title: A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients.
abstract: BACKGROUND
  Although radiologic size criteria (Milan/University of California, San Francisco [UCSF]) have led to improved outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC), recurrence remains a significant challenge. We analyzed our 30-year experience with LT for HCC to identify predictors of recurrence.
  
  
  METHODS
  A novel clinicopathologic risk score and prognostic nomogram predicting post-transplant HCC recurrence was developed from a multivariate competing-risk Cox regression analysis of 865 LT recipients with HCC between 1984 and 2013.
  
  
  RESULTS
  Overall patient and recurrence-free survivals were 83%, 68%, 60% and 79%, 63%, and 56% at 1-, 3-, and 5-years, respectively. Hepatocellular carcinoma recurred in 117 recipients, with a median time to recurrence of 15 months, involving the lungs (59%), abdomen/pelvis (38%), liver (35%), bone (28%), pleura/mediastinum (12%), and brain (5%). Multivariate predictors of recurrence included tumor grade/differentiation (G4/poor diff hazard ratio [HR] 8.86; G2-3/mod-poor diff HR 2.56), macrovascular (HR 7.82) and microvascular (HR 2.42) invasion, nondownstaged tumors outside Milan criteria (HR 3.02), nonincidental tumors with radiographic maximum diameter ≥ 5 cm (HR 2.71) and <5 cm (HR 1.55), and pretransplant neutrophil-to-lymphocyte ratio (HR 1.77 per log unit), maximum alpha fetoprotein (HR 1.21 per log unit), and total cholesterol (HR 1.14 per SD). A pretransplantation model incorporating only known radiographic and laboratory parameters had improved accuracy in predicting HCC recurrence (C statistic 0.79) compared with both Milan (C statistic 0.64) and UCSF (C statistic 0.64) criteria alone. A novel clinicopathologic prognostic nomogram included explant pathology and had an excellent ability to predict post-transplant recurrence (C statistic 0.85).
  
  
  CONCLUSIONS
  In the largest single-institution experience with LT for HCC, excellent long-term survival was achieved. Incorporation of routine pretransplantation biomarkers to existing radiographic size criteria significantly improves the ability to predict post-transplant recurrence, and should be considered in recipient selection. A novel clinicopathologic prognostic nomogram accurately predicts HCC recurrence after LT and may guide frequency of post-transplantation surveillance and adjuvant therapy.
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Vatche G
authors.initials: VG
authors.lastname: Agopian
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Harlander-Locke
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Ali
authors.initials: A
authors.lastname: Zarrinpar
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Fady M
authors.initials: FM
authors.lastname: Kaldas
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Farmer
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Yersiz
authors.affiliation: Division of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finn
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Myron
authors.initials: M
authors.lastname: Tong
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Hiatt
authors.affiliation: Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA. Electronic address: rbusuttil@mednet.ucla.edu.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D009367:Neoplasm Staging / Q000379:methods*; D049451:Nomograms; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012495:San Francisco / Q000453:epidemiology; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D066027:Transplant Recipients; D047368:Tumor Burden; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins