Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Apr 27, 2020; 12(4): 149-158
Published online Apr 27, 2020. doi: 10.4240/wjgs.v12.i4.149
Mammalian target of rapamycin inhibitors after post-transplant hepatocellular carcinoma recurrence: Is it too late?
Kin Pan Au, Kenneth Siu Ho Chok
Kin Pan Au, Department of Surgery, Queen Mary Hospital, Hong Kong 999077, China
Kenneth Siu Ho Chok, Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong 999077, China
Author contributions: Chok KSH proposed the study; Au KP and Chok KSH conducted the study and wrote the manuscript.
Institutional review board statement: Institutional review board approval was not required for this study as it was a retrospective analysis of data and thus treatments given to patients were not affected by the study.
Informed consent statement: No informed consent forms were required as this was a retrospective cohort study.
Conflict-of-interest statement: None of the authors has any conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Kenneth Siu Ho Chok, FACS, FRCS (Ed), MBBS, Associate Professor, Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong 999077, China. chok6275@hku.hk
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: January 28, 2020
Revised: March 21, 2020
Accepted: March 26, 2020
Article in press: March 26, 2020
Published online: April 27, 2020
Processing time: 114 Days and 22.1 Hours
ARTICLE HIGHLIGHTS
Research 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.

Research motivation

It is unknown whether mTOR inhibitor still confers survival benefits following HCC recurrence. Recommendations for mTOR inhibitor under this context are based on expert opinions. To address this knowledge gap in the literature, the current study was undertaken to quantify survival following post-transplant HCC recurrence with regard to the administration of mTOR inhibitors.

Research objectives

The objective was to ascertain any survival benefits conferred by mTOR inhibitors following HCC recurrence after liver transplantation.

Research methods

A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed. The patients were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression. The primary endpoint was post-recurrence survival.

Research 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. There were no survival differences between patients treated with mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor.

Research conclusions

mTOR inhibitors prolonged survival after post-transplant HCC recurrence.

Research perspectives

The role of mTOR inhibitor therapy in post-transplant HCC recurrences should be confirmed with further prospective randomized studies. A further area of study should include patient selection for mTOR inhibitor treatment following HCC recurrence.