Skip to main content
Top
Published in: European Radiology 5/2017

01-05-2017 | Oncology

Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus 90Y-radioembolization for hepatocellular carcinoma

Authors: Johannes M. Ludwig, Di Zhang, Minzhi Xing, Hyun S. Kim

Published in: European Radiology | Issue 5/2017

Login to get access

Abstract

Objective

To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 (90Y)-radioembolization for hepatocellular carcinoma (HCC).

Methods

Studies comparing conventional (c)TACE versus 90Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus 90Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger’s and Begg’s tests.

Results

Fourteen studies comparing DEB-TACE or 90Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over 90Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate.

Conclusion

DEB-TACE and 90Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to 90Y-radioembolization but direct comparison is warranted for further evaluation.

Key Points

This meta-analysis shows greater 1-year survival benefit for DEB-TACE over 90 Y-radioembolization.
DEB-TACE has a favourable 2- & 3-year survival benefit trend over 90 Y-radioembolization.
No significant difference for tumour response was detected.
Direct comparison of these methods for a more robust evaluation is warranted.
Literature
2.
go back to reference Ferlay J, Soerjomataram I, Dikshit R et al (2014) Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. doi:10.1002/ijc.29210 PubMed Ferlay J, Soerjomataram I, Dikshit R et al (2014) Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. doi:10.​1002/​ijc.​29210 PubMed
3.
go back to reference Khan AS, Fowler KJ, Chapman WC (2014) Current surgical treatment strategies for hepatocellular carcinoma in North America. World J Gastroenterol 20:15007–15017CrossRefPubMedPubMedCentral Khan AS, Fowler KJ, Chapman WC (2014) Current surgical treatment strategies for hepatocellular carcinoma in North America. World J Gastroenterol 20:15007–15017CrossRefPubMedPubMedCentral
4.
go back to reference European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRef European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRef
6.
go back to reference Boulin M, Hillon P, Cercueil JP et al (2014) Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial. Aliment Pharmacol Ther 39:1301–1313CrossRefPubMed Boulin M, Hillon P, Cercueil JP et al (2014) Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial. Aliment Pharmacol Ther 39:1301–1313CrossRefPubMed
7.
go back to reference Abdel-Rahman O, Elsayed ZA (2013) Combination trans arterial chemoembolization (TACE) plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review of the literature. Dig Dis Sci 58:3389–3396CrossRefPubMed Abdel-Rahman O, Elsayed ZA (2013) Combination trans arterial chemoembolization (TACE) plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review of the literature. Dig Dis Sci 58:3389–3396CrossRefPubMed
8.
go back to reference Fong ZV, Tanabe KK (2014) The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review. Cancer 120:2824–2838CrossRefPubMed Fong ZV, Tanabe KK (2014) The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review. Cancer 120:2824–2838CrossRefPubMed
9.
go back to reference Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481CrossRefPubMed Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481CrossRefPubMed
10.
go back to reference Huang K, Zhou Q, Wang R, Cheng D, Ma Y (2013) Doxorubicin-eluting bead versus conventional transarterial chemoembolization for the treatment of HCC: a meta-analysis (Provisional abstract). J Gastroenterol Hepatol Huang K, Zhou Q, Wang R, Cheng D, Ma Y (2013) Doxorubicin-eluting bead versus conventional transarterial chemoembolization for the treatment of HCC: a meta-analysis (Provisional abstract). J Gastroenterol Hepatol
11.
go back to reference Vente MAD, Wondergem M, van der Tweel I et al (2009) Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: A structured meta-analysis. Eur Radiol 19:951–959CrossRefPubMed Vente MAD, Wondergem M, van der Tweel I et al (2009) Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: A structured meta-analysis. Eur Radiol 19:951–959CrossRefPubMed
12.
go back to reference Murthy R, Kamat P, Nunez R, Salem R (2008) Radioembolization of yttrium-90 microspheres for hepatic malignancy. Semin Interv Radiol 25:48–57CrossRef Murthy R, Kamat P, Nunez R, Salem R (2008) Radioembolization of yttrium-90 microspheres for hepatic malignancy. Semin Interv Radiol 25:48–57CrossRef
13.
go back to reference Xing M, Kokabi N, Camacho JC, Kooby DA, El-Rayes BF, Kim HS (2013) 90Y radioembolization versus chemoembolization in the treatment of hepatocellular carcinoma: an analysis of comparative effectiveness. J Comp Eff Res 2:435–444CrossRefPubMed Xing M, Kokabi N, Camacho JC, Kooby DA, El-Rayes BF, Kim HS (2013) 90Y radioembolization versus chemoembolization in the treatment of hepatocellular carcinoma: an analysis of comparative effectiveness. J Comp Eff Res 2:435–444CrossRefPubMed
14.
go back to reference Pitton MB, Kloeckner R, Ruckes C et al (2014) Randomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular Carcinoma. Cardiovasc Intervent Radiol. doi:10.1007/s00270-014-1012-0 PubMedPubMedCentral Pitton MB, Kloeckner R, Ruckes C et al (2014) Randomized Comparison of Selective Internal Radiotherapy (SIRT) Versus Drug-Eluting Bead Transarterial Chemoembolization (DEB-TACE) for the Treatment of Hepatocellular Carcinoma. Cardiovasc Intervent Radiol. doi:10.​1007/​s00270-014-1012-0 PubMedPubMedCentral
15.
go back to reference Seinstra BA, Defreyne L, Lambert B et al (2012) Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial. Trials 13:144CrossRefPubMedPubMedCentral Seinstra BA, Defreyne L, Lambert B et al (2012) Transarterial radioembolization versus chemoembolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial. Trials 13:144CrossRefPubMedPubMedCentral
16.
go back to reference Golfieri R, Giampalma E, Renzulli M et al (2014) Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer 111:255–264CrossRefPubMedPubMedCentral Golfieri R, Giampalma E, Renzulli M et al (2014) Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer 111:255–264CrossRefPubMedPubMedCentral
17.
go back to reference Recchia F, Passalacqua G, Filauri P et al (2012) Chemoembolization of unresectable hepatocellular carcinoma: Decreased toxicity with slow-release doxorubicineluting beads compared with lipiodol. Oncol Rep 27:1377–1383PubMed Recchia F, Passalacqua G, Filauri P et al (2012) Chemoembolization of unresectable hepatocellular carcinoma: Decreased toxicity with slow-release doxorubicineluting beads compared with lipiodol. Oncol Rep 27:1377–1383PubMed
18.
go back to reference Song MJ, Chun HJ, do Song S et al (2012) Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Hepatol 57:1244–1250CrossRefPubMed Song MJ, Chun HJ, do Song S et al (2012) Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Hepatol 57:1244–1250CrossRefPubMed
19.
go back to reference Sacco R, Bargellini I, Bertini M et al (2011) Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 22:1545–1552CrossRefPubMed Sacco R, Bargellini I, Bertini M et al (2011) Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol 22:1545–1552CrossRefPubMed
20.
go back to reference Ferrer Puchol MD, la Parra C, Esteban E et al (2011) Comparison of doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma. Radiologia 53:246–253CrossRefPubMed Ferrer Puchol MD, la Parra C, Esteban E et al (2011) Comparison of doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma. Radiologia 53:246–253CrossRefPubMed
21.
go back to reference Wiggermann P, Sieron D, Brosche C et al (2011) Transarterial Chemoembolization of Child-A hepatocellular carcinoma: drug-eluting bead TACE (DEB TACE) vs. TACE with cisplatin/lipiodol (cTACE). Med Sci Monit 17:CR189–CR195CrossRefPubMedPubMedCentral Wiggermann P, Sieron D, Brosche C et al (2011) Transarterial Chemoembolization of Child-A hepatocellular carcinoma: drug-eluting bead TACE (DEB TACE) vs. TACE with cisplatin/lipiodol (cTACE). Med Sci Monit 17:CR189–CR195CrossRefPubMedPubMedCentral
22.
go back to reference Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS (2010) Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol 101:476–480PubMed Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS (2010) Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol 101:476–480PubMed
23.
go back to reference Kolligs FT, Bilbao JI, Jakobs T et al (2014) Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma. Liver Int. doi:10.1111/liv.12750 PubMed Kolligs FT, Bilbao JI, Jakobs T et al (2014) Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma. Liver Int. doi:10.​1111/​liv.​12750 PubMed
24.
go back to reference El Fouly A, Ertle J, El Dorry A et al (2015) In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int 35:627–635CrossRefPubMed El Fouly A, Ertle J, El Dorry A et al (2015) In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int 35:627–635CrossRefPubMed
25.
go back to reference Moreno-Luna LE, Yang JD, Sanchez W et al (2013) Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol 36:714–723CrossRefPubMed Moreno-Luna LE, Yang JD, Sanchez W et al (2013) Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol 36:714–723CrossRefPubMed
26.
go back to reference Salem R, Lewandowski RJ, Kulik L et al (2011) Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 140:497–507, e492CrossRefPubMed Salem R, Lewandowski RJ, Kulik L et al (2011) Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 140:497–507, e492CrossRefPubMed
27.
go back to reference Lance C, McLennan G, Obuchowski N et al (2011) Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma. J Vasc Interv Radiol 22:1697–1705CrossRefPubMed Lance C, McLennan G, Obuchowski N et al (2011) Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma. J Vasc Interv Radiol 22:1697–1705CrossRefPubMed
28.
go back to reference Kooby DA, Egnatashvili V, Srinivasan S et al (2010) Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol 21:224–230CrossRefPubMed Kooby DA, Egnatashvili V, Srinivasan S et al (2010) Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol 21:224–230CrossRefPubMed
29.
go back to reference Carr BI, Kondragunta V, Buch SC, Branch RA (2010) Therapeutic equivalence in survival for hepatic arterial chemoembolization and yttrium 90 microsphere treatments in unresectable hepatocellular carcinoma: a two-cohort study. Cancer 116:1305–1314CrossRefPubMedPubMedCentral Carr BI, Kondragunta V, Buch SC, Branch RA (2010) Therapeutic equivalence in survival for hepatic arterial chemoembolization and yttrium 90 microsphere treatments in unresectable hepatocellular carcinoma: a two-cohort study. Cancer 116:1305–1314CrossRefPubMedPubMedCentral
30.
31.
32.
go back to reference Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMed Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558CrossRefPubMed
33.
go back to reference Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50:683–691CrossRefPubMed Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50:683–691CrossRefPubMed
34.
go back to reference Sacks D, McClenny TE, Cardella JF, Lewis CA (2003) Society of interventional radiology clinical practice guidelines. J Vasc Interv Radiol 14:S199–S202CrossRefPubMed Sacks D, McClenny TE, Cardella JF, Lewis CA (2003) Society of interventional radiology clinical practice guidelines. J Vasc Interv Radiol 14:S199–S202CrossRefPubMed
35.
go back to reference Salem R, Lewandowski RJ, Gates VL et al (2011) Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol 22:265–278 Salem R, Lewandowski RJ, Gates VL et al (2011) Research reporting standards for radioembolization of hepatic malignancies. J Vasc Interv Radiol 22:265–278
36.
go back to reference Sangro B, Salem R (2014) Transarterial chemoembolization and radioembolization. Semin Liver Dis 34:435–443CrossRefPubMed Sangro B, Salem R (2014) Transarterial chemoembolization and radioembolization. Semin Liver Dis 34:435–443CrossRefPubMed
37.
go back to reference Salem R, Lewandowski RJ, Mulcahy MF et al (2010) Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 138:52–64CrossRefPubMed Salem R, Lewandowski RJ, Mulcahy MF et al (2010) Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology 138:52–64CrossRefPubMed
38.
go back to reference Gorodetski B, Chapiro J, Schernthaner R et al (2016) Advanced-stage hepatocellular carcinoma with portal vein thrombosis: conventional versus drug-eluting beads transcatheter arterial chemoembolization. Eur Radiol. doi:10.1007/s00330-016-4445-9 PubMed Gorodetski B, Chapiro J, Schernthaner R et al (2016) Advanced-stage hepatocellular carcinoma with portal vein thrombosis: conventional versus drug-eluting beads transcatheter arterial chemoembolization. Eur Radiol. doi:10.​1007/​s00330-016-4445-9 PubMed
39.
go back to reference Salem R, Gilbertsen M, Butt Z et al (2013) Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol 11:1358–1365, e1351CrossRefPubMed Salem R, Gilbertsen M, Butt Z et al (2013) Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol 11:1358–1365, e1351CrossRefPubMed
40.
go back to reference Prajapati HJ, Rafi S, El-Rayes BF, Kauh JS, Kooby DA, Kim HS (2012) Safety and feasibility of same-day discharge of patients with unresectable hepatocellular carcinoma treated with doxorubicin drug-eluting bead transcatheter chemoembolization. J Vasc Interv Radiol 23:1286–1293, e1281CrossRefPubMed Prajapati HJ, Rafi S, El-Rayes BF, Kauh JS, Kooby DA, Kim HS (2012) Safety and feasibility of same-day discharge of patients with unresectable hepatocellular carcinoma treated with doxorubicin drug-eluting bead transcatheter chemoembolization. J Vasc Interv Radiol 23:1286–1293, e1281CrossRefPubMed
41.
go back to reference Song F, Altman DG, Glenny AM, Deeks JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 326:472CrossRefPubMedPubMedCentral Song F, Altman DG, Glenny AM, Deeks JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 326:472CrossRefPubMedPubMedCentral
42.
go back to reference Glenny AM, Altman DG, Song F et al (2005) Indirect comparisons of competing interventions. Health Technol Assess 9:1–134, iii-ivCrossRefPubMed Glenny AM, Altman DG, Song F et al (2005) Indirect comparisons of competing interventions. Health Technol Assess 9:1–134, iii-ivCrossRefPubMed
43.
go back to reference Cornell JE (2014) Random-effects meta-analysis of inconsistent effects. In response. Ann Intern Med 161:380CrossRefPubMed Cornell JE (2014) Random-effects meta-analysis of inconsistent effects. In response. Ann Intern Med 161:380CrossRefPubMed
44.
go back to reference Chiappelli F, Brant XMC, Neagos N, Oluwadara OO, Ramchandani MH (2010) Evidence-based practice: toward optimizing clinical outcomes. Springer, Berlin HeidelbergCrossRef Chiappelli F, Brant XMC, Neagos N, Oluwadara OO, Ramchandani MH (2010) Evidence-based practice: toward optimizing clinical outcomes. Springer, Berlin HeidelbergCrossRef
Metadata
Title
Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus 90Y-radioembolization for hepatocellular carcinoma
Authors
Johannes M. Ludwig
Di Zhang
Minzhi Xing
Hyun S. Kim
Publication date
01-05-2017
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 5/2017
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-016-4548-3

Other articles of this Issue 5/2017

European Radiology 5/2017 Go to the issue