Yasushi Ishida1, Dongmei Qiu2, Miho Maeda3, Junichiro Fujimoto4, Hisato Kigasawa5, Ryoji Kobayashi6, Maho Sato7, Jun Okamura8, Shinji Yoshinaga9, Takeshi Rikiishi10, Hiroyuki Shichino11, Chikako Kiyotani12, Kazuko Kudo13, Keiko Asami14, Hiroki Hori15, Hiroshi Kawaguchi16, Hiroko Inada17, Souichi Adachi18, Atsushi Manabe19, Tatsuo Kuroda20. 1. Pediatric Medical Center, Ehime Prefectural Central Hospital, Ehime 83 Kasuga-machi, Matsuyama-city, Ehime, Japan. yaishida2009@yahoo.co.jp. 2. Department of Drug Dependence Research, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, Japan. 3. Department of Pediatrics, Nippon Medical School, Tokyo, Japan. 4. Epidemiology and Clinical Research Center for Children's Cancer, National Center for Child Health and Development, Tokyo, Japan. 5. Division of Hematology-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan. 6. Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan. 7. Division of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 8. Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan. 9. Division of Research Center for Radiation Protection, National Institute of Radiological Science, Chiba, Japan. 10. Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan. 11. Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan. 12. Department of Child Cancer Center, National Center for Child Health and Development, Tokyo, Japan. 13. Division of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan. 14. Division of Pediatrics, Niigata Cancer Center, Niigata, Japan. 15. Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan. 16. Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan. 17. Department of Pediatrics, Kurume University School of Medicine, Kurume, Japan. 18. Department of Human Health Sciences, Kyoto University School of Medicine, Kyoto, Japan. 19. Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan. 20. Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, 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.
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.
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