title: Second malignancy risk among pediatric, adolescent, and young adult survivors of fusion-positive and fusion-negative sarcomas: Results from the SEER database, 1992 through 2012.
abstract: BACKGROUND
  The current study builds on the hypothesis that cancer-predisposing germline mutations are less common among patients with fusion-positive (F+) sarcomas compared to those with fusion-negative (F-) sarcomas, resulting in a lower risk of developing second malignant neoplasms (SMNs) in those with F + sarcomas.
  
  
  METHODS
  Standardized incidence ratios (SIRs) for developing SMNs were evaluated in 4822 survivors of F + and 3963 survivors of F- sarcomas that were diagnosed between 1992 and 2012 in pediatric, adolescent, and young adult patients (aged birth-39 years) and reported in the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards models (adjusted hazard ratio [aHR]) and competing risk methods (subhazard ratio [sHR]) were used to evaluate SMN risk in those with F- versus F + sarcomas while controlling for demographic and clinical variables.
  
  
  RESULTS
  SMN risk was found to be nearly 2-fold greater among survivors of F + sarcomas (SIR, 1.86; 95% confidence interval [95% CI], 1.48-2.30) and nearly 3-fold greater among survivors of F- sarcomas (SIR, 2.89; 95% CI, 2.30-3.59) compared with the reference population. Although SMN types were noted to be similar between the fusion groups, the rate of any SMN was noted to be greater among survivors of F- sarcomas (aHR, 1.38 [95% CI, 1.01-1.89] and sHR, 1.27 [95% CI, 0.94-1.73]) when compared with survivors of F + sarcomas. The difference was most notable for solid tumor SMNs after index sarcomas were diagnosed between 2002 and 2012, for which rates of SMN were >2-fold greater among survivors of F- sarcomas (aHR, 2.31 [95% CI, 1.20-4.48] and sHR, 2.24 [95% CI, 1.13-4.43]).
  
  
  CONCLUSIONS
  The findings of the current study highlight the increased SMN risk experienced by survivors of sarcoma and demonstrate higher SMN rates in survivors of F- sarcomas compared to those with a history of F + sarcomas. Cancer 2016;122:3492-3500. © 2016 American Cancer Society.
authors.affiliation: Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.affiliation: Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Austin L
authors.initials: AL
authors.lastname: Brown
authors.affiliation: Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Hettmer
keywords: Epidemiology; Surveillance; and End Results (SEER); epidemiology; fusion status; sarcoma; second malignant neoplasm