Abstract
Hepatocellular carcinoma (HCC), the most common primary liver neoplasia, represents the fifth most common malignant disease in men. Percutaneous ablation treatment is recommended among the treatments suggested for HCC patients in the very early/early stage. In the last decade, very important results in terms of survival benefits have been obtained with local ablative therapies, also outside the standard indications, thanks to many technical innovations. In particular, important results of ablation as a safe and effective technique have been obtained in the treatment of intermediate- or advanced-stage patients with HCC, and in the treatment of unfavourable tumour locations. Moreover, awareness is growing regarding the necessity of overcoming the rigidity of traditional guidelines in the treatment of HCC due to the complexity of patients with HCC, focusing on Precision Medicine. In this context, it is important to know the standard and non-standard indications of ablation in the treatment of HCC in order to offer the best therapeutic option tailored for each patient. The aim of this study was to analyse the possible clinical applications of ablative therapies for HCC patients, beyond the traditional indications recommended in the most widespread clinical practice guidelines for the management of HCC.
Similar content being viewed by others
References
Himoto T, Kurokohchi K, Watanabe S, Masaki T. Recent advances in radiofrequency ablation for the management of hepatocellular carcinoma. Hepat Mon. 2012;12:e5945.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.
Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018.
Tiniakos DG, Maurício J, Reeves HL, et al. Fatty liver disease and hepatocellular carcinoma: the pathologist’s view. Adv Exp Med Biol. 2018;1032:55–69.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236.
Dimitroulis D, Damaskos C, Valsami S, et al. From diagnosis to treatment of hepatocellular carcinoma: an epidemic problem for both developed and developing world. World J Gastroenterol. 2017;23(29):5282–94.
Nault JC, Sutter O, Nahon P, et al. Percutaneous treatment of hepatocellular carcinoma: state of the art and innovations. Hepatology. 2018;68(4):783–97.
Giannini EG, Bucci L, Garuti F, et al. Patients with advanced hepatocellular carcinoma need a personalized management: a lesson from clinical practice. Hepatology. 2018;67(5):1784–96.
Putzer D, Schullian P, Braunwarth E, et al. Integrating interventional oncology in the treatment of liver tumors D. Eur Surg. 2018;50(3):117–24.
Poulou LS, Botsa E, Thanou I, et al. Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma. World J Hepatol. 2015;7(8):1054–63.
Facciorusso A, Serviddio G, Muscatiello N. Local ablative treatments for hepatocellular carcinoma: an updated review. World J Gastrointest Pharmacol Ther. 2016;7(4):477–89.
European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL–EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.
Kokudo N, Hasegawa K, Akahane M, et al. Evidence-based clinical practice guidelines for hepatocellular carcinoma: the Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res. 2015. https://doi.org/10.1111/hepr.12464.
Renzulli M, Golfieri R, Bologna Liver Oncology Group (BLOG) (2016) Proposal of a new diagnostic algorithm for hepatocellular carcinoma based on the Japanese guidelines but adapted to the Western world for patients under surveillance for chronic liver disease. J Gastroenterol Hepatol 31(1):69–80.
Heimbach J, Kulik LM, Finn R, et al. AASLD Guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358–80.
Tovoli F, Negrini G, Bolondi L. Comparative analysis of current guidelines for the treatment of hepatocellular carcinoma. Hepatol Oncol. 2016;3(2):119–36.
D’Avola D, Iñarrairaegui M, Pardo F, et al. Prognosis of hepatocellular carcinoma in relation to treatment across BCLC stages. Ann Surg Oncol. 2011;18(7):1964–71.
Ho EY, Cozen ML, Shen H, et al. Expanded use of aggressive therapies improves survival in early and intermediate hepatocellular carcinoma. HPB (Oxf). 2014;16(8):758–67.
Pecorelli A, Lenzi B, Gramenzi A, et al. Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma. Liver Int. 2016;37(3):423–33.
Bolondi L, Burroughs A, Dufour JF, et al. Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012;32(4):348–59.
Iezzi R, Pompili M, Posa A, Coppola G, Gasbarrini A, Bonomo L. Combined locoregional treatment of patients with hepatocellular carcinoma: state of the art. World J Gastroenterol. 2016;22(6):1935–42.
Di Costanzo GG, Tortora R. Intermediate hepatocellular carcinoma: how to choose the best treatment modality? World J Hepatol. 2015;7(9):1184–91.
Brace CL, Sampson LA, Hinshaw JL, Sandhu N, Lee FT Jr. Radiofrequency ablation: simultaneous application of multiple electrodes via switching creates larger, more confluent ablations than sequential application in a large animal model. J Vasc Interv Radiol. 2009;20(1):118–24.
Livraghi T, Goldberg SN, Lazzaroni S, et al. Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology. 2000;214(3):761–8.
Sangiovanni A, Colombo M. Treatment of hepatocellular carcinoma: beyond international guidelines. Liver Int. 2016;36:124–9.
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(3):309–14.
Wang Y, Deng T, Zeng L, Chen W. Efficacy and safety of radiofrequency ablation and transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a meta-analysis. Hepatol Res. 2016;46(1):58–71.
Ni JY, Liu SS, Xu LF, Sun HL, Chen YT. Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol. 2013;19(24):3872–82.
Marelli L, Stigliano R, Triantos C, et al. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies. Cancer Treat Rev. 2006;32(8):594–606.
Lu Z, Wen F, Guo Q, Liang H, Mao X, Sun H. Radiofrequency ablation plus chemoembolization versus radiofrequency ablation alone for hepatocellular carcinoma: a meta-analysis of randomized-controlled trials. Eur J Gastroenterol Hepatol. 2013;25(2):187–94.
Wang W, Shi J, Xie WF. Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta-analysis. Liver Int. 2010;30(5):741–9.
Wang N, Guan Q, Wang K, et al. TACE combined with PEI versus TACE alone in the treatment of HCC: a meta-analysis. Med Oncol. 2011;28(4):1038–43.
Kudo M, Matsui O, Izumi N, et al. JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer. 2014;3(3–4):458–68.
Commissione “Epatocarcinoma” dell’Associazione Italiana per lo Studio del Fegato. Epatocarcinoma: Linee Guida per la Diagnosi e la Terapia. Bologna: TipografiaModerna; 1998.
Benson AB III, Abrams TA, Ben-Josef E, et al. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Cancer Netw. 2009;7(4):350–91.
Ahrar K, Newman RA, Pang J, Vijjeswarapu MK, Wallace MJ, Wright KC. Dr. Gary J. Becker Young Investigator Award: Relative thermosensitivity of cytotoxic drugs used in transcatheter arterial chemoembolization. J Vasc Interv Radiol. 2004;15(9):901–5.
Cha CH, Saif MW, Yamane BH, Weber SM. Hepatocellular carcinoma: current management. Curr Probl Surg. 2010;47:10–67.
Lee MW, Kim YJ, Park SW, et al. Biplane fluoroscopy-guided radiofrequency ablation combined with chemoembolisation for hepatocellular carcinoma: initial experience. Br J Radiol. 2011;84:691–7.
Iezzi R, Cesario V, Siciliani L, et al. Single-step multimodal locoregional treatment for unresectable hepatocellular carcinoma: balloon-occluded percutaneous radiofrequency thermal ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE). Radiol Med. 2013;118(4):555–69.
Nouso K, Kariyama K, Nakamura S, et al. Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma. J Gastroenterol Hepatol. 2017;32(3):695–700.
Lin CC, Cheng YT, Chen M WT, Lin SM. The effectiveness of multiple electrode radiofrequency ablation in patients with hepatocellular carcinoma with lesions more than 3 cm in size and Barcelona Clinic Liver Cancer Stage A to B2. Liver Cancer. 2016;5(1):8–20.
Kariyama K, Wakuta A, Nishimura M, et al. Percutaneous radiofrequency ablation for intermediate-stage hepatocellular carcinoma. Oncology. 2015;89:19–26.
Hou YF, Wei YG, Yang JY, et al. Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC. Hepatobiliary Pancreat Dis Int. 2016;15(4):378–85.
Azuma S, Asahina Y, Nishimura-Sakurai Y, et al. Efficacy of additional radiofrequency ablation after transcatheter arterial chemoembolization for intermediate hepatocellular carcinoma. Hepatol Res. 2016;46(4):312–9.
Xu RC, Liu HC, Li JL, et al. Long-term outcome of transcatheter arterial chemoembolization after radiofrequency ablation as a combined therapy for Chinese patients with hepatocellular carcinoma. Curr Med Res Opin. 2015;31(8):1553–600.
Yin X, Zhang L, Wang YH, et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma. BMC Cancer. 2014;14:849.
Hoffmann R, Rempp H, Syha R, et al. Transarterial chemoembolization using drug eluting beads and subsequent percutaneous MR-guided radiofrequency ablation in the therapy of intermediate sized hepatocellular carcinoma. Eur J Radiol. 2014;83(10):1793–8.
Min JH, Lee MW, Cha DI, et al. Radiofrequency ablation combined with chemoembolization for intermediate-sized (3–5 cm) hepatocellular carcinomas under dual guidance of biplane fluoroscopy and ultrasonography. Korean J Radiol. 2013;14(2):248–58.
Ashoori N, Paprottka P, Trumm C, et al. Multimodality treatment with conventional transcatheter arterial chemoembolization and radiofrequency ablation for unresectable hepatocellular carcinoma. Digestion. 2012;85(1):18–26.
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):5452–60.
Zhao M, Wang JP, Pan CC, et al. CT-guided radiofrequency ablation after with transarterial chemoembolization in treating unresectable hepatocellular carcinoma with long overall survival improvement. Eur J Radiol. 2012;81(10):2717–25.
Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol. 2014;20(15):4115–277.
Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: beyond the known frontiers. World J Gastroenterol. 2019;25(31):4360–82.
Ricke J, Klümpen HJ, Amthauer H, et al. Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma. J Hepatol. 2019;71(6):1164–74.
Chow PKH, Gandhi M, Tan SB, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol. 2018;36(19):1913–21.
Vilgrain V, Pereira H, Assenat E, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017;18(12):1624–36.
Giorgio A, Merola MG, Montesarchio L, et al. Sorafenib combined with radio-frequency ablation compared with sorafenib alone in treatment of hepatocellular carcinoma invading portal vein: a Western Randomized Controlled Trial. Anticancer Res. 2016;36:6179–83.
Lu ZH, Shen F, Yan ZL, et al. Treatment of portal vein tumor thrombus of hepatocellular carcinoma with percutaneous laser ablation. J Cancer Res Clin Oncol. 2009;135:783–9.
Zheng JS, Long J, Sun B, et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation can improve survival of patients with hepatocellular carcinoma with portal vein tumour thrombosis: extending the indication for ablation? Clin Radiol. 2014;69:e253–e263263.
Tovoli F, Casadei-Gardini A, Benevento F, Piscaglia F. Immunotherapy for hepatocellular carcinoma: a review of potential new drugs based on ongoing clinical studies as of 2019. Dig Liver Dis. 2019;51(8):1067–73.
Roche’s Group. In: Roche’s Tecentriq in combination with Avastin increased overall survival and progression-free survival in people with unresectable hepatocellular carcinoma. https://www.roche.com/media/releases/med-cor-2019-10-21.htm. 2019. Accessed 15 Nov 2019.
Kang TW, Lim HK, Lee MW, et al. Long-term therapeutic outcomes of radiofrequency ablation for subcapsular vs. nonsubcapsular hepatocellular carcinoma: a propensity score matched study. Radiology. 2016;280:300–12.
Francica G, Meloni MF, de Sio I, et al. Radiofrequency and microwave ablation of subcapsular hepatocellular carcinoma accessed by direct puncture: safety and efficacy. Eur J Radiol. 2016;85:739–43.
Ni JY, Liu SS, Xu LF, Sun HL, Chen YT. Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol. 2013;19:3872–82.
Fukuda H, Numata K, Moriya S, et al. Hepatocellular carcinoma: concomitant sorafenib promotes necrosis after radiofrequency ablation—propensity score matching analysis. Radiology. 2014;272:598–604.
Renzulli M, Buonfiglioli F, Conti F, et al. Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis. Eur Radiol. 2018;28:506–13.
Tovoli F, Renzulli M, Negrini G, et al. Inter-operator variability and source of errors in tumour response assessment for hepatocellular carcinoma treated with sorafenib. Eur Radiol. 2018;28(9):3611–20.
Renzulli M, Clemente A, Brocchi S, et al. LI-RADS: a great opportunity not to be missed. Eur J Gastroenterol Hepatol. 2019;31(3):283–8.
Golfieri R, Garzillo G, Ascanio S, Renzulli M. Focal lesions in the cirrhotic liver: their pivotal role in gadoxetic acid-enhanced MRI and recognition by the Western guidelines. Dig Dis. 2014;32:696–704.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no competing interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Renzulli, M., Tovoli, F., Clemente, A. et al. Ablation for hepatocellular carcinoma: beyond the standard indications. Med Oncol 37, 23 (2020). https://doi.org/10.1007/s12032-020-01348-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12032-020-01348-y