TY - JOUR
T1 - Radiation-related new primary solid cancers in the childhood cancer survivor study
T2 - Comparative radiation dose response and modification of treatment effects
AU - Inskip, Peter D.
AU - Sigurdson, Alice J.
AU - Veiga, Lene
AU - Bhatti, Parveen
AU - Ronckers, Cécile
AU - Rajaraman, Preetha
AU - Boukheris, Houda
AU - Stovall, Marilyn
AU - Smith, Susan
AU - Hammond, Sue
AU - Henderson, Tara O.
AU - Watt, Tanya C.
AU - Mertens, Ann C.
AU - Leisenring, Wendy
AU - Stratton, Kayla
AU - Whitton, John
AU - Donaldson, Sarah S.
AU - Armstrong, Gregory T.
AU - Robison, Leslie L.
AU - Neglia, Joseph P.
N1 - Funding Information:
Supported by the National Cancer Institute ( CA55727 ; G.T. Armstrong, Principal Investigator) and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. Dr Ronckers is supported by the Dutch Cancer Society.
Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016/3/15
Y1 - 2016/3/15
N2 - Objectives The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose-response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. Methods This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site-specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). Results Linear dose-response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. Conclusions The results suggest that the effect of high-dose irradiation is consistent with a linear dose-response for most organs, but they also reveal important organ-specific and host-specific differences in susceptibility and interactions between different aspects of treatment.
AB - Objectives The majority of childhood cancer patients now achieve long-term survival, but the treatments that cured their malignancy often put them at risk of adverse health outcomes years later. New cancers are among the most serious of these late effects. The aims of this review are to compare and contrast radiation dose-response relationships for new solid cancers in a large cohort of childhood cancer survivors and to discuss interactions among treatment and host factors. Methods This review is based on previously published site-specific analyses for subsequent primary cancers of the brain, breast, thyroid gland, bone and soft tissue, salivary glands, and skin among 12,268 5-year childhood cancer survivors in the Childhood Cancer Survivor Study. Analyses included tumor site-specific, individual radiation dose reconstruction based on radiation therapy records. Radiation-related second cancer risks were estimated using conditional logistic or Poisson regression models for excess relative risk (ERR). Results Linear dose-response relationships over a wide range of radiation dose (0-50 Gy) were seen for all cancer sites except the thyroid gland. The steepest slopes occurred for sarcoma, meningioma, and nonmelanoma skin cancer (ERR/Gy > 1.00), with glioma and cancers of the breast and salivary glands forming a second group (ERR/Gy = 0.27-0.36). The relative risk for thyroid cancer increased up to 15-20 Gy and then decreased with increasing dose. The risk of thyroid cancer also was positively associated with chemotherapy, but the chemotherapy effect was not seen among those who also received very high doses of radiation to the thyroid. The excess risk of radiation-related breast cancer was sharply reduced among women who received 5 Gy or more to the ovaries. Conclusions The results suggest that the effect of high-dose irradiation is consistent with a linear dose-response for most organs, but they also reveal important organ-specific and host-specific differences in susceptibility and interactions between different aspects of treatment.
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U2 - 10.1016/j.ijrobp.2015.11.046
DO - 10.1016/j.ijrobp.2015.11.046
M3 - Article
C2 - 26972653
AN - SCOPUS:84959512645
SN - 0360-3016
VL - 94
SP - 800
EP - 807
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 4
ER -