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Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan

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International Journal of Clinical Oncology Aims and scope Submit manuscript

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.

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Abbreviations

SIR:

Standardized incidence ratio

CI:

Confidence interval

CCSS:

Childhood Cancer Survivor Study

BCCSS:

British Childhood Cancer Survivor Study

AML:

Acute myeloid leukemia

MDS:

Myelodysplastic syndrome

AER:

Absolute excess risk

ALL:

Acute lymphoblastic leukemia

CML:

Chronic myeloid leukemia

NHL:

Non-Hodgkin’s lymphoma

PNET:

Primitive neuroectodermal tumor

HR:

Hazard ratio

OS:

Overall survival

OR:

Odds ratio

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Acknowledgments

The authors thank the medical staff of the following participating hospitals: (1) Pediatrics, Tohoku University School of Medicine, Sendai, Japan. (2) Pediatrics, St. Luke’s International Hospital, Tokyo, Japan. (3) Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan. (4) Child Cancer Center, National Center for Child Health and Development, Tokyo, Japan. (5) Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan. (6) Pediatrics, Niigata Cancer Center, Niigata, Japan. (7) Pediatrics, Mie University Graduate School of Medicine, Mie, Japan. (8) Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. (9) Pediatrics, Hiroshima University Hospital, Hiroshima, Japan. (10) Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan. (11) Pediatrics, Kurume University School of Medicine, Kurume, Japan. (12) Pediatrics, Nippon Medical School, Tokyo, Japan. (13) Hematology, Kanagawa Children’s Medical Center, Yokohama, Japan. (14) Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan. (15) Pediatrics, Kyoto University School of Medicine, Kyoto, Japan.

Author information

Authors and Affiliations

  1. Pediatric Medical Center, Ehime Prefectural Central Hospital, Ehime 83 Kasuga-machi, Matsuyama-city, Ehime, Japan

    Yasushi Ishida

  2. Department of Drug Dependence Research, National Center of Neurology and Psychiatry, National Institute of Mental Health, Tokyo, Japan

    Dongmei Qiu

  3. Department of Pediatrics, Nippon Medical School, Tokyo, Japan

    Miho Maeda

  4. Epidemiology and Clinical Research Center for Children’s Cancer, National Center for Child Health and Development, Tokyo, Japan

    Junichiro Fujimoto

  5. Division of Hematology-Oncology/Regenerative Medicine, Kanagawa Children’s Medical Center, Yokohama, Japan

    Hisato Kigasawa

  6. Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan

    Ryoji Kobayashi

  7. Division of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

    Maho Sato

  8. Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    Jun Okamura

  9. Division of Research Center for Radiation Protection, National Institute of Radiological Science, Chiba, Japan

    Shinji Yoshinaga

  10. Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan

    Takeshi Rikiishi

  11. Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan

    Hiroyuki Shichino

  12. Department of Child Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Chikako Kiyotani

  13. Division of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    Kazuko Kudo

  14. Division of Pediatrics, Niigata Cancer Center, Niigata, Japan

    Keiko Asami

  15. Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan

    Hiroki Hori

  16. Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan

    Hiroshi Kawaguchi

  17. Department of Pediatrics, Kurume University School of Medicine, Kurume, Japan

    Hiroko Inada

  18. Department of Human Health Sciences, Kyoto University School of Medicine, Kyoto, Japan

    Souichi Adachi

  19. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    Atsushi Manabe

  20. Department of Pediatric Surgery, Keio University School of Medicine, Tokyo, Japan

    Tatsuo Kuroda

Authors
  1. Yasushi Ishida
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  2. Dongmei Qiu
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  3. Miho Maeda
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  14. Keiko Asami
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  15. Hiroki Hori
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  16. Hiroshi Kawaguchi
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  17. Hiroko Inada
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  18. Souichi Adachi
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  19. Atsushi Manabe
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  20. Tatsuo Kuroda
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Corresponding author

Correspondence to Yasushi Ishida.

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Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by a research grant ‘Research on the construction of a long term follow-up center to know childhood cancer incidence and to evaluate the late effects and secondary cancers after childhood cancers’’ from the Japanese Ministry of Health, Labor and Welfare and in part by a grant from and a research grant from the St. Luke’s Life Science Institute.

Electronic supplementary material

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Supplemental Fig. 1

Overall survival proportions of 2-month survivors (PDF 49 kb)

Supplemental Fig. 2

Comparison of secondary cancer distribution among previous reports (all/2-month survivors and 5-year survivors) (PDF 77 kb)

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Ishida, Y., Qiu, D., Maeda, M. et al. Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan. Int J Clin Oncol 21, 506–516 (2016). https://doi.org/10.1007/s10147-015-0927-z

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  • DOI: https://doi.org/10.1007/s10147-015-0927-z

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