title: Rate of tumor growth predicts recurrence of hepatocellular carcinoma after liver transplantation in patients beyond Milan or UCSF criteria.
abstract: BACKGROUND
  It is likely that some patients whose tumor burdens exceed the current transplant criteria have favorable tumor biology, and that these patients would have low risk of tumor recurrence after liver transplantation (LT). To assess the rate of tumor growth as selection criteria for LT in patients with hepatocellular carcinoma (HCC).
  
  
  METHODS
  We identified all patients who underwent LT for HCC in our institution from 2002 to 2008. Total tumor volume (TTV) was calculated as the sum of the volumes of all tumors on pretransplantation imaging [(4/3)πr3, where r is the maximum radius of each HCC]. The rate of tumor growth was calculated as per-month change in TTV on sequential pretransplantation imaging before any locoregional therapy. A Kaplan-Meier plot was constructed and Cox regression analysis performed.
  
  
  RESULTS
  Ninety-two patients were included in the study. The median follow-up was 19.5 (range 10.7-30.7) months during which 12 patients (13%) experienced recurrence of HCC. Twenty-four patients (26%) had HCC beyond the Milan criteria, and the overall survival rate of the entire group was 72%. Higher pre-LT alpha-fetoprotein (hazard ratio [HR] 1.01; P=.001), poorly differentiated tumors (HR 13; P=.039), the presence of microvascular invasion (HR 7.9; P=.001), higher TTV (HR 1.03; P<.001), and faster tumor growth (HR 1.09; P<.001) were significantly associated with the risk of recurrence. A cutoff value of tumor growth of 1.61 cm3/mo was chosen on the basis of the risk of recurrence with the use of a receiver operating characteristic curve. Patients beyond the Milan criteria with tumor growth<1.61 cm3/mo experienced less recurrence (11% vs 58%; P=.023) than those beyond the Milan criteria with tumor growth>1.61 cm3/mo. Similarly, rate of tumor growth predicted HCC recurrence in those beyond the University of California of San Francisco (UCSF) criteria.
  
  
  CONCLUSIONS
  Patients with slowly growing tumor who would be currently excluded from LT because tumor burden exceeds traditional Milan and UCSF criteria may have a favorable posttransplantation outcome.
authors.affiliation: Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Hanouneh
authors.forename: C
authors.initials: C
authors.lastname: Macaron
authors.forename: R
authors.initials: R
authors.lastname: Lopez
authors.forename: F
authors.initials: F
authors.lastname: Aucejo
authors.forename: N N
authors.initials: NN
authors.lastname: Zein
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000601:surgery*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009820:Ohio; D018579:Patient Selection; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: C097353:AFP protein, human; D000509:alpha-Fetoproteins