Download PDF
Semin intervent Radiol 2019; 36(04): 303-309
DOI: 10.1055/s-0039-1697641
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Ablation plus Transarterial Embolic Therapy for Hepatocellular Carcinoma Larger than 3 cm: Science, Evidence, and Future Directions

Andrew R. Lewis
1   Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
,
Carlos A. Padula
1   Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
,
J Mark McKinney
1   Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
,
Beau B. Toskich
1   Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
› Author Affiliations
Further Information

Publication History

Publication Date:
31 October 2019 (online)

Also available at
    Permissions and Reprints

Abstract

Thermal ablation is widely regarded as definitive therapy for early-stage hepatocellular carcinoma, but its efficacy decreases in tumors greater than 3 cm. Extensive clinical studies have supported improved outcomes provided through combining transarterial embolic therapy with ablation in the treatment of larger tumors. This article will provide a survey of the science and data for combination therapy in both thermal and nonthermal ablation modalities, as well as describe emerging applications.

Keywords

hepatocellular carcinoma - radiofrequency ablation - microwave ablation - transarterial chemoembolization - transarterial embolization - cryoablation - thermal ablation - combination therapy - ablation - embolization
 

  • References

  • 1 Liu PH, Hsu CY, Hsia CY. , et al. Surgical resection versus radiofrequency ablation for single hepatocellular carcinoma ≤ 2 cm in a propensity score model. Ann Surg 2016; 263 (03) 538-545
    CrossrefPubMedSearch in Google Scholar
  • 2 Shiina S, Tateishi R, Arano T. , et al. Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol 2012; 107 (04) 569-577 , quiz 578
    CrossrefPubMedSearch in Google Scholar
  • 3 Livraghi T, Giorgio A, Marin G. , et al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 1995; 197 (01) 101-108
    CrossrefPubMedSearch in Google Scholar
  • 4 Chevallier P, Baudin G, Anty R. , et al. Treatment of hepatocellular carcinomas by thermal ablation and hepatic transarterial chemoembolization. Diagn Interv Imaging 2015; 96 (06) 637-646
    CrossrefPubMedSearch in Google Scholar
  • 5 Lee HJ, Kim JW, Hur YH. , et al. Conventional chemoembolization plus radiofrequency ablation versus surgical resection for single, medium-sized hepatocellular carcinoma: propensity-score matching analysis. J Vasc Interv Radiol 2019; 30 (03) 284-292.e1
    CrossrefPubMedSearch in Google Scholar
  • 6 Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K. 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 2010; 116 (23) 5452-5460
    CrossrefPubMedSearch in Google Scholar
  • 7 Takayasu K, Arii S, Ikai I. , et al; Liver Cancer Study Group of Japan. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006; 131 (02) 461-469
    CrossrefPubMedSearch in Google Scholar
  • 8 Sabel MS. Cryo-immunology: a review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology 2009; 58 (01) 1-11
    CrossrefPubMedSearch in Google Scholar
  • 9 Takaki H, Cornelis F, Kako Y, Kobayashi K, Kamikonya N, Yamakado K. Thermal ablation and immunomodulation: from preclinical experiments to clinical trials. Diagn Interv Imaging 2017; 98 (09) 651-659
    CrossrefPubMedSearch in Google Scholar
  • 10 Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999; 210 (03) 655-661
    CrossrefPubMedSearch in Google Scholar
  • 11 Livraghi T, Goldberg SN, Lazzaroni S. , et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology 2000; 214 (03) 761-768
    CrossrefPubMedSearch in Google Scholar
  • 12 Chinn SB, Lee Jr FT, Kennedy GD. , et al. Effect of vascular occlusion on radiofrequency ablation of the liver: results in a porcine model. AJR Am J Roentgenol 2001; 176 (03) 789-795
    CrossrefPubMedSearch in Google Scholar
  • 13 Mostafa EM, Ganguli S, Faintuch S, Mertyna P, Goldberg SN. Optimal strategies for combining transcatheter arterial chemoembolization and radiofrequency ablation in rabbit VX2 hepatic tumors. J Vasc Interv Radiol 2008; 19 (12) 1740-1748
    CrossrefPubMedSearch in Google Scholar
  • 14 Rossi S, Garbagnati F, Lencioni R. , et al. Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000; 217 (01) 119-126
    CrossrefPubMedSearch in Google Scholar
  • 15 Duan X, Zhou G, Han X. , et al. Radiofrequency ablation combined with transcatheter therapy in rabbit VX2 liver tumors: effects and histopathological characteristics. Acta Radiol 2015; 56 (01) 87-96
    CrossrefPubMedSearch in Google Scholar
  • 16 Brown KT, Do RK, Gonen M. , et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol 2016; 34 (17) 2046-2053
    CrossrefPubMedSearch in Google Scholar
  • 17 Meyer T, Kirkwood A, Roughton M. , et al. A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma. Br J Cancer 2013; 108 (06) 1252-1259
    CrossrefPubMedSearch in Google Scholar
  • 18 Facciorusso A, Bellanti F, Villani R. , et al. Transarterial chemoembolization vs bland embolization in hepatocellular carcinoma: a meta-analysis of randomized trials. United European Gastroenterol J 2017; 5 (04) 511-518
    CrossrefPubMedSearch in Google Scholar
  • 19 Lee IJ, Kim YI, Kim KW. , et al. Radiofrequency ablation combined with transcatheter arterial embolisation in rabbit liver: investigation of the ablation zone according to the time interval between the two therapies. Br J Radiol 2012; 85 (1019): e987-e994
    CrossrefPubMedSearch in Google Scholar
  • 20 Bhattacharya S, Novell JR, Winslet MC, Hobbs KEF. Iodized oil in the treatment of hepatocellular carcinoma. Br J Surg 1994; 81 (11) 1563-1571
    CrossrefPubMedSearch in Google Scholar
  • 21 Wissniowski TT, Hänsler J, Neureiter D. , et al. Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res 2003; 63 (19) 6496-6500
    PubMedSearch in Google Scholar
  • 22 Chen T, Guo J, Han C, Yang M, Cao X. Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J Immunol 2009; 182 (03) 1449-1459
    CrossrefPubMedSearch in Google Scholar
  • 23 Duan XH, Li TF, Zhou GF. , et al. Transcatheter arterial embolization combined with radiofrequency ablation activates CD8(+) T-cell infiltration surrounding residual tumors in the rabbit VX2 liver tumors. OncoTargets Ther 2016; 9: 2835-2844
    PubMedSearch in Google Scholar
  • 24 Peng ZW, Zhang YJ, Chen MS. , et al. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol 2013; 31 (04) 426-432
    PubMedSearch in Google Scholar
  • 25 Chen QW, Ying HF, Gao S. , et al. Radiofrequency ablation plus chemoembolization versus radiofrequency ablation alone for hepatocellular carcinoma: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2016; 40 (03) 309-314
    CrossrefPubMedSearch in Google Scholar
  • 26 Vogl TJ, Qian J, Tran A. , et al. Study on the effect of chemoembolization combined with microwave ablation for the treatment of hepatocellular carcinoma in rats. Diagn Interv Radiol 2017; 23 (02) 150-155
    CrossrefPubMedSearch in Google Scholar
  • 27 Puza CJ, Wang Q, Kim CY. Evaluation of the heat sink effect after transarterial embolization when performed in combination with thermal ablation of the liver in a rabbit model. Cardiovasc Intervent Radiol 2018; 41 (11) 1773-1778
    CrossrefPubMedSearch in Google Scholar
  • 28 Yi Y, Zhang Y, Wei Q. , et al. Radiofrequency ablation or microwave ablation combined with transcatheter arterial chemoembolization in treatment of hepatocellular carcinoma by comparing with radiofrequency ablation alone. Chin J Cancer Res 2014; 26 (01) 112-118
    PubMedSearch in Google Scholar
  • 29 Thornton LM, Cabrera R, Kapp M, Lazarowicz M, Vogel JD, Toskich BB. Radiofrequency vs microwave ablation after neoadjuvant transarterial bland and drug-eluting microsphere chembolization for the treatment of hepatocellular carcinoma. Curr Probl Diagn Radiol 2017; 46 (06) 402-409
    CrossrefPubMedSearch in Google Scholar
  • 30 Vietti Violi N, Duran R, Guiu B. , et al. Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. lancet. Gastroenterol Hepatol 2018; 3 (05) 317-325
    PubMedSearch in Google Scholar
  • 31 Kollmar O, Richter S, Schilling MK, Menger MD, Pistorius GA. Advanced hepatic tissue destruction in ablative cryosurgery: potentials of intermittent freezing and selective vascular inflow occlusion. Cryobiology 2004; 48 (03) 263-272
    CrossrefPubMedSearch in Google Scholar
  • 32 Mala T, Frich L, Aurdal L. , et al. Hepatic vascular inflow occlusion enhances tissue destruction during cryoablation of porcine liver. J Surg Res 2003; 115 (02) 265-271
    CrossrefPubMedSearch in Google Scholar
  • 33 Guo Z, Ni H, Hu Yh, Xing Wg, Liu F. [Experimental study of hepatic bloodflow to the effect of cryoablation]. Beijing Da Xue Xue Bao 2008; 40 (02) 139-142
    PubMedSearch in Google Scholar
  • 34 Zeng JY, Piao XH, Zou Z-Y. , et al. Cryoablation with drug-loaded bead embolization in the treatment of unresectable hepatocellular carcinoma: safety and efficacy analysis. Oncotarget 2018; 9 (07) 7557-7566
    CrossrefPubMedSearch in Google Scholar
  • 35 Xu KC, Niu LZ, Zhou Q. , et al. Sequential use of transarterial chemoembolization and percutaneous cryosurgery for hepatocellular carcinoma. World J Gastroenterol 2009; 15 (29) 3664-3669
    CrossrefPubMedSearch in Google Scholar
  • 36 Huang M, Wang X, Bin H. Effect of transcatheter arterial chemoembolization combined with argon-helium cryosurgery system on the changes of NK cells and T cell subsets in peripheral blood of hepatocellular carcinoma patients. Cell Biochem Biophys 2015; 73 (03) 787-792
    CrossrefPubMedSearch in Google Scholar
  • 37 Pacella CM, Bizzarri G, Francica G. , et al. Percutaneous laser ablation in the treatment of hepatocellular carcinoma with small tumors: analysis of factors affecting the achievement of tumor necrosis. J Vasc Interv Radiol 2005; 16 (11) 1447-1457
    CrossrefPubMedSearch in Google Scholar
  • 38 Ferrari FS, Megliola A, Scorzelli A. , et al. Treatment of small HCC through radiofrequency ablation and laser ablation. Comparison of techniques and long-term results. Radiol Med (Torino) 2007; 112 (03) 377-393
    CrossrefPubMedSearch in Google Scholar
  • 39 Sturesson C, Liu DL, Stenram U, Andersson-Engels S. Hepatic inflow occlusion increases the efficacy of interstitial laser-induced thermotherapy in rat. J Surg Res 1997; 71 (01) 67-72
    CrossrefPubMedSearch in Google Scholar
  • 40 Zangos S, Eichler K, Balzer JO. , et al. Large-sized hepatocellular carcinoma (HCC): a neoadjuvant treatment protocol with repetitive transarterial chemoembolization (TACE) before percutaneous MR-guided laser-induced thermotherapy (LITT). Eur Radiol 2007; 17 (02) 553-563
    CrossrefPubMedSearch in Google Scholar
  • 41 Pacella CM, Bizzarri G, Cecconi P. , et al. Hepatocellular carcinoma: long-term results of combined treatment with laser thermal ablation and transcatheter arterial chemoembolization. Radiology 2001; 219 (03) 669-678
    CrossrefPubMedSearch in Google Scholar
  • 42 Ferrari FS, Stella A, Gambacorta D. , et al. Treatment of large hepatocellular carcinoma: comparison between techniques and long term results. Radiol Med (Torino) 2004; 108 (04) 356-371
    PubMedSearch in Google Scholar
  • 43 Zhou Y-F. High intensity focused ultrasound in clinical tumor ablation. World J Clin Oncol 2011; 2 (01) 8-27
    CrossrefPubMedSearch in Google Scholar
  • 44 Zhao LY, Liu S, Chen ZG, Zou JZ, Wu F. Cavitation enhances coagulated size during pulsed high-intensity focused ultrasound ablation in an isolated liver perfusion system. Int J Hyperthermia 2017; 33 (03) 343-353
    CrossrefPubMedSearch in Google Scholar
  • 45 Jin C, Zhu H, Wang Z. , et al. High-intensity focused ultrasound combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: long-term follow-up and clinical analysis. Eur J Radiol 2011; 80 (03) 662-669
    CrossrefPubMedSearch in Google Scholar
  • 46 Lewandowski RJ, Gabr A, Abouchaleh N. , et al. Radiation segmentectomy: potential curative therapy for early hepatocellular carcinoma. Radiology 2018; 287 (03) 1050-1058
    CrossrefPubMedSearch in Google Scholar
  • 47 Riaz A, Gates VL, Atassi B. , et al. Radiation segmentectomy: a novel approach to increase safety and efficacy of radioembolization. Int J Radiat Oncol Biol Phys 2011; 79 (01) 163-171
    CrossrefPubMedSearch in Google Scholar
  • 48 Salem R, Gordon AC, Mouli S. , et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2016; 151 (06) 1155-1163.e2
    CrossrefPubMedSearch in Google Scholar
  • 49 Padia SA, Johnson GE, Horton KJ. , et al. Segmental yttrium-90 radioembolization versus segmental chemoembolization for localized hepatocellular carcinoma: results of a single-center, retrospective, propensity score-matched study. J Vasc Interv Radiol 2017; 28 (06) 777-785.e1
    CrossrefPubMedSearch in Google Scholar
  • 50 Shiina S, Tagawa K, Unuma T. , et al. Percutaneous ethanol injection therapy for hepatocellular carcinoma. A histopathologic study. Cancer 1991; 68 (07) 1524-1530
    CrossrefPubMedSearch in Google Scholar
  • 51 Vilana R, Bruix J, Bru C, Ayuso C, Solé M, Rodés J. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Hepatology 1992; 16 (02) 353-357
    CrossrefPubMedSearch in Google Scholar
  • 52 Knab LM, Salem R, Mahvi DM. Minimally invasive therapies for hepatic malignancy. Curr Probl Surg 2013; 50 (04) 146-179
    CrossrefPubMedSearch in Google Scholar
  • 53 Tanaka K, Okazaki H, Nakamura S. , et al. Hepatocellular carcinoma: treatment with a combination therapy of transcatheter arterial embolization and percutaneous ethanol injection. Radiology 1991; 179 (03) 713-717
    CrossrefPubMedSearch in Google Scholar
  • 54 Fu Y, Zhao X, Yun Q. , et al. Transarterial chemoembolization (TACE) plus percutaneous ethanol injection (PEI) for the treatment of unresectable hepatocellular carcinoma: a meta-analysis of randomized controlled trials. Int J Clin Exp Med 2015; 8 (07) 10388-10400
    PubMedSearch in Google Scholar
  • 55 Bujold A, Massey CA, Kim JJ. , et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 2013; 31 (13) 1631-1639
    CrossrefPubMedSearch in Google Scholar
  • 56 Demaria S, Coleman CN, Formenti SC. Radiotherapy: changing the game in immunotherapy. Trends Cancer 2016; 2 (06) 286-294
    PubMedSearch in Google Scholar
  • 57 Murray LJ, Dawson LA. Advances in stereotactic body radiation therapy for hepatocellular carcinoma. Semin Radiat Oncol 2017; 27 (03) 247-255
    CrossrefPubMedSearch in Google Scholar
  • 58 Su TS, Lu HZ, Cheng T. , et al. Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma >5 cm. BMC Cancer 2016; 16 (01) 834
    CrossrefPubMedSearch in Google Scholar
  • 59 Charpentier KP, Wolf F, Noble L, Winn B, Resnick M, Dupuy DE. Irreversible electroporation of the liver and liver hilum in swine. HPB (Oxford) 2011; 13 (03) 168-173
    CrossrefPubMedSearch in Google Scholar
  • 60 Guo Y, Zhang Y, Jin N. , et al. Electroporation-mediated transcatheter arterial chemoembolization in the rabbit VX2 liver tumor model. Invest Radiol 2012; 47 (02) 116-120
    CrossrefPubMedSearch in Google Scholar
  • 61 Vollherbst D, Bertheau RC, Fritz S. , et al. Electrochemical effects after transarterial chemoembolization in combination with percutaneous irreversible electroporation: observations in an acute porcine liver model. J Vasc Interv Radiol 2016; 27 (06) 913-921.e2
    CrossrefPubMedSearch in Google Scholar
  • 62 Isfort P, Rauen P, Na HS. , et al. Does drug-eluting bead TACE enhance the local effect of IRE? Imaging and histopathological evaluation in a porcine model. Cardiovasc Intervent Radiol 2019; 42 (06) 880-885
    CrossrefPubMedSearch in Google Scholar
  • 63 Mukaida N, Nakamoto Y. Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma. World J Gastroenterol 2018; 24 (17) 1839-1858
    CrossrefPubMedSearch in Google Scholar
  • 64 Behm B, Di Fazio P, Michl P. , et al. Additive antitumour response to the rabbit VX2 hepatoma by combined radio frequency ablation and toll like receptor 9 stimulation. Gut 2016; 65 (01) 134-143
    CrossrefPubMedSearch in Google Scholar
  • 65 Niu LZ, Li JL, Zeng JY. , et al. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer. World J Gastroenterol 2013; 19 (22) 3473-3480
    CrossrefPubMedSearch in Google Scholar
  • 66 Weng DS, Zhou J, Zhou QM. , et al. Minimally invasive treatment combined with cytokine-induced killer cells therapy lower the short-term recurrence rates of hepatocellular carcinomas. J Immunother 2008; 31 (01) 63-71
    CrossrefPubMedSearch in Google Scholar
  • 67 Lin M, Liang S, Wang X. , et al. Cryoablation combined with allogenic natural killer cell immunotherapy improves the curative effect in patients with advanced hepatocellular cancer. Oncotarget 2017; 8 (47) 81967-81977
    CrossrefPubMedSearch in Google Scholar
  • 68 Li X, Dai D, Song X, Liu J, Zhu L, Xu W. A meta-analysis of cytokine-induced killer cells therapy in combination with minimally invasive treatment for hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2014; 38 (05) 583-591
    CrossrefPubMedSearch in Google Scholar
  • 69 Nakamoto Y, Mizukoshi E, Kitahara M. , et al. Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization. Clin Exp Immunol 2011; 163 (02) 165-177
    CrossrefPubMedSearch in Google Scholar
  • 70 Tang C, Shen J, Feng W. , et al. Combination therapy of radiofrequency ablation and transarterial chemoembolization for unresectable hepatocellular carcinoma: a retrospective study. Medicine (Baltimore) 2016; 95 (20) e3754
    PubMedSearch in Google Scholar
  • 71 Lin J, Jiang X, Jin X, Lu L, Bao L. Clinical outcomes of radiofrequency ablation combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma: a single-center experience. Chinese J Oncol 2013; 35 (02) 144-147
    PubMedSearch in Google Scholar