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http://dx.doi.org/10.3346/jkms.2018.33.e283

Efficacy of Sorafenib for the Treatment of Post-Transplant Hepatocellular Carcinoma Recurrence  

Kang, Seong Hee (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine)
Cho, Hyeki (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine)
Cho, Eun Ju (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine)
Lee, Jeong-Hoon (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine)
Yu, Su Jong (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine)
Kim, Yoon Jun (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine)
Yi, Nam-Joon (Department of Surgery, Seoul National University College of Medicine)
Lee, Kwang-Woong (Department of Surgery, Seoul National University College of Medicine)
Suh, Kyung-Suk (Department of Surgery, Seoul National University College of Medicine)
Yoon, Jung-Hwan (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine)
Publication Information
Journal of Korean Medical Science / v.33, no.45, 2018 , pp. 283.1-283.10 More about this Journal
Abstract
Background: The role of sorafenib in patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been rarely studied. The aim of this study was to evaluate the efficacy of sorafenib in post-LT era. Methods: Consecutive patients with post-transplant HCC recurrence not eligible to resection or locoregional therapy were included. Patients receiving best supportive care (BSC) until 2007 were compared with those treated by sorafenib thereafter. Results: Of a total of 65 patients, 20 patients received BSC and 45 received sorafenib. Clinical characteristics were similar between two groups except that sorafenib group received tacrolimus and mammalian target-of-rapamycin inhibitors more frequently than BSC group. Treatment with sorafenib conferred a survival advantage as compared with BSC for survival after recurrence (median, 14.2 vs. 6.8 months; P = 0.01). In multivariate analyses, high serum ${\alpha}$-fetoprotein level, synchronous intrahepatic recurrence and distant metastasis at the time of recurrence, and BSC were independently associated with poorer survival after recurrence. Sorafenib treatment was associated with better survival after recurrence as compared with BSC (hazard ratio, 0.25; 95% confidence interval, 0.10-0.62; P = 0.002). In addition, sorafenib group showed tolerable toxicity in the post-transplant setting. Conclusion: Sorafenib may be beneficial in patients with post-transplant HCC recurrence.
Keywords
Sorafenib; Liver Transplantation; Hepatocellular Carcinoma; Recurrence;
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1 Wang Z, Zhou J, Fan J, Qiu SJ, Yu Y, Huang XW, et al. Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 2008;14(16):5124-30.   DOI
2 Piguet AC, Saar B, Hlushchuk R, St-Pierre MV, McSheehy PM, Radojevic V, et al. Everolimus augments the effects of sorafenib in a syngeneic orthotopic model of hepatocellular carcinoma. Mol Cancer Ther 2011;10(6):1007-17.   DOI
3 Koeberle D, Dufour JF, Demeter G, Li Q, Ribi K, Samaras P, et al. Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29). Ann Oncol 2016;27(5):856-61.   DOI
4 Geissler EK, Schnitzbauer AA, Zulke C, Lamby PE, Proneth A, Duvoux C, et al. Sirolimus use in liver transplant recipients with hepatocellular carcinoma: a randomized, multicenter, open-label phase 3 trial. Transplantation 2016;100(1):116-25.   DOI
5 Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001;33(6):1394-403.   DOI
6 Davis E, Wiesner R, Valdecasas J, Kita Y, Rossi M, Schwartz M. Treatment of recurrent hepatocellular carcinoma after liver transplantation. Liver Transpl 2011;17 Suppl 2:S162-6.   DOI
7 Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334(11):693-9.   DOI
8 Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A, et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012;13(1):e11-22.   DOI
9 Hollebecque A, Decaens T, Boleslawski E, Mathurin P, Duvoux C, Pruvot FR, et al. Natural history and therapeutic management of recurrent hepatocellular carcinoma after liver transplantation. Gastroenterol Clin Biol 2009;33(5):361-9.   DOI
10 European Association for the Study of the Liver. EASL clinical practice guidelines: liver transplantation. J Hepatol 2016;64(2):433-85.   DOI
11 Lee HW, Suh KS. Liver transplantation for advanced hepatocellular carcinoma. Clin Mol Hepatol 2016;22(3):309-18.   DOI
12 Wang P, Li H, Shi B, Que W, Wang C, Fan J, et al. Prognostic factors in patients with recurrent hepatocellular carcinoma treated with salvage liver transplantation: a single-center study. Oncotarget 2016;7(23):35071-83.
13 de'Angelis N, Landi F, Carra MC, Azoulay D. Managements of recurrent hepatocellular carcinoma after liver transplantation: a systematic review. World J Gastroenterol 2015;21(39):11185-98.   DOI
14 Roayaie S, Schwartz JD, Sung MW, Emre SH, Miller CM, Gondolesi GE, et al. Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis. Liver Transpl 2004;10(4):534-40.   DOI
15 Park MS, Lee KW, Yi NJ, Choi YR, Kim H, Hong G, et al. Optimal tailored screening protocol after living donor liver transplantation for hepatocellular carcinoma. J Korean Med Sci 2014;29(10):1360-6.   DOI
16 Sheiner PA, Magliocca JF, Bodian CA, Kim-Schluger L, Altaca G, Guarrera JV, et al. Long-term medical complications in patients surviving > or = 5 years after liver transplant. Transplantation 2000;69(5):781-9.   DOI
17 Lee JY, Kim YH, Yi NJ, Kim HS, Lee HS, Lee BK, et al. Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation. Clin Mol Hepatol 2014;20(2):192-203.   DOI
18 Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378-90.   DOI
19 Sposito C, Mariani L, Germini A, Flores Reyes M, Bongini M, Grossi G, et al. Comparative efficacy of sorafenib versus best supportive care in recurrent hepatocellular carcinoma after liver transplantation: a case-control study. J Hepatol 2013;59(1):59-66.   DOI
20 Weinmann A, Niederle IM, Koch S, Hoppe-Lotichius M, Heise M, Duber C, et al. Sorafenib for recurrence of hepatocellular carcinoma after liver transplantation. Dig Liver Dis 2012;44(5):432-7.   DOI
21 Zavaglia C, Airoldi A, Mancuso A, Vangeli M, Vigano R, Cordone G, et al. Adverse events affect sorafenib efficacy in patients with recurrent hepatocellular carcinoma after liver transplantation: experience at a single center and review of the literature. Eur J Gastroenterol Hepatol 2013;25(2):180-6.   DOI
22 Toso C, Cader S, Mentha-Dugerdil A, Meeberg G, Majno P, Morard I, et al. Factors predicting survival after post-transplant hepatocellular carcinoma recurrence. J Hepatobiliary Pancreat Sci 2013;20(3):342-7.   DOI
23 Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011;53(3):1020-2.   DOI
24 Gomez-Martin C, Bustamante J, Castroagudin JF, Salcedo M, Garralda E, Testillano M, et al. Efficacy and safety of sorafenib in combination with mammalian target of rapamycin inhibitors for recurrent hepatocellular carcinoma after liver transplantation. Liver Transpl 2012;18(1):45-52.   DOI
25 de'Angelis N, Landi F, Nencioni M, Palen A, Lahat E, Salloum C, et al. Role of sorafenib in patients with recurrent hepatocellular carcinoma after liver transplantation. Prog Transplant 2016;26(4):348-55.   DOI
26 Korean Liver Cancer Study Group (KLCSG); National Cancer Center, Korea (NCC). 2014 KLCSG-NCC Korea practice guideline for the management of hepatocellular carcinoma. Gut Liver 2015;9(3):267-317.   DOI
27 Lee HW, Suh KS. Expansion of the criteria for living donor liver transplantation for hepatocellular carcinoma. Curr Opin Organ Transplant 2016;21(2):231-7.   DOI
28 Hong SK, Lee KW, Kim HS, Yoon KC, Yi NJ, Suh KS. Living donor liver transplantation for hepatocellular carcinoma in Seoul National University. Hepatobiliary Surg Nutr 2016;5(6):453-60.   DOI
29 Park MS, Lee KW, Suh SW, You T, Choi Y, Kim H, et al. Living-donor liver transplantation associated with higher incidence of hepatocellular carcinoma recurrence than deceased-donor liver transplantation. Transplantation 2014;97(1):71-7.   DOI
30 Grant RC, Sandhu L, Dixon PR, Greig PD, Grant DR, McGilvray ID. Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis. Clin Transplant 2013;27(1):140-7.   DOI
31 Vakili K, Pomposelli JJ, Cheah YL, Akoad M, Lewis WD, Khettry U, et al. Living donor liver transplantation for hepatocellular carcinoma: increased recurrence but improved survival. Liver Transpl 2009;15(12):1861-6.   DOI
32 Man K, Fan ST, Lo CM, Liu CL, Fung PC, Liang TB, et al. Graft injury in relation to graft size in right lobe live donor liver transplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression. Ann Surg 2003;237(2):256-64.   DOI
33 Kulik L, Abecassis M. Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology 2004;127(5 Suppl 1):S277-82.   DOI
34 Alsina AE, Makris A, Nenos V, Sucre E, Arrobas J, Franco E, et al. Can sorafenib increase survival for recurrent hepatocellular carcinoma after liver transplantation? A pilot study. Am Surg 2014;80(7):680-4.
35 Bhoori S, Toffanin S, Sposito C, Germini A, Pellegrinelli A, Lampis A, et al. Personalized molecular targeted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation: a proof of principle. J Hepatol 2010;52(5):771-5.   DOI