title: An Increased Risk of Second Malignant Neoplasms After Rhabdomyosarcoma: Population-Based Evidence for a Cancer Predisposition Syndrome?
abstract: BACKGROUND
  Rhabdomyosarcoma survivors have an increased risk of developing second malignant neoplasms (SMN); this risk is traditionally attributed to the effects of multidisciplinary management required for cure. However, the impact of constitutional predisposition has not been properly analyzed.
  
  
  METHODS
  We analyzed the risk of SMN among 1,151 children diagnosed with rhabdomyosarcoma and reported to the Surveillance, Epidemiology, and End Results registries (SEER-9) from 1973 to 2010. Standardized incidence ratios (SIR) and corresponding 95% confidence intervals (CI) were calculated using SEERStat 8.1.2.
  
  
  RESULTS
  Children with pleomorphic and embryonal rhabdomyosarcoma had an increased risk of developing a SMN (SIR = 15.77, 95%CI 1.91-56.96 and SIR = 5.6, 95%CI 3.32-8.85, respectively). The risk was age-dependent; the highest was among children <2 years (SIR = 13.38, 95%CI 4.34-31.22) and the lowest was in children >10 years (SIR = 3.35, 95%CI 1.53-6.35). The risk for the youngest patients was higher for those with embryonal rhabdomyosarcoma (SIR = 14.72, 95%CI 4.01-37.70) compared to other histiotypes. Additionally, the risk of SMN was independent of the use of radiation to the primary (SIR = 6.50, 95%CI 3.97-10.03 and SIR = 4.57, 95%CI 2.09-8.68, for children receiving and not receiving radiation, respectively). The pattern of SMN observed was consistent with the Li-Fraumeni spectrum.
  
  
  CONCLUSIONS
  Children with rhabdomyosarcoma are at high risk of developing SMN. This risk is higher for a subgroup of young children with pleomorphic and embryonal histologies, and is independent of the use of radiation. This suggests that a subgroup of children with pleomorphic and embryonal rhabdomyosarcoma may have a constitutional cancer predisposition.
authors.affiliation: Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Archer
authors.affiliation: Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil.
authors.forename: Renata Parada
authors.initials: RP
authors.lastname: Amorim
authors.affiliation: Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil.
authors.forename: Rafaela
authors.initials: R
authors.lastname: Naves
authors.affiliation: Department of Pediatric Hematology and Oncology, University of Freiburg, Freiburg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Hettmer
authors.affiliation: Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Diller
authors.affiliation: Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil.
authors.forename: Karina Braga
authors.initials: KB
authors.lastname: Ribeiro
authors.affiliation: Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodriguez-Galindo
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D012307:Risk Factors; D018426:SEER Program; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D013577:Syndrome; D055815:Young Adult
keywords: SEER program; TP53; anaplasia; rhabdomyosarcoma; second malignancy