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Long Term Survival Analysis in a Cohort of 125 Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using Small Drug Eluting Beads

CardioVascular and Interventional Radiology volume 45, pages 54–61 (2022)Cite this article

Abstract

Purpose

Different types of drug-eluting beads have been proposed for hepatocellular carcinoma (HCC) treatment, but long-term results are not well known. We report safety, efficacy and long-term overall survival of HCC patients not amenable of curative therapies treated with transcatheter arterial chemoembolization (TACE) using drug-eluting beads sized 70–150 micron.

Materials and Methods

This single-center retrospective study included 125 patients with Barcelona Clinic Liver Cancer stage A (80), B (45) and compensated cirrhosis. TACE was executed injecting drug-elutings microparticles loaded with 75 mg of Doxorubicine and was repeated in patients with partial response or stable disease after one month. Adverse events, response according to modified Response Evaluation Criteria in Solid Tumors and overall survival were assessed.

Results

Chemoembolization with 70–150 micron beads revealed an objective response rate of 88% according to mRECIST criteria and complete response was 60%. After a median follow-up of 53.3 months, overall survival was 36.6 months. Data were censored at the date of liver transplantation in 35 patients. 33 on 125 patients (26,4%) experienced at least one adverse event. We recorded a total of 102 adverse events and 18 were of a high grade (G3–G4). 30 day mortality was 0%.

Conclusion

Chemoembolization with very small particles (70–150 µm) is an effective and safe treatment in unresectable HCC both as a primary therapy or as bridge to transplantation.

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References

  1. Corrigendum to ‘EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma’ [J Hepatol 69 (2018) 182–236],” J. Hepatol., 2019;70:(4). https://doi.org/10.1016/j.jhep.2019.01.020.

  2. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003. https://doi.org/10.1053/jhep.2003.50047.

    Article  PubMed  Google Scholar 

  3. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011. https://doi.org/10.1002/hep.24199.

    Article  PubMed  Google Scholar 

  4. Llovet JM, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002. https://doi.org/10.1016/S0140-6736(02)08649-X.

    Article  PubMed  Google Scholar 

  5. Facciorusso A. Drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma: current state of the art. World J Gastroenterology. 2018. https://doi.org/10.3748/wjg.v24.i2.161.

    Article  Google Scholar 

  6. Varela M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007. https://doi.org/10.1016/j.jhep.2006.10.020.

    Article  PubMed  Google Scholar 

  7. Vogl TJ, 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. Am J Roentgenol. 2011. https://doi.org/10.2214/AJR.10.4379.

    Article  Google Scholar 

  8. Reyes DK, 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. https://doi.org/10.1097/PPO.0b013e3181c5214b.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lo CM, et al. Randomized controlled trial of transarterial Lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002. https://doi.org/10.1053/jhep.2002.33156.

    Article  PubMed  Google Scholar 

  10. Padia SA, et al. Safety and efficacy of drug-eluting bead chemoembolization for hepatocellular carcinoma: comparison of small-versus medium-size particles. J Vasc Interv Radiol. 2013. https://doi.org/10.1016/j.jvir.2012.11.023.

    Article  PubMed  Google Scholar 

  11. Prajapati HJ, et al. Survival, efficacy, and safety of small versus large doxorubicin drug-eluting beads TACE chemoembolization in patients with unresectable HCC. Am J Roentgenol. 2014. https://doi.org/10.2214/AJR.13.12308.

    Article  Google Scholar 

  12. Malagari K, et al. Chemoembolization of hepatocellular carcinoma with hepasphere 30–60 μm. Safety and efficacy study. Cardiovasc Interv Radiol. 2014. https://doi.org/10.1007/s00270-013-0777-x.

    Article  Google Scholar 

  13. Richter G, 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(4):587–93. https://doi.org/10.1007/s00270-017-1839-2.

    Article  Google Scholar 

  14. Aliberti C, 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. https://doi.org/10.1016/j.jvir.2017.07.020.

    Article  PubMed  Google Scholar 

  15. Llovet JM, et al. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012. https://doi.org/10.1016/j.jhep.2011.12.001.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Oken MM, Creech RH, Davis TE. Toxicology and response criteria of the eastern cooperative oncology group. Am J Clin Oncol Cancer Clin Trials. 1982. https://doi.org/10.1097/00000421-198212000-00014.

    Article  Google Scholar 

  17. National Institute of Health, “National Cancer Institute Common Terminology Criteria for Adverse Events ( CTCAE ) version 5.0,” NIH Publication, 2017.

  18. Lencioni R, Llovet JM. Modified recist (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010. https://doi.org/10.1055/s-0030-1247132.

    Article  PubMed  Google Scholar 

  19. Kim BK, et al. Complete response at first chemoembolization is still the most robust predictor for favorable outcome in hepatocellular carcinoma. J Hepatol. 2015. https://doi.org/10.1016/j.jhep.2015.01.022.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Malagari K, et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Interv Radiol. 2010. https://doi.org/10.1007/s00270-009-9750-0.

    Article  Google Scholar 

  21. Lammer J, 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. https://doi.org/10.1007/s00270-009-9711-7.

    Article  Google Scholar 

  22. Van Malenstein H, et al. A randomized phase II study of drug-eluting beads versus transarterial chemoembolization for unresectable hepatocellular carcinoma. Onkologie. 2011. https://doi.org/10.1159/000329602.

    Article  PubMed  Google Scholar 

  23. Sacco R, et al. Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2011. https://doi.org/10.1016/j.jvir.2011.07.002.

    Article  PubMed  Google Scholar 

  24. Golfieri R, et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014. https://doi.org/10.1038/bjc.2014.199.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Poon RTP, et al. A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol. 2007. https://doi.org/10.1016/j.cgh.2007.04.021.

    Article  PubMed  Google Scholar 

  26. Lewis AL, et al. DC BeadM1TM: towards an optimal transcatheter hepatic tumour therapy. J Mater Sci Mater Med. 2016. https://doi.org/10.1007/s10856-015-5629-6.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Spreafico C, et al. Transarterial chemoembolization for hepatocellular carcinoma with a new generation of beads: clinical-radiological outcomes and safety profile. Cardiovasc Interv Radiol. 2015. https://doi.org/10.1007/s00270-014-0907-0.

    Article  Google Scholar 

  28. Aal AKA, et al. Survival outcomes of very small drug-eluting beads used in chemoembolization of unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2019;30(9):1325-1334.e2. https://doi.org/10.1016/j.jvir.2019.05.006.

    Article  PubMed  Google Scholar 

  29. Urbano J, et al. Multicentre prospective study of drug-eluting bead chemoembolisation safety using tightly calibrated small microspheres in non-resectable hepatocellular carcinoma. Eur J Radiol. 2020. https://doi.org/10.1016/j.ejrad.2020.108966.

    Article  PubMed  Google Scholar 

  30. Malagari K, et al. Five-years outcome analysis of 142 consecutive hepatocellular carcinoma patients treated with doxorubicin eluting microspheres 30–60 μm: results from a single-centre prospective phase II trial. Cardiovasc Intervent Radiol. 2019;42(11):1551–62. https://doi.org/10.1007/s00270-019-02260-3.

    Article  CAS  PubMed  Google Scholar 

  31. Kang YJ, et al. Conventional versus small doxorubicin-eluting bead transcatheter arterial chemoembolization for treating barcelona clinic liver cancer stage 0/A hepatocellular carcinoma. Cardiovasc Interv Radiol. 2020;43(1):55–64. https://doi.org/10.1007/s00270-019-02349-9.

    Article  Google Scholar 

  32. Balli H, Aksungur E, Khalatai B, Aikimbaev K. Super-selective transarterial chemoembolization with doxorubicin-loaded drug-eluting beads sized below and above 100 microns in hepatocellular carcinoma: a comparative study. J Belgian Soc Radiol. 2019. https://doi.org/10.5334/JBSR.1841.

    Article  Google Scholar 

  33. Greco G, et al. Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma. World J Radiol. 2017;9(5):245. https://doi.org/10.4329/wjr.v9.i5.245.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Deipolyi AR, Oklu R, Al-Ansari S, Zhu AX, Goyal L, Ganguli S. Safety and efficacy of 70–150 μm and 100–300 μm drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2015. https://doi.org/10.1016/j.jvir.2014.12.020.

    Article  PubMed  Google Scholar 

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Funding

This study was not supported by any funding.

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Authors and Affiliations

  1. Interventional Vascular and Hepatobiliary Unit, Department of Radiodiagnostics and Radiotherapy, IRCCS Fondazione Istituto Nazionale Tumori di Milano, Milan, Italy

    Tommaso Cascella, Enrico Matteo Garanzini, Rodolfo Lanocita, Carlo Morosi, Giorgio Greco, Alfonso Marchianò & Carlo Spreafico

  2. General Surgery and Liver Transplantation Unit, IRCCS Fondazione Istituto Nazionale Tumori di Milano, Milan, Italy

    Carlo Sposito & Vincenzo Mazzaferro

  3. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    Carlo Sposito & Vincenzo Mazzaferro

  4. Postgraduation School of Radiology, University of Milan, Milan, Italy

    Federica Riva

Authors
  1. Tommaso Cascella
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  2. Enrico Matteo Garanzini
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  3. Rodolfo Lanocita
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  4. Carlo Morosi
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  5. Federica Riva
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  6. Giorgio Greco
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  7. Carlo Sposito
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  8. Vincenzo Mazzaferro
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  10. Carlo Spreafico
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Corresponding author

Correspondence to Enrico Matteo Garanzini.

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Cascella, T., Garanzini, E.M., Lanocita, R. et al. Long Term Survival Analysis in a Cohort of 125 Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using Small Drug Eluting Beads. Cardiovasc Intervent Radiol 45, 54–61 (2022). https://doi.org/10.1007/s00270-021-02991-2

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  • DOI: https://doi.org/10.1007/s00270-021-02991-2

Keywords

  • HCC
  • Chemoembolization
  • Drug eluting beads
  • Survival analysis