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Secondary cancer after a childhood cancer diagnosis: viewpoints considering primary cancer

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Backgrounds

Multidisciplinary therapy has increased the risk of subsequent late effects, but detailed analyses on secondary cancers in childhood cancer survivors (CCSs) are limited in Asian countries.

Methods

This was a retrospective cohort study comprising 10,069 CCSs who were diagnosed between 1980 and 2009 across 15 Japanese hospitals. We conducted secondary analyses to estimate the incidence of secondary cancer according to each primary malignancy and to elucidate the association between primary and secondary cancers. We also explored the risk factors for the development of secondary cancer in each independent primary malignancy.

Results

The cumulative incidence of secondary cancer at 20 years varied among primary cancers: hematological malignancy, 3.1% (95% CI 2.2–4.3); retinoblastoma, 6.6% (95% CI 1.5–16.8); pediatric solid tumor, 2.5% (95% CI 1.3–4.2); brain tumors, 5.2% (95% CI 1.7–11.8) bone/soft tissue sarcoma, 5.2% (95% CI 2.3–10.1); and others, 3.3% (95% CI 1.6–6.0) (p = 0.015). The cumulative incidence of secondary cancers is highest in those with osteosarcoma (13.1%) followed by those with hepatoblastoma (8.4%) and retinoblastoma (6.6%). Close association between the primary and secondary cancer diagnoses was found. The risk factors for secondary cancer development depended on the primary cancer, but autologous/allogeneic stem cell transplantation was a relatively common risk factor.

Conclusion

The cumulative incidence of secondary cancer varied among primary cancers. The primary cancer was closely associated with the secondary cancer but stem cell transplantation was a common risk factor for secondary cancers among CCSs.

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Abbreviations

CCS:

Childhood cancer survivor

CCSS:

Childhood Cancer Survivor Study

BCCSS:

British Childhood Cancer Survivor Study

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

MDS:

Myelodysplastic syndrome

SCT:

Stem cell transplantation

HR:

Hazard ratio

SD:

Standard deviation

CI:

Confidence interval

PNET:

Primitive neuroectodermal tumor

MPNST:

Malignant peripheral nerve sheath tumor

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Acknowledgements

The authors thank the medical staffs 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) Children’s 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.

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’ (PI; Tatsuo Kuroda) from the Japanese Ministry of Health, Labor and Welfare and a AMED research grant ‘Establishment of standardized treatment for childhood myeloid leukemia’ (PI; Souichi Adachi) from the Japanese Ministry of Health, Labour and Welfare (Grant no. 17ck0106329h0001).

Author information

Authors and Affiliations

  1. Pediatric Medical Center, Ehime Prefectural Central Hospital, 83 Kasuga-machi, Matsuyama, Ehime, 790-0024, Japan

    Yasushi Ishida

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

    Miho Maeda

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

    Souichi Adachi

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

    Hiroko Inada

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

    Hiroshi Kawaguchi

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

    Hiroki Hori

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

    Atsushi Ogawa

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

    Kazuko Kudo

  9. Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

    Chikako Kiyotani

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

    Hiroyuki Shichino

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

    Takeshi Rikiishi

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

    Ryoji Kobayashi

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

    Maho Sato

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

    Jun Okamura

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

    Hiroaki Goto

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

    Atsushi Manabe

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

    Shinji Yoshinaga

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

    Dongmei Qiu

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

    Junichiro Fujimoto

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

    Tatsuo Kuroda

Authors
  1. Yasushi Ishida
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  2. Miho Maeda
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  3. Souichi Adachi
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  4. Hiroko Inada
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  5. Hiroshi Kawaguchi
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  6. Hiroki Hori
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  7. Atsushi Ogawa
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  8. Kazuko Kudo
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  9. Chikako Kiyotani
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  10. Hiroyuki Shichino
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  11. Takeshi Rikiishi
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  12. Ryoji Kobayashi
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  13. Maho Sato
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  14. Jun Okamura
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  15. Hiroaki Goto
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  16. Atsushi Manabe
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  17. Shinji Yoshinaga
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  18. Dongmei Qiu
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  19. Junichiro Fujimoto
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  20. Tatsuo Kuroda
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Contributions

Conception and design: YI, MM, JF, RK, SY and TK, Financial support: TK, SA and YI. Administrative support: YI and TK, Provision of study patients: YI, MM, SA, HI, HK, HH, AO, KK, CK, HS, TR, RK, MS, JO, HG, AM. Collection and assembly of data: YI and DQ. Data analysis and interpretation: YI. Manuscript writing: YI.

Corresponding author

Correspondence to Yasushi Ishida.

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Conflict of interest

All authors indicated no potential conflicts of interest.

Electronic supplementary material

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Supplemental Fig. 1

. Cumulative incidence of secondary cancers in neuroblastoma. Cumulative incidence of secondary cancers as a function of time after the primary cancer diagnosis over a maximum follow-up of 30 years as analyzed using the Gray method: (A) age groups at primary cancer diagnosis, (B) sex, (C) chemotherapy, (D) radiotherapy, (E) surgery, and (F) autologous stem cell transplantation (SCT). (TIF 194 KB)

Supplemental Fig. 2

Cumulative incidence of secondary cancers in those with primary cancer of rhabdomyosarcoma and other soft tissue sarcoma. Cumulative incidence of secondary cancers as a function of time after the primary cancer diagnosis over a maximum follow-up of 30 years as analyzed using the Gray method: (A) age groups at primary cancer diagnosis, (B) sex, (C) chemotherapy, (D) radiotherapy, (E) surgery, and (F) autologous stem cell transplantation (SCT). (TIF 204 KB)

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Ishida, Y., Maeda, M., Adachi, S. et al. Secondary cancer after a childhood cancer diagnosis: viewpoints considering primary cancer. Int J Clin Oncol 23, 1178–1188 (2018). https://doi.org/10.1007/s10147-018-1303-6

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  • DOI: https://doi.org/10.1007/s10147-018-1303-6

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