Radiation-related new primary solid cancers in the childhood cancer survivor study: Comparative radiation dose response and modification of treatment effects

Peter D. Inskip, Alice J. Sigurdson, Lene Veiga, Parveen Bhatti, Cécile Ronckers, Preetha Rajaraman, Houda Boukheris, Marilyn Stovall, Susan Smith, Sue Hammond, Tara O. Henderson, Tanya C. Watt, Ann C. Mertens, Wendy Leisenring, Kayla Stratton, John Whitton, Sarah S. Donaldson, Gregory T. Armstrong, Leslie L. Robison, Joseph P. Neglia

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)800-807
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume94
Issue number4
DOIs
StatePublished - Mar 15 2016

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Survivors
cancer
Radiation
dosage
radiation
Neoplasms
Thyroid Gland
Therapeutics
Breast Neoplasms
Thyroid Neoplasms
Radiation Dose-Response Relationship
breast
thyroid gland
salivary glands
Salivary Gland Neoplasms
Drug Therapy
chemotherapy
Second Primary Neoplasms
organs
Meningioma

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Radiation-related new primary solid cancers in the childhood cancer survivor study : Comparative radiation dose response and modification of treatment effects. / Inskip, Peter D.; Sigurdson, Alice J.; Veiga, Lene; Bhatti, Parveen; Ronckers, Cécile; Rajaraman, Preetha; Boukheris, Houda; Stovall, Marilyn; Smith, Susan; Hammond, Sue; Henderson, Tara O.; Watt, Tanya C.; Mertens, Ann C.; Leisenring, Wendy; Stratton, Kayla; Whitton, John; Donaldson, Sarah S.; Armstrong, Gregory T.; Robison, Leslie L.; Neglia, Joseph P.

In: International Journal of Radiation Oncology Biology Physics, Vol. 94, No. 4, 15.03.2016, p. 800-807.

Research output: Contribution to journalArticle

Inskip, PD, Sigurdson, AJ, Veiga, L, Bhatti, P, Ronckers, C, Rajaraman, P, Boukheris, H, Stovall, M, Smith, S, Hammond, S, Henderson, TO, Watt, TC, Mertens, AC, Leisenring, W, Stratton, K, Whitton, J, Donaldson, SS, Armstrong, GT, Robison, LL & Neglia, JP 2016, 'Radiation-related new primary solid cancers in the childhood cancer survivor study: Comparative radiation dose response and modification of treatment effects', International Journal of Radiation Oncology Biology Physics, vol. 94, no. 4, pp. 800-807. https://doi.org/10.1016/j.ijrobp.2015.11.046
Inskip, Peter D. ; Sigurdson, Alice J. ; Veiga, Lene ; Bhatti, Parveen ; Ronckers, Cécile ; Rajaraman, Preetha ; Boukheris, Houda ; Stovall, Marilyn ; Smith, Susan ; Hammond, Sue ; Henderson, Tara O. ; Watt, Tanya C. ; Mertens, Ann C. ; Leisenring, Wendy ; Stratton, Kayla ; Whitton, John ; Donaldson, Sarah S. ; Armstrong, Gregory T. ; Robison, Leslie L. ; Neglia, Joseph P. / Radiation-related new primary solid cancers in the childhood cancer survivor study : Comparative radiation dose response and modification of treatment effects. In: International Journal of Radiation Oncology Biology Physics. 2016 ; Vol. 94, No. 4. pp. 800-807.
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abstract = "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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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.

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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.

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