Download PDF
Semin Liver Dis 2014; 34(04): 435-443
DOI: 10.1055/s-0034-1394142
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Transarterial Chemoembolization and Radioembolization

Bruno Sangro
1   Liver Unit, Clinica Universidad de Navarra and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Pamplona, Spain
,
Riad Salem
2   Department of Vascular and Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois
› Author Affiliations
Further Information

Publication History

Publication Date:
04 November 2014 (online)

    Permissions and Reprints

Abstract

Transarterial chemoembolization (TACE) and radioembolization (RE) are frequently used to treat patients with hepatocellular carcinoma who cannot receive curative therapies. Transarterial chemoembolization is a heterogeneous group of procedures; based on two positive clinical trials and three meta-analyses, conventional TACE is the standard of care for patients in the intermediate stage. Transarterial chemoembolization with drug-eluting beads has been recently introduced as a more standardized way of performing TACE with similar outcomes and less systemic effects. Radioembolization is a form of brachytherapy in which microspheres are used as a source of internal radiation. Evidence supporting the use of RE derives from consistent, large-cohort series involving patients with more advanced hepatocellular carcinoma, not suitable for TACE or for those who have failed TACE. Transarterial chemoembolization and RE should not be considered competing therapies, but rather complementary tools. The clinical indications for TACE and RE will be further refined as results of ongoing large-scale studies become available.

Keywords

transarterial chemoembolization - drug-eluting bead transarterial chemoembolization - yttrium - selective internal radiation therapy - radioembolization
 

  • References

  • 1 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61 (2) 69-90
    CrossrefPubMedGoogle Scholar
  • 2 Bruix J, Sherman M ; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005; 42 (5) 1208-1236
    CrossrefPubMedGoogle Scholar
  • 3 European Association for the Study of the Liver ; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56 (4) 908
    CrossrefPubMedGoogle Scholar
  • 4 Villanueva A, Hernandez-Gea V, Llovet JM. Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nat Rev Gastroenterol Hepatol 2013; 10 (1) 34-42
    PubMedGoogle Scholar
  • 5 Solomon B, Soulen MC, Baum RA, Haskal ZJ, Shlansky-Goldberg RD, Cope C. 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) 793-798
    CrossrefPubMedGoogle Scholar
  • 6 Kan Z, McCuskey PA, Wright KC, Wallace S. Role of Kupffer cells in iodized oil embolization. Invest Radiol 1994; 29 (11) 990-993
    CrossrefPubMedGoogle Scholar
  • 7 Bilbao JI, de Luis E, García de Jalón JA , et al. Comparative study of four different spherical embolic particles in an animal model: a morphologic and histologic evaluation. J Vasc Interv Radiol 2008; 19 (11) 1625-1638
    CrossrefPubMedGoogle Scholar
  • 8 Chang JM, Tzeng WS, Pan HB, Yang CF, Lai KH. Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study. Cancer 1994; 74 (9) 2449-2453
    CrossrefPubMedGoogle Scholar
  • 9 Kawai S, Okamura J, Ogawa M , et al; The Cooperative Study Group for Liver Cancer Treatment of Japan. Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma—a comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). Cancer Chemother Pharmacol 1992; 31 (Suppl): S1-S6
    CrossrefPubMedGoogle Scholar
  • 10 Cammà C, Schepis F, Orlando A , et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002; 224 (1) 47-54
    CrossrefPubMedGoogle Scholar
  • 11 Marelli L, Stigliano R, Triantos C , et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 2007; 30 (1) 6-25
    CrossrefPubMedGoogle Scholar
  • 12 Raoul JL, Sangro B, Forner A , et al. Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev 2011; 37 (3) 212-220
    CrossrefPubMedGoogle Scholar
  • 13 Llovet JM, Real MI, Montaña X , et al; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002; 359 (9319) 1734-1739
    CrossrefPubMedGoogle Scholar
  • 14 Lo CM, Ngan H, Tso WK , et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002; 35 (5) 1164-1171
    CrossrefPubMedGoogle Scholar
  • 15 Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003; 37 (2) 429
    CrossrefPubMedGoogle Scholar
  • 16 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) 955-965
    CrossrefPubMedGoogle Scholar
  • 17 Meyer T, Kirkwood A, Roughton M , et al. A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma. Br J Cancer 2013; 108 (6) 1252-1259
    CrossrefPubMedGoogle Scholar
  • 18 Lammer J, Malagari K, Vogl T , et al; PRECISION V Investigators. 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
  • 19 Sieghart W, Hucke F, Pinter M , et al. The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology 2013; 57 (6) 2261-2273
    CrossrefPubMedGoogle Scholar
  • 20 Malagari K, Pomoni M, Moschouris H , et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc Intervent Radiol 2012; 35 (5) 1119-1128
    CrossrefPubMedGoogle Scholar
  • 21 Burrel M, Reig M, Forner A , et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads. Implications for clinical practice and trial design. J Hepatol 2012; 56 (6) 1330-1335
    CrossrefPubMedGoogle Scholar
  • 22 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
  • 23 Mazzaferro V, Sposito C, Bhoori S , et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 2013; 57 (5) 1826-1837
    CrossrefPubMedGoogle Scholar
  • 24 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) 1741-1749
    CrossrefPubMedGoogle Scholar
  • 25 Sangro B, Carpanese L, Cianni R , et al; 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 2011; 54 (3) 868-878
    CrossrefPubMedGoogle Scholar
  • 26 Takayasu K, Arii S, Ikai I , et al; Liver Cancer Study Group of Japan. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006; 131 (2) 461-469
    CrossrefPubMedGoogle Scholar
  • 27 O'Suilleabhain CB, Poon RTP, Yong JL, Ooi GC, Tso WK, Fan ST. Factors predictive of 5-year survival after transarterial chemoembolization for inoperable hepatocellular carcinoma. Br J Surg 2003; 90 (3) 325-331
    CrossrefPubMedGoogle Scholar
  • 28 Poon RT, Ngan H, Lo CM, Liu CL, Fan ST, Wong J. Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence. J Surg Oncol 2000; 73 (2) 109-114
    CrossrefPubMedGoogle Scholar
  • 29 Katyal S, Oliver JH, Peterson MS, Chang PJ, Baron RL, Carr BI. Prognostic significance of arterial phase CT for prediction of response to transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma: a retrospective analysis. AJR Am J Roentgenol 2000; 175 (6) 1665-1672
    CrossrefPubMedGoogle Scholar
  • 30 Bronowicki JP, Vetter D, Dumas F , et al. Transcatheter oily chemoembolization for hepatocellular carcinoma. A 4-year study of 127 French patients. Cancer 1994; 74 (1) 16-24
    CrossrefPubMedGoogle Scholar
  • 31 Herber SCA, Otto G, Schneider J , et al. Transarterial chemoembolization in patients not eligible for liver transplantation: single-center results. AJR Am J Roentgenol 2008; 190 (4) 1035-1042
    CrossrefPubMedGoogle Scholar
  • 32 Lladó L, Virgili J, Figueras J , et al. A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer 2000; 88 (1) 50-57
    CrossrefPubMedGoogle Scholar
  • 33 Wang J-H, Changchien C-S, Hu T-H , et al. The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma - Survival analysis of 3892 patients. Eur J Cancer 2008; 44 (7) 1000-1006
    CrossrefPubMedGoogle Scholar
  • 34 Hsu K-F, Chu C-H, Chan D-C , et al. Superselective transarterial chemoembolization vs hepatic resection for resectable early-stage hepatocellular carcinoma in patients with Child-Pugh class a liver function. Eur J Radiol 2012; 81 (3) 466-471
    CrossrefPubMedGoogle Scholar
  • 35 Chen C-H, Hu F-C, Huang G-T , et al. Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method—analysis of 2010 Taiwanese patients. Eur J Cancer 2009; 45 (9) 1630
    CrossrefPubMedGoogle Scholar
  • 36 Ho M-C, Huang G-T, Tsang Y-M , et al. Liver resection improves the survival of patients with multiple hepatocellular carcinomas. Ann Surg Oncol 2009; 16 (4) 848-855
    CrossrefPubMedGoogle Scholar
  • 37 Moreno-Luna LE, Yang JD, Sanchez W , et al. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol 2013; 36 (3) 714-723
    CrossrefPubMedGoogle Scholar
  • 38 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
    CrossrefPubMedGoogle Scholar
  • 39 Jung ES, Kim JH, Yoon EL , et al. Comparison of the methods for tumor response assessment in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. J Hepatol 2013; 58 (6) 1181-1187
    PubMedGoogle Scholar
  • 40 Luo J, Guo R-P, Lai ECH , et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol 2011; 18 (2) 413-420
    CrossrefPubMedGoogle Scholar
  • 41 Chung GE, Lee J-H, 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 (2) 627-634
    CrossrefPubMedGoogle Scholar
  • 42 Iñarrairaegui M, Thurston KG, Bilbao JI , et al. Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 2010; 21 (8) 1205-1212
    CrossrefPubMedGoogle Scholar
  • 43 Huo T-I, Wu J-C, Lee P-C, Chang F-Y, Lee S-D. Incidence and risk factors for acute renal failure in patients with hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective study. Liver Int 2004; 24 (3) 210-215
    CrossrefPubMedGoogle Scholar
  • 44 Kim KM, Kim JH, Park IS , et al. Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion. J Gastroenterol Hepatol 2009; 24 (5) 806-814
    CrossrefPubMedGoogle Scholar
  • 45 Chung JW, Park JH, Han JK , et al. Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology 1996; 198 (1) 33-40
    CrossrefPubMedGoogle Scholar
  • 46 Pietrosi G, Miraglia R, Luca A , et al. Arterial chemoembolization/embolization and early complications after hepatocellular carcinoma treatment: a safe standardized protocol in selected patients with Child class A and B cirrhosis. J Vasc Interv Radiol 2009; 20 (7) 896-902
    CrossrefPubMedGoogle Scholar
  • 47 Yu J-S, Kim KW, Jeong M-G, Lee DH, Park M-S, Yoon S-W. Predisposing factors of bile duct injury after transcatheter arterial chemoembolization (TACE) for hepatic malignancy. Cardiovasc Intervent Radiol 2002; 25 (4) 270-274
    CrossrefPubMedGoogle Scholar
  • 48 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) 407-412
    CrossrefPubMedGoogle Scholar
  • 49 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) 323-326
    CrossrefPubMedGoogle Scholar
  • 50 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) 474-481
    CrossrefPubMedGoogle Scholar
  • 51 Lencioni R, de Baere T, Burrel M , et al. Transcatheter treatment of hepatocellular carcinoma with doxorubicin-loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 2012; 35 (5) 980-985
    CrossrefPubMedGoogle Scholar
  • 52 Grosso M, Vignali C, Quaretti P , et al. Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: preliminary results from an Italian multicentre study. Cardiovasc Intervent Radiol 2008; 31 (6) 1141-1149
    CrossrefPubMedGoogle Scholar
  • 53 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) 541-551
    CrossrefPubMedGoogle Scholar
  • 54 Malagari K, Pomoni M, Spyridopoulos TN , et al. Safety profile of sequential transcatheter chemoembolization with DC Bead™: results of 237 hepatocellular carcinoma (HCC) patients. Cardiovasc Intervent Radiol 2011; 34 (4) 774-785
    CrossrefPubMedGoogle Scholar
  • 55 Vogl TJ, Lammer J, Lencioni R , et al. Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial. AJR Am J Roentgenol 2011; 197 (4) W562-70
    PubMedGoogle Scholar
  • 56 Kennedy A, Coldwell D, Sangro B, Wasan H, Salem R. Radioembolization for the treatment of liver tumors general principles. Am J Clin Oncol 2012; 35 (1) 91-99
    CrossrefPubMedGoogle Scholar
  • 57 Kulik LM, Carr BI, Mulcahy MF , et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology 2008; 47 (1) 71-81
    CrossrefPubMedGoogle Scholar
  • 58 Salem R, Gilbertsen M, Butt Z , et al. Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol 2013; 11 (10) 1358-1365 , e1
    CrossrefPubMedGoogle Scholar
  • 59 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) 1920-1928
    CrossrefPubMedGoogle Scholar
  • 60 Llovet JM, Ricci S, Mazzaferro V , et al; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359 (4) 378-390
    CrossrefPubMedGoogle Scholar
  • 61 Cheng A-L, Kang Y-K, 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
  • 62 Bilbao JI, de Martino A, de Luis E , et al. Biocompatibility, inflammatory response, and recannalization characteristics of nonradioactive resin microspheres: histological findings. Cardiovasc Intervent Radiol 2009; 32 (4) 727-736
    CrossrefPubMedGoogle Scholar
  • 63 Memon K, Kulik L, Lewandowski RJ , et al. Radioembolization for hepatocellular carcinoma with portal vein thrombosis: impact of liver function on systemic treatment options at disease progression. J Hepatol 2013; 58 (1) 73-80
    CrossrefPubMedGoogle Scholar
  • 64 Bruix J, Raoul J-L, Sherman M , et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 2012; 57 (4) 821-829
    CrossrefPubMedGoogle Scholar
  • 65 Bolondi L, Burroughs A, Dufour J-F , et al. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis 2012; 32 (4) 348-359
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Salem R, Mazzaferro V, Sangro B. Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives. Hepatology 2013; 58 (6) 2188-2197
    CrossrefPubMedGoogle Scholar
  • 67 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) 1185-1193
    CrossrefPubMedGoogle Scholar
  • 68 Gaba RC, Lewandowski RJ, Kulik LM , et al. Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization. Ann Surg Oncol 2009; 16 (6) 1587-159
    CrossrefPubMedGoogle Scholar
  • 69 Iñarrairaegui M, Pardo F, Bilbao JI , 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 (7) 594-601
    CrossrefPubMedGoogle Scholar
  • 70 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 (3) 337-341
    CrossrefPubMedGoogle Scholar
  • 71 Leung TW, Lau WY, Ho SK , 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 (4) 919-924
    CrossrefPubMedGoogle Scholar
  • 72 Carr BI. Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl 2004; 10 (2) (Suppl. 01) S107-S110
    CrossrefPubMedGoogle Scholar
  • 73 Carretero C, Munoz-Navas M, Betes M , et al. Gastroduodenal injury after radioembolization of hepatic tumors. Am J Gastroenterol 2007; 102 (6) 1216-1220
    CrossrefPubMedGoogle Scholar
  • 74 Geschwind J-FH, Salem R, Carr BI , et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology 2004; 127 (5) (Suppl. 01) S194-S205
    CrossrefPubMedGoogle Scholar
  • 75 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) 1627-1639
    CrossrefPubMedGoogle Scholar
  • 76 Woodall CE, Scoggins CR, Ellis SF , et al. Is selective internal radioembolization safe and effective for patients with inoperable hepatocellular carcinoma and venous thrombosis?. J Am Coll Surg 2009; 208 (3) 375-382
    CrossrefPubMedGoogle Scholar
  • 77 Gil-Alzugaray B, Chopitea A, Iñarrairaegui M , et al. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology 2013; 57 (3) 1078-1087
    CrossrefPubMedGoogle Scholar