Among Individuals Irradiated for Benign Conditions in Childhood, Developing Thyroid Cancer Does Not Affect All-Cause Survival.

Background: Whether radiation-induced thyroid cancer affects survival rates has not been clearly elucidated. Survival could be affected by the thyroid cancer itself, its treatment, or by being a sign of susceptibility to other cancers. The objective of the current study was to determine if the development of thyroid cancer is associated with a differential survival in radiation-exposed individuals. Methods: We conducted a matched prospective cohort mortality follow-up study based on data from a cohort of 4296 individuals who were irradiated predominantly for enlarged tonsils during their childhood (between 1939 and 1962) and were prospectively followed since 1974. The study matched an irradiated subject who developed (was exposed to) thyroid cancer (a "case") and two irradiated subjects, who had not developed (were not exposed to) thyroid cancer ("controls") by the time of case incidence. The two controls were randomly matched to cases by sex, year of birth, age at radiation treatment, and radiation dose. Then, using a stratified Cox analysis, we compared survival time from the date of thyroid cancer diagnosis or time of selection to either date of death or the end of the observation period (December 31, 2016). Vital status and causes of death were determined using the National Death Index (1979-2016), the Social Security Death Index (1974-1979), and study files. Cause of death was categorized as cardiovascular, malignancy, or other. Results: A total of 1008 subjects were included in the analysis, including 353 thyroid cancer cases. At the end of the study period, 162 of 655 (24.7%) of individuals without thyroid cancer had died compared with 100 of 353 (28.3%) of the subjects with thyroid cancer. The hazard ratio (HR) for all-cause mortality, comparing the thyroid cancer cases to controls, was close to unity (HR = 1.01 [0.77-1.33]). HRs remained insignificant after eliminating matched sets with microcarcinomas, defined as tumor size <10 mm (HR = 1.39 [0.96-2.03]). Distribution of the causes of death taking into account age and the time of observation differed between cases and controls (p < 0.05). Neither increased cardiovascular-related nor malignancy-related mortality was associated with radiation-induced thyroid cancer. Conclusions: Among individuals irradiated for benign conditions in childhood, development of thyroid cancer was not associated with decreased all-cause survival.

Role of biomarkers in predicting the occurrence of thyroid neoplasms in radiation-exposed children.

With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid nodules and cancer in a cohort of radiation-exposed children. 764 subjects who were irradiated in the neck area as children were examined and followed for up to 25 years. All subjects underwent a clinical examination, measurements of thyrotropin, thyroglobulin levels and thyroid imaging. At baseline, 216 subjects had thyroid nodules and 548 did not. Of those with nodules, 176 underwent surgery with 55 confirmed thyroid cancers. During the follow-up, 147 subjects developed thyroid nodules including 22 with thyroid cancer. Thyroglobulin levels were higher in subjects with prevalent thyroid nodules (26.1 ng/mL vs 9.37 ng/mL; P < 0.001) and in those who had an initial normal examination but later developed thyroid nodules (11.2 ng/mL vs 8.87 ng/mL; P = 0.017). There was no relationship between baseline thyrotropin levels and the prevalent presence or absence of thyroid nodules, whether a prevalent neoplasm was benign or malignant, subsequent development of thyroid nodules during follow-up or whether an incident nodule was benign or malignant. In conclusion, in radiation-exposed children, higher thyroglobulin levels indicated an increased risk of developing thyroid nodules but did not differentiate between benign and malignant neoplasms. There was no association between the baseline TSH level and the risk of developing thyroid nodules or cancer.