title: Antitumor efficacy of mammalian target of rapamycin inhibitor therapy in liver transplant recipients with oncological disease: a case-control study.
abstract: BACKGROUND
  The reported incidences of de novo malignancy following orthotopic liver transplantation (OLT) are significantly greater than those in the general population. We have analyzed the efficacy of mammalian target of rapamycin inhibitor (mTORi) as immunosuppressant therapy in patients with de novo malignancies or those engrafted because of a primary liver cancer.
  
  
  METHODS
  We performed a case-control study of patients with hepatocellular carcinoma (HCC; n = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven patients with these tumors were treated with mTORi, and 167, with calcineurin inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the CNI over 15 days, until obtaining levels of 5-10 ng/dL.
  
  
  RESULTS
  No incidence of rejection, serious adverse events, or death was observed with an overall actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group. Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05). Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05).
  
  
  CONCLUSIONS
  Surprising differences in survival and tumor recurrence rates were observed among the mTORi-treated group compared with controls. Switching from CNI to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable to employ this strategy in liver transplant patients with primary hepatic or "de novo" neoplasms.
authors.affiliation: Liver Transplant Unit, Virgen del Rocío Hospital, Seville, Spain. jmalamom@hotmail.com
authors.forename: J M
authors.initials: JM
authors.lastname: Alamo
authors.forename: C
authors.initials: C
authors.lastname: Bernal
authors.forename: L M
authors.initials: LM
authors.lastname: Marín
authors.forename: G
authors.initials: G
authors.lastname: Suárez
authors.forename: J
authors.initials: J
authors.lastname: Serrano
authors.forename: L
authors.initials: L
authors.lastname: Barrera
authors.forename: J M
authors.initials: JM
authors.lastname: Sousa
authors.forename: F J
authors.initials: FJ
authors.lastname: Padillo
authors.forename: M A
authors.initials: MA
authors.lastname: Gómez-Bravo
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000601:surgery*; D016031:Liver Transplantation; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases