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Published in: BMC Gastroenterology 1/2014

Open Access 01-12-2014 | Research article

Radiofrequency ablation following first-line transarterial chemoembolization for patients with unresectable hepatocellular carcinoma beyond the Milan criteria

Authors: Lan Zhang, Xin Yin, Yu-hong Gan, Bo-heng Zhang, Ju-bo Zhang, Yi Chen, Xiao-ying Xie, Ning-lin Ge, Yan-hong Wang, Sheng-long Ye, Zheng-gang Ren

Published in: BMC Gastroenterology | Issue 1/2014

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Abstract

Background

Recent studies suggest that a combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have theoretical advantages over TACE alone for treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the effectiveness and safety of radiofrequency ablation following first-line TACE treatment in the management of HCC beyond the Milan Criteria.

Methods

Forty-five patients who consecutively underwent RFA following first-line TACE treatment for HCC beyond the Milan criteria were enrolled in this study. RFA was performed within 1–2 months after TACE treatment in patients who had incomplete necrotic tumor nodules. Primary effectiveness, complications, survival rates, and prognostic factors were evaluated retrospectively.

Results

Complete ablation was achieved in 76.2% of the lesions according to 1-month follow-up computed tomography/magnetic resonance imaging evaluation. The mean follow-up period was 30.9 months (range 3–94 months). There were no major complications after RFA therapy. The median overall survival was 29 months (range 20–38 months), with 1-, 2-, and 3-year survival of 89%, 61%, and 43%, respectively. Multivariate analysis revealed that tumor diameter (P = 0.045, hazard ratio [HR] = 0.228, 95% confidence interval [CI]: 0.054-0.968) and pretreatment serum alpha-fetoprotein level (P = 0.024, HR = 2.239, 95% CI: 1.114-4.500) were independent predictors for long-term survival.

Conclusions

HCC beyond the Milan criteria can be completely and safely ablated by radiofrequency ablation following first-line TACE treatment with a low rate of complications and favorable survival outcome. Further assessment of the survival benefits of combination treatment for HCCs beyond the Milan Criteria is warranted.
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Literature
1.
go back to reference Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC: From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics. 2004, 3: 73-81.CrossRefPubMed Ding SJ, Li Y, Tan YX, Jiang MR, Tian B, Liu YK, Shao XX, Ye SL, Wu JR, Zeng R, Wang HY, Tang ZY, Xia QC: From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics. 2004, 3: 73-81.CrossRefPubMed
2.
go back to reference Altekruse SF, McGlynn KA, Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009, 27: 1485-1491. 10.1200/JCO.2008.20.7753.CrossRefPubMedPubMedCentral Altekruse SF, McGlynn KA, Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009, 27: 1485-1491. 10.1200/JCO.2008.20.7753.CrossRefPubMedPubMedCentral
3.
go back to reference Sangiovanni A, Del Ninno E, Fasani P, De F, Ronchi G, Romeo R, Morabito A, De Franchis R, Colombo M: Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 2004, 126: 1005-1014. 10.1053/j.gastro.2003.12.049.CrossRefPubMed Sangiovanni A, Del Ninno E, Fasani P, De F, Ronchi G, Romeo R, Morabito A, De Franchis R, Colombo M: Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 2004, 126: 1005-1014. 10.1053/j.gastro.2003.12.049.CrossRefPubMed
4.
go back to reference Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J: Arterial embolisation or chemoembolisation versus symptomatic treatment in patient with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet. 2002, 359: 1734-1739. 10.1016/S0140-6736(02)08649-X.CrossRefPubMed Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J: Arterial embolisation or chemoembolisation versus symptomatic treatment in patient with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet. 2002, 359: 1734-1739. 10.1016/S0140-6736(02)08649-X.CrossRefPubMed
5.
go back to reference Lo CM, Nqan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J: Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002, 35: 1164-1167. 10.1053/jhep.2002.33156.CrossRefPubMed Lo CM, Nqan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J: Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002, 35: 1164-1167. 10.1053/jhep.2002.33156.CrossRefPubMed
6.
go back to reference Llovet JM, Bruix J: Systematic review of randomize trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003, 37: 429-442. 10.1053/jhep.2003.50047.CrossRefPubMed Llovet JM, Bruix J: Systematic review of randomize trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003, 37: 429-442. 10.1053/jhep.2003.50047.CrossRefPubMed
7.
go back to reference Jansen MC, van Hillegersberg R, Chamuleau RA, van Delden OM, Gouma DJ, van Guilk TM: Outcome of regional and local ablative therapies for hepatocellular carcinoma: a collective review. Eur J Surg Oncol. 2005, 31: 331-347. 10.1016/j.ejso.2004.10.011.CrossRefPubMed Jansen MC, van Hillegersberg R, Chamuleau RA, van Delden OM, Gouma DJ, van Guilk TM: Outcome of regional and local ablative therapies for hepatocellular carcinoma: a collective review. Eur J Surg Oncol. 2005, 31: 331-347. 10.1016/j.ejso.2004.10.011.CrossRefPubMed
8.
go back to reference McGahan JF, Dodd GD: Radiofrequency ablation of the liver: current status. Am J Roentgenol. 2001, 176: 3-16. 10.2214/ajr.176.1.1760003.CrossRef McGahan JF, Dodd GD: Radiofrequency ablation of the liver: current status. Am J Roentgenol. 2001, 176: 3-16. 10.2214/ajr.176.1.1760003.CrossRef
9.
go back to reference Lencioni R, Allgaier HP, Cioni D, Olschewski M, Deibert P, Crocetti L, Fring H, Laubenberger J, Zuber I, Blum HE, Bartolozzi C: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003, 228: 235-240. 10.1148/radiol.2281020718.CrossRefPubMed Lencioni R, Allgaier HP, Cioni D, Olschewski M, Deibert P, Crocetti L, Fring H, Laubenberger J, Zuber I, Blum HE, Bartolozzi C: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003, 228: 235-240. 10.1148/radiol.2281020718.CrossRefPubMed
10.
go back to reference Buscarini L, Buscarini E, Di Stasi M, Vallisa D, Quaretti P, Rocca A: Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long term results. Eur Radiol. 2001, 11: 914-921. 10.1007/s003300000659.CrossRefPubMed Buscarini L, Buscarini E, Di Stasi M, Vallisa D, Quaretti P, Rocca A: Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long term results. Eur Radiol. 2001, 11: 914-921. 10.1007/s003300000659.CrossRefPubMed
11.
go back to reference Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Ierace T, Solbiati L, Gazelle GS: Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology. 2000, 214: 761-768. 10.1148/radiology.214.3.r00mr02761.CrossRefPubMed Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Ierace T, Solbiati L, Gazelle GS: Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions. Radiology. 2000, 214: 761-768. 10.1148/radiology.214.3.r00mr02761.CrossRefPubMed
12.
go back to reference Dupuy DE, Goldberg SN: Image-guided radiofrequency tumor ablation: challenges and opportunities–part II. J Vasc Interv Radiol. 2001, 12: 1135-1148. 10.1016/S1051-0443(07)61670-4.CrossRefPubMed Dupuy DE, Goldberg SN: Image-guided radiofrequency tumor ablation: challenges and opportunities–part II. J Vasc Interv Radiol. 2001, 12: 1135-1148. 10.1016/S1051-0443(07)61670-4.CrossRefPubMed
13.
go back to reference Curley SA: Radiofrequency ablation of malignant liver tumors. Ann Surg Oncol. 2003, 10: 338-347. 10.1245/ASO.2003.07.017.CrossRefPubMed Curley SA: Radiofrequency ablation of malignant liver tumors. Ann Surg Oncol. 2003, 10: 338-347. 10.1245/ASO.2003.07.017.CrossRefPubMed
14.
go back to reference Hsu CY, Huang YH, Chiou YY, Su CW, Lin HC, Lee RC, Chiang JH, Huo TI, Lee FY, Lee SD: Comparison of radiofrequency ablation and transarterial chemoembolization for hepatocellular carcinoma within the Milan Criteria: A propensity score analysis. Liver Transpl. 2011, 17: 556-566. 10.1002/lt.22273.CrossRefPubMed Hsu CY, Huang YH, Chiou YY, Su CW, Lin HC, Lee RC, Chiang JH, Huo TI, Lee FY, Lee SD: Comparison of radiofrequency ablation and transarterial chemoembolization for hepatocellular carcinoma within the Milan Criteria: A propensity score analysis. Liver Transpl. 2011, 17: 556-566. 10.1002/lt.22273.CrossRefPubMed
15.
go back to reference Peng ZW, Chen MS, Liang HH, Gao HJ, Zhang YJ, Li JQ, Zhang YQ, Lau WY: A case–control study comparing percutaneous radiofrequency ablation alone or combined with transcatheter arterial chemoembolization for hepatocellular carcinoma. Eur J Surg Oncol. 2010, 36: 257-263. 10.1016/j.ejso.2009.07.007.CrossRefPubMed Peng ZW, Chen MS, Liang HH, Gao HJ, Zhang YJ, Li JQ, Zhang YQ, Lau WY: A case–control study comparing percutaneous radiofrequency ablation alone or combined with transcatheter arterial chemoembolization for hepatocellular carcinoma. Eur J Surg Oncol. 2010, 36: 257-263. 10.1016/j.ejso.2009.07.007.CrossRefPubMed
16.
go back to reference Takaki H, Yamakado K, Uraki J, Nakatsuka A, Fuke H, Yamamoto N, Shiraki K, Yamada T, Takeda K: Radiofrequency ablation combined with chemoembolization for the treatment of hepatocellular carcinomas larger than 5 cm. J Vasc Interv Radiol. 2009, 20: 217-224. 10.1016/j.jvir.2008.10.019.CrossRefPubMed Takaki H, Yamakado K, Uraki J, Nakatsuka A, Fuke H, Yamamoto N, Shiraki K, Yamada T, Takeda K: Radiofrequency ablation combined with chemoembolization for the treatment of hepatocellular carcinomas larger than 5 cm. J Vasc Interv Radiol. 2009, 20: 217-224. 10.1016/j.jvir.2008.10.019.CrossRefPubMed
17.
go back to reference Kirikoshi H, Saito S, Yoneda M, Fujita K, Mawatari H, Uchiyama T, Higurashi T, Goto A, Takahashi H, Abe Y, Inamori M, Kobayashi N, Kubota K, Sakaguchi T, Ueno N, Nakajima A: Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma. Hepatol Res. 2009, 39: 553-562. 10.1111/j.1872-034X.2009.00490.x.CrossRefPubMed Kirikoshi H, Saito S, Yoneda M, Fujita K, Mawatari H, Uchiyama T, Higurashi T, Goto A, Takahashi H, Abe Y, Inamori M, Kobayashi N, Kubota K, Sakaguchi T, Ueno N, Nakajima A: Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma. Hepatol Res. 2009, 39: 553-562. 10.1111/j.1872-034X.2009.00490.x.CrossRefPubMed
19.
go back to reference Yang B, Zou J, Xia J, Ren Z, Gan Y, Wang Y, Zhang B, Ge N, Wang D, Chen Y, Chen R, Li L, Ye S, Wang X: Risk factors for recurrence of small hepatocellular carcinoma after long-term follow-up of precutaneous radiofrequency ablation. Eur J Radiol. 2011, 79: 196-200. 10.1016/j.ejrad.2010.02.010.CrossRefPubMed Yang B, Zou J, Xia J, Ren Z, Gan Y, Wang Y, Zhang B, Ge N, Wang D, Chen Y, Chen R, Li L, Ye S, Wang X: Risk factors for recurrence of small hepatocellular carcinoma after long-term follow-up of precutaneous radiofrequency ablation. Eur J Radiol. 2011, 79: 196-200. 10.1016/j.ejrad.2010.02.010.CrossRefPubMed
20.
go back to reference Lau WY, Leung TW, Yu SC, Ho SK: Percutaneous local ablative therapy for hepatocellular carcinoma: a review and look into the future. Ann Surg. 2003, 237: 171-179.PubMedPubMedCentral Lau WY, Leung TW, Yu SC, Ho SK: Percutaneous local ablative therapy for hepatocellular carcinoma: a review and look into the future. Ann Surg. 2003, 237: 171-179.PubMedPubMedCentral
21.
go back to reference de Baere T, Elias D, Dromain C, Din MG, Kuoch V, Ducreux M, Boige V, Lassau N, Marteau V, Lasser P, Roche A: Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol. 2000, 175: 1619-1625. 10.2214/ajr.175.6.1751619.CrossRefPubMed de Baere T, Elias D, Dromain C, Din MG, Kuoch V, Ducreux M, Boige V, Lassau N, Marteau V, Lasser P, Roche A: Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol. 2000, 175: 1619-1625. 10.2214/ajr.175.6.1751619.CrossRefPubMed
22.
go back to reference Yamasaki T, Kurokawa F, Shirahashi H, Kusano N, Hironaka K, Okita K: Percutaneous radiofrequency ablation therapy for patients with hepatocellular carcinoma during occlusion of hepatic blood flow. Comparison with standard percutaneous radiofrequency ablation therapy. Cancer. 2002, 95: 2353-2360. 10.1002/cncr.10966.CrossRefPubMed Yamasaki T, Kurokawa F, Shirahashi H, Kusano N, Hironaka K, Okita K: Percutaneous radiofrequency ablation therapy for patients with hepatocellular carcinoma during occlusion of hepatic blood flow. Comparison with standard percutaneous radiofrequency ablation therapy. Cancer. 2002, 95: 2353-2360. 10.1002/cncr.10966.CrossRefPubMed
23.
go back to reference Rossi S, Garbagnati F, De Francesco I, Accocella F, Leonardi L, Quaretti P, Zangrandi A, Paties C, Lencioni R: Relationship between the shape and size of radiofrequency-induced thermal lesions and hepatic vascularization. Tumori. 1999, 85: 128-132.PubMed Rossi S, Garbagnati F, De Francesco I, Accocella F, Leonardi L, Quaretti P, Zangrandi A, Paties C, Lencioni R: Relationship between the shape and size of radiofrequency-induced thermal lesions and hepatic vascularization. Tumori. 1999, 85: 128-132.PubMed
24.
go back to reference Buscarini L, Buscarini E, Di Stasi M, Quaretti P, Zangrandi A: Percutaneous radiofrequency thermal ablation combined with transcatheter arterial embolization in the treatment of large hepatocellular carcinoma. Ultraschall Med. 1999, 20: 47-53. 10.1055/s-1999-14233.CrossRefPubMed Buscarini L, Buscarini E, Di Stasi M, Quaretti P, Zangrandi A: Percutaneous radiofrequency thermal ablation combined with transcatheter arterial embolization in the treatment of large hepatocellular carcinoma. Ultraschall Med. 1999, 20: 47-53. 10.1055/s-1999-14233.CrossRefPubMed
25.
go back to reference Lencioni R, Cioni D, Donati F, Bartolozzi C: Combination of interventional therapies in hepatocellular carcinoma. Hepatogastroenterology. 2001, 48: 8-14.PubMed Lencioni R, Cioni D, Donati F, Bartolozzi C: Combination of interventional therapies in hepatocellular carcinoma. Hepatogastroenterology. 2001, 48: 8-14.PubMed
26.
go back to reference Vogl TJ, Mack MG, Balzer JO, Engelmann K, Straub R, Eichler K, Woitaschek D, Zangos S: Liver metastases: neoadjuvant downsizing with trans-arterial chemoembolization before laser-induced thermotheraphy. Radiology. 2003, 229: 457-464. 10.1148/radiol.2292021329.CrossRefPubMed Vogl TJ, Mack MG, Balzer JO, Engelmann K, Straub R, Eichler K, Woitaschek D, Zangos S: Liver metastases: neoadjuvant downsizing with trans-arterial chemoembolization before laser-induced thermotheraphy. Radiology. 2003, 229: 457-464. 10.1148/radiol.2292021329.CrossRefPubMed
27.
go back to reference Veltri A, Moretto P, Doriguzzi A, Pagano E, Carrara G, Gandini G: Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC). Eur Radiol. 2006, 16: 661-669. 10.1007/s00330-005-0029-9.CrossRefPubMed Veltri A, Moretto P, Doriguzzi A, Pagano E, Carrara G, Gandini G: Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC). Eur Radiol. 2006, 16: 661-669. 10.1007/s00330-005-0029-9.CrossRefPubMed
28.
go back to reference Liao GS, Yu CY, Shih ML, Chan DC, Liu YC, Yu JC, Chen TW, Hsieh CB: Radiofrequency ablation after transarterial embolization as therapy for patients with unresectable hepatocellular carcinoma. Eur J Surg Oncol. 2008, 34: 61-66. 10.1016/j.ejso.2007.02.006.CrossRefPubMed Liao GS, Yu CY, Shih ML, Chan DC, Liu YC, Yu JC, Chen TW, Hsieh CB: Radiofrequency ablation after transarterial embolization as therapy for patients with unresectable hepatocellular carcinoma. Eur J Surg Oncol. 2008, 34: 61-66. 10.1016/j.ejso.2007.02.006.CrossRefPubMed
29.
go back to reference Stuart KE, Anand AJ, Jennins RL: Hepatocellular carcinoma in the United States. Cancer. 1996, 77: 2217-2222. 10.1002/(SICI)1097-0142(19960601)77:11<2217::AID-CNCR6>3.0.CO;2-M.CrossRefPubMed Stuart KE, Anand AJ, Jennins RL: Hepatocellular carcinoma in the United States. Cancer. 1996, 77: 2217-2222. 10.1002/(SICI)1097-0142(19960601)77:11<2217::AID-CNCR6>3.0.CO;2-M.CrossRefPubMed
30.
go back to reference Mondazzi L, Bottelli R, Brambilla G, Rampoldi A, Rezakovic I, Zavaglia C, Alberti A, Ideo G: Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma:A multivariate analysis of prognostic factors. Hepatology. 1994, 19: 1115-1123. 10.1002/hep.1840190508.CrossRefPubMed Mondazzi L, Bottelli R, Brambilla G, Rampoldi A, Rezakovic I, Zavaglia C, Alberti A, Ideo G: Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma:A multivariate analysis of prognostic factors. Hepatology. 1994, 19: 1115-1123. 10.1002/hep.1840190508.CrossRefPubMed
Metadata
Title
Radiofrequency ablation following first-line transarterial chemoembolization for patients with unresectable hepatocellular carcinoma beyond the Milan criteria
Authors
Lan Zhang
Xin Yin
Yu-hong Gan
Bo-heng Zhang
Ju-bo Zhang
Yi Chen
Xiao-ying Xie
Ning-lin Ge
Yan-hong Wang
Sheng-long Ye
Zheng-gang Ren
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2014
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-14-11

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