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Article Dans Une Revue Annals of Surgery Année : 2020

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors

1 Universitätsklinikum Frankfurt
2 CHB - Centre Hépato-Biliaire [Hôpital Paul Brousse]
3 HUS - Les Hôpitaux Universitaires de Strasbourg
4 UKSH - University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein
5 IRCCS Istituto Nazionale dei Tumori [Milano]
6 Vall d'Hebron University Hospital [Barcelona]
7 Universitätsklinikum Münster
8 Unipd - Università degli Studi di Padova = University of Padua
9 CHU Saint-Antoine [AP-HP]
10 Azienda Ospedaliera di Padova
11 Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy]
12 Hôpital Henri Mondor
13 UniversitätsKlinikum Heidelberg
14 CHU Nice - Centre Hospitalier Universitaire de Nice
15 LUMC - Leiden University Medical Center
16 CUH - Cambridge University Hospitals - NHS
17 Addenbrooke's Hospital
18 UMCG - University Medical Center Groningen [Groningen]
19 University of Groningen [Groningen]
20 Uniklinik Essen - Universitätsklinikum Essen [Universität Duisburg-Essen]
21 MHH - Medizinische Hochschule Hannover = Hannover Medical School
22 University of Alberta
23 UCL - Université Catholique de Louvain = Catholic University of Louvain
24 HUS - Helsinki University Hospital [Finland]
25 University Hospitals Birmingham [Birmingham, Royaume-Uni]
26 Queens Elizabeth Hospital [Birmingham]
27 Universitätsklinikum Tübingen - University Hospital of Tübingen
28 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
29 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
30 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
31 Policlinico S. Orsola-malpighi
32 UZLeuven
33 Royal Infirmary of Edinburgh
34 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
35 Sahlgrenska University Hospital [Gothenburg]
36 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
37 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
38 CHUM - Centre Hospitalier de l'Université de Montréal
39 Uppsala University Hospital
40 Universitätsklinikum Jena [Jena]
41 Medizinische Universität Wien = Medical University of Vienna
42 Royal Prince Alfred Hospital
43 Karolinska University Hospital [Stockholm]
44 Ghent University Hospital
45 Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain]
46 University Hospital Regensburg
47 Fraunhofer ITEM - Fraunhofer Institute for Toxicology and Experimental Medicine
Jaques Pirenne
  • Fonction : Auteur


Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). Summary and background data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial ( NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. Patients and methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. Results: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). Conclusions: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients.



Dates et versions

hal-03340865 , version 1 (10-09-2021)



Andreas Schnitzbauer, Natalie Filmann, René Adam, Philippe Bachellier, Wolf Bechstein, et al.. mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors. Annals of Surgery, 2020, 272 (5), pp.855-862. ⟨10.1097/SLA.0000000000004280⟩. ⟨hal-03340865⟩
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