title: Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan.
abstract: BACKGROUND
  The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan.
  
  
  METHODS
  A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis.
  
  
  RESULTS
  One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9-1.4) at 10 years and 2.6 % (95 % CI 2.1-3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-year survivors (n = 5,387), confirmed these low incidence rates. The SIR of secondary cancers was 12.1 (95 % CI 10.1-14.4). In the Cox analysis, the hazard ratios for secondary cancers were 3.81 (95 % CI 1.53-9.47) for retinoblastoma, 2.78 (95 % CI 1.44-5.38) for bone/soft tissue sarcomas, and 1.81 (95 % CI 1.16-2.83) for allogeneic stem cell transplantation.
  
  
  CONCLUSIONS
  The cumulative incidence of secondary cancers in children in Japan was not high; however, the SIR was relatively high. Retinoblastoma or sarcoma in addition to allogeneic stem cell transplantation were significant risk factors for secondary cancers.
authors.affiliation: Pediatric Medical Center, Ehime Prefectural Central Hospital, Ehime 83 Kasuga-machi, Matsuyama-city, Ehime, Japan. yaishida2009@yahoo.co.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Department of Drug Dependence Research, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, Japan.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Qiu
authors.affiliation: Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Epidemiology and Clinical Research Center for Children's Cancer, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Fujimoto
authors.affiliation: Division of Hematology-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Kigasawa
authors.affiliation: Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Division of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
authors.affiliation: Division of Research Center for Radiation Protection, National Institute of Radiological Science, Chiba, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshinaga
authors.affiliation: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Rikiishi
authors.affiliation: Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shichino
authors.affiliation: Department of Child Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Kiyotani
authors.affiliation: Division of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Division of Pediatrics, Niigata Cancer Center, Niigata, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Asami
authors.affiliation: Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Department of Pediatrics, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Inada
authors.affiliation: Department of Human Health Sciences, Kyoto University School of Medicine, Kyoto, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Manabe
authors.affiliation: Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kuroda
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D007564:Japan; D008297:Male; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D016016:Proportional Hazards Models; D019572:Retinal Neoplasms / Q000628:therapy*; D012175:Retinoblastoma / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D012509:Sarcoma / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000706:statistics & numerical data; D011795:Surveys and Questionnaires; D015996:Survival Rate; D017741:Survivors / Q000706:statistics & numerical data*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000706:statistics & numerical data; D055815:Young Adult
keywords: Childhood cancer; Cumulative incidence; Risk factors; Secondary cancers; Standardized incidence ratio