title: Second solid malignancies among children, adolescents, and young adults diagnosed with malignant bone tumors after 1976: follow-up of a Children's Oncology Group cohort.
abstract: BACKGROUND
  The growing number of individuals surviving childhood cancer has increased the awareness of adverse long-term sequelae. One of the most worrisome complications after cancer therapy is the development of second malignant neoplasms (SMNs).
  
  
  METHODS
  The authors describe the incidence of solid organ SMN in survivors of pediatric malignant bone tumors who were treated on legacy Children's Cancer Group/Pediatric Oncology Group protocols from 1976 to 2005. This retrospective cohort study included 2842 patients: 1686 who were treated for osteosarcoma (OS) and 1156 who were treated for Ewing sarcoma (ES).
  
  
  RESULTS
  The cohort included 56% boys/young men and 44% girls/young women, and the median age at primary diagnosis was 13 years. The median length of follow-up was 6.1 years (range, 0-20.9 years). In this analysis, 64% of patients were alive. Seventeen patients with solid organ SMN were identified. The standardized incidence ratio was 2.9 (95% confidence interval [CI], 1.4-5.4) for patients who were treated for OS and 5.0 (95% CI, 2.6-9.4) for patients who were treated for ES. The median time from diagnosis to development of solid SMN was 7 years (range, 1-13 years). The 10-year cumulative incidence of solid organ SMN for the entire cohort was 1.4% (95%CI 0.6%-2%).
  
  
  CONCLUSIONS
  The magnitude of risk of solid SMNs was modest after treatment for malignant bone tumors. However, radiation-related solid SMNs will increase with longer follow-up. Because nearly 33% of patients die from their disease, recurrence remains the most significant problem. The development of improved therapies with fewer long-term consequences is paramount. Follow-up should focus on monitoring for both recurrence of primary malignancies and development of SMNs.
authors.affiliation: Department of Pediatric Oncology, University of California-San Francisco Children's Hospital, San Francisco, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldsby
authors.forename: Cynthia
authors.initials: C
authors.lastname: Burke
authors.forename: Rajaram
authors.initials: R
authors.lastname: Nagarajan
authors.forename: Tianni
authors.initials: T
authors.lastname: Zhou
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Neyssa
authors.initials: N
authors.lastname: Marina
authors.forename: Debra
authors.initials: D
authors.lastname: Friedman
authors.forename: Joseph
authors.initials: J
authors.lastname: Neglia
authors.forename: Paul
authors.initials: P
authors.lastname: Chuba
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000150:complications* / Q000175:diagnosis* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D015996:Survival Rate