title: Association of Sirolimus Use With Risk for Skin Cancer in a Mixed-Organ Cohort of Solid-Organ Transplant Recipients With a History of Cancer.
abstract: OBJECTIVE
  Solid-organ transplant recipients (OTRs) are at an increased risk for skin cancer. Prior studies have demonstrated a reduced incidence of skin cancer in renal OTRs treated with sirolimus. However, little information exists on the use of sirolimus for the prevention of skin cancer in nonrenal OTRs or those already diagnosed as having a posttransplant cancer.
  
  
  OBJECTIVE
  To compare subsequent skin cancer formation in a mixed-organ cohort of OTRs who were or were not treated with sirolimus after developing a posttransplant index cancer of any type.
  
  
  METHODS
  A 9-year retrospective cohort study at 2 academic tertiary care centers. Electronic medical records were reviewed for OTRs diagnosed as having a posttransplant cancer of any type to determine the type of organ transplanted, pretransplant and posttransplant cancer, and immunosuppressive medications. Patients underwent transplant from January 1, 2000, to December 31, 2008. Data were collected from July 30, 2011, to December 31, 2012, when follow-up was completed, and analyzed from April 28, 2013, to October 4, 2014.
  
  
  METHODS
  Factors associated with subsequent skin cancer development were evaluated via multivariate Cox regression analysis.
  
  
  RESULTS
  Of 329 OTRs with an index posttransplant cancer (100 women and 229 men; mean [SD] age, 56 [19] years), 177 (53.8%) underwent renal transplant; 58 (17.6%), heart transplant; 54 (16.4%), lung transplant; 34 (10.3%), liver transplant; and 6 (1.8%), mixed-organ transplant. Ninety-seven OTRs (29.5%) underwent conversion to sirolimus therapy after diagnosis. One hundred thirty OTRs (39.5%) developed second posttransplant cancers, of which 115 cases (88.5%) were skin cancers. An 11.6% reduction in skin cancer risk was observed in the sirolimus-treated vs non-sirolimus-treated groups overall (26 of 97 [26.8%] vs 89 of 232 [38.4%]; P = .045) and among nonrenal OTRs only (8 of 34 [23.5%] vs 44 of 112 [39.3%], respectively), although the latter difference was not significant (P = .09). Independent predictors of skin cancer formation after the index posttransplant cancer were history of pretransplant skin cancer (subhazard ratio, 2.1; 95% CI, 1.2-3.7), skin cancer as the index posttransplant cancer (subhazard ratio, 5.5; 95% CI, 2.5-6.4), and sirolimus treatment (subhazard ratio, 0.6; 95% CI, 0.4-0.9). These same risk factors were associated with skin cancer formation when the analysis was limited to nonrenal OTRs. No difference was found in allograft rejection or death between sirolimus-treated and non-sirolimus-treated groups.
  
  
  CONCLUSIONS
  In this mixed-organ cohort of OTRs, patients taking sirolimus after developing posttransplant cancer had a lower risk of developing subsequent skin cancer, with no increased risk for overall mortality. Thus, conversion to sirolimus therapy may be considered in OTRs who develop cancer if the risk for skin cancer is of concern. Larger studies are needed to quantify sirolimus-associated risk reduction for other cancer types.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Pritesh S
authors.initials: PS
authors.lastname: Karia
authors.affiliation: Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jamil R
authors.initials: JR
authors.lastname: Azzi
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston4Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: Eliot C
authors.initials: EC
authors.lastname: Heher
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Hills
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Chrysalyne D
authors.initials: CD
authors.lastname: Schmults
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000473:pathology; D016377:Organ Transplantation / Q000379:methods*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D062606:Tertiary Care Centers; D066027:Transplant Recipients
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus