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New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

Abstract

BACKGROUND

Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the dose-response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined.

METHODS

Subsequent primary neoplasms of the CNS occurring within a cohort of 14,361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site-specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data.

RESULTS

Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% CI = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 [95% CI = 0.07 to 1.71] per Gy, and for meningioma, slope = 1.06 [95% CI = 0.21 to 8.15] per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10,000 person-years.

CONCLUSIONS

Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation.

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  • Authors+Show Affiliations

    ,

    Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN, USA. jneglia@umn.edu

    , , , , , , , , , ,

    Source

    Journal of the National Cancer Institute 98:21 2006 Nov 01 pg 1528-37

    MeSH

    Adolescent
    Adult
    Age Factors
    Brain
    Brain Neoplasms
    Canada
    Case-Control Studies
    Central Nervous System Neoplasms
    Child
    Child, Preschool
    Dose-Response Relationship, Radiation
    Female
    Glioma
    Humans
    Incidence
    Logistic Models
    Male
    Meningioma
    Neoplasms
    Neoplasms, Second Primary
    Odds Ratio
    Radiometry
    Radiotherapy
    Retrospective Studies
    Risk Assessment
    Risk Factors
    Survivors
    United States

    Pub Type(s)

    Journal Article
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17077355

    Citation

    Neglia, Joseph P., et al. "New Primary Neoplasms of the Central Nervous System in Survivors of Childhood Cancer: a Report From the Childhood Cancer Survivor Study." Journal of the National Cancer Institute, vol. 98, no. 21, 2006, pp. 1528-37.
    Neglia JP, Robison LL, Stovall M, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006;98(21):1528-37.
    Neglia, J. P., Robison, L. L., Stovall, M., Liu, Y., Packer, R. J., Hammond, S., ... Inskip, P. D. (2006). New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Journal of the National Cancer Institute, 98(21), pp. 1528-37.
    Neglia JP, et al. New Primary Neoplasms of the Central Nervous System in Survivors of Childhood Cancer: a Report From the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006 Nov 1;98(21):1528-37. PubMed PMID: 17077355.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. AU - Neglia,Joseph P, AU - Robison,Leslie L, AU - Stovall,Marilyn, AU - Liu,Yan, AU - Packer,Roger J, AU - Hammond,Sue, AU - Yasui,Yutaka, AU - Kasper,Catherine E, AU - Mertens,Ann C, AU - Donaldson,Sarah S, AU - Meadows,Anna T, AU - Inskip,Peter D, PY - 2006/11/2/pubmed PY - 2006/12/9/medline PY - 2006/11/2/entrez SP - 1528 EP - 37 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 98 IS - 21 N2 - BACKGROUND: Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the dose-response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined. METHODS: Subsequent primary neoplasms of the CNS occurring within a cohort of 14,361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site-specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data. RESULTS: Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% CI = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 [95% CI = 0.07 to 1.71] per Gy, and for meningioma, slope = 1.06 [95% CI = 0.21 to 8.15] per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10,000 person-years. CONCLUSIONS: Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/17077355/New_primary_neoplasms_of_the_central_nervous_system_in_survivors_of_childhood_cancer:_a_report_from_the_Childhood_Cancer_Survivor_Study_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djj411 DB - PRIME DP - Unbound Medicine ER -