title: Validation of a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score for Hepatocellular Carcinoma Recurrence After Liver Transplant.
abstract: OBJECTIVE
  Several factors are associated with increased hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence.
  
  
  OBJECTIVE
  We aimed to develop and validate a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for patients with HCC meeting Milan criteria by imaging.
  
  
  METHODS
  Predictors of recurrence were tested in a development cohort of 721 patients who underwent LT between 2002 and 2012 at 3 academic transplant centers (University of California-San Francisco; Mayo Clinic, Rochester; and Mayo Clinic, Jacksonville) to create the RETREAT score. This was subsequently validated in a cohort of 341 patients also meeting Milan criteria by imaging who underwent LT at the University of Toronto transplant center using the C concordance statistic and net reclassification index.
  
  
  METHODS
  Characteristics associated with post-LT HCC recurrence.
  
  
  RESULTS
  A total of 1061 patients participated in the study; 77.8% (825) were men, and the median (IQR) age was 58.2 (53.3-63.9) years in the development cohort and 56.4 (51.7-61.0) years in the validation cohort (P < .001). In the development cohort of 721 patients (542 men), median α-fetoprotein (AFP) level at the time of LT was 8.3 ng/mL; 9.4% had microvascular invasion (n = 68), and 22.1% were beyond Milan criteria on explant (n = 159) owing to understaging by pretransplantation imaging. Cumulative probabilities of HCC recurrence at 1 and 5 years were 5.7% and 12.8%, respectively. On multivariable Cox proportional hazards regression, 3 variables were independently associated with HCC recurrence: microvascular invasion, AFP at time of LT, and the sum of the largest viable tumor diameter and number of viable tumors on explant. The RETREAT score was created using these 3 variables, with scores ranging from 0 to 5 or higher that were highly predictive of HCC recurrence (C statistic, 0.77). RETREAT was able to stratify 5-year post-LT recurrence risk ranging from less than 3% with a score of 0 to greater than 75% with a score of 5 or higher. The validation cohort (n = 340; 283 men) had significantly higher microvascular invasion (23.8% [n = 81], P < .001), explant beyond Milan criteria (37.3% [n = 159], P < .001), and HCC recurrence at 5 years (17.9% [n = 159], P = .03). RETREAT showed good model discrimination (C statistic, 0.82; 95% CI, 0.77-0.86) and superior recurrence risk classification compared with explant Milan criteria (net reclassification index, 0.40; P = .001) in the validation cohort.
  
  
  CONCLUSIONS
  We have developed and validated a simple and novel prognostic score that may improve post-LT HCC surveillance strategies and help identify patients who may benefit from future adjuvant therapies.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California-San Francisco.
authors.forename: Neil
authors.initials: N
authors.lastname: Mehta
authors.affiliation: Division of Transplantation, Department of Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Julie
authors.initials: J
authors.lastname: Heimbach
authors.affiliation: Department of Transplantation, Mayo Clinic, Jacksonville, Florida.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Harnois
authors.affiliation: Multi-Organ Transplant Program, Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Sapisochin
authors.affiliation: Division of Transplant Surgery, Department of Surgery, University of California-San Francisco.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dodge
authors.affiliation: Department of Transplantation, Mayo Clinic, Jacksonville, Florida.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Transplantation, Mayo Clinic, Jacksonville, Florida.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Burns
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: William
authors.initials: W
authors.lastname: Sanchez
authors.affiliation: Multi-Organ Transplant Program, Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Greig
authors.affiliation: Multi-Organ Transplant Program, Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Grant
authors.affiliation: Division of Transplant Surgery, Department of Surgery, University of California-San Francisco.
authors.forename: John P
authors.initials: JP
authors.lastname: Roberts
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California-San Francisco5Division of Transplant Surgery, Department of Surgery, University of California-San Francisco.
authors.forename: Francis Y
authors.initials: FY
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000509:alpha-Fetoproteins