar
  37. 37.
    Kettenbach J, Stadler A, Katzler IV, et al. Drug-loaded microspheres for the treatment of liver cancer: review of current results. Cardiovasc Interv Radiol. 2008;31:468–76.Google Scholar
  38. 38.
    Aliberti C, Carandina R, Sarti D, et al. Chemoembolization adopting polyethylene glycol drug-eluting embolics loaded with doxorubicin for the treatment of hepatocellular carcinoma. AJR Am J Roentgenol. 2017;209:430–4.PubMedGoogle Scholar
  39. 39.
    Duan F, Wang EQ, Lam MG, et al. Superselective chemoembolization of HCC: comparison of short-term safety and efficacy between drug-eluting LC beads, quadraspheres, and conventional ethiodized oil emulsion. Radiology. 2016;278:612–21.PubMedGoogle Scholar
  40. 40.
    Levy EB, Krishnasamy VP, Lewis AL, et al. First human experience with directly image-able iodinated embolization microbeads. Cardiovasc Interv Radiol. 2016;39:1177–86.Google Scholar
  41. 41.
    Richter G, Radeleff B, Stroszczynski C, et al. Safety and feasibility of chemoembolization with doxorubicin-loaded small calibrated microspheres in patients with hepatocellular carcinoma: results of the MIRACLE I prospective multicenter study. Cardiovasc Interv Radiol. 2018;41:587–93.Google Scholar
  42. 42.
    Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: a systematic review of efficacy and safety data. Hepatology. 2016;64:106–16.PubMedGoogle Scholar
  43. 43.
    Sahara S, Kawai N, Sato M, et al. Prospective comparison of transcatheter arterial chemoembolization with lipiodol-epirubicin and lipiodol-cisplatin for treatment of recurrent hepatocellular carcinoma. Jpn J Radiol. 2010;28:362–8.PubMedGoogle Scholar
  44. 44.
    Ikeda M, Kudo M, Aikata H, et al. Transarterial chemoembolization with miriplatin vs. epirubicin for unresectable hepatocellular carcinoma: a phase III randomized trial. J Gastroenterol. 2018;53:281–90.PubMedGoogle Scholar
  45. 45.
    Kubota K, Hidaka H, Nakazawa T, et al. Prospective, randomized, controlled study of the efficacy of transcatheter arterial chemoembolization with miriplatin for hepatocellular carcinoma. Hepatol Res. 2018;48:E98–E106.PubMedGoogle Scholar
  46. 46.
    Shi M, Lu LG, Fang WQ, et al. Roles played by chemolipiodolization and embolization in chemoembolization for hepatocellular carcinoma: single-blind, randomized trial. J Natl Cancer Inst. 2013;105:59–68.PubMedGoogle Scholar
  47. 47.
    Liu B, Huang JW, Li Y, et al. Single-agent versus combination doxorubicin-based transarterial chemoembolization in the treatment of hepatocellular carcinoma: a single-blind, randomized, phase II trial. Oncology. 2015;89:23–30.PubMedGoogle Scholar
  48. 48.
    Gomes AS, Monteleone PA, Sayre JW, et al. Comparison of triple-drug transcatheter arterial chemoembolization (TACE) with single-drug TACE using doxorubicin-eluting beads: long-term survival in 313 patients. AJR Am J Roentgenol. 2017;209:722–32.PubMedGoogle Scholar
  49. 49.
    Sahara S, Kawai N, Sato M, et al. Prospective evaluation of transcatheter arterial chemoembolization (TACE) with multiple anti-cancer drugs (epirubicin, cisplatin, mitomycin c, 5-fluorouracil) compared with TACE with epirubicin for treatment of hepatocellular carcinoma. Cardiovasc Interv Radiol. 2012;35:1363–71.Google Scholar
  50. 50.
    Yang H, Seon J, Sung PS, et al. Dexamethasone prophylaxis to alleviate postembolization syndrome after transarterial chemoembolization for hepatocellular carcinoma: a randomized, double-blinded, placebo-controlled study. J Vasc Interv Radiol 2017;28:1503–1511 e2.PubMedGoogle Scholar
  51. 51.
    Ogasawara S, Chiba T, Ooka Y, et al. A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization. Hepatology. 2017.Google Scholar
  52. 52.
    Padia SA, Lewandowski RJ, Johnson GE, et al. Radioembolization of hepatic malignancies: background, quality improvement guidelines, and future directions. J Vasc Interv Radiol JVIR. 2017;28(1):1–15.PubMedGoogle Scholar
  53. 53.
    Srinivas SM, Nasr EC, Kunam VK, Bullen JA, Purysko AS. Administered activity and outcomes of glass versus resin 90Y microsphere radioembolization in patients with colorectal liver metastases. J Gastrointest Oncol. 2016;7(4):530–9.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Lau W-Y, Kennedy AS, Kim YH, et al. Patient selection and activity planning guide for selective internal radiotherapy with yttrium-90 resin microspheres. Int J Radiat Oncol Biol Phys. 2012;82(1):401–7.PubMedGoogle Scholar
  55. 55.
    Garin E, Lenoir L, Edeline J, et al. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept. Eur J Nucl Med Mol Imaging. 2013;40(7):1057–68.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Biederman DM, Titano JJ, Tabori NE, et al. Outcomes of radioembolization in the treatment of hepatocellular carcinoma with portal vein invasion: resin versus glass microspheres. J Vasc Interv Radiol. 2016;27(6):812–821.e2.PubMedGoogle Scholar
  57. 57.
    Van Der Gucht A, Jreige M, Denys A, et al. Resin versus glass microspheres for 90Y transarterial radioembolization: comparing survival in unresectable hepatocellular carcinoma using pretreatment partition model dosimetry. J Nucl Med Off Publ Soc Nucl Med. 2017;58(8):1334–40.Google Scholar
  58. 58.
    Kallini JR, Gabr A, Thorlund K, et al. Comparison of the adverse event profile of TheraSphere® with SIR-Spheres® for the treatment of unresectable hepatocellular carcinoma: a systematic review. Cardiovasc Intervent Radiol. 2017;40(7):1033–43.PubMedGoogle Scholar
  59. 59.
    Weinstein JL, Ahmed M. Percutaneous ablation for hepatocellular carcinoma. AJR Am J Roentgenol. 2018;210(6):1368–75.PubMedGoogle Scholar
  60. 60.
    •• Peng Z-W, Zhang Y-J, Liang H-H, Lin X-J, Guo R-P, Chen M-S. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. 2012;262(2):689–700 This RCT of TACE-ablate approach for 3–5 cm HCC demonstrated superior survival by using this approach.PubMedGoogle Scholar
  61. 61.
    Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K. Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer. 2010;116(23):5452–60.PubMedGoogle Scholar
  62. 62.
    •• Peng Z-W, Zhang Y-J, Chen M-S, et al. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(4):426–32 This RCT of TACE-ablate approach for 3–5 cm HCC demonstrated superior survival by using this approach.Google Scholar
  63. 63.
    Bruix J, Takayama T, Mazzaferro V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16(13):1344–54.PubMedGoogle Scholar
  64. 64.
    Liao M, Zhu Z, Wang H, Huang J. Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis. Scand J Gastroenterol. 2017;52:624–34.PubMedGoogle Scholar
  65. 65.
    Wang Z, Ren Z, Chen Y, et al. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study. Clin Cancer Res. 2018.Google Scholar
  66. 66.
    van Lienden KP, van den Esschert JW, de Graaf W, et al. Portal vein embolization before liver resection: a systematic review. Cardiovasc Intervent Radiol. 2013;36(1):25–34.PubMedGoogle Scholar
  67. 67.
    Lewandowski RJ, Donahue L, Chokechanachaisakul A, et al. (90) Y radiation lobectomy: outcomes following surgical resection in patients with hepatic tumors and small future liver remnant volumes. J Surg Oncol. 2016;114(1):99–105.PubMedGoogle Scholar
  68. 68.
    Riaz A, Gates VL, Atassi B, et al. Radiation segmentectomy: a novel approach to increase safety and efficacy of radioembolization. Int J Radiat Oncol Biol Phys. 2011;79(1):163–71.PubMedGoogle Scholar
  69. 69.
    Biederman DM, Titano JJ, Bishay VL, et al. Radiation segmentectomy versus TACE combined with microwave ablation for unresectable solitary hepatocellular carcinoma up to 3 cm: a propensity score matching study. Radiology. 2017;283(3):895–905.PubMedGoogle Scholar
  70. 70.
    Vouche M, Habib A, Ward TJ, et al. Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: multicenter radiology-pathology correlation and survival of radiation segmentectomy. Hepatol Baltim Md. 2014;60(1):192–201.Google Scholar
  71. 71.
    • Lewandowski RJ, Gabr A, Abouchaleh N, et al. Radiation segmentectomy: potential curative therapy for early hepatocellular carcinoma. Radiology. 2018;171768 This is a description of a new technique for TARE for small HCC that may be potentially curative.Google Scholar
  72. 72.
    Sofocleous CT, Boas FE. Radiation segmentectomy for hepatocellular carcinoma: ready for prime time? Radiology. 2018;180163.Google Scholar
  73. 73.
    Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatol Baltim Md. 2018;67(1):358–80.Google Scholar
  74. 74.
    Yin X, Zhang L, Wang YH, et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma. BMC Cancer. 2014;14:849.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Hirooka M, Hiraoka A, Ochi H, et al. Transcatheter arterial chemoembolization with or without radiofrequency ablation: outcomes in patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma. AJR Am J Roentgenol. 2018;210:891–8.PubMedGoogle Scholar
  76. 76.
    Fu Y, Zhao X, Yun Q, et al. Transarterial chemoembolization (TACE) plus percutaneous ethanol injection (PEI) for the treatment of unresectable hepatocellular carcinoma: a meta-analysis of randomized controlled trials. Int J Clin Exp Med. 2015;8:10388–400.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Erhardt A, Kolligs F, Dollinger M, et al. TACE plus sorafenib for the treatment of hepatocellular carcinoma: results of the multicenter, phase II SOCRATES trial. Cancer Chemother Pharmacol. 2014;74:947–54.PubMedGoogle Scholar
  78. 78.
    Chao Y, Chung YH, Han G, et al. The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: final results of the START trial. Int J Cancer. 2015;136:1458–67.PubMedGoogle Scholar
  79. 79.
    Pawlik TM, Reyes DK, Cosgrove D, Kamel IR, Bhagat N, Geschwind JF. Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol. 2011;29:3960–7.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Sansonno D, Lauletta G, Russi S, Conteduca V, Sansonno L, Dammacco F. Transarterial chemoembolization plus sorafenib: a sequential therapeutic scheme for HCV-related intermediate-stage hepatocellular carcinoma: a randomized clinical trial. Oncologist. 2012;17:359–66.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Kudo M, Imanaka K, Chida N, et al. Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer. 2011;47:2117–27.PubMedGoogle Scholar
  82. 82.
    Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol. 2016;64:1090–8.PubMedGoogle Scholar
  83. 83.
    Tong AKT, Kao YH, Too CW, Chin KFW, Ng DCE, Chow PKH. Yttrium-90 hepatic radioembolization: clinical review and current techniques in interventional radiology and personalized dosimetry. Br J Radiol. 2016;89(1062):20150943.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Pitton MB, Kloeckner R, Ruckes C, et al. Randomized comparison of selective internal radiotherapy (SIRT) versus drug-eluting bead transarterial chemoembolization (DEB-TACE) for the treatment of hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2015;38(2):352–60.PubMedGoogle Scholar
  85. 85.
    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.e2.PubMedGoogle Scholar
  86. 86.
    Zhang Y, Li Y, Ji H, Zhao X, Lu H. Transarterial Y90 radioembolization versus chemoembolization for patients with hepatocellular carcinoma: a meta-analysis. Biosci Trends. 2015;9(5):289–98.PubMedGoogle Scholar
  87. 87.
    Facciorusso A, Serviddio G, Muscatiello N. Transarterial radioembolization vs chemoembolization for hepatocarcinoma patients: a systematic review and meta-analysis. World J Hepatol. 2016;8(18):770–8.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedGoogle Scholar
  89. 89.
    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;10:25–34.PubMedGoogle Scholar
  90. 90.
    Sinn DH, Cho J-Y, Gwak G-Y, et al. Different survival of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma patients by the extent of portal vein invasion and the type of extrahepatic spread. PLoS One. 2015;10(4):e0124434.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Chung GE, Lee JH, Kim HY, et al. Transarterial chemoembolization can be safely performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival. Radiology. 2011;258:627–34.PubMedGoogle Scholar
  92. 92.
    Choi GH, Shim JH, Kim MJ, et al. Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: results of propensity score analyses. Radiology. 2013;269:603–11.PubMedGoogle Scholar
  93. 93.
    Zhang Y, Fan W, Wang Y, et al. Sorafenib with and without transarterial chemoembolization for advanced hepatocellular carcinoma with main portal vein tumor thrombosis: a retrospective analysis. Oncologist. 2015;20:1417–24.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Geschwind JF, Kudo M, Marrero JA, et al. TACE treatment in patients with sorafenib-treated unresectable hepatocellular carcinoma in clinical practice: final analysis of GIDEON. Radiology. 2016;279:630–40.PubMedGoogle Scholar
  95. 95.
    Finn RS, Zhu AX, Farah W, et al. Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: a systematic review and meta-analysis. Hepatology. 2018;67:422–35.PubMedGoogle Scholar
  96. 96.
    Huo YR, Eslick GD. Transcatheter arterial chemoembolization plus radiotherapy compared with chemoembolization alone for hepatocellular carcinoma: a systematic review and meta-analysis. JAMA Oncol. 2015;1:756–65.PubMedGoogle Scholar
  97. 97.
    Yoon SM, Ryoo BY, Lee SJ, et al. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial. JAMA Oncol. 2018.Google Scholar
  98. 98.
    •• Vilgrain V, Pereira H, Assenat E, 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(12):1624–36 Randomized controlled trial comparing sorafenib and TARE for BCLC-C patients demonstrating no difference in overall survival but reduced side effects with TARE (see text for discussion).PubMedGoogle Scholar
  99. 99.
    •• Chow PKH, Gandhi M, Tan S-B, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2018;JCO2017760892. Randomized controlled trial comparing sorafenib and TARE for BCLC-C patients demonstrating no difference in overall survival but reduced side effects with TARE (see text for discussion). Google Scholar
  100. 100.
    Hermann A-L, Dieudonné A, Maxime R, et al. PS-018 - role of 99mTc-macroaggregated albumin SPECT/CT based dosimetry in predicting survival and tumor response of patients with locally advanced and inoperable hepatocellular carcinoma (HCC) treated by selective intra-arterial radiation therapy (SIRT) with yttrium-90 resin microspheres, a cohort from SARAH study. J Hepatol. 2018;68:S13.Google Scholar
  101. 101.
    AbdelRazek M, Khalaf M, Abdelmaksoud M, et al. 3:27 PM abstract no. 124 MIRD-based activity calculation may improve outcomes over body surface area for resin microsphere radioembolization of metastatic colorectal carcinoma. J Vasc Interv Radiol. 2018;29(4):S56.Google Scholar
  102. 102.
    Kulik L, Heimbach JK, Zaiem F, et al. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: a systematic review and meta-analysis. Hepatology. 2018;67:381–400.PubMedGoogle Scholar
  103. 103.
    Parikh ND, Waljee AK, Singal AG. Downstaging hepatocellular carcinoma: a systematic review and pooled analysis. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2015;21(9):1142–52.Google Scholar
  104. 104.
    Otto G, Herber S, Heise M, et al. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl. 2006;12:1260–7.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Radiology, Division of Vascular and Interventional RadiologyBeth Israel Deaconess Medical Center/Harvard Medical SchoolBostonUSA

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