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

• Authors: Peter D. Inskip, National Cancer Institute; Alice J. Sigurdson, National Cancer Institute; Lene Veiga, National Cancer Institute; Parveen Bhatti, National Cancer Institute; Cecile Ronckers, National Cancer Institute; Preetha Rajaraman, National Cancer Institute; Houda Boukheris, National Cancer Institute; Marilyn Stovall, University of Texas M.D. Anderson Cancer Center; Susan Smith, University of Texas M.D. Anderson Cancer Center; Sue Hammond, Children's Hospital; Tara O. Henderson, University of Chicago; Tanya C. Watt, University of Texas Southwestern Medical Center; Ann Mertens, Emory University; Wendy Leisenring, Fred Hutchinson Cancer Research Center; Kayla Stratton, Fred Hutchinson Cancer Research Center; John Whitton, Fred Hutchinson Cancer Research Center; Sarah S. Donaldson, Stanford University; Gregory T. Armstrong, St. Jude Children's Research Hospital; Leslie L. Robison, St. Jude Children's Research Hospital; Joseph P. Neglia, University of Minnesota
• Journal Title: International Journal of Radiation Oncology - Biology - Physics
• Volume: Volume 94, Number 4
• Publisher: Elsevier | 2016-03-15, Pages 800-807
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.ijrobp.2015.11.046
• Subjects: Health Sciences, Oncology; Health Sciences, Public Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Radiology, Nuclear Medicine & Medical Imaging; PRIMARY THYROID-CANCER; BREAST-CANCER; IONIZING-RADIATION; 5-YEAR SURVIVORS; NERVOUS-SYSTEM; RISK; CHEMOTHERAPY; TUMORS; RADIOTHERAPY; NEOPLASMS

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.