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Published in: Annals of Surgical Oncology 7/2017

01-07-2017 | Hepatobiliary Tumors

Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma

Authors: Aloysious D. Aravinthan, MBBS, MRCP, MRCP (Gastroenterology), PhD, Silvio G. Bruni, MD, Adam C. Doyle, MD, Hla-Hla Thein, MD, MPH, PhD, Nicolas Goldaracena, MD, Assaf Issachar, MD, Leslie B. Lilly, MSc, MD, FRCPC, Nazia Selzner, MD, PhD, Mamatha Bhat, MD, MSc, FRCPC, Boraiah Sreeharsha, MD, Markus Selzner, MD, Anand Ghanekar, MD, PhD, FRCSC, Mark S. Cattral, MD, MSc, FRCSC, Ian D. McGilvray, MD, FRCSC, PhD, Paul D. Greig, MD, FRCSC, FACS, Eberhard L. Renner, MD, FRCPC, David R. Grant, MD, FRCSC, Gonzalo Sapisochin, MD

Published in: Annals of Surgical Oncology | Issue 7/2017

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Abstract

Background

Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).

Methods

All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.

Results

Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p = 0.02) and tumor burden (p < 0.001). The majority of those listed underwent LT (n = 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599–15.464; p = 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660–12.768; p = 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (n = 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p = 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%.

Conclusion

Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.
Appendix
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Literature
1.
2.
go back to reference European Association for the Study of the L, European Organisation for R, Treatment of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.CrossRef European Association for the Study of the L, European Organisation for R, Treatment of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.CrossRef
3.
go back to reference Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.CrossRefPubMed Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.CrossRefPubMed
4.
go back to reference Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.CrossRefPubMed Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.CrossRefPubMed
5.
go back to reference Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394–403.CrossRefPubMed Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394–403.CrossRefPubMed
6.
go back to reference Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587–96.CrossRefPubMed Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587–96.CrossRefPubMed
7.
go back to reference Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:835–53.CrossRefPubMed Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:835–53.CrossRefPubMed
9.
go back to reference Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.CrossRefPubMed Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.CrossRefPubMed
10.
go back to reference Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–71.CrossRefPubMed Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–71.CrossRefPubMed
11.
go back to reference Cillo U, Giuliani T, Polacco M, et al. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol. 2016;22:232–52.CrossRefPubMedPubMedCentral Cillo U, Giuliani T, Polacco M, et al. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol. 2016;22:232–52.CrossRefPubMedPubMedCentral
12.
go back to reference Sapisochin G, Goldaracena N, Laurence JM, et al. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. 2016;64:2077–88.CrossRefPubMed Sapisochin G, Goldaracena N, Laurence JM, et al. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. 2016;64:2077–88.CrossRefPubMed
13.
go back to reference Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.CrossRefPubMed Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.CrossRefPubMed
14.
go back to reference Sandroussi C, Dawson LA, Lee M, et al. Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma. Transpl Int. 2010;23:299–306.CrossRefPubMed Sandroussi C, Dawson LA, Lee M, et al. Radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma. Transpl Int. 2010;23:299–306.CrossRefPubMed
15.
go back to reference Toso C, Meeberg G, Hernandez-Alejandro R, et al. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62:158–65.CrossRefPubMed Toso C, Meeberg G, Hernandez-Alejandro R, et al. Total tumor volume and alpha-fetoprotein for selection of transplant candidates with hepatocellular carcinoma: a prospective validation. Hepatology. 2015;62:158–65.CrossRefPubMed
16.
go back to reference Yang P, Zeng ZC, Wang BL, et al. The degree of Lipiodol accumulation can be an indicator of successful treatment for unresectable hepatocellular carcinoma (HCC) patients—in the case of transcatheter arterial chemoembolization (TACE) and external beam radiotherapy (EBRT). J Cancer. 2016;7:1413–20.CrossRefPubMedPubMedCentral Yang P, Zeng ZC, Wang BL, et al. The degree of Lipiodol accumulation can be an indicator of successful treatment for unresectable hepatocellular carcinoma (HCC) patients—in the case of transcatheter arterial chemoembolization (TACE) and external beam radiotherapy (EBRT). J Cancer. 2016;7:1413–20.CrossRefPubMedPubMedCentral
17.
go back to reference Zhao Y, Li H, Bai W, et al. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: a multicenter clinical study of 606 HCC patients. Int J Cancer. 2016;139:928–37.CrossRefPubMed Zhao Y, Li H, Bai W, et al. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: a multicenter clinical study of 606 HCC patients. Int J Cancer. 2016;139:928–37.CrossRefPubMed
18.
go back to reference Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol. 2016;64:1090–8.CrossRefPubMed Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol. 2016;64:1090–8.CrossRefPubMed
19.
go back to reference Lance C, McLennan G, Obuchowski N, et al. 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. 2011;22:1697–705.CrossRefPubMed Lance C, McLennan G, Obuchowski N, et al. 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. 2011;22:1697–705.CrossRefPubMed
20.
go back to reference Moreno-Luna LE, Yang JD, Sanchez W, et al. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2013;36:714–23.CrossRefPubMed Moreno-Luna LE, Yang JD, Sanchez W, et al. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2013;36:714–23.CrossRefPubMed
21.
go back to reference El Fouly A, Ertle J, El Dorry A, et al. In intermediate-stage hepatocellular carcinoma: radioembolization with yttrium-90 or chemoembolization? Liver Int. 2015;35:627–35.CrossRefPubMed El Fouly A, Ertle J, El Dorry A, et al. In intermediate-stage hepatocellular carcinoma: radioembolization with yttrium-90 or chemoembolization? Liver Int. 2015;35:627–35.CrossRefPubMed
22.
go back to reference Thein HH, Isaranuwatchai W, Campitelli MA, et al. Health care costs associated with hepatocellular carcinoma: a population-based study. Hepatology. 2013;58:1375–84.CrossRefPubMed Thein HH, Isaranuwatchai W, Campitelli MA, et al. Health care costs associated with hepatocellular carcinoma: a population-based study. Hepatology. 2013;58:1375–84.CrossRefPubMed
23.
go back to reference Belli LS, Berenguer M, Cortesi PA, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol. 2016;65:524–31.CrossRefPubMed Belli LS, Berenguer M, Cortesi PA, et al. Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: a European study. J Hepatol. 2016;65:524–31.CrossRefPubMed
24.
25.
26.
go back to reference Olthoff KM, Smith AR, Abecassis M, et al. Defining long-term outcomes with living donor liver transplantation in North America. Ann Surg. 2015;262:465–75, discussion 473–465.CrossRefPubMedPubMedCentral Olthoff KM, Smith AR, Abecassis M, et al. Defining long-term outcomes with living donor liver transplantation in North America. Ann Surg. 2015;262:465–75, discussion 473–465.CrossRefPubMedPubMedCentral
27.
go back to reference Selzner M, Kashfi A, Cattral MS, et al. Live donor liver transplantation in high MELD score recipients. Ann Surg. 2010;251:153–7.CrossRefPubMed Selzner M, Kashfi A, Cattral MS, et al. Live donor liver transplantation in high MELD score recipients. Ann Surg. 2010;251:153–7.CrossRefPubMed
28.
go back to reference Rossler F, Sapisochin G, Song G, et al. Defining benchmarks for major liver surgery: a multicenter analysis of 5202 living liver donors. Ann Surg. 2016;264:492–500.CrossRefPubMed Rossler F, Sapisochin G, Song G, et al. Defining benchmarks for major liver surgery: a multicenter analysis of 5202 living liver donors. Ann Surg. 2016;264:492–500.CrossRefPubMed
29.
go back to reference Bittermann T, Niu B, Hoteit MA, Goldberg D. Waitlist priority for hepatocellular carcinoma beyond milan criteria: a potentially appropriate decision without a structured approach. Am J Transplant. 2014;14:79–87.CrossRefPubMed Bittermann T, Niu B, Hoteit MA, Goldberg D. Waitlist priority for hepatocellular carcinoma beyond milan criteria: a potentially appropriate decision without a structured approach. Am J Transplant. 2014;14:79–87.CrossRefPubMed
30.
go back to reference Schmitt TM, Kumer SC, Shah N, et al. Liver transplantation for T3 lesions has higher waiting list mortality but similar survival compared to T1 and T2 lesions. Ann Hepatol. 2010;9:390–6.PubMed Schmitt TM, Kumer SC, Shah N, et al. Liver transplantation for T3 lesions has higher waiting list mortality but similar survival compared to T1 and T2 lesions. Ann Hepatol. 2010;9:390–6.PubMed
31.
go back to reference Mehta N, Sarkar M, Dodge JL, et al. Intention to treat outcome of T1 hepatocellular carcinoma with the “wait and not ablate” approach until meeting T2 criteria for liver transplant listing. Liver Transpl. 2016;22:178–87.CrossRefPubMedPubMedCentral Mehta N, Sarkar M, Dodge JL, et al. Intention to treat outcome of T1 hepatocellular carcinoma with the “wait and not ablate” approach until meeting T2 criteria for liver transplant listing. Liver Transpl. 2016;22:178–87.CrossRefPubMedPubMedCentral
32.
go back to reference Vitale A, D’Amico F, Frigo AC, et al. Response to therapy as a criterion for awarding priority to patients with hepatocellular carcinoma awaiting liver transplantation. Ann Surg Oncol. 2010;17:2290–302.CrossRefPubMed Vitale A, D’Amico F, Frigo AC, et al. Response to therapy as a criterion for awarding priority to patients with hepatocellular carcinoma awaiting liver transplantation. Ann Surg Oncol. 2010;17:2290–302.CrossRefPubMed
33.
go back to reference Merani S, Majno P, Kneteman NM, et al. The impact of waiting list alpha-fetoprotein changes on the outcome of liver transplant for hepatocellular carcinoma. J Hepatol. 2011;55:814–9.CrossRefPubMed Merani S, Majno P, Kneteman NM, et al. The impact of waiting list alpha-fetoprotein changes on the outcome of liver transplant for hepatocellular carcinoma. J Hepatol. 2011;55:814–9.CrossRefPubMed
34.
go back to reference Sapisochin G, Goldaracena N, Astete S, et al. Benefit of treating hepatocellular carcinoma recurrence after liver transplantation and analysis of prognostic factors for survival in a large Euro-American series. Ann Surg Oncol. 2015;22:2286–94.CrossRefPubMed Sapisochin G, Goldaracena N, Astete S, et al. Benefit of treating hepatocellular carcinoma recurrence after liver transplantation and analysis of prognostic factors for survival in a large Euro-American series. Ann Surg Oncol. 2015;22:2286–94.CrossRefPubMed
35.
go back to reference Bodzin AS, Lunsford KE, Markovic D, et al. Predicting mortality in patients developing recurrent hepatocellular carcinoma after liver transplantation: impact of treatment modality and recurrence characteristics. Ann Surg. 2016. Bodzin AS, Lunsford KE, Markovic D, et al. Predicting mortality in patients developing recurrent hepatocellular carcinoma after liver transplantation: impact of treatment modality and recurrence characteristics. Ann Surg. 2016.
36.
go back to reference Yao FY. Liver transplantation for hepatocellular carcinoma: beyond the Milan criteria. Am J Transplant. 2008;8:1982–9.CrossRefPubMed Yao FY. Liver transplantation for hepatocellular carcinoma: beyond the Milan criteria. Am J Transplant. 2008;8:1982–9.CrossRefPubMed
37.
go back to reference Toso C, Mentha G, Kneteman NM, Majno P. The place of downstaging for hepatocellular carcinoma. J Hepatol. 2010;52:930–6.CrossRefPubMed Toso C, Mentha G, Kneteman NM, Majno P. The place of downstaging for hepatocellular carcinoma. J Hepatol. 2010;52:930–6.CrossRefPubMed
38.
go back to reference Roberts JP, Venook A, Kerlan R, Yao F. Hepatocellular carcinoma: ablate and wait versus rapid transplantation. Liver Transpl. 2010;16:925–9.CrossRefPubMed Roberts JP, Venook A, Kerlan R, Yao F. Hepatocellular carcinoma: ablate and wait versus rapid transplantation. Liver Transpl. 2010;16:925–9.CrossRefPubMed
39.
go back to reference Pomfret EA, Washburn K, Wald C, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16:262–78.CrossRefPubMed Pomfret EA, Washburn K, Wald C, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16:262–78.CrossRefPubMed
40.
go back to reference Mulligan DC. The ongoing quest to find the appropriate patients to transplant with hepatocellular carcinoma: Milan to San Francisco to Toronto and beyond. Hepatology. 2016;64:1853–55.CrossRefPubMed Mulligan DC. The ongoing quest to find the appropriate patients to transplant with hepatocellular carcinoma: Milan to San Francisco to Toronto and beyond. Hepatology. 2016;64:1853–55.CrossRefPubMed
41.
go back to reference Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.CrossRefPubMed Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.CrossRefPubMed
43.
go back to reference Moray G, Karakayali F, Yilmaz U, et al. Expanded criteria for hepatocellular carcinoma and liver transplantation. Transplant Proc. 2007;39:1171–4.CrossRefPubMed Moray G, Karakayali F, Yilmaz U, et al. Expanded criteria for hepatocellular carcinoma and liver transplantation. Transplant Proc. 2007;39:1171–4.CrossRefPubMed
Metadata
Title
Liver Transplantation is a Preferable Alternative to Palliative Therapy for Selected Patients with Advanced Hepatocellular Carcinoma
Authors
Aloysious D. Aravinthan, MBBS, MRCP, MRCP (Gastroenterology), PhD
Silvio G. Bruni, MD
Adam C. Doyle, MD
Hla-Hla Thein, MD, MPH, PhD
Nicolas Goldaracena, MD
Assaf Issachar, MD
Leslie B. Lilly, MSc, MD, FRCPC
Nazia Selzner, MD, PhD
Mamatha Bhat, MD, MSc, FRCPC
Boraiah Sreeharsha, MD
Markus Selzner, MD
Anand Ghanekar, MD, PhD, FRCSC
Mark S. Cattral, MD, MSc, FRCSC
Ian D. McGilvray, MD, FRCSC, PhD
Paul D. Greig, MD, FRCSC, FACS
Eberhard L. Renner, MD, FRCPC
David R. Grant, MD, FRCSC
Gonzalo Sapisochin, MD
Publication date
01-07-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 7/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-017-5789-3

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