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. 2016 Mar 15;94(4):800-7.
doi: 10.1016/j.ijrobp.2015.11.046. Epub 2015 Dec 15.

Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects

Affiliations

Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects

Peter D Inskip et al. Int J Radiat Oncol Biol Phys. .

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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Conflict of interest statement

Notification: No actual or potential conflicts of interest exist.

Figures

Figure 1
Figure 1
Fitted radiation dose-response by type of second cancer, based on results from published studies described in Table 2. The order of second cancers from top to bottom in the graph is the same as in the key to the right of the panel. BCC=basal cell carcinoma.
Figure 2
Figure 2
Risk of glioma following radiotherapy for first cancer, by age at first cancer [data from Neglia et al. (10)]
Figure 3
Figure 3
Breast cancer risk by radiation dose to the breast and ovary. Reproduced from Inskip et al. (11).

References

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