Transarterial Embolization Alone Versus Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma

Summary

Developed in Japan in the 1980s, TACE became the most frequent treatment for unresectable hepatocellular carcinoma (HCC) in patients with preserved hepatic function after 2002, when two radiochemotherapies (RCTs) showed survival benefits for HCC patients who underwent conventional Lipiodol-based TACE (cTACE). Nowadays, nearly half of HCC patients undergo this procedure during their clinical history. In the last ten years, cTACE has been challenged by an alternative procedure, drug-eluting beads-TACE (DEB-TACE), after the introduction of calibrated embolizing microspheres loaded with a chemotherapeutic agent. DEB-TACE is considered to be less toxic and better standardized than cTACE, with reported no differences in patient survival. Since 2006, DEB-TACE has become the standard in many centers worldwide. Though, the need of adding doxorubicin to small beads embolization alone (TAE) remains unsettled. Though cTACE/DEB-TACE and TAE have been compared in several RCTs, no study demonstrated a clear survival benefit associated with the former. Our study aims to compare first-line DEB-TACE and TAE on a random sample of HCC with the hypothesis that the addition of drug to embolization with small size beads is not associated with a survival benefit when compared to embolization alone performed with tiny calibrated microspheres. HCC is considered a chemo-resistant tumor and to date there is no clear evidence of benefits in associating anticancer agents to TAE. On the other hand, the optimal size of embolic agents has still to be defined. A comparative evaluation of TACE and TAE is essential for two additional reasons: a) it is still unclear whether side effects following embolization procedures are related to the embolization itself, to drug addition or both; b) DEB-TACE procedure is more expensive than TAE and, given the current attention on cancer-related health care cost control, identification of opportunities for cost savings in HCC treatments of an increasingly common cancer would be valuable.

Timeline

Start

2019-12-04

Primary completion

2022-04-30

Completion

2022-04-30

Publications

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• Background Meyer T, Kirkwood A, Roughton M, Beare S, Tsochatzis E, Yu D, Davies N, Williams E, Pereira SP, Hochhauser D, Mayer A, Gillmore R, O'Beirne J, Patch D, Burroughs AK. A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma. Br J Cancer. 2013 Apr 2;108(6):1252-9. doi: 10.1038/bjc.2013.85. Epub 2013 Feb 28.
• Background Brown KT, Do RK, Gonen M, Covey AM, Getrajdman GI, Sofocleous CT, Jarnagin WR, D'Angelica MI, Allen PJ, Erinjeri JP, Brody LA, O'Neill GP, Johnson KN, Garcia AR, Beattie C, Zhao B, Solomon SB, Schwartz LH, DeMatteo R, Abou-Alfa GK. Randomized Trial of Hepatic Artery Embolization for Hepatocellular Carcinoma Using Doxorubicin-Eluting Microspheres Compared With Embolization With Microspheres Alone. J Clin Oncol. 2016 Jun 10;34(17):2046-53. doi: 10.1200/JCO.2015.64.0821. Epub 2016 Feb 1.
• Background Massarweh NN, Davila JA, El-Serag HB, Duan Z, Temple S, May S, Sada YH, Anaya DA. Transarterial bland versus chemoembolization for hepatocellular carcinoma: rethinking a gold standard. J Surg Res. 2016 Feb;200(2):552-9. doi: 10.1016/j.jss.2015.09.034. Epub 2015 Oct 3.
• Background Osuga K, Hori S, Hiraishi K, Sugiura T, Hata Y, Higashihara H, Maeda N, Tomoda K, Nakamura H. Bland embolization of hepatocellular carcinoma using superabsorbent polymer microspheres. Cardiovasc Intervent Radiol. 2008 Nov-Dec;31(6):1108-16. doi: 10.1007/s00270-008-9369-6. Epub 2008 Jun 10.
• Background Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M, Makuuchi M, Yamaoka Y; Liver Cancer Study Group of Japan. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006 Aug;131(2):461-9. doi: 10.1053/j.gastro.2006.05.021.
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• Background Tsochatzis E, Meyer T, O'Beirne J, Burroughs AK. Transarterial chemoembolisation is not superior to embolisation alone: the recent European Association for the Study of the Liver (EASL) - European Organisation for Research and Treatment of Cancer (EORTC) guidelines. Eur J Cancer. 2013 Apr;49(6):1509-10. doi: 10.1016/j.ejca.2012.11.012. Epub 2012 Dec 8. No abstract available.
• Background Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008 May 21;100(10):698-711. doi: 10.1093/jnci/djn134. Epub 2008 May 13.
• Background Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010 Feb;30(1):52-60. doi: 10.1055/s-0030-1247132. Epub 2010 Feb 19.
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• Background Bruix J, Reig M, Sherman M. Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology. 2016 Apr;150(4):835-53. doi: 10.1053/j.gastro.2015.12.041. Epub 2016 Jan 12.
• Background Park Y, Kim SU, Kim BK, Park JY, Kim DY, Ahn SH, Park YE, Park JH, Lee YI, Yun HR, Han KH. Addition of tumor multiplicity improves the prognostic performance of the hepatoma arterial-embolization prognostic score. Liver Int. 2016 Jan;36(1):100-7. doi: 10.1111/liv.12878. Epub 2015 Jun 22.
• Background Cappelli A, Cucchetti A, Cabibbo G, Mosconi C, Maida M, Attardo S, Pettinari I, Pinna AD, Golfieri R. Refining prognosis after trans-arterial chemo-embolization for hepatocellular carcinoma. Liver Int. 2016 May;36(5):729-36. doi: 10.1111/liv.13029. Epub 2015 Dec 23.
• Background Italian Association for the Study of the Liver (AISF); AISF Expert Panel; AISF Coordinating Committee; Bolondi L, Cillo U, Colombo M, Craxi A, Farinati F, Giannini EG, Golfieri R, Levrero M, Pinna AD, Piscaglia F, Raimondo G, Trevisani F, Bruno R, Caraceni P, Ciancio A, Coco B, Fraquelli M, Rendina M, Squadrito G, Toniutto P. Position paper of the Italian Association for the Study of the Liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis. 2013 Sep;45(9):712-23. doi: 10.1016/j.dld.2013.01.012. Epub 2013 Feb 23.

Drugs

Indications