Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults.

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.

Brain cancer after radiation exposure from CT examinations of children and young adults: results from the EPI-CT cohort study.

BACKGROUND: The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer. METHODS: We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination. FINDINGS: We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4-10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51-2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36-2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded. INTERPRETATION: The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible. FUNDING: EU FP7; Belgian Cancer Registry; La Ligue contre le Cancer, L'Institut National du Cancer, France; Ministry of Health, Labour and Welfare of Japan; German Federal Ministry of Education and Research; Worldwide Cancer Research; Dutch Cancer Society; Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat de Catalunya, Spain; US National Cancer Institute; UK National Institute for Health Research; Public Health England.

Dose Estimation for Exposure to Radioactive Fallout from Nuclear Detonations.

ABSTRACT: In recent years, the prospects that a nuclear device might be detonated due to a regional or global political conflict, by violation of present nuclear weapons test ban agreements, or due to an act of terrorism, has increased. Thus, the need exists for a well conceptualized, well described, and internally consistent methodology for dose estimation that takes full advantage of the experience gained over the last 70 y in both measurement technology and dose assessment methodology. Here, the models, rationale, and data needed for a detailed state-of-the-art dose assessment for exposure to radioactive fallout from nuclear detonations discussed in five companion papers are summarized. These five papers present methods and data for estimating radionuclide deposition of fallout radionuclides, internal and external dose from the deposited fallout, and discussion of the uncertainties in the assessed doses. In addition, this paper includes a brief discussion of secondary issues related to assessments of radiation dose from fallout. The intention of this work is to provide a usable and consistent methodology for both prospective and retrospective assessments of exposure from radioactive fallout from a nuclear detonation.

A Methodology for Estimating External Doses to Individuals and Populations Exposed to Radioactive Fallout from Nuclear Detonations.

ABSTRACT: A methodology of assessment of the doses from external irradiation resulting from the ground deposition of radioactive debris (fallout) from a nuclear detonation is proposed in this paper. The input data used to apply this methodology for a particular location are the outdoor exposure rate at any time after deposition of fallout and the time-of-arrival of fallout, as indicated and discussed in a companion paper titled "A Method for Estimating the Deposition Density of Fallout on the Ground and on Vegetation from a Low-yield Low-altitude Nuclear Detonation." Example doses are estimated for several age categories and for all radiosensitive organs and tissues identified in the most recent ICRP publications. Doses are calculated for the first year after the detonation, when more than 90% of the external dose is delivered for populations close to the detonation site over a time period of 70 y, which is intended to represent the lifetime dose. Modeled doses in their simplest form assume no environmental remediation, though modifications can be introduced. Two types of dose assessment are considered: (1) initial, for a rapid but only approximate dose estimation soon after the nuclear detonation; and (2) improved, for a later, more accurate, dose assessment following the analysis of post-detonation measurements of radiation exposure and fallout deposition and the access of information on the lifestyle of the exposed population.

Dose Estimation for the European Epidemiological Study on Pediatric Computed Tomography (EPI-CT).

Within the European Epidemiological Study to Quantify Risks for Paediatric Computerized Tomography (EPI-CT study), a cohort was assembled comprising nearly one million children, adolescents and young adults who received over 1.4 million computed tomography (CT) examinations before 22 years of age in nine European countries from the late 1970s to 2014. Here we describe the methods used for, and the results of, organ dose estimations from CT scanning for the EPI-CT cohort members. Data on CT machine settings were obtained from national surveys, questionnaire data, and the Digital Imaging and Communications in Medicine (DICOM) headers of 437,249 individual CT scans. Exposure characteristics were reconstructed for patients within specific age groups who received scans of the same body region, based on categories of machines with common technology used over the time period in each of the 276 participating hospitals. A carefully designed method for assessing uncertainty combined with the National Cancer Institute Dosimetry System for CT (NCICT, a CT organ dose calculator), was employed to estimate absorbed dose to individual organs for each CT scan received. The two-dimensional Monte Carlo sampling method, which maintains a separation of shared and unshared error, allowed us to characterize uncertainty both on individual doses as well as for the entire cohort dose distribution. Provided here are summaries of estimated doses from CT imaging per scan and per examination, as well as the overall distribution of estimated doses in the cohort. Doses are provided for five selected tissues (active bone marrow, brain, eye lens, thyroid and female breasts), by body region (i.e., head, chest, abdomen/pelvis), patient age, and time period (1977-1990, 1991-2000, 2001-2014). Relatively high doses were received by the brain from head CTs in the early 1990s, with individual mean doses (mean of 200 simulated values) of up to 66 mGy per scan. Optimization strategies implemented since the late 1990s have resulted in an overall decrease in doses over time, especially at young ages. In chest CTs, active bone marrow doses dropped from over 15 mGy prior to 1991 to approximately 5 mGy per scan after 2001. Our findings illustrate patterns of age-specific doses and their temporal changes, and provide suitable dose estimates for radiation-induced risk estimation in epidemiological studies.

Fluoroscopy X-Ray Organ-Specific Dosimetry System (FLUXOR) for Estimation of Organ Doses and Their Uncertainties in the Canadian Fluoroscopy Cohort Study.

As part of ongoing efforts to assess lifespan disease mortality and incidence in 63,715 patients from the Canadian Fluoroscopy Cohort Study (CFCS) who were treated for tuberculosis between 1930 and 1969, we developed a new FLUoroscopy X-ray ORgan-specific dosimetry system (FLUXOR) to estimate radiation doses to various organs and tissues. Approximately 45% of patients received medical procedures accompanied by fluoroscopy, including artificial pneumothorax (air in pleural cavity to collapse of lungs), pneumoperitoneum (air in peritoneal cavity), aspiration of fluid from pleural cavity and gastrointestinal series. In addition, patients received chest radiographs for purposes of diagnosis and monitoring of disease status. FLUXOR utilizes age-, sex- and body size-dependent dose coefficients for fluoroscopy and radiography exams, estimated using radiation transport simulations in up-to-date computational hybrid anthropomorphic phantoms. The phantoms include an updated heart model, and were adjusted to match the estimated mean height and body mass of tuberculosis patients in Canada during the relevant time period. Patient-specific data (machine settings, exposure duration, patient orientation) used during individual fluoroscopy or radiography exams were not recorded. Doses to patients were based on parameter values inferred from interviews with 91 physicians practicing at the time, historical literature, and estimated number of procedures from patient records. FLUXOR uses probability distributions to represent the uncertainty in the unknown true, average value of each dosimetry parameter. Uncertainties were shared across all patients within specific subgroups of the cohort, defined by age at treatment, sex, type of procedure, time period of exams and region (Nova Scotia or other provinces). Monte Carlo techniques were used to propagate uncertainties, by sampling alternative average values for each parameter. Alternative average doses per exam were estimated for patients in each subgroup, with the total average dose per individual determined by the number of exams received. This process was repeated to produce alternative cohort vectors of average organ doses per patient. This article presents estimates of doses to lungs, female breast, active bone marrow and heart wall. Means and 95% confidence intervals (CI) of average organ doses across all 63,715 patients were 320 (160, 560) mGy to lungs, 250 (120, 450) mGy to female breast, 190 (100, 340) mGy to heart wall and 92 (47, 160) mGy to active bone marrow. Approximately 60% of all patients had average doses to the four studied organs of less than 10 mGy, 10% received between 10 and 100 mGy, 25% between 100 and 1,000 mGy, and 5% above 1,000 mGy. Pneumothorax was the medical procedure that accounted for the largest contribution to cohort average doses. The major contributors to uncertainty in estimated doses per procedure for the four organs of interest are the uncertainties in exposure duration, tube voltage, tube output, and patient orientation relative to the X-ray tube, with the uncertainty in exposure duration being most often the dominant source. Uncertainty in patient orientation was important for doses to female breast, and, to a lesser degree, for doses to heart wall. The uncertainty in number of exams was an important contributor to uncertainty for ∼30% of patients. The estimated organ doses and their uncertainties will be used for analyses of incidence and mortality of cancer and non-cancer diseases. The CFCS cohort is an important addition to existing radio-epidemiological cohorts, given the moderate-to-high doses received fractionated over several years, the type of irradiation (external irradiation only), radiation type (X rays only), a balanced combination of both genders and inclusion of people of all ages.

Accounting for Unfissioned Plutonium from the Trinity Atomic Bomb Test.

The Trinity test device contained about 6 kg of plutonium as its fission source, resulting in a fission yield of 21 kT. However, only about 15% of the Pu actually underwent fission. The remaining unfissioned plutonium eventually was vaporized in the fireball and after cooling, was deposited downwind from the test site along with the various fission and activation products produced in the explosion. Using data from radiochemical analyses of soil samples collected postshot (most many years later), supplemented by model estimates of plutonium deposition density estimated from reported exposure rates at 12 h postshot, we have estimated the total activity and geographical distribution of the deposition density of this unfissioned plutonium in New Mexico. A majority (about 80%) of the unfissioned plutonium was deposited within the state of New Mexico, most in a relatively small area about 30-100 km downwind (the Chupadera Mesa area). For most of the state, the deposition density was a small fraction of the subsequent deposition density of Pu from Nevada Test Site tests (1951-1958) and later from global fallout from the large US and Russian thermonuclear tests (1952-1962). The fraction of the total unfissioned Pu that was deposited in New Mexico from Trinity was greater than the fraction of fission products deposited. Due to plutonium being highly refractory, a greater fraction of the Pu was incorporated into large particles that fell out closer to the test site as opposed to more volatile fission products (such as Cs and I) that tend to deposit on the surface of smaller particles that travel farther before depositing. The plutonium deposited as a result of the Trinity test was unlikely to have resulted in significant health risks to the downwind population.

Methods and Findings on Diet and Lifestyle Used to Support Estimation of Radiation Doses from Radioactive Fallout from the Trinity Nuclear Test.

The Trinity nuclear test was detonated in south-central New Mexico on 16 July 1945; in the early 2000s, the National Cancer Institute undertook a dose and cancer risk projection study of the possible health impacts of the test. In order to conduct a comprehensive dose assessment for the Trinity test, we collected diet and lifestyle data relevant to the populations living in New Mexico around the time of the test. This report describes the methodology developed to capture the data used to calculate radiation exposures and presents dietary and lifestyle data results for the main exposure pathways considered in the dose reconstruction. Individual interviews and focus groups were conducted in 2017 among older adults who had lived in the same New Mexico community during the 1940s or 1950s. Interview questions and guided group discussions focused on specific aspects of diet, water, type of housing, and time spent outdoors for different age groups. Thirteen focus groups and 11 individual interviews were conducted among Hispanic, White, and Native American participants. Extensive written notes and audio recordings aided in the coding of all responses used to derive ranges, prevalence, means, and standard deviations for each exposure variable for various age categories by region and ethnicity. Children aged 11-15 y in 1940s or 1950s from the rural plains had the highest milk intakes (993 mL d), and lowest intakes were among 11- to 15-y-olds in mountainous regions (191 mL d). Lactose intolerance rates were 7-71%, and prevalence was highest among Native Americans. Meat was not commonly consumed in the summer in most communities, and if consumed, it was among those aged 11-15 y of age or older who had relatively small amounts of 100-200 g d. Most drinking and cooking water came from covered wells, and most homes were made of adobe, which provided more protection from external radiation than wooden structures. The use of multiple approaches to trigger memory and collect participant reports on diet and other factors from the distant past seemed effective. These data were summarized, and together with other information, these data have been used to estimate radiation doses for representative persons of all ages in the main ethnic groups residing in New Mexico at the time of the Trinity nuclear test.

Estimated Radiation Doses Received by New Mexico Residents from the 1945 Trinity Nuclear Test.

The National Cancer Institute study of projected health risks to New Mexico residents from the 1945 Trinity nuclear test provides best estimates of organ radiation absorbed doses received by representative persons according to ethnicity, age, and county. Doses to five organs/tissues at significant risk from exposure to radioactive fallout (i.e., active bone marrow, thyroid gland, lungs, stomach, and colon) from the 63 most important radionuclides in fresh fallout from external and internal irradiation were estimated. The organ doses were estimated for four resident ethnic groups in New Mexico (Whites, Hispanics, Native Americans, and African Americans) in seven age groups using: (1) assessment models described in a companion paper, (2) data on the spatial distribution and magnitude of radioactive fallout derived from historical documents, and (3) data collected on diets and lifestyles in 1945 from interviews and focus groups conducted in 2015-2017 (described in a companion paper). The organ doses were found to vary widely across the state with the highest doses directly to the northeast of the detonation site and at locations close to the center of the Trinity fallout plume. Spatial heterogeneity of fallout deposition was the largest cause of variation of doses across the state with lesser differences due to age and ethnicity, the latter because of differences in diets and lifestyles. The exposure pathways considered included both external irradiation from deposited fallout and internal irradiation via inhalation of airborne radionuclides in the debris cloud as well as resuspended ground activity and ingestion of contaminated drinking water (derived both from rivers and rainwater cisterns) and foodstuffs including milk products, beef, mutton, and pork, human-consumed plant products including leafy vegetables, fruit vegetables, fruits, and berries. Tables of best estimates of county population-weighted average organ doses by ethnicity and age are presented. A discussion of our estimates of uncertainty is also provided to illustrate a lower and upper credible range on our best estimates of doses. Our findings indicate that only small geographic areas immediately downwind to the northeast received exposures of any significance as judged by their magnitude relative to natural radiation. The findings presented are the most comprehensive and well-described estimates of doses received by populations of New Mexico from the Trinity nuclear test.

Projected Cancer Risks to Residents of New Mexico from Exposure to Trinity Radioactive Fallout.

The Trinity nuclear test, conducted in 1945, exposed residents of New Mexico to varying degrees of radioactive fallout. Companion papers in this issue have detailed the results of a dose reconstruction that has estimated tissue-specific radiation absorbed doses to residents of New Mexico from internal and external exposure to radioactive fallout in the first year following the Trinity test when more than 90% of the lifetime dose was received. Estimated radiation doses depended on geographic location, race/ethnicity, and age at the time of the test. Here, these doses were applied to sex- and organ-specific risk coefficients (without applying a dose and dose rate effectiveness factor to extrapolate from a population with high-dose/high-dose rates to those with low-dose/low-dose rates) and combined with baseline cancer rates and published life tables to estimate and project the range of radiation-related excess cancers among 581,489 potentially exposed residents of New Mexico. The total lifetime baseline number of all solid cancers [excluding thyroid and non-melanoma skin cancer (NMSC)] was estimated to be 183,000 from 1945 to 2034. Estimates of ranges of numbers of radiation-related excess cancers and corresponding attributable fractions from 1945 to 2034 incorporate various sources of uncertainty. We estimated 90% uncertainty intervals (UIs) of excess cancer cases to be 210 to 460 for all solid cancers (except thyroid cancer and NMSC), 80 to 530 for thyroid cancer, and up to 10 for leukemia (except chronic lymphocytic leukemia), with corresponding attributable fractions ranging from 0.12% to 0.25%, 3.6% to 20%, and 0.02% to 0.31%, respectively. In the counties of Guadalupe, Lincoln, San Miguel, Socorro, and Torrance, which received the greatest fallout deposition, the 90% UI for the projected fraction of thyroid cancers attributable to radioactive fallout from the Trinity test was estimated to be from 17% to 58%. Attributable fractions for cancer types varied by race/ethnicity, but 90% UIs overlapped for all race/ethnicity groups for each cancer grouping. Thus, most cancers that have occurred or will occur among persons exposed to Trinity fallout are likely to be cancers unrelated to exposures from the Trinity nuclear test. While these ranges are based on the most detailed dose reconstruction to date and rely largely on methods previously established through scientific committee agreement, challenges inherent in the dose estimation, and assumptions relied upon both in the risk projection and incorporation of uncertainty are important limitations in quantifying the range of radiation-related excess cancer risk.

Occupational radiation and haematopoietic malignancy mortality in the retrospective cohort study of US radiologic technologists, 1983-2012.

OBJECTIVES: To evaluate cumulative occupational radiation dose response and haematopoietic malignancy mortality risks in the US radiologic technologist cohort. METHODS: Among 110 297 radiologic technologists (83 655 women, 26 642 men) who completed a baseline questionnaire sometime during 1983-1998, a retrospective cohort study was undertaken to assess cumulative, low-to-moderate occupational radiation dose and haematopoietic malignancy mortality risks during 1983-2012. Cumulative bone marrow dose (mean 8.5 mGy, range 0-430 mGy) was estimated based on 921 134 badge monitoring measurements during 1960-1997, work histories and historical data; 35.4% of estimated doses were based on badge measurements. Poisson regression was used to estimate excess relative risk of haematopoietic cancers per 100 milligray (ERR/100 mGy) bone-marrow absorbed dose, adjusting for attained age, sex and birth year. RESULTS: Deaths from baseline questionnaire completion through 2012 included 133 myeloid neoplasms, 381 lymphoid neoplasms and 155 leukaemias excluding chronic lymphocytic leukaemia (CLL). Based on a linear dose-response, no significant ERR/100 mGy occurred for acute myeloid leukaemia (ERR=0.0002, 95% CI <-0.02 to 0.24, p-trend>0.5, 85 cases) or leukaemia excluding CLL (ERR=0.05, 95% CI <-0.09 to 0.24, p-trend=0.21, 155 cases). No significant dose-response trends were observed overall for CLL (ERR<-0.023, 95% CI <-0.025 to 0.18, p-trend=0.45, 32 cases), non-Hodgkin lymphoma (ERR=0.03, 95% CI <-0.2 to 0.18, p-trend=0.4, 201 cases) or multiple myeloma (ERR=0.003, 95% CI -0.02 to 0.16, p-trend>0.5, 112 cases). Findings did not differ significantly by demographic factors, smoking or specific radiological procedures performed. CONCLUSION: After follow-up averaging 22 years, there was little evidence of a relationship between occupational radiation exposure and myeloid or lymphoid haematopoietic neoplasms.

Lung cancer mortality associated with protracted low-dose occupational radiation exposures and smoking behaviors in U.S. radiologic technologists, 1983-2012.

In the Japanese atomic bomb survivors, risk of lung cancer has been shown to increase with greater acute exposure to ionizing radiation. Although similar findings have been observed in populations exposed to low-dose, protracted radiation, such studies lack information on cigarette smoking history, a potential confounder. In a cohort of 106 068 U.S. radiologic technologists, we examined the association between estimated cumulative lung absorbed dose from occupational radiation exposure and lung cancer mortality. Poisson regression models, adjusted for attained age, sex, birth cohort, pack-years smoked and years since quitting smoking, were used to calculate linear excess relative risks (ERR) per 100 mGy, using time-dependent cumulative lung absorbed dose, lagged 10 years. Mean cumulative absorbed dose to the lung was 25 mGy (range: 0-810 mGy). During the 1983 to 2012 follow-up, 1090 participants died from lung cancer. Greater occupational radiation lung dose was not associated with lung cancer mortality overall (ERR per 100 mGy: -0.02, 95% CI: <0-0.13). However, significant dose-response relationships were observed for some subgroups, which might be false-positive results given the number of statistical tests performed. As observed in other studies of radiation and smoking, the interaction between radiation and smoking appeared to be sub-multiplicative with an ERR per 100 mGy of 0.41 (95% CI: 0.01-1.15) for those who smoked <20 pack-years and -0.03 (95% CI: <0-0.15) for those who smoked ≥20 pack-years. Our study provides some evidence that greater protracted radiation exposure in the low-dose range is positively associated with lung cancer mortality.

Occupational radiation exposure and excess additive risk of cataract incidence in a cohort of US radiologic technologists.

OBJECTIVES: Previous analyses of cataract in radiation-exposed populations have assessed relative risk; radiogenic excess additive risk (EAR), arguably of more public health importance, has not been estimated. Previous analysis of a large prospective cohort of US radiologic technologists (USRT) quantified excess relative risk of cataract in relation to occupational radiation dose. We aim to assess EARs of cataract. METHODS: We estimated EARs of cataract/cataract surgery in the USRT cohort using generalised additive models in relation to occupational radiation exposure, and assessed risk modification by a priori-selected cataract risk factors (diabetes, body mass index, smoking, race, sex, birth-year, ultraviolet B (UVB) radiation exposure). RESULTS: There were 11 345 cataract diagnoses and 5440 of cataract surgery during 832 462 and 888 402 person-years of follow-up, respectively. Cumulative occupational radiation exposure was associated with self-reported cataract, but not with cataract surgery, with EAR/104 person-year Gy=94 (95% CI: 47 to 143, p<0.001) and EAR/104 person-year Gy=13 (95% CI: <0 to 57, p=0.551), respectively. There was marked (p<0.001) variation of EAR by age and by diabetes status, with risk higher among persons ≥75 years and diabetics. There were indications of elevated risk among those with higher UVB radiation (p=0.045), whites (p=0.056) and among those with higher levels of cigarette smoking (p=0.062). Elevated additive risk was observed for estimated occupational radiation eye-lens doses <100 mGy (p=0.004) with no dose-response curvature (p=0.903). CONCLUSIONS: The elevated additive risks associated with low-dose radiation, if confirmed elsewhere, have important public health and clinical implications for radiation workers as well as regulatory measures.

Association of Radioactive Iodine Treatment With Cancer Mortality in Patients With Hyperthyroidism.

IMPORTANCE: Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hyperthyroidism. OBJECTIVE: To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. DESIGN, SETTING, AND PARTICIPANTS: This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18 805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR = 1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. EXPOSURES: Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). MAIN OUTCOMES AND MEASURES: Site-specific and all solid-cancer mortality. RESULTS: A total of 18 805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14 671 [78.0%]), and most had a Graves disease diagnosis (17 615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n = 1984; RR at 100-mGy dose to the stomach = 1.06; 95% CI, 1.02-1.10; P = .002), including female breast cancer (n = 291; RR at 100-mGy dose to the breast = 1.12; 95% CI, 1.003-1.32; P = .04) and all other solid cancers combined (n = 1693; RR at 100-mGy dose to the stomach = 1.05; 95% CI, 1.01-1.10; P = .01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. CONCLUSIONS AND RELEVANCE: In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

Cataract risk in US radiologic technologists assisting with fluoroscopically guided interventional procedures: a retrospective cohort study.

OBJECTIVES: To assess radiation exposure-related work history and risk of cataract and cataract surgery among radiologic technologists assisting with fluoroscopically guided interventional procedures (FGIP). METHODS: This retrospective study included 35 751 radiologic technologists who reported being cataract-free at baseline (1994-1998) and completed a follow-up questionnaire (2013-2014). Frequencies of assisting with 21 types of FGIP and use of radiation protection equipment during five time periods (before 1970, 1970-1979, 1980-1989, 1990-1999, 2000-2009) were derived from an additional self-administered questionnaire in 2013-2014. Multivariable-adjusted relative risks (RRs) for self-reported cataract diagnosis and cataract surgery were estimated according to FGIP work history. RESULTS: During follow-up, 9372 technologists reported incident physician-diagnosed cataract; 4278 of incident cases reported undergoing cataract surgery. Technologists who ever assisted with FGIP had increased risk for cataract compared with those who never assisted with FGIP (RR: 1.18, 95% CI 1.11 to 1.25). Risk increased with increasing cumulative number of FGIP; the RR for technologists who assisted with >5000 FGIP compared with those who never assisted was 1.38 (95% CI 1.24 to 1.53; p trend <0.001). These associations were more pronounced for FGIP when technologists were located ≤3 feet (≤0.9 m) from the patient compared with >3 feet (>0.9 m) (RRs for >5000 at ≤3 feet vs never FGIP were 1.48, 95% CI 1.27 to 1.74 and 1.15, 95% CI 0.98 to 1.35, respectively; pdifference=0.04). Similar risks, although not statistically significant, were observed for cataract surgery. CONCLUSION: Technologists who reported assisting with FGIP, particularly high-volume FGIP within 3 feet of the patient, had increased risk of incident cataract. Additional investigation should evaluate estimated dose response and medically validated cataract type.

Estimation of Radiation Doses to U.S. Military Test Participants from Nuclear Testing: A Comparison of Historical Film-Badge Measurements, Dose Reconstruction and Retrospective Biodosimetry.

Retrospective radiation dose estimations, whether based on physical or biological measurements, or on theoretical dose reconstruction, are limited in their precision and reliability, particularly for exposures that occurred many decades ago. Here, we studied living U.S. military test participants, believed to have received high-dose radiation exposures during nuclear testing-related activities approximately six decades ago, with two primary goals in mind. The first was to compare three different approaches of assessing past radiation exposures: 1. Historical personnel monitoring data alone; 2. Dose reconstruction based on varying levels of completeness of individual information, which can include film badge data; and 3. Retrospective biodosimetry using chromosome aberrations in peripheral blood lymphocytes. The second goal was to use the collected data to make the best possible estimates of bone marrow dose received by a group with the highest military recorded radiation doses of any currently living military test participants. Six nuclear test participants studied had been on Rongerik Atoll during the 1954 CASTLE Bravo nuclear test. Another six were present at the Nevada Test Site (NTS) and/or Pacific Proving Ground (PPG) and were believed to have received relatively high-dose exposures at those locations. All were interviewed, and all provided a blood sample for cytogenetic analysis. Military dose records for each test participant, as recorded in the Defense Threat Reduction Agency's Nuclear Test Review and Information System, were used as the basis for historical film badge records and provided exposure scenario information to estimate dose via dose reconstruction. Dose to bone marrow was also estimated utilizing directional genomic hybridization (dGH) for high-resolution detection of radiation-induced chromosomal translocations and inversions, the latter being demonstrated for the first time for the purpose of retrospective biodosimetry. As the true dose for each test participant is not known these many decades after exposure, this study gauged the congruence of different methods by assessing the degree of correlation and degree of systematic differences. Overall, the best agreement between methods, defined by statistically significant correlations and small systematic differences, was between doses estimated by a dose reconstruction methodology that exploited all the available individual detail and the biodosimetry methodology derived from a weighted average dose determined from chromosomal translocation and inversion rates. Employing such a strategy, we found that the Rongerik veterans who participated in this study appear to have received, on average, bone marrow equivalent doses on the order of 300-400 mSv, while the NTS/ PPG participants appear to have received approximately 250-300 mSv. The results show that even for nuclear events that occurred six decades in the past, biological signatures of exposure are still present, and when taken together, chromosomal translocations and inversions can serve as reliable retrospective biodosimeters, particularly on a group-average basis, when doses received are greater than statistically-determined detection limits for the biological assays used.

Chromosome Translocations, Inversions and Telomere Length for Retrospective Biodosimetry on Exposed U.S. Atomic Veterans.

It has now been over 60 years since U.S. nuclear testing was conducted in the Pacific islands and Nevada, exposing military personnel to varying levels of ionizing radiation. Actual doses are not well-established, as film badges in the 1950s had many limitations. We sought a means of independently assessing dose for comparison with historical film badge records and dose reconstruction conducted in parallel. For the purpose of quantitative retrospective biodosimetry, peripheral blood samples from 12 exposed veterans and 12 age-matched (>80 years) veteran controls were collected and evaluated for radiation-induced chromosome damage utilizing directional genomic hybridization (dGH), a cytogenomics-based methodology that facilitates simultaneous detection of translocations and inversions. Standard calibration curves were constructed from six male volunteers in their mid-20s to reflect the age range of the veterans at time of exposure. Doses were estimated for each veteran using translocation and inversion rates independently; however, combining them by a weighted-average generally improved the accuracy of dose estimations. Various confounding factors were also evaluated for potential effects on chromosome aberration frequencies. Perhaps not surprisingly, smoking and age-associated increases in background frequencies of inversions were observed. Telomere length was also measured, and inverse relationships with both age and combined weighted dose estimates were observed. Interestingly, smokers in the non-exposed control veteran cohort displayed similar telomere lengths as those in the never-smoker exposed veteran group, suggesting that chronic smoking had as much effect on telomere length as a single exposure to radioactive fallout. Taken together, we find that our approach of combined chromosome aberration-based retrospective biodosimetry provided reliable dose estimation capability, particularly on a group average basis, for exposures above statistical detection limits.

Occupational radiation exposure and risk of cataract incidence in a cohort of US radiologic technologists.

It has long been known that relatively high-dose ionising radiation exposure (> 1 Gy) can induce cataract, but there has been no evidence that this occurs at low doses (< 100 mGy). To assess low-dose risk, participants from the US Radiologic Technologists Study, a large, prospective cohort, were followed from date of mailed questionnaire survey completed during 1994-1998 to the earliest of self-reported diagnosis of cataract/cataract surgery, cancer other than non-melanoma skin, or date of last survey (up to end 2014). Cox proportional hazards models with age as timescale were used, adjusted for a priori selected cataract risk factors (diabetes, body mass index, smoking history, race, sex, birth year, cumulative UVB radiant exposure). 12,336 out of 67,246 eligible technologists reported a history of diagnosis of cataract during 832,479 person years of follow-up, and 5509 from 67,709 eligible technologists reported undergoing cataract surgery with 888,420 person years of follow-up. The mean cumulative estimated 5-year lagged eye-lens absorbed dose from occupational radiation exposures was 55.7 mGy (interquartile range 23.6-69.0 mGy). Five-year lagged occupational radiation exposure was strongly associated with self-reported cataract, with an excess hazard ratio/mGy of 0.69 × 10-3 (95% CI 0.27 × 10-3 to 1.16 × 10-3, p < 0.001). Cataract risk remained statistically significant (p = 0.030) when analysis was restricted to < 100 mGy cumulative occupational radiation exposure to the eye lens. A non-significantly increased excess hazard ratio/mGy of 0.34 × 10-3 (95% CI - 0.19 × 10-3 to 0.97 × 10-3, p = 0.221) was observed for cataract surgery. Our results suggest that there is excess risk for cataract associated with radiation exposure from low-dose and low dose-rate occupational exposures.