Geissler, Edward K. and Schnitzbauer, Andreas A. and Zuelke, Carl and Lamby, Philipp E. and Proneth, Andrea and Duvoux, Christophe and Burra, Patrizia and Jauch, Karl-Walter and Rentsch, Markus and Ganten, Tom M. and Schmidt, Jan and Settmacher, Utz and Heise, Michael and Rossi, Giorgio and Cillo, Umberto and Kneteman, Norman and Adam, Rene and van Hoek, Bart and Bachellier, Philippe and Wolf, Philippe and Rostaing, Lionel and Bechstein, Wolf O. and Rizell, Magnus and Powell, James and Hidalgo, Ernest and Gugenheim, Jean and Wolters, Heiner and Brockmann, Jens and Roy, Andre and Mutzbauer, Ingrid and Schlitt, Angela and Beckebaum, Susanne and Graeb, Christian and Nadalin, Silvio and Valente, Umberto and Sanchez Turrion, Victor and Jamieson, Neville and Scholz, Tim and Colledan, Michele and Faendrich, Fred and Becker, Thomas and Soderdahl, Gunnar and Chazouilleres, Olivier and Makisalo, Heikki and Pageaux, Georges-Philippe and Steininger, Rudolf and Soliman, Thomas and de Jong, Koert P. and Pirenne, Jacques and Margreiter, Raimund and Pratschke, Johann and Pinna, Antonio D. and Hauss, Johann and Schreiber, Stefan and Strasser, Simone and Klempnauer, Juergen and Troisi, Roberto I. and Bhoori, Sherrie and Lerut, Jan and Bilbao, Itxarone and Klein, Christian G. and Koenigsrainer, Alfred and Mirza, Darius F. and Otto, Gerd and Mazzaferro, Vincenzo and Neuhaus, Peter and Schlitt, Hans J. (2016) Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. TRANSPLANTATION, 100 (1). pp. 116-125. ISSN 0041-1337, 1534-6080
Full text not available from this repository. (Request a copy)Abstract
Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age 60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RENAL-CELL CARCINOMA; RAPAMYCIN INHIBITORS; IMMUNOSUPPRESSION; RECURRENCE; SURVIVAL; TARGET; CANCER; METAANALYSIS; PROGRESSION; EVEROLIMUS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Mar 2019 10:05 |
| Last Modified: | 15 Mar 2019 10:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2703 |
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