Radiation-induced Thyroid Cancer Research Articles

A post-irradiation-induced replication stress promotes RET proto-oncogene breakage.

Ionizing radiation generates genomic instability by promoting the accumulation of chromosomal rearrangements. The oncogenic translocation RET/PTC1 is present in more than 70% of radiation-induced thyroid cancers. Both RET and CCDC6, the genes implicated in RET/PTC1, are found within common fragile sites - chromosomal regions prone to DNA breakage during slight replication stress. Given that irradiated cells become more susceptible to genomic destabilization due to the accumulation of replication-stress-related double-strand breaks (DSBs), we explored whether RET and CCDC6 exhibit DNA breakage under replicative stress several days post-irradiation of thyroid cells. We analyzed the dynamic of DNA replication in human thyroid epithelial cells (HThy-ori-3.1) 4 days post a 5-Gy exposure using molecular DNA combing. The DNA replication schedule was evaluated through replication-timing experiments. We implemented a ChIP-qPCR assay to determine whether the RET and CCDC6 genes break following irradiation. Our study indicates that replicative stress, occurring several days post-irradiation in thyroid cells, primarily causes DSBs in the RET gene. We discovered that both the RET and CCDC6 genes undergo late replication in thyroid cells. However, only RET's replication rate is notably delayed after irradiation. The findings suggest that post-irradiation in the RET gene causes a breakage in the replication fork, which could potentially invade another genomic area, including CCDC6. As a result, this could greatly contribute to the high prevalence of chromosomal RET/PTC rearrangements seen in patients exposed to external radiation.

ПРОГНОЗ РАДИАЦИОННЫХ РИСКОВ РАКА ЩИТОВИДНОЙ ЖЕЛЕЗЫ СРЕДИ НАСЕЛЕНИЯ РАЙОНОВ БРЯНСКОЙ ОБЛАСТИ, ЗАГРЯЗНЕННЫХ ВСЛЕДСТВИЕ АВАРИИ НА ЧЕРНОБЫЛЬСКОЙ АЭС, С УЧЕТОМ НЕОПРЕДЕЛЕННОСТЕЙ ОЦЕНОК МОДЕЛЕЙ РИСКА

Purpose: Forecasting the lifetime attributable radiation risk of incidence with malignant neoplasm (MN) of the thyroid gland and identifying groups of increased radiation risk (HR) for the population of the Bryansk region currently (at the beginning of 2023) living in six areas most contaminated with radionuclides after the accident at Chernobyl NPP, based on a conservative approach, taking into account dose uncertainty factors and parameters of mathematical risk models. Material and methods: The mathematical model of the radiation risk of thyroid cancer is the model recommended by the International Commission on Radiological Protection (ICRP). The uncertainty assessment of radiation risks was carried out by simulation modeling, i.e. by multiple calculation of random realizations of the risk using the normal or log-normal distribution of all parameters involved in the calculation of this risk. Based on a set of random realizations, 95 % confidence limits of risks were estimated. The Unified Federal Database of the National Radiation and Epidemiological Register (NRER) containing reconstructed absorbed doses in the thyroid gland in the population was used as the initial data for the calculation. Results: At the beginning of 2023, the group of 37–40-year-old women is characterized by the maximum radiation risks of thyroid cancer. According to conservative estimates (according to the upper 95 % confidence limits of radiation risk assessments), up to 19.9 % of people from this group may experience the development of radiation-induced thyroid cancer in the future, and for 37-year-old women this proportion can be up to 30.0 %. The greatest risk is predicted for people living in the Krasnogorsk district of the Bryansk region. Radiation-induced thyroid cancer can develop in 40.1 % of individuals from this group. Radiation risks of thyroid cancer in men are up to 10 times lower than in women. For 74.5 % of the population of the entire studied cohort, it is predicted that the maximum individual risk of 5.0×10-5, established by NRB-99/2009 for the population under normal operation of ionizing radiation sources, will be exceeded. Conclusions: At present (since 2023 and for life), the population of the most polluted districts of the Bryansk region continues to be at a high risk of developing radiation-induced thyroid cancers. Women at the age of 0–3 years at the time of exposure (in 1986) should be allocated to the maximum risk group. The results of this work can be used in the preparation of recommendations by health authorities to improve medical monitoring of exposed citizens.

Prevention of iodine deficiency diseases: focus on regional targeted programs

The strategy for the elimination of diseases associated with iodine deficiency throughout the Russian Federation is based on the adoption of a federal law providing for the use of iodized salt as a means of mass (population) iodine prophylaxis. Chronic iodine deficiency that exists in Russia leads to dramatic consequences: the development of mental and physical retardation in children, cretinism, thyroid diseases, and infertility. Under conditions of iodine deficiency, the risk of radiation-induced thyroid cancer in children in the event of nuclear disasters increases hundreds of times. By definition, all iodine deficiency diseases (IDDs) can be prevented, while changes caused by iodine deficiency during fetal development and in early childhood are irreversible and practically defy treatment and rehabilitation. The actual average consumption of iodine by a resident of Russia is only 40-80 mcg per day, which is 3 times less than theestablished norm (150-250 mcg). Every year, more than 1.5 million adults and 650 thousand children with various thyroid diseases turn to medical institutions. The cause of 65% of cases of thyroid disease in adults and 95% in children is insufficient intake of iodine from the diet. At the stage of preparing the relevant legislative act, the development and implementation of regional programs for the prevention of IDD is of utmost importance. A typical draft of such a program is proposed in this article for its adaptation and use at the regional level.

Young people\u2019s perspectives of thyroid cancer screening and its harms after the nuclear accident in Fukushima Prefecture: a questionnaire survey indicating opt-out screening strategy of the thyroid examination as an ethical issue

BackgroundOverdiagnosis of thyroid cancer has become a major global medical issue. Ultrasound-based thyroid cancer screening has promoted overdiagnosis, and recently international recommendations state that it should not be conducted, even after a nuclear accident. The Fukushima thyroid cancer screening program was initiated in 2011 as a health policy after the nuclear accident. The risk of radiation-induced thyroid cancer was unlikely given the low radiation levels, but the thyroid cancer screening program has continued at 2-year intervals with a relatively high participation rate and is now in its fifth round. It is therefore crucial to clarify whether those targeted for screening understand the disadvantages of screening, and to identify factors that influenced their decision to participate.MethodsWe conducted an anonymous mail-based questionnaire among young people from Fukushima Prefecture (subjects) and a neighboring prefecture that was not targeted for screening (non-subjects). We asked them about the significance of the thyroid cancer screening in Fukushima Prefecture, their reasons for accepting or refusing screening, their perception of the harms of screening, and their opinions on thyroid examination at school. We compared the results of the questionnaire between subjects and non-subjects and between examinees (who were screened) and non-examinees (who declined screening).ResultsOnly 16.5% of respondents were aware of the harms associated with thyroid cancer screening, with most perceiving that the benefits outweighed the harms. Comparison of subjects’ and non-subjects’ responses showed there were no significant differences between the two groups. Among subjects, there were also no differences in responses between examinees and non-examinees. The most common reason for participation in screening was that the screening was conducted in schools and perceived as obligatory.ConclusionsThese results highlighted a serious ethical issue in that school-based screening leads to making young people think that it is mandatory screening in an opt-out and default setting manner, with a lack of knowledge about the disadvantages of screening. Based on the autonomy of the subjects and the ethical principle of the post-disaster, surveys after a nuclear disaster should be conducted in an opt-in style without an opt-out style such as school-based screening.

Comparison of early forecasts of the incidence of thyroid cancer in residents of the Russian Federation after the Chernobyl accident with observational data

A review of methods for assessing doses in the thyroid gland, predictions of the long-term consequences of its irradiation and the actual incidence of thyroid cancer in residents of four regions of the Russian Federation with the most significant radioactive fallout after the Chernobyl accident are presented. The method for assessing doses in the thyroid gland is based on the results of monitoring in May-June 1986 of radioiodine in the environment, food and in the body of residents. Thyroid doses in the population were used to justify medical and social protection measures, as well as epidemiological studies. In addition, the authorities needed forecasts of the possible morbidity of the population in order to organize adequate medical care. Most of the thyroid cancer cases were predicted among the adult population, which was not confirmed by observations 35 years after the accident. The prognosis of the incidence of thyroid cancer in preschool children differed in different studies due to the use of different coefficients of reducing the biological effectiveness of 131I radiation in the thyroid gland and long-term external and internal irradiation of the whole body with a low dose rate compared to the effect of acute exposure. The increase in the incidence of thyroid cancer among children began five years after the accident at the Chernobyl nuclear power plant. Examples of the dynamics of the incidence for children in the Bryansk region of the Russian Federation are given. The 2018 UNSCEAR Report showed that for 1986-2015, among children and adolescents under 18 years of age on the day of the accident in Belarus, Ukraine and four regions of Russia, more than 19 thousand thyroid cancer cases were detected, of which the share of radiation-induced diseases was estimated at 25%. For four regions of Russia, this amounts to 460 cases with a range of possible estimates from 130 to 900 cases. The highest morbidity was manifested among younger children exposed at the age of 0-4 years. In older children and adolescents, the proportion of radiation-induced diseases has significantly decreased 30 years after the accident. In general, early forecasts of radiation-induced thyroid cancer incidence in children in four regions of the Russian Federation with high levels of radioactive fallout are consistent with the data of subsequent 30-year epidemiological observations within an order of magnitude. With regard to thyroid cancer in adults, such a comparison is difficult, since no radiogenic increase in the incidence has been detected.

Estimated Effective Lifetime Risks of Radiation-Induced Thyroid Cancer in Computed Tomography (CT) Brain Examination

Thyroid is one of the most radiosensitive organs in the human body. Although the scanning range of brain computed tomography (CT) does not include lower neck region, there is possibility for thyroid to be irradiated due to scattered radiation because of its location near to the external beam collimation. The objective of this study was to evaluate effective lifetime risk of radiation-induced thyroid cancer in young adults following brain CT examination. A total of 306 patient data within the age range between 18 and 39 years old were retrospectively analysed. Absorbed dose of the thyroid organ was obtained through the input of data using WAZA- ARI v2. Effective lifetime risk was calculated by multiplying equivalent dose of the thyroid organ with the lifetime attributable cancer risk adapted from Biological Effects in Ionising Radiation (BEIR) Report V11. The effective lifetime risks were recorded as 0.45 ± 0.70 per 100 000 and 0.93 ± 1.52 per 100 000 for single and multiple exposures, respectively. In terms of gender, woman data (0.99 ± 0.76; 1.95 ± 2.15) were found higher as compared to man data (0.13 ± 0.39; 0.35 ± 0.45) for both single and multiple exposure. The percentage difference of effective lifetime risks between single and multiple exposures was up to 107%. The effective lifetime risk noted in this study may be low, however, the long-term risk of cancer development should be considered. This study serves as preliminary reference when revising clinical protocol especially in those involving repeated exposures in young adult patients. Future study should include other radiosensitive organs exploring the effective lifetime risk of radiation induced cancer following CT procedure.

28492 Doxycycline pigmentation in a patient with vandetanib-induced acne

We present a case of doxycycline-induced hyperpigmentation in a 49-year-old male with a history of Hodgkins lymphoma, melanoma, and radiation-induced medullary thyroid cancer (MTC). The MTC was treated with the oral kinase inhibitor, vandetanib. Shortly thereafter he developed pustular acne. This was treated with oral doxycycline and after 6 weeks he developed blue-gray discoloration within depressed acne scars on the face and scalp. This case highlights that shorter courses of doxycycline can induce cutaneous hyperpigmentation that may be irreversible.

Can computed tomography scanning in adults lead to an increased risk of thyroid cancer? A nationwide nested case-control study.

To evaluate the association between computed tomography (CT) scanning and newly diagnosed thyroid cancer cases in relation to the confounding effect of the healthcare utilization rate. This nested case-control study used the Korean National Health Insurance Service-National Sample Cohort 2002-2015: 3557 adult thyroid cancer cases were matched to 17,785 controls by age, sex, and diagnosis date. Odds ratios (ORs) were estimated for thyroid cancer associated with cumulative exposure to CT scanning > 3 years before cancer diagnosis. Changes in estimated ORs with and without adjustment for outpatient visit frequency were investigated. ORs for newly diagnosed thyroid cancer increased according to the higher number of total CT scans and thyroid-exposing CT scans (CT scans of the head, neck, or chest compartment; OR and 95% confidence interval [CI], 1.09 [1.03-1.16] and 1.28 [1.05-1.57], respectively). ORs for thyroid cancer increased according to higher outpatient visit frequency. The association between thyroid cancer incidence and CT scans became insignificant when outpatient visit frequency was adjusted in the models (OR [95% CI], 1.03 [0.97-1.10]: total CT scans, 1.14 [0.93-1.41]: thyroid-exposing CT scans). Subgroup analyses stratified by age, sex, and history of other malignancies did not reveal independent associations between CT scanning and thyroid cancer. The high incidence of thyroid cancer in adults exposed to ionizing radiation during CT scanning can be largely explained by the confounding effect of the healthcare utilization rate. These effects should be considered to avoid overestimation of the CT scanning-associated risk of thyroid cancer. • Studies indicate that diagnostic imaging using low-ionizing radiation may increase risks for thyroid cancer in adults. • Our findings suggest that the risk for radiation-induced thyroid cancer following CT scanning in adults may have been overestimated in observational studies due to medical surveillance-related biases.

Dose Characteristics of Radiation-Induced (I-131) Thyroid Cancer

The first scientifically confirmed stochastic effect after the Chernobyl accident was an increase in the incidence of Thyroid Cancer (TC) among children, first in Belarus, and then in Ukraine and the Russian Federation...

Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. On the basis of self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diagnostic procedures during childhood and adulthood in two case-control studies conducted in France. A total of 1,071 differentiated thyroid cancer (DTC) cases and 1,188 controls from the combined studies were genotyped using a custom-made Illumina OncoArray DNA chip. We focused our analysis on variants in genes involved in DNA damage response and repair pathways, representing a total of 5,817 SNPs in 571 genes. We estimated the OR per milli-Gray (OR/mGy) of the radiation dose delivered to the thyroid gland using conditional logistic regression. We then used an unconditional logistic regression model to assess the association between DNA repair gene variants and DTC risk. We performed a meta-analysis of the two studies. The OR/mGy was 1.02 (95% confidence interval, 1.00-1.03). We found significant associations between DTC and rs7164173 in CHD2 (P = 5.79 × 10-5), rs6067822 in NFATc2 (P = 9.26 × 10-5), rs1059394 and rs699517 both in ENOSF1/THYS, rs12702628 in RPA3, and an interaction between rs7068306 in MGMT and thyroid radiation doses (P = 3.40 × 10-4). Our results suggest a role for variants in CDH2, NFATc2, ENOSF1/THYS, RPA3, and MGMT in DTC risk. CDH2, NFATc2, ENOSF1/THYS, and RPA3 have not previously been shown to be associated with DTC risk.

Change of Age Distribution of Childhood and Adolescent Thyroid Cancer after the Fukushima Nuclear Accident Compared with the Chernobyl Cases

Background and Methods: Comparison of age patterns of childhood and adolescent childhood thyroid cancer after the nuclear accidents in Fukushima and Chernobyl is often used as a criterion of radiationinduced thyroid cancer in Fukushima. The Fukushima Health Management Survey reports that thyroid cancers in Fukushima are unlikely to be radiation-induced, and one reason for the conclusion was no case was found in the age of 0-5 years at exposure. Published data on the health effects of the Chernobyl accident were analysed to assess whether there was one age pattern common in Chernobyl to be used as a criterion of radiation-induced thyroid cancer. Various age distributions of thyroid cancer as to the age at exposure and age at diagnosis, which depend on the country and the extent of radiation contamination, were studied as a function of years after exposure. Results and Conclusion: The highest incidence of thyroid cancer for infants aged 0-4 at exposure was observed only in Belarus. The high incidence of age group 0-4 AE became apparent only after 12 years from the accident in Ukraine and Russia. Age distribution of diagnosed or suspected thyroid cancer cases in Fukushima by age at exposure shifts to younger age side, average age from 14.9 to 8.3 years in 9 years after the accident. This trend agrees with the one in Ukraine and Russia. Because there is no common age pattern in Chernobyl, we should better not use age pattern as a simple criterion of radiation-induced thyroid cancer.

Mutational analysis of radiation-induced subsequent thyroid cancers in pediatric patients.

e22531 Background: The genetic landscape of radiation induced pediatric thyroid cancers is unclear. Radiation (RT) induced thyroid cancers frequently demonstrate tumorigenesis driven by fusion oncogenes. However, data is limited to children exposed to radioactive contamination after the Chernobyl nuclear accident. Little is known about the genetic landscape of subsequent pediatric thyroid cancers after RT exposure for the treatment of a primary malignancy or conditioning regimens prior to bone marrow transplantation (BMT). The objective of this study was to assess the prevalence of different mutations in a small cohort of pediatric patients who developed a subsequent thyroid cancer after RT exposure for the treatment of a primary disease. Methods: This is a single-center retrospective study. Thyroid tissue blocks from 10 pediatric patients who underwent thyroidectomy between 2010 and 2019 for subsequent thyroid cancers after RT for treatment of a primary malignancy or BMT were analyzed for genetic alterations using targeted next-generation sequencing for alterations in 112 genes linked to thyroid cancer. Thyroid cancers included 7 papillary (PTC) and 3 follicular thyroid carcinomas (FTC). Results: Ten samples (6 females) were genotyped. The mean age at thyroid cancer diagnosis was 15.7 years (range 11–22 years) at a mean of 10.3 years (range 6 – 19 years) after RT exposure. The mean RT dose was 2618 cGy (range 400 – 10,080 cGy) delivered to the head, neck, and/or chest. Mutations were noted in 6/10 (60%) of patients. Mutations were detected in 6/7 (85.7%) of PTC cases: EMLA/NTRK in 2 cases, STRN/ALK in 2 cases, RET in 1 case, and CCDC30/ROS in 1 case. A DICER.1 c.5438A > C p.E1813A was also identified in a patient with an EMLA/NTRK fusion. Of 3 FTC patients, (2/3) 67% had copy number alterations, but no mutations were observed. BRAFV600E mutations were not present in any tissues analyzed. Conclusions: An exceedinlgy rare ROS fusion was identified. Multiple RT induced thyroid lesions were positive for classic therapeutic targets including NTRK3, ALK, ROS1, and RET fusions, demonstrating a potential role for tyrosine kinase inhibitor therapy for refractory, recurrent or metastatic disease. All cases were negative for mutant BRAFV600E consistent with the pathogenesis of RT induced thyroid cancers primarily activated by fusions rather than point mutations. Larger, pediatric cohorts with RT induced thyroid cancers followed long term will enable the genotypic variability, clinical presentation, and response to therapy to be better assessed.

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.

Genetic Susceptibility to Radiation Induced Thyroid Cancer

Genetic Susceptibility to Radiation Induced Thyroid Cancer

Radiation-Induced Thyroid Cancers: Overview of Molecular Signatures.

Enormous amounts of childhood thyroid cancers, mostly childhood papillary thyroid carcinomas (PTCs), after the Chernobyl nuclear power plant accident have revealed a mutual relationship between the radiation exposure and thyroid cancer development. While the internal exposure to radioactive 131I is involved in the childhood thyroid cancers after the Chernobyl accident, people exposed to the external radiation, such as atomic-bomb (A-bomb) survivors, and the patients who received radiation therapy, have also been epidemiologically demonstrated to develop thyroid cancers. In order to elucidate the mechanisms of radiation-induced carcinogenesis, studies have aimed at defining the molecular changes associated with the thyroid cancer development. Here, we overview the literatures towards the identification of oncogenic alterations, particularly gene rearrangements, and discuss the existence of radiation signatures associated with radiation-induced thyroid cancers.

Radiation-induced papillary thyroid cancer: is it a distinct clinical entity?

To present the current status of knowledge regarding radiation-induced papillary thyroid cancer (RIPTC), defining its epidemiologic, pathologic, and clinical characteristics, with ensuing possible therapeutic and prognostic consequences. Cumulative evidence shows that RIPTC resembles sporadic papillary thyroid cancer (PTC) of comparable age, both in terms of clinical-pathological features and prognosis. Therefore, more aggressive treatment does not seem to be required when managing RIPTC as its prognosis is comparable to that of never-irradiated patients. Radiation exposure in childhood is a well-documented risk factor for development of PTC. Therefore, increased exposure to medical or environmental radiation may be in part responsible, along with increased screening, of the recent burgeoning incidence of PTC. A specific morphological and molecular portrait of RIPTC is unlikely to exist. The more aggressive histologic and clinical features initially reported in radiation-induced cases are consistent with the expectations in nonradiation-related PTC of a comparable age. Aggressive histology, nodal, and distant metastases correlate with early age at onset rather than with radiation exposure. Although relapses are frequent in children, long-term cancer-specific mortality is approximately 1%, lower than that observed for adults and comparable between irradiated and nonirradiated cohorts. RIPTC does not require more aggressive surgery or more adjuvant treatments, as prognosis is as good as that of sporadic PTC when matched for stage and treatment received.

Short Call Abstracts

Short Call Abstracts

Comparative Histopathologic Analysis of "Radiogenic" and "Sporadic" Papillary Thyroid Carcinoma: Patients Born Before and After the Chernobyl Accident.

The issue of whether radiation-induced thyroid cancer is pathologically different from sporadic remains not fully answered. This study compared structural characteristics and invasive features of papillary thyroid carcinoma (PTC) in two age-matched groups: patients who were children (≤4 years old) at the time of the Chernobyl accident and who lived in three regions of Ukraine most contaminated by radioactive iodine 131I ("radiogenic" cancer), and those who lived in the same regions but who were born after 1987 and were not exposed to 131I ("sporadic" cancer). Further, the histopathologic features of PTC were analyzed in relation to age and individual 131I thyroid dose. The study included 301 radiogenic and 194 sporadic PTCs. According to age at surgery, patients were subdivided into children (≤14 years old), adolescents (15-18 years old), and adults (19-28 years old). Statistical analyses included univariate tests and multivariable logistic regression within and across the age subgroups. Analyses of morphological features related to 131I doses were conducted among exposed patients on categorical and continuous scales controlling for sex and age. Among children, radiogenic PTC displayed a significantly higher frequency of tumors with a dominant solid growth pattern, intrathyroidal spread, extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adolescents more frequently displayed extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adults more frequently had intrathyroidal spread and extrathyroidal extension. The frequency of PTC with dominant papillary pattern and oxyphilic cell metaplasia was significantly lower in radiogenic compared to sporadic tumors for all age groups. Manifestations of tumor aggressiveness were most frequent in children compared to adolescents and adults regardless of etiology. Radiogenic PTC is less likely to demonstrate a dominant papillary growth pattern and more likely to display more aggressive tumor behavior than sporadic PTC. Histopathologic tumor aggressiveness declines with patient age in both radiogenic and sporadic cases.

Lessons from Fukushima: Latest Findings of Thyroid Cancer After the Fukushima Nuclear Power Plant Accident.

The increase in risk for late-onset thyroid cancer due to radiation exposure is a potential health effect after a nuclear power plant accident mainly due to the release of radioiodine in fallout. The risk is particularly elevated in those exposed during infancy and adolescence. To estimate the possibility and extent of thyroid cancer occurrence after exposure, it is of utmost importance to collect and analyze epidemiological information providing the basis for evaluation of radiation risk, and to consider radiobiology and molecular genetics. In this regard, the dose–response of cancer risk, temporal changes in the rates of thyroid cancer, its histopathological types and subtypes, and frequency of underlying genetic abnormalities are important. At present, however, it is difficult or impossible to distinguish radiation-induced thyroid cancer from spontaneous/sporadic thyroid cancer because molecular radiation signatures, biomarkers of radiation exposure, or genetic factors specific to radiation-induced cancer have not yet been identified. The large-scale ultrasound screening in Fukushima Prefecture of Japan demonstrated a high detection rate of thyroid cancer in young individuals, revealing 116 and 71 cases in the first and second rounds, respectively, among the same cohort of approximately 300,000 subjects. These findings raised concerns among residents and the public that it might be due to putative exposure to radiation from the accident at Fukushima Daiichi Nuclear Power Plant. This review summarizes evaluations by international organizations and reviews scientific publications by the authors and others on childhood thyroid cancer, especially those relevant to radiation, including basic studies on molecular mechanisms of thyroid carcinogenesis. Clinical details are also provided on surgical cases in Fukushima Prefecture, and the effect of thyroid ultrasound screening is discussed. Correct understanding of issues relating to radiation and the thyroid are essential for interpretation of thyroid cancer in Fukushima.

Abstract ID: 185 Monte Carlo simulation of “Out-of-Field” dose distributions in a pediatric phantom in external radiotherapy – Comparison with Gafchromic film measurements

Introduction Patients undergoing radiotherapy are exposed to out-of-field scattered and leakage radiation, which may induce secondary cancer in long-term survivors. The induction of secondary cancer in pediatric patients is an increased concern, because they have increasingly higher life expectancy, and tend to receive higher secondary organ doses than adults due to geometrical factors. Radiation-induced thyroid and breast cancers have been observed in pediatrics after receiving doses as low as 100 mGy [1] . While the dosimetric accuracy of treatment planning systems (TPS) is known to decrease in the out-of-field region, Monte Carlo (MC) is nowadays the most reliable method in dose calculation. A PENELOPE based MC code named PRIMO was tested for out-of-field dose estimation in pediatric irradiation. Material and methods a 5-year pediatric anthropomorphic phantom was irradiated by Varian Triology linac, using three 6MV static fields beams for a brain tumor. The treatment plan was calculated in Varian Eclipse TPS, using Analytic Anisotropic Algorithm (AAA). The 2D dose distributions at thyroid and lung levels were measured using Gafcromic EBT3 films. The plan was simulated in PRIMO after adjusting the primary beam parameters based on reference data in water phantom. PRIMO output data was reshaped, manipulated and re-written as DICOM files for comparisons with both measured and TPS calculated dose using 2D Gamma Function (3%, 3 mm) on DoseLab Pro software. Results The maximum measured doses per 1 Gy at isocenter (0 cm) were 1.5 cGy and 8 mGy at thyroid (10.25 cm) and lung levels (15.25 cm) respectively. Comparing simulated and measured dose distribution one obtained 82.6% and 88.8% of gamma points 1 at thyroid and lung levels respectively. The difference between measured and TPS calculated dose distributions could easily be accessed visually. Conclusion For secondary induced cancer risk estimation, the present TPS, even using a reliable algorithm as AAA, is not generally satisfactory for out-of-field dosimetry. Alternative tools, like MC simulations are necessary if correct dose estimation must be obtained for risk models application.