Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria.


Journal

Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946

Informations de publication

Date de publication:
12 2020
Historique:
received: 12 09 2019
revised: 29 12 2019
accepted: 05 02 2020
pubmed: 4 3 2020
medline: 5 5 2021
entrez: 4 3 2020
Statut: ppublish

Résumé

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). 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). 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.

Sections du résumé

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.

Identifiants

pubmed: 32124453
doi: 10.1002/hep.31210
doi:

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

2014-2028

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© 2020 by the American Association for the Study of Liver Diseases.

Références

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Auteurs

Ani Kardashian (A)

Vatche and Tamar Manoukian Division of Digestive Diseases, University of California, Los Angeles, Los Angeles, CA.

Sander S Florman (SS)

Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY.

Brandy Haydel (B)

Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY.

Richard M Ruiz (RM)

Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.

Goran B Klintmalm (GB)

Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.

David D Lee (DD)

Department of Transplantation, Mayo Clinic, Jacksonville, FL.

C Burcin Taner (CB)

Department of Transplantation, Mayo Clinic, Jacksonville, FL.

Federico Aucejo (F)

Cleveland Clinic Foundation, Cleveland, OH.

Amit D Tevar (AD)

Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA.

Abhinav Humar (A)

Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA.

Elizabeth C Verna (EC)

New York-Presbyterian Hospital, Columbia University, New York, NY.

Karim J Halazun (KJ)

New York-Presbyterian Hospital, Weill Cornell, New York, NY.

William C Chapman (WC)

Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO.

Neeta Vachharajani (N)

Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO.

Maarouf Hoteit (M)

Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA.

Matthew H Levine (MH)

Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA.

Mindie H Nguyen (MH)

Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA.

Marc L Melcher (ML)

Department of Surgery, Stanford University, Palo Alto, CA.

Alan N Langnas (AN)

Department of Surgery, University of Nebraska Medical Center, Omaha, NE.

Carol A Carney (CA)

Department of Surgery, University of Nebraska Medical Center, Omaha, NE.

Constance Mobley (C)

Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX.

Mark Ghobrial (M)

Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX.

Beth Amundsen (B)

Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

James F Markmann (JF)

Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Debra L Sudan (DL)

Department of Surgery, Duke University Medical Center, Durham, NC.

Christopher M Jones (CM)

Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, KY.

Jennifer Berumen (J)

Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA.

Alan W Hemming (AW)

Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA.

Johnny C Hong (JC)

Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI.

Joohyun Kim (J)

Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI.

Michael A Zimmerman (MA)

Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI.

Trevor L Nydam (TL)

Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Denver, CO.

Abbas Rana (A)

Department of Surgery, Baylor College of Medicine, Houston, TX.

Michael L Kueht (ML)

Department of Surgery, Baylor College of Medicine, Houston, TX.

Thomas M Fishbein (TM)

Medstar Georgetown Transplant Institute, Georgetown University, Washington, DC.

Daniela Markovic (D)

Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Ronald W Busuttil (RW)

Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Vatche G Agopian (VG)

Dumont-UCLA (University of California, Los Angeles) Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.

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