; Jauch, Karl-Walter ; Rentsch, Markus ; Ganten, Tom M. ; Schmidt, Jan ; Settmacher, Utz ; Heise, Michael ; Rossi, Giorgio
; Cillo, Umberto ; Kneteman, Norman ; Adam, René ; van Hoek, Bart ; Bachellier, Philippe ; Wolf, Philippe ; Rostaing, Lionel ; Bechstein, Wolf O.
; Rizell, Magnus ; Powell, James ; Hidalgo, Ernest ; Gugenheim, Jean ; Wolters, Heiner ; Brockmann, Jens ; Roy, André ; Mutzbauer, Ingrid ; Schlitt, Angela ; Beckebaum, Susanne ; Graeb, Christian ; Nadalin, Silvio ; Valente, Umberto ; Turrión, Victor Sánchez ; Jamieson, Neville ; Scholz, Tim ; Colledan, Michele
; Fändrich, Fred ; Becker, Thomas ; Söderdahl, Gunnar ; Chazouillères, Olivier ; Mäkisalo, Heikki ; Pageaux, Georges-Philippe ; Steininger, Rudolf ; Soliman, Thomas ; de Jong, Koert P. ; Pirenne, Jacques
; Margreiter, Raimund ; Pratschke, Johann ; Pinna, Antonio D. ; Hauss, Johann ; Schreiber, Stefan ; Strasser, Simone ; Klempnauer, Jürgen ; Troisi, Roberto I. ; Bhoori, Sherrie
; Lerut, Jan ; Bilbao, Itxarone ; Klein, Christian G. ; Königsrainer, Alfred ; Mirza, Darius F. ; Otto, Gerd ; Mazzaferro, Vincenzo
; Neuhaus, Peter ; Schlitt, Hans J. | Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Transplantation | ||||
| Publisher: | Lippincott | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 100 | ||||
| Number of Issue or Book Chapter: | 1 | ||||
| Page Range: | pp. 116-125 | ||||
| Date: | 2016 | ||||
| Institutions: | Medicine > Lehrstuhl für Chirurgie | ||||
| Identification Number: |
| ||||
| Keywords: | RENAL-CELL CARCINOMA; RAPAMYCIN INHIBITORS; IMMUNOSUPPRESSION; RECURRENCE; SURVIVAL; TARGET; CANCER; METAANALYSIS; PROGRESSION; EVEROLIMUS; | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 42078 |
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 ...

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.
Metadata last modified: 17 Mar 2020 11:11
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