Premium
Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria
Author(s) -
Kardashian Ani,
Florman Sander S.,
Haydel Brandy,
Ruiz Richard M.,
Klintmalm Goran B.,
Lee David D.,
Taner C. Burcin,
Aucejo Federico,
Tevar Amit D.,
Humar Abhinav,
Verna Elizabeth C.,
Halazun Karim J.,
Chapman William C.,
Vachharajani Neeta,
Hoteit Maarouf,
Levine Matthew H.,
Nguyen Mindie H.,
Melcher Marc L.,
Langnas Alan N.,
Carney Carol A.,
Mobley Constance,
Ghobrial Mark,
Amundsen Beth,
Markmann James F.,
Sudan Debra L.,
Jones Christopher M.,
Berumen Jennifer,
Hemming Alan W.,
Hong Johnny C.,
Kim Joohyun,
Zimmerman Michael A.,
Nydam Trevor L.,
Rana Abbas,
Kueht Michael L.,
Fishbein Thomas M.,
Markovic Daniela,
Busuttil Ronald W.,
Agopian Vatche G.
Publication year - 2020
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31210
Subject(s) - milan criteria , medicine , hepatocellular carcinoma , liver transplantation , gastroenterology , overall survival , cohort , multivariate analysis , carcinoma , oncology , transplantation
Background and Aims The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down‐staged (DS) with locoregional therapy (LRT). We evaluated post‐LT outcomes, predictors of down‐staging, and the impact of LRT in patients with beyond‐MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002‐2013). Approach and Results Clinicopathologic characteristics, overall survival (OS), recurrence‐free survival (RFS), and HCC recurrence (HCC‐R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down‐staged (DS, n = 465), treated with LRT and not down‐staged (LRT‐NoDS, n = 242), or untreated (NoLRT‐NoDS, n = 82). Five‐year post‐LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P < 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5‐year HCC‐R (18% vs. 32%, P < 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5‐year HCC‐R of 15.5% in DS/<5 cm and 39.1% in NoDS/>5 cm, P < 0.001). Multivariate predictors of down‐staging included alpha‐fetoprotein response to LRT, pathologic tumor number and size, and wait time >12 months. LRT‐NoDS had greater HCC‐R compared with NoLRT‐NoDS (34.1% vs. 26.1%, P < 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P < 0.001) and inverse probability of treatment‐weighted propensity matching (HR = 1.82, P < 0.001). Conclusions In LT recipients with HCC presenting beyond MC, successful down‐staging is predicted by wait time, alpha‐fetoprotein response to LRT, and tumor burden and results in excellent post‐LT outcomes, justifying expansion of LT criteria. In LRT‐NoDS patients, higher HCC‐R compared with NoLRT‐NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.