Literature DB >> 32426094

Mammalian target of rapamycin inhibitors after post-transplant hepatocellular carcinoma recurrence: Is it too late?

Kin Pan Au1, Kenneth Siu Ho Chok2.   

Abstract

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma (HCC). However, their role in established post-transplant HCC recurrence is uncertain. AIM: To investigate whether mTOR inhibitor offers a survival benefit in post-transplant HCC recurrence.
METHODS: A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed. They were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression. The primary endpoint was post-recurrence survival.
RESULTS: Seventy-nine (55%) patients received an mTOR inhibitor-based immunosuppressive regime, while 64 (45%) patients did not. The mTOR inhibitor group had a lower number of recurrent tumours (2 vs 5, P = 0.02) and received more active treatments including radiotherapy (39 vs 22%, P = 0.03) and targeted therapy (59 vs 23%, P < 0.001). The median post-recurrence survival was 21.0 ± 4.1 mo in the mTOR inhibitor group and 11.2 ± 2.5 mo in the control group. Multivariate Cox regression analysis confirmed that mTOR inhibitor therapy was independently associated with improved post-recurrence survival (P = 0.04, OR = 0.482, 95%CI: 0.241-0.966). The number of recurrent tumours and use of other treatment modalities did not affect survival. No survival difference was observed between mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor.
CONCLUSION: mTOR inhibitors prolonged survival after post-transplant HCC recurrence. ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

Entities:  

Keywords:  Hepatocellular carcinoma; Liver transplant; Mammalian target of rapamycin inhibitor; Outcomes; Recurrence; Survival

Year:  2020        PMID: 32426094      PMCID: PMC7215969          DOI: 10.4240/wjgs.v12.i4.149

Source DB:  PubMed          Journal:  World J Gastrointest Surg


  24 in total

1.  Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study.

Authors:  Lutz Fischer; Faouzi Saliba; Gernot M Kaiser; Luciano De Carlis; Herold J Metselaar; Paolo De Simone; Christophe Duvoux; Frederik Nevens; John J Fung; Gaohong Dong; Barbara Rauer; Guido Junge
Journal:  Transplantation       Date:  2015-07       Impact factor: 4.939

Review 2.  Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression.

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Journal:  Clin Biochem       Date:  1998-07       Impact factor: 3.281

3.  Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor.

Authors:  Markus Guba; Philipp von Breitenbuch; Markus Steinbauer; Gudrun Koehl; Stefanie Flegel; Matthias Hornung; Christiane J Bruns; Carl Zuelke; Stefan Farkas; Matthias Anthuber; Karl-Walter Jauch; Edward K Geissler
Journal:  Nat Med       Date:  2002-02       Impact factor: 53.440

4.  Oligometastases.

Authors:  S Hellman; R R Weichselbaum
Journal:  J Clin Oncol       Date:  1995-01       Impact factor: 44.544

5.  Meta-analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma.

Authors:  K V Menon; A R Hakeem; N D Heaton
Journal:  Aliment Pharmacol Ther       Date:  2012-12-20       Impact factor: 8.171

6.  Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma.

Authors:  Christian Toso; Shaheed Merani; David L Bigam; A M James Shapiro; Norman M Kneteman
Journal:  Hepatology       Date:  2010-04       Impact factor: 17.425

Review 7.  Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators.

Authors:  Michael A Zimmerman; R Mark Ghobrial; Myron J Tong; Jonathan R Hiatt; Andrew M Cameron; Johnny Hong; Ronald W Busuttil
Journal:  Arch Surg       Date:  2008-02

8.  Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation.

Authors:  Srinath Chinnakotla; Gary L Davis; Sugam Vasani; Peter Kim; Koji Tomiyama; Edmund Sanchez; Nicholas Onaca; Robert Goldstein; Marlon Levy; Göran B Klintmalm
Journal:  Liver Transpl       Date:  2009-12       Impact factor: 5.799

9.  Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.

Authors:  V Mazzaferro; E Regalia; R Doci; S Andreola; A Pulvirenti; F Bozzetti; F Montalto; M Ammatuna; A Morabito; L Gennari
Journal:  N Engl J Med       Date:  1996-03-14       Impact factor: 176.079

10.  Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

Authors:  Edward K Geissler; Andreas A Schnitzbauer; Carl Zülke; Philipp E Lamby; Andrea Proneth; Christophe Duvoux; Patrizia Burra; Karl-Walter Jauch; Markus Rentsch; Tom M Ganten; Jan Schmidt; Utz Settmacher; Michael Heise; Giorgio Rossi; Umberto Cillo; Norman Kneteman; René Adam; Bart van Hoek; Philippe Bachellier; Philippe Wolf; Lionel Rostaing; Wolf O Bechstein; Magnus Rizell; James Powell; Ernest Hidalgo; Jean Gugenheim; Heiner Wolters; Jens Brockmann; André Roy; Ingrid Mutzbauer; Angela Schlitt; Susanne Beckebaum; Christian Graeb; Silvio Nadalin; Umberto Valente; Victor Sánchez Turrión; Neville Jamieson; Tim Scholz; Michele Colledan; Fred Fändrich; Thomas Becker; Gunnar Söderdahl; Olivier Chazouillères; Heikki Mäkisalo; Georges-Philippe Pageaux; Rudolf Steininger; Thomas Soliman; Koert P de Jong; Jacques Pirenne; Raimund Margreiter; Johann Pratschke; Antonio D Pinna; Johann Hauss; Stefan Schreiber; Simone Strasser; Jürgen Klempnauer; Roberto I Troisi; Sherrie Bhoori; Jan Lerut; Itxarone Bilbao; Christian G Klein; Alfred Königsrainer; Darius F Mirza; Gerd Otto; Vincenzo Mazzaferro; Peter Neuhaus; Hans J Schlitt
Journal:  Transplantation       Date:  2016-01       Impact factor: 4.939

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  4 in total

Review 1.  The management of post-transplantation recurrence of hepatocellular carcinoma.

Authors:  Luckshi Rajendran; Tommy Ivanics; Marco Paw Claasen; Hala Muaddi; Gonzalo Sapisochin
Journal:  Clin Mol Hepatol       Date:  2021-10-05

2.  Performance of Dual-tracer PET-CT for Staging Post-Liver Transplant Hepatocellular Carcinoma Recurrence.

Authors:  Kin-Pan Au; Wing-Chiu Dai; Albert Chi-Yan Chan; Tan-To Cheung; Chung-Mau Lo; Kenneth Siu-Ho Chok
Journal:  Transplant Direct       Date:  2021-09-20

3.  Impact of Tumour Biology on Outcomes of Radical Therapy for Hepatocellular Carcinoma Oligo-Recurrence after Liver Transplantation.

Authors:  Kin-Pan Au; James Yan-Yue Fung; Wing-Chiu Dai; Albert Chi-Yan Chan; Chung-Mau Lo; Kenneth Siu-Ho Chok
Journal:  J Clin Med       Date:  2022-07-28       Impact factor: 4.964

4.  Sirolimus vs tacrolimus: Which one is the best therapeutic option for patients undergoing liver transplantation for hepatocellular carcinoma?

Authors:  Faiza Ahmed; Faiza Zakaria; Godsgift Enebong Nya; Mohamad Mouchli
Journal:  World J Gastrointest Surg       Date:  2022-08-27
  4 in total

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