Retraction for Fusco et al., "A mos Oncogene-Containing Retrovirus, Myeloproliferative Sarcoma Virus, Transforms Rat Thyroid Epithelial Cells and Irreversibly Blocks Their Differentiation Pattern".

[This retracts the article DOI: 10.1128/JVI.56.1.284-292.1985.].

The effect of surveillance for differentiated thyroid carcinoma in childhood cancer survivors on survival rates: a decision-tree-based analysis.

Background: Childhood cancer survivors (CCS) who received radiation therapy exposing the thyroid gland are at increased risk of developing differentiated thyroid cancer (DTC). Therefore, the International Guideline Harmonization Group (IGHG) on late effects of childhood cancer therefore recommends surveillance. It is unclear whether surveillance reduces mortality. Aim: The aim of this study was to compare four strategies for DTC surveillance in CCS with the aim of reducing mortality: Strategy-1, no surveillance; Strategy-2, ultrasound alone; Strategy-3, ultrasound followed by fine-needle biopsy (FNB); Strategy-4, palpation followed by ultrasound and FNB. Materials and methods: A decision tree was formulated with 10-year thyroid cancer-specific survival as the endpoint, based on data extracted from literature. Results: It was calculated that 12.6% of CCS will develop DTC. Using Strategy-1, all CCS with DTC would erroneously not be operated upon, but no CCS would have unnecessary surgery. With Strategy-2, all CCS with and 55.6% of CCS without DTC would be operated. Using Strategy-3, 11.1% of CCS with DTC would be correctly operated upon, 11.2% without DTC would be operated upon and 1.5% with DTC would not be operated upon. With Strategy-4, these percentages would be 6.8, 3.9 and 5.8%, respectively. Median 10-year survival rates would be equal across strategies (0.997). Conclusion: Different surveillance strategies for DTC in CCS all result in the same high DTC survival. Therefore, the indication for surveillance may lie in a reduction of surgery-related morbidity rather than DTC-related mortality. In accordance with the IGHG guidelines, the precise strategy should be decided upon in a process of shared decision-making.

Thyroid Collars in Dental Radiology: 2021 Update.

Background: In 2013, the American Thyroid Association (ATA) issued a "Policy Statement on Thyroid Shielding During Diagnostic Medical and Dental Radiology." The recently updated National Council on Radiation Protection and Measurement Radiation Protection in Dentistry and Oral and Maxillofacial Imaging (NCRP Report No. 177) prompts this review of progress related to patient thyroid shielding since the ATA statement was published. Summary: Relevant publications appearing since the ATA statement were identified by querying PubMed for "thyroid and dental and (collar or shielding)" and substituting specific dental radiographic procedures in the search. The search was expanded by reviewing the cited papers in the PubMed-retrieved papers and by use of the Web of Science to retrieve papers citing the PubMed retrieved publications. Although many quantitative studies have appeared reflective of current dental radiographic instrumentation and practice, much more can be done to foster minimizing radiation to the thyroid. Conclusions: We list seven areas that should be pursued. Among them are harmonizing guidelines for the use of thyroid collars based on the recent studies and a comprehensive survey of current dental radiological practice patterns.

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.

Clinical considerations for the treatment of secondary differentiated thyroid carcinoma in childhood cancer survivors.

The incidence of differentiated thyroid carcinoma (DTC) has increased rapidly over the past several years. Thus far, the only conclusively established risk factor for developing DTC is exposure to ionizing radiation, especially when the exposure occurs in childhood. Since the number of childhood cancer survivors (CCS) is increasing due to improvements in treatment and supportive care, the number of patients who will develop DTC after surviving childhood cancer (secondary thyroid cancer) is also expected to rise. Currently, there are no recommendations for management of thyroid cancer specifically for patients who develop DTC as a consequence of cancer therapy during childhood. Since complications or late effects from prior cancer treatment may elevate the risk of toxicity from DTC therapy, the medical history of CCS should be considered carefully in choosing DTC treatment. In this paper, we emphasize how the occurrence and treatment of the initial childhood malignancy affects the medical and psychosocial factors that will play a role in the diagnosis and treatment of a secondary DTC. We present considerations for clinicians to use in the management of patients with secondary DTC, based on the available evidence combined with experience-based opinions of the authors.

Size, number, and distribution of thyroid nodules and the risk of malignancy in radiation-exposed patients who underwent surgery.

CONTEXT: The chance that a thyroid nodule is malignant is higher when there is a history of childhood radiation exposure. OBJECTIVE: The objective of the study was to determine how the size of a thyroid nodule, the number of nodules, and the distribution of nodules influence the risk of cancer in irradiated patients. PATIENTS: From a cohort of 4296 radiation-exposed people, we studied the 1059 that underwent thyroid surgery. DESIGN AND OUTCOMES: We studied the association between the size, number, distribution, and rank order of thyroid nodules and the chance of malignancy. RESULTS: There were 612 malignant nodules in 358 patients and 2037 benign ones in 930 patients. There was no change in the risk that a nodule was malignant with increasing size (odds ratio 0.91/cm, P = 0.11) among the 1709 nodules that were 0.5 cm or greater. A solitary nodule had a similar likelihood of being malignant as a nodule that was one of several (18.8 vs. 17.3%), whereas patients with multiple nodules were more likely to have thyroid cancer than those with solitary nodules [30.7 vs. 18.7%; risk ratio 1.64 (1.27-2.13)]. Aspirating only the largest nodule would have missed 111 of the cancers (42%), whereas aspirating the two largest nodules would have missed 45 of the cases (17%), although none would have been 10 mm or greater. CONCLUSIONS: In radiation-exposed patients, the following conclusions were made: 1) the likelihood that a nodule is malignant is independent of nodule number and size; 2) the likelihood of cancer is increased if more than one nodule is present; 3) evaluating the two largest nodules by fine-needle aspiration would have resulted in a significant number of cases being missed but none with large cancers; and 4) more than half of the patients with thyroid cancer had multifocal tumors.

Acoustic neuromas following childhood radiation treatment for benign conditions of the head and neck.

Childhood radiation exposure has been associated with an increased risk for developing several neoplasms, particularly benign and malignant thyroid tumors, but little is known about the risk of developing acoustic neuromas. The aim of this study was to confirm whether there is a risk for acoustic neuromas and, if so, to determine its magnitude and duration. We investigated the time trend and dose-response relationships for acoustic neuroma incidence in a cohort of 3,112 individuals who were irradiated as children between 1939 and 1962. Most of the patients were treated to reduce the size of their tonsils and adenoids and received substantial radiation exposure to the cerebellopontine angle, the site of acoustic neuromas. Forty-three patients developed benign acoustic neuromas, forty of them surgically resected, far in excess of what might be expected from data derived from brain tumor registries. The mean dose (+/-SD) to the cerebellopontine angle was 4.6 +/- 1.9 Gy. The relative risk per Gy was 1.14 (95% confidence interval 1.0-1.3). The earliest case occurred 20.4 years after exposure and the latest 55 years after exposure (mean 38.3 +/- 10.1 years). Our study provides support for an association between acoustic neuromas and childhood radiation exposure. Although acoustic neuromas are usually benign and often asymptomatic, many cause significant morbidity. Following childhood radiation exposure, they appear after a long latency and continue to occur many decades afterward. Any symptoms of an acoustic neuroma in a patient with a history of radiation to the head and neck area should be investigated carefully, and the threshold for employing imaging should be lowered.

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.

Factors related to the recurrence of thyroid nodules after surgery for benign radiation-related nodules.

OBJECTIVE: Benign thyroid nodules are increased by radiation exposure and recurrences are common. The goal of this study was to determine the factors related to recurrence of nodular disease and the efficacy of thyroid hormone therapy in reducing them. DESIGN, SETTING, AND SUBJECTS: The study population was drawn from a cohort of 4296 people treated before the age of 16 with conventional external radiation for benign conditions of the head and neck between 1939 and the early 1960s. The study group consisted of 632 subjects who had benign nodules removed surgically. At the discretion of their physicians, 426 subjects were treated with thyroid hormone after surgery, 198 were not, and in 8 subjects, thyroid hormone treatment status was unknown. MAIN OUTCOMES: There were 129 (20.4%) subjects who developed new nodules during follow-up. Women had a greater risk of recurrent nodules than men (27.5% vs. 13.5%) and the rate of recurrence correlated inversely with the extent of surgery. The group who took thyroid hormone had a lower recurrence rate than the untreated group (14.2% vs. 34.2%). The risk of recurrence was reduced to 0.69 (0.47-1.01) in thyroid hormone-treated subjects, regardless of extent of surgery, and to 0.66 (0.46-0.97) when only the subjects with less than 75% of their thyroid removed were considered. CONCLUSION: Thyroid hormone therapy reduced recurrences in this irradiated cohort. It should be recommended to all patients with irradiated thyroids and previous thyroid surgery.

American Thyroid Association Scientific Statement on the Use of Potassium Iodide Ingestion in a Nuclear Emergency.

This document serves to summarize the issues and the American Thyroid Association (ATA) position regarding the use of potassium iodide as a thyroid blocking agent in the event of a nuclear accident. The purpose is to provide a review and updated position statement regarding the advanced distribution, stockpiling, and availability of potassium iodide in the event of nuclear radiation emergencies in the United States.

Thyroid Cancer Following Childhood Low-Dose Radiation Exposure: A Pooled Analysis of Nine Cohorts.

Context: The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and the radiosensitive thyroid gland. Objectives: Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray (Gy); evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure. Design and Setting: Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 Gy. Participants: Cohorts included the following: childhood cancer survivors (n = 2); children treated for benign diseases (n = 6); and children who survived the atomic bombings in Japan (n = 1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in nonirradiated individuals. Intervention: There were no interventions. Main Outcome Measure: Incident thyroid cancers. Results: For both <0.2 and <0.1 Gy, RRs increased with thyroid dose (P < 0.01), without significant departure from linearity (P = 0.77 and P = 0.66, respectively). Estimates of threshold dose ranged from 0.0 to 0.03 Gy, with an upper 95% confidence bound of 0.04 Gy. The increasing dose-response trend persisted >45 years after exposure, was greater at younger age at exposure and younger attained age, and was similar by sex and number of treatments. Conclusions: Our analyses reaffirmed linearity of the dose response as the most plausible relationship for "as low as reasonably achievable" assessments for pediatric low-dose radiation-associated thyroid cancer risk.

Low frequency of BRAF mutations in adult patients with papillary thyroid cancers following childhood radiation exposure.

Radiation exposure at a young age is the only environmental factor known to cause thyroid cancer, predominantly of the papillary type. We have previously reported a high percentage (86.7%) of RET-positive papillary thyroid cancers in a cohort of individuals exposed to external radiation of the head and neck area before the age of 16. Recently, we and others have reported that point mutations of the BRAF gene occur with high frequency among sporadic adult papillary thyroid carcinomas, but occur at a much lower frequency in the population exposed after the Chernobyl accident. We here report that there is a similar low frequency of BRAF mutations among our cohort of those exposed to external beam radiation as children who later developed papillary thyroid cancer as adults. Samples were analyzed by mutation allele-specific amplification (MASA) for the most common T1799A mutation in exon 15 that converts amino acid 600 from valine to glutamate. In 23 cases, only 1 sample was positive. These results are further evidence that BRAF mutations, while common in sporadic adult papillary thyroid cancers, are rare events in cancers seen in subjects exposed to radiation as children.

Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies.

Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies.

BACKGROUND: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. METHODS: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. RESULTS: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5 cm) = 1.07 [1.04-1.10], BMI (per 5 kg/m2) = 1.06 [1.02-1.10], waist circumference (per 5 cm) = 1.03 [1.01-1.05], young-adult BMI (per 5 kg/m2) = 1.13 [1.02-1.25], and adulthood BMI gain (per 5 kg/m2) = 1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p = 0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. CONCLUSION: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.

Ultrasound-detected thyroid nodules in radiation-exposed patients: changes over time.

The relationship between radiation exposure and thyroid cancer is well known, but whether all irradiated patients should have thyroid ultrasounds is unresolved. We have performed follow-up ultrasound examinations of patients in a cohort who were exposed to conventional external radiation during 1939-63 for benign conditions of the head and neck area prior to their 16th birthday. Of 54 subjects who had normal radionuclide scans in 1974-76 and were reexamined in 1996-97 by thyroid ultrasonography, 42 remained eligible and 34 agreed to participate in the present ultrasound study. After an additional 4-8 years of follow-up and using an ultrasound machine with increased resolution, we found 160 nodules (in 33 of these 34 subjects), compared with 96 nodules (in 29 of the 34 subjects) detected in the previous examination. Only four of the new nodules were > or =10 mm. Of the previously diagnosed large (> or =10 mm) nodules, four nodules in four subjects resolved; nine nodules in six subjects regressed to <10 mm; 14 nodules in 13 subjects remained at > or =10 mm. The four new large nodules appeared in four subjects, and six small nodules increased to > or =10 mm in six other subjects. The total volume of the thyroid nodules decreased in the 13 subjects on thyroid hormone (by 0.20 cm(3)) and increased in the 21 subjects who were not (by 0.34 cm(3), p < 0.05 by unpaired t-test). In summary, thyroid nodules are extremely common in irradiated subjects. Many new ones may be observed over time, but most are small and seen because of the increased resolution of ultrasound machines. Compared to patients on no medication, nodules in patients on thyroid hormone tended to regress. Since FNA of all thyroid nodules in irradiated patients is not feasible, ultrasound is useful in identifying those lesions that are growing.