TY - JOUR
T1 - Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria
AU - Kardashian, Ani
AU - Florman, Sander S.
AU - Haydel, Brandy
AU - Ruiz, Richard M.
AU - Klintmalm, Goran B.
AU - Lee, David D.
AU - Taner, C. Burcin
AU - Aucejo, Federico
AU - Tevar, Amit D.
AU - Humar, Abhinav
AU - Verna, Elizabeth C.
AU - Halazun, Karim J.
AU - Chapman, William C.
AU - Vachharajani, Neeta
AU - Hoteit, Maarouf
AU - Levine, Matthew H.
AU - Nguyen, Mindie H.
AU - Melcher, Marc L.
AU - Langnas, Alan N.
AU - Carney, Carol A.
AU - Mobley, Constance
AU - Ghobrial, Mark
AU - Amundsen, Beth
AU - Markmann, James F.
AU - Sudan, Debra L.
AU - Jones, Christopher M.
AU - Berumen, Jennifer
AU - Hemming, Alan W.
AU - Hong, Johnny C.
AU - Kim, Joohyun
AU - Zimmerman, Michael A.
AU - Nydam, Trevor L.
AU - Rana, Abbas
AU - Kueht, Michael L.
AU - Fishbein, Thomas M.
AU - Markovic, Daniela
AU - Busuttil, Ronald W.
AU - Agopian, Vatche G.
N1 - Publisher Copyright:
© 2020 by the American Association for the Study of Liver Diseases.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85088292834&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088292834&partnerID=8YFLogxK
U2 - 10.1002/hep.31210
DO - 10.1002/hep.31210
M3 - Article
C2 - 32124453
AN - SCOPUS:85088292834
SN - 0270-9139
VL - 72
SP - 2014
EP - 2028
JO - Hepatology
JF - Hepatology
IS - 6
ER -