CardioVascular and Interventional Radiology

, Volume 35, Issue 5, pp 1119–1128 | Cite as

Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

  • Katerina Malagari
  • Mary Pomoni
  • Hippocrates Moschouris
  • Evanthia Bouma
  • John Koskinas
  • Aspasia Stefaniotou
  • Athanasios Marinis
  • Alexios Kelekis
  • Efthymia Alexopoulou
  • Achilles Chatziioannou
  • Katerina Chatzimichael
  • Spyridon Dourakis
  • Nikolaos Kelekis
  • Spyros Rizos
  • Dimitrios Kelekis
Clinical Investigation



The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand.

Materials and Methods

173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 ± 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 ± 2.1 cm. Lesion morphology was one dominant ≤5 cm (22 %), one dominant >5 cm (41.6 %), multifocal ≤5 (26 %), and multifocal >5 (10.4 %).


Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2–64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions ≤5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival.


DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.


Hepatocellular carcinoma Transarterial chemoembolization Drug-eluting beads Survival Doxorubicin loaded drug eluting beads Embolization in unresectable hepatocellular carcinoma 


  1. 1.
    Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35(5):1164–1171PubMedCrossRefGoogle Scholar
  2. 2.
    Llovet JM, Real MI, Montana X et al (2002) Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359(9319):1734–1739PubMedCrossRefGoogle Scholar
  3. 3.
    Lammer J, Malagari K, Vogl T et al (2010) 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 33(1):41–52PubMedCrossRefGoogle Scholar
  4. 4.
    Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46(3):474–481PubMedCrossRefGoogle Scholar
  5. 5.
    Poon RN, Tso WK, Pang RWC et al (2007) A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol 5(9):1100–1108PubMedCrossRefGoogle Scholar
  6. 6.
    Kettenbach J, Stadler A, Katzler I et al (2008) Drug-loaded microspheres for the treatment of liver cancer: review of current results. Cardiovasc Intervent Radiol 31(3):468–476PubMedCrossRefGoogle Scholar
  7. 7.
    Malagari K, Chatzimichael K, Alexopoulou E et al (2008) Transarterial chemoembolisation of unresectable hepatocellular carcinoma (HCC) with drug eluting beads (DEB)” Results of an open label study of 62 patients. Cardiovasc Intervent Radiol 31(2):269–280PubMedCrossRefGoogle Scholar
  8. 8.
    Malagari K, Alexopoulou E, Chatzimichail K et al (2008) Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC BeadTM. Abdom Imaging 33(5):512–519PubMedCrossRefGoogle Scholar
  9. 9.
    Reyes DK, Vossen JA, Kamel IR et al (2009) 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 15(6):526–532PubMedCrossRefGoogle Scholar
  10. 10.
    Poggi G, Quaretti P, Minoia C et al (2008) Transhepatic arterial chemoembolization with oxaliplatin-eluting microspheres (OEM-TACE) for unresectable hepatic tumors. Anticancer Res 28(6B):3835–3842PubMedGoogle Scholar
  11. 11.
    Biondi M, Fusco S, Lewis AL et al (2012) New insights into the mechanisms of the interactions between doxorubicin and the ion-exchange hydrogel DC Bead™ for use in transarterial chemoembolization (TACE). J Biomater Sci Polym Ed 23(1–4):333–354PubMedCrossRefGoogle Scholar
  12. 12.
    Malagari K, Pomoni M, Spyridopoulos TN et al (2011) Safety profile of sequential transcatheter chemoembolization with DC Bead(™): results of 237 hepatocellular carcinoma (HCC) patients. Cardiovasc Intervent Radiol 34(4):774–785PubMedCrossRefGoogle Scholar
  13. 13.
    National Cancer Institute (2003) Common Terminology Criteria for Adverse Events, version 3.0. National Cancer Institute, Bethesda, MarylandGoogle Scholar
  14. 14.
    Common Terminology Criteria for Adverse Events (CTCAE) v3.0 (2003) Notice of Modifications March 31, 2003–June 10, 2003Google Scholar
  15. 15.
    Bruix J, Sherman M, Llovet JM et al (2001) EASL panel of experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35(3):421–430PubMedCrossRefGoogle Scholar
  16. 16.
    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(1):6–25PubMedCrossRefGoogle Scholar
  17. 17.
    Vogl TJ, Naguib NN, Nour-Eldin NE et al (2009) Review on transarterial chemoembolization in hepatocellular carcinoma: palliative, combined, neoadjuvant, bridging, and symptomatic indications. Eur J Radiol 72(3):116–505Google Scholar
  18. 18.
    Bruix J, Llovet JM (2009) Major achievements in hepatocellular carcinoma. Lancet 373(9664):614–616PubMedCrossRefGoogle Scholar
  19. 19.
    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(3):212–220PubMedCrossRefGoogle Scholar
  20. 20.
    O’Suilleabhain CB, Poon RTP, Yong JL et al (2003) Factors predictive of 5-year survival after transarterial chemoembolization for inoperable hepatocellular carcinoma. Br J Surg 90(3):325–331PubMedCrossRefGoogle Scholar
  21. 21.
    Takayasu K, Arii S, Ikai I et al (2006) Liver Cancer Study Group of Japan. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8,510 patients. Gastroenterology 131(2):461–469PubMedCrossRefGoogle Scholar
  22. 22.
    Maeda S, Fujiyama S, Tanaka M et al (2002) Survival and local recurrence rates of hepatocellular carcinoma patients treated by transarterial chemolipiodolization with and without embolization. Hepatol Res 23(3):202–210PubMedCrossRefGoogle Scholar
  23. 23.
    Hayashi K, Ina H, Tezuka M et al (2007) Local therapeutic results of computed tomography-guided transcatheter arterial chemoembolization for hepatocellular carcinoma: results of 265 tumors in 79 patients. Cardiovasc Intervent Radiol 30(6):1144–1155PubMedCrossRefGoogle Scholar
  24. 24.
    Lencioni R, Cioni D, Crocetti L et al (2005) Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology 234(3):961–967PubMedCrossRefGoogle Scholar
  25. 25.
    Montorsi M, Santambrogio R, Bianchi P et al (2005) Survival and recurrences after hepatic resection or radiofrequency for hepatocellular carcinoma in cirrhotic patients: a multivariate analysis. J Gastrointest Surg 9(1):62–68PubMedCrossRefGoogle Scholar
  26. 26.
    Omata M, Tateishi R, Yoshida H et al (2004) Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: ethanol injection therapy and radiofrequency ablation. Gastroenterology 127(5 Suppl 1):159–166CrossRefGoogle Scholar
  27. 27.
    Lam VW, Ng KK, Chok KS et al (2008) Risk factors and prognostic factors of local recurrence after radiofrequency ablation of hepatocellular carcinoma. J Am Coll Surg 207(1):20–29PubMedCrossRefGoogle Scholar
  28. 28.
    Lee KH, Liapi E, Vossen JA et al (2008) 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 19(10):1490–1496PubMedCrossRefGoogle Scholar
  29. 29.
    Burrel M, Reig M, Forner A, et al. (2012) Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolization (TACE) using DC Beads. Implications for clinical practice and trial design. J Hepatol. doi:10.1016/j.jhep.2012.01.008
  30. 30.
    Lee JK, Chung YH, Song BC et al (2002) Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization. J Gastroenterol Hepatol 17(1):52–58PubMedCrossRefGoogle Scholar
  31. 31.
    Grieco A, Marcoccia S, Miele L et al (2003) Transarterial hemoembolisation (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival. Hepatogastroenterology 50(49):207–212PubMedGoogle Scholar
  32. 32.
    Memon K, Kulik L, Lewandowski RJ et al (2011) Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times. Gastroenterology 141(2):526–535PubMedCrossRefGoogle Scholar
  33. 33.
    Kwok PC, Lam TW, Chan SC et al (2000) A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma. J Hepatol 32(6):955–964PubMedCrossRefGoogle Scholar
  34. 34.
    Ernst O, Sergent G, Mizrahi D et al (1999) Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization: comparison of planned periodic chemoembolization and chemoembolization based on tumor response. AJR Am J Roentgenol 172(1):59–64PubMedGoogle Scholar
  35. 35.
    Herber SC, Otto G, Schneider J et al (2008) Transarterial chemoembolization in patients not eligible for liver transplantation: single-center results. AJR Am J Roentgenol 190(4):1035–1042PubMedCrossRefGoogle Scholar
  36. 36.
    Venook AP, Stagg RJ, Lewis BJ et al (1990) Chemoembolization for hepatocellular carcinoma. J Clin Oncol 8(6):1108–1114PubMedGoogle Scholar
  37. 37.
    Lencioni R, De Baere Th, Burrel M, et al. (2011) Transcatheter treatment of hepatocellular carcinoma with doxorubicin loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol. doi:10.1007/s00270-011-0287-7
  38. 38.
    Brown DB, Nikolic B, Covey AM et al (2012) Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy. J Vasc Interv Radiol 23:287–294PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2012

Authors and Affiliations

  • Katerina Malagari
    • 1
  • Mary Pomoni
    • 2
  • Hippocrates Moschouris
    • 3
  • Evanthia Bouma
    • 2
  • John Koskinas
    • 6
  • Aspasia Stefaniotou
    • 2
  • Athanasios Marinis
    • 4
  • Alexios Kelekis
    • 1
  • Efthymia Alexopoulou
    • 1
  • Achilles Chatziioannou
    • 5
  • Katerina Chatzimichael
    • 1
  • Spyridon Dourakis
    • 6
  • Nikolaos Kelekis
    • 1
  • Spyros Rizos
    • 4
  • Dimitrios Kelekis
    • 2
  1. 1.Second Department of RadiologyUniversity of AthensAthensGreece
  2. 2.Imaging and Research UnitUniversity of AthensAthensGreece
  3. 3.Department of RadiologyTzanion HospitalPireusGreece
  4. 4.Department of SurgeryTzanion HospitalPireusGreece
  5. 5.First Department of RadiologyUniversity of AthensAthensGreece
  6. 6.Department of Internal Medicine and HepatologyIppokration Hospital, University of AthensAthensGreece

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