title: Occurrence of multiple subsequent neoplasms in long-term survivors of childhood cancer: a report from the childhood cancer survivor study.
abstract: OBJECTIVE
  Childhood cancer survivors experience an increased incidence of subsequent neoplasms (SNs). Those surviving the first SN (SN1) remain at risk to develop multiple SNs. Because SNs are a common cause of late morbidity and mortality, characterization of rates of multiple SNs is needed.
  
  
  METHODS
  In a total of 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, analyses were carried out among 1,382 survivors with an SN1. Cumulative incidence of second subsequent neoplasm (SN2), either malignant or benign, was calculated.
  
  
  RESULTS
  A total of 1,382 survivors (9.6%) developed SN1, of whom 386 (27.9%) developed SN2. Of those with SN2, 153 (39.6%) developed more than two SNs. Cumulative incidence of SN2 was 46.9% (95% CI, 41.6% to 52.2%) at 20 years after SN1. The cumulative incidence of SN2 among radiation-exposed survivors was 41.3% (95% CI, 37.2% to 45.4%) at 15 years compared with 25.7% (95% CI, 16.5% to 34.9%) for those not treated with radiation. Radiation-exposed survivors who developed an SN1 of nonmelanoma skin cancer (NMSC) had a cumulative incidence of subsequent malignant neoplasm (SMN; ie, malignancies excluding NMSC) of 20.3% (95% CI, 13.0% to 27.6%) at 15 years compared with only 10.7% (95% CI, 7.2% to 14.2%) for those who were exposed to radiation and whose SN1 was an invasive SMN (excluding NMSC).
  
  
  CONCLUSIONS
  Multiple SNs are common among aging survivors of childhood cancer. SN1 of NMSC identifies a population at high risk for invasive SMN. Survivors not exposed to radiation who develop multiple SNs represent a population of interest for studying genetic susceptibility to neoplasia.
authors.affiliation: MSCE, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas Pl, Mail Stop 735, Memphis, TN, USA. greg.armstrong@stjude.org
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Sue
authors.initials: S
authors.lastname: Hammond
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Neglia
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Deokumar
authors.initials: D
authors.lastname: Srivastava
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D015999:Multivariate Analysis; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics; D012878:Skin Neoplasms / Q000453:epidemiology; D015996:Survival Rate; D017741:Survivors / Q000706:statistics & numerical data*; D055815:Young Adult