Darren Jun Hao Tan1, Wen Hui Lim2, Jie Ning Yong2, Cheng Han Ng2, Mark D Muthiah3, Eunice X Tan3, Jieling Xiao2, Snow Yunni Lim2, Ansel Shao Pin Tang2, Xin Hui Pan2, Tousif Kabir4, Glenn K Bonney5, Raghav Sundar6, Nicholas Syn7, Beom Kyung Kim8, Yock Young Dan9, Mazen Noureddin10, Rohit Loomba11, Daniel Q Huang12. 1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: darrentan.j.h@gmail.com. 2. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 3. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore. 4. Department of General Surgery, Sengkang General Hospital, Singapore; Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore. 5. Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital, National University Health System, Singapore, Singapore. 6. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore. 7. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. 8. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea. 9. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. 10. Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California. 11. NAFLD Research Center, Division of Medicine, University of California San Diego, La Jolla, California. 12. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; NAFLD Research Center, Division of Medicine, University of California San Diego, La Jolla, California. Electronic address: daniel_huang@nus.edu.sg.
Abstract
BACKGROUND & AIMS: Down-staging is commonly used to select patients with hepatocellular carcinoma (HCC) beyond Milan criteria (MC) for liver transplantation (LT), but outcomes are heterogenous. We aimed to estimate pooled down-staging success rates, HCC recurrence, and overall survival (OS), stratified by criteria used for baseline tumor burden. METHODS: We searched Pubmed and EMBASE databases from inception until August 2021 for studies reporting down-staging success (reduction of tumor burden to within MC) and outcomes of adult HCC patients. In addition, we performed a pooled analysis using reconstructed individual participant data to obtain robust estimates for OS. RESULTS: We screened 1059 articles and included 25 articles involving 3997 patients. Overall, 55.16% (45.49%-64.46%) underwent successful down-staging, and 31.52% (24.03%-40.11%) received LT (by intention-to-treat analysis [ITT]). Among patients who received LT, 16.01% (11.80%-21.37%) developed HCC recurrence. Comparing studies that used the United Network for Organ Sharing Down-Staging (UNOS-DS) criteria versus studies beyond UNOS-DS or did not specify criteria, down-staging success (by ITT) was 83.21% versus 45.93%, P < .001; the proportion who received LT (by ITT) was 48.61% vs 28.60%, P = .030; and HCC recurrence (among patients who received LT) occurred in 9.06% versus 20.42%, P < .001. Among studies that used UNOS-DS criteria, ITT 1- and 5-year OS from the initiation of down-staging treatment was 86% and 58%, respectively, whereas 1- and 5-year post-LT OS was 94% and 74%, respectively. CONCLUSIONS: Among studies that adhered to UNOS-DS criteria, down-staging was successful in four-fifths of patients, >50% received LT, and post-LT outcomes were excellent. These data provide clinical validation for the utilization of UNOS-DS criteria.
BACKGROUND & AIMS: Down-staging is commonly used to select patients with hepatocellular carcinoma (HCC) beyond Milan criteria (MC) for liver transplantation (LT), but outcomes are heterogenous. We aimed to estimate pooled down-staging success rates, HCC recurrence, and overall survival (OS), stratified by criteria used for baseline tumor burden. METHODS: We searched Pubmed and EMBASE databases from inception until August 2021 for studies reporting down-staging success (reduction of tumor burden to within MC) and outcomes of adult HCC patients. In addition, we performed a pooled analysis using reconstructed individual participant data to obtain robust estimates for OS. RESULTS: We screened 1059 articles and included 25 articles involving 3997 patients. Overall, 55.16% (45.49%-64.46%) underwent successful down-staging, and 31.52% (24.03%-40.11%) received LT (by intention-to-treat analysis [ITT]). Among patients who received LT, 16.01% (11.80%-21.37%) developed HCC recurrence. Comparing studies that used the United Network for Organ Sharing Down-Staging (UNOS-DS) criteria versus studies beyond UNOS-DS or did not specify criteria, down-staging success (by ITT) was 83.21% versus 45.93%, P < .001; the proportion who received LT (by ITT) was 48.61% vs 28.60%, P = .030; and HCC recurrence (among patients who received LT) occurred in 9.06% versus 20.42%, P < .001. Among studies that used UNOS-DS criteria, ITT 1- and 5-year OS from the initiation of down-staging treatment was 86% and 58%, respectively, whereas 1- and 5-year post-LT OS was 94% and 74%, respectively. CONCLUSIONS: Among studies that adhered to UNOS-DS criteria, down-staging was successful in four-fifths of patients, >50% received LT, and post-LT outcomes were excellent. These data provide clinical validation for the utilization of UNOS-DS criteria.
Authors: Darren Jun Hao Tan; Cheng Han Ng; Phoebe Wen Lin Tay; Nicholas Syn; Mark D Muthiah; Wen Hui Lim; Ansel Shao Pin Tang; Kai En Lim; Grace En Hui Lim; Nobuharu Tamaki; Beom Kyung Kim; Margaret Li Peng Teng; James Fung; Rohit Loomba; Mindie H Nguyen; Daniel Q Huang Journal: JAMA Netw Open Date: 2022-06-01