Skip to main content
Springer Nature Link
Log in

Treatment outcomes of transcatheter arterial chemoembolization combined with local ablative therapy versus monotherapy in hepatocellular carcinoma: a meta-analysis

  • Review
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the effectiveness comparing the combination of TACE with local ablative therapy and monotherapy on the treatment of HCC using meta-analytical techniques.

Methods

Randomized controlled trials and clinical studies comparing TACE plus local ablative therapy with monotherapy for HCC were included in this meta-analysis. Response rate, 1-, 2-, 3-, and 5-year survival rate, and overall survival (OS) were analyzed and compared.

Results

Eighteen studies included a total of 2,120 patients with HCC 1,071 and 1,049 patients for treatment with combination therapy and monotherapy, respectively. The combination therapy group had a significantly better survival in terms of 1-, 2-, 3-, and 5-year survival rate (RR 1.10, 95 % CI 1.03–1.18, P = 0.005; RR 1.20, 95 % CI 1.10–1.30, P < 0.0001; RR 1.43, 95 % CI 1.18–1.73, P < 0.0001; RR 1.40, 95 % CI 1.22–1.61, P < 0.0001, respectively), OS (HR 0.66, 95 % CI 0.51–0.85, P = 0.001), and response rate (RR 1.54, 95 % CI 1.09–2.18, P = 0.013) than that monotherapy group in patients with HCC.

Conclusions

The meta-analysis indicates that the combination of TACE with local ablative therapy was superior to monotherapy in the treatment for patients with HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Allgaier HP, Deibert P, Olschewski M et al (1998) Survival benefit of patients with inoperable hepatocellular carcinoma treated by a combination of transarterial chemoembolization and percutaneous ethanol injection—a single-center analysis including 132 patients. Int J Cancer 79:601–605

    Article  CAS  PubMed  Google Scholar 

  • Ansari D, Andersson R (2012) Radiofrequency ablation or percutaneous ethanol injection for the treatment of liver tumors. World J Gastroenterol 18:1003–1008

    Article  PubMed  Google Scholar 

  • Bartolozzi C, Lencioni R, Caramella D et al (1995) Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization. Radiology 197:812–818

    CAS  PubMed  Google Scholar 

  • Baust J, Gage AA, Ma H et al (1997) Minimally invasive cryosurgery—technological advances. Cryobiology 34(4):373–384

    Article  CAS  PubMed  Google Scholar 

  • Becker G, Soezgen T, Olschewski M et al (2005) Combined TACE and PEI for palliative treatment of unresectable hepatocellular carcinoma. World J Gastroenterol 11:6104–6109

    PubMed  Google Scholar 

  • Bigourdan JM, Jaeck D, Meyer N et al (2003) Small hepatocellular carcinoma in Child A cirrhotic patients: hepatic resection versus transplantation. Liver Transpl 9:513–520

    Article  PubMed  Google Scholar 

  • Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022

    Article  PubMed Central  PubMed  Google Scholar 

  • Bruix J, Sala M, Llovet JM (2004) Chemoembolization for hepatocellular carcinoma. Gastroenterology 127:S179–S188

    Article  CAS  PubMed  Google Scholar 

  • Chen XM, Luo PF, Lin HH et al (2004) Long-term result of combination of transcatheter arterial chemoembolization and percutaneous ethanol injection for treatment of hepatocellular carcinoma. Ai Zheng 23(7):829–832

    PubMed  Google Scholar 

  • Cheng BQ, Jia CQ, Liu CT et al (2008) Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial. JAMA 299:1669–1677

    Article  CAS  PubMed  Google Scholar 

  • Cho YK, Kim JK, Kim MY et al (2009) Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology (Baltimore, MD) 49(2):453–459

    Article  Google Scholar 

  • Ebara M, Kita K, Sugiura N et al (1995) Therapeutic effect of percutaneous ethanol injection on small hepatocellular carcinoma: evaluation with CT. Radiology 195(2):371–377

    CAS  PubMed  Google Scholar 

  • Ferrari FS, Stella A, Gambacorta D et al (2004) Treatment of large hepatocellular carcinoma: comparison between techniques and long term results. Radiol Med (Torino) 108(4):356–371

    Google Scholar 

  • Figueras J, Jaurrieta E, Valls C et al (2000) Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy. J Am Coll Surg 190:580–587

    Article  CAS  PubMed  Google Scholar 

  • Groupe d’Etude et de Traitement du Carcinome Hépato-cellulaire (1995) A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire. N Engl J Med 332:1256–1261

    Article  Google Scholar 

  • Hasegawa S, Yamasaki N, Hiwaki T et al (1999) Factors that predict intrahepatic recurrence of hepatocellular carcinoma in 81 patients initially treated by percutaneous ethanol injection. Cancer 86(9):1682–1690

    Article  CAS  PubMed  Google Scholar 

  • Huo TI, Huang YH, Wu JC et al (2003) Sequential transarterial chemoembolization and percutaneous acetic acid injection therapy versus repeated percutaneous acetic acid injection for unresectable hepatocellular carcinoma: a prospective study. Ann Onco 14(11):1648–1653

    Article  Google Scholar 

  • Huo TI, Huang YH, Wu JC et al (2004) Induction of complete tumor necrosis may reduce intrahepatic metastasis and prolong survival in patients with hepatocellular carcinoma undergoing locoregional therapy: a prospective study. Ann Oncol 15(5):775–780

    Article  PubMed  Google Scholar 

  • Jadad AR, Moore RA, Carroll D et al (1999) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12

    Article  Google Scholar 

  • Kamada K, Kitamoto M, Aikata H et al (2002) Combination of transcatheter arterial chemoembolization using cisplatin-lipiodol suspension and percutaneous ethanol injection for treatment of advanced small hepatocellular carcinoma. Am J Surg 184:284–290

    Article  CAS  PubMed  Google Scholar 

  • Kato T, Saito Y, Niwa M et al (1994) Combination therapy of transcatheter chemoembolization and percutaneous ethanol injection therapy for unresectable hepatocellular carcinoma. Cancer Chemother Pharmacol 33(Suppl):S115–S118

    Article  PubMed  Google Scholar 

  • Kim JH, Won HJ, Shin YM et al (2011) Medium-sized (3.1–5.0 cm) hepatocellular carcinoma: transarterial chemoembolization plus radiofrequency ablation versus radiofrequency ablation alone. Ann Surg Oncol 18(6):1624–1629

    Article  PubMed  Google Scholar 

  • Kim JW, Kim JH, Won HJ et al (2012) Hepatocellular carcinomas 2–3 cm in diameter: transarterial chemoembolization plus radiofrequency ablation vs. radiofrequency ablation alone. Eur J Radiol 81(3):e189–e193

    Article  PubMed  Google Scholar 

  • Koda M, Murawaki Y, Mitsuda A et al (2001) Combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection compared with percutaneous ethanol injection alone for patients with small hepatocellular carcinoma: a randomized control study. Cancer 92:1516–1524

    Article  CAS  PubMed  Google Scholar 

  • Kudo M (2010) The 2008 Okuda lecture: management of hepatocellular carcinoma: from surveillance to molecular targeted therapy. J Gastroenterol Hepatol 25:439–452

    Article  CAS  PubMed  Google Scholar 

  • Kudo M, Imanaka K, Chida N et al (2011) Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. Eur J Cancer 47:2117–2127

    Article  CAS  PubMed  Google Scholar 

  • Lau WY, Lai EC (2008) Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int 7(3):237–257

    PubMed  Google Scholar 

  • Lencioni R, Bartolozzi C, Caramella D et al (1995) Treatment of small hepatocellular carcinoma with percutaneous ethanol injection. Analysis of prognostic factors in 105 Western patients. Cancer 76(10):1737–1746

    Article  CAS  PubMed  Google Scholar 

  • Li C, Zhang W, Zhang R et al (2010) Therapeutic effects and prognostic factors in high-intensity focused ultrasound combined with chemoembolisation for larger hepatocellular carcinoma. Eur J Cancer 46:2513–2521

    Article  PubMed  Google Scholar 

  • Llovet JM, Bruix J (2008) Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 48(Suppl 1):S20–S37

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Fuster J, Bruix J (1999) Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30:1434–1440

    Article  CAS  PubMed  Google Scholar 

  • 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 30:6–25

    Article  PubMed  Google Scholar 

  • Margarit C, Escartin A, Castells L et al (2005) Resection for hepatocellular carcinoma is a good option in Child–Turcotte–Pugh class A patients with cirrhosis who are eligible for liver transplantation. Liver Transpl 11:1242–1251

    Article  PubMed  Google Scholar 

  • Morimoto M, Numata K, Kondou M et al (2010) Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer 116:5452–5460

    Article  PubMed  Google Scholar 

  • Ohnishi K, Nomura F, Ito S et al (1996a) Prognosis of small hepatocellular carcinoma (less than 3 cm) after percutaneous acetic acid injection: study of 91 cases. Hepatology (Baltimore, MD) 23(5):994–1002

    Article  CAS  Google Scholar 

  • Ohnishi K, Yoshioka H, Ito S et al (1996b) Treatment of nodular hepatocellular carcinoma larger than 3 cm with ultrasound-guided percutaneous acetic acid injection. Hepatology (Baltimore, MD) 24(6):1379–1385

    Article  CAS  Google Scholar 

  • Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834

    Article  CAS  PubMed  Google Scholar 

  • Peng ZW, Chen MS, Liang HH et al (2009) A case–control study comparing percutaneous radiofrequency ablation alone or combined with transcatheter arterial chemoembolization for hepatocellular carcinoma. Eur J Surg Oncol 36(3):257–263

    Article  PubMed  Google Scholar 

  • Peng ZW, Zhang YJ, Liang HH et al (2012) Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology 262(2):689–700

    Article  PubMed  Google Scholar 

  • Peng ZW, Zhang YJ, Chen MS et al (2013) Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol 31:426–432

    Article  PubMed  Google Scholar 

  • Seinstra BA, van Delden OM, van Erpecum KJ et al (2010) Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma: what is the evidence today? Insights Imaging 1(3):167–181

    Article  PubMed Central  PubMed  Google Scholar 

  • Sergio A, Cristofori C, Cardin R et al (2008) Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol 103:914–921

    Article  PubMed  Google Scholar 

  • Shen SQ, Xiang JJ, Xiong CL et al (2005) Intraoperative radiofrequency thermal ablation combined with portal vein infusion chemotherapy and transarterial chemoembolization for unresectable HCC. Hepatogastroenterology 52(65):1403–1407

    PubMed  Google Scholar 

  • Shibata T, Maetani Y, Isoda H et al (2006) Radiofrequency ablation for small hepatocellular carcinoma: prospective comparison of internally cooled electrode and expandable electrode. Radiology 238(1):346–353

    Article  PubMed  Google Scholar 

  • Shibata T, Isoda H, Hirokawa Y et al (2009) Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment? Radiology 252:905–913

    Article  PubMed  Google Scholar 

  • Shim JH, Park JW, Kim JH et al (2008) Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Cancer Sci 99:2037–2044

    CAS  PubMed  Google Scholar 

  • Signoriello S, Annunziata A, Lama N et al (2012) Survival after locoregional treatments for hepatocellular carcinoma: a cohort study in real-world patients. Sci World J 2012:564706

    Article  Google Scholar 

  • Takayasu K, Arii S, Ikai I et al (2006) Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 131:461–469

    Article  CAS  PubMed  Google Scholar 

  • Tesdal IK, Wikstrom M, Flechtenmacher C et al (2006) Percutaneous treatment of hepatocellular carcinoma in patients with transjugular intrahepatic portosystemic shunts. Cardiovasc Intervent Radiol 29(5):778–784

    Article  PubMed  Google Scholar 

  • Tierney JF, Stewart LA, Ghersi D (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16

    Article  PubMed Central  PubMed  Google Scholar 

  • Tiong L, Maddern GJ (2011) Systematic review and meta-analysis of survival and disease recurrence after radiofrequency ablation for hepatocellular carcinoma. British J Surg 98(9):1210–1224

    Article  CAS  Google Scholar 

  • Trevisani F, De Notariis S, Rossi C et al (2001) Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies? J Clin Gastroenterol 32:383–389

    Article  CAS  PubMed  Google Scholar 

  • Wang YB, Chen MH, Yan K et al (2007) Quality of life after radiofrequency ablation combined with transcatheter arterial chemoembolization for hepatocellular carcinoma: comparison with transcatheter arterial chemoembolization alone. Qual Life Res 16(3):389–397

    Article  PubMed  Google Scholar 

  • Wu F, Wang ZB, Chen WZ et al (2005) Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization. Radiology 235:659–667

    Article  PubMed  Google Scholar 

  • Wu Y, Li J, Zhang SJ et al (2012) Clinical observation on high intensity focused ultrasound combined with transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma. Zhonghua Wai Ke Za Zhi 50:691–694 (in Chinese)

    PubMed  Google Scholar 

  • Xu HX, Lu MD, Xie XY et al (2005) Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients. Clin Radiol 60(9):1018–1025

    Article  PubMed  Google Scholar 

  • Xu KC, Niu LZ, Zhou Q et al (2009) Sequential use of transarterial chemoembolization and percutaneous cryosurgery for hepatocellular carcinoma. World J Gastroenterol 15(29):3664–3669

    Article  PubMed  Google Scholar 

  • Yang P, Liang M, Zhang Y et al (2008) Clinical application of a combination therapy of lentinan, multi-electrode RFA and TACE in HCC. Adv Ther 25:787–794

    Article  CAS  PubMed  Google Scholar 

  • Yang W, Chen MH, Wang MQ et al (2009) Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment. Hepatol Res 39(3):231–240

    Article  CAS  PubMed  Google Scholar 

  • Yu YQ, Xu DB, Zhou XD et al (1993) Experience with liver resection after hepatic arterial chemoembolization for hepatocellular carcinoma. Cancer 71:62–65

    Article  CAS  PubMed  Google Scholar 

  • Zhao JD, Liu J, Ren ZG et al (2010) Maintenance of Sorafenib following combined therapy of three-dimensional conformal radiation therapy/intensity-modulated radiation therapy and transcatheter arterial chemoembolization in patients with locally advanced hepatocellular carcinoma: a phase I/II study. Radiat Oncol 5:12

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Natural Science Foundation of China (71373175), the National Public Health Grand Research Foundation (201202017) and the National High Technology Research and Development Program of China (2012AA021003).

Conflict of interest

We declared that there is no conflict of interest in this article.

Author information

Authors and Affiliations

  1. Tianjin Haihe Hospital, Tianjin, People’s Republic of China

    Huiling Liu & Yan Luo

  2. Department of Health Statistics, College of Public Health, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Heping District, Tianjin, 300070, People’s Republic of China

    Lili Gu, Linlin Fan, Zhuang Cui, Yuanyuan Liu, Changping Li & Jun Ma

  3. Tianjin Tianhe Hospital, Tianjin, People’s Republic of China

    Yuanjun Lv

  4. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 An Shan Xi Road, Nankai District, Tianjin, 300193, People’s Republic of China

    Lili Gu

  5. Department of Biology, School of Basic Medical, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Heping District, Tianjin, 300070, People’s Republic of China

    Guang Li

Authors
  1. Lili Gu
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Huiling Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Linlin Fan
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Yuanjun Lv
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Zhuang Cui
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Yan Luo
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Yuanyuan Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Guang Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Changping Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Jun Ma
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding authors

Correspondence to Guang Li, Changping Li or Jun Ma.

Additional information

Lili Gu, Huiling Liu, and Linlin Fan have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gu, L., Liu, H., Fan, L. et al. Treatment outcomes of transcatheter arterial chemoembolization combined with local ablative therapy versus monotherapy in hepatocellular carcinoma: a meta-analysis. J Cancer Res Clin Oncol 140, 199–210 (2014). https://doi.org/10.1007/s00432-013-1528-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-013-1528-8

Keywords