Thyroid cancer incidence in cohorts exposed in childhood to 131I released during the Windscale nuclear reactor accident at Sellafield, England, in 1957.

A fire in one of the Windscale nuclear reactors at Sellafield (Cumbria, England) in October 1957 released 1,800 TBq of 131I (half-life, 8 days) to atmosphere. Measurements of 131I activity in thyroids of exposed children showed typical thyroid doses of tens of milligray, but with some exceeding 100 mGy. Radiation exposure in childhood is known to increase the risk of thyroid cancer. Consequently, an investigation was conducted into whether raised numbers of thyroid cancer cases occurred in those exposed to 131I as young children in Cumbria. A database of Cumbrian births from 1950 onwards allowed cohorts of 56,086 births during 1950-1958 and 137,444 births during 1959-1980 to be constructed, periods including children potentially exposed and unexposed, respectively, to 131I. Three areas of Cumbria with different 131I contamination levels were identified from monitoring data, and births assigned to these three areas for the two periods of birth. Members of these six sub-cohorts were linked to incident thyroid cancer cases in Great Britain during 1981-2020 using national cancer registration databases, providing thyroid cancer incidence rates. Incidence rate ratios (IRRs), with the lowest contamination area as a reference, were computed. No IRR differed discernibly from unity. For births during 1950-1958, the IRR for the combined highest and intermediate 131I contamination areas was 0.68 (95% confidence interval: 0.24, 1.56), and no case of thyroid cancer was found in the small cohort born in the highest contamination area. In conclusion, no increased risk of thyroid cancer in those exposed to 131I as young children in Cumbria in 1957 was detected. This study adds to the evidence on the long-term risk of thyroid cancer following childhood exposure to low and moderate levels of 131I, such as occurred following the Fukushima nuclear accident in 2011.

A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

Recurrent medical imaging exposures for the care of patients: one way forward.

Medical imaging is both valuable and essential in the care of patients. Much of this imaging depends on ionizing radiation with attendant responsibilities for judicious use when performing an examination. This responsibility applies in settings of both individual as well as multiple (recurrent) imaging with associated repeated radiation exposures. In addressing the roles and responsibilities of the medical communities in the paradigm of recurrent imaging, both the International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) have issued position statements, each affirmed by other organizations. The apparent difference in focus and approach has resulted in a lack of clarity and continued debate. Aiming towards a coherent approach in dealing with radiation exposure in recurrent imaging, the IAEA convened a panel of experts, the purpose of which was to identify common ground and reconcile divergent perspectives. The effort has led to clarifying recommendations for radiation exposure aspects of recurrent imaging, including the relevance of patient agency and the provider-patient covenant in clinical decision-making. CLINICAL RELEVANCE STATEMENT: An increasing awareness, generating some lack of clarity and divergence in perspectives, with patients receiving relatively high radiation doses (e.g., ≥ 100 mSv) from recurrent imaging warrants a multi-stakeholder accord for the benefit of patients, providers, and the imaging community. KEY POINTS: • Recurrent medical imaging can result in an accumulation of exposures which exceeds 100 milli Sieverts. • Professional organizations have different perspectives on roles and responsibilities for recurrent imaging. • An expert panel reconciles differing perspectives for addressing radiation exposure from recurrent medical imaging.

The ICRP, MELODI, and ALLIANCE workshop on effects of ionizing radiation exposure in offspring and next generations: a summary of discussions.

PURPOSE: Task Group 121 - Effects of ionizing radiation exposure in offspring and next generations - is a task group under the Committee 1 of the International Commission on Radiological Protection (ICRP), approved by the Main Commission on 18th November 2021. The main goals of Task Group 121 are to (1) review and update the scientific literature of relevance to radiation-related effects in the offspring of parent(s) exposed to ionizing radiation in both human and non-human biota; (2) to assess preconceptional and intrauterine effects of radiation exposure and related morbidity and mortality; and, (3) to provide advice about the level of evidence and how to consider these preconceptional and postconceptional effects in the system of radiological protection for humans and non-human biota. METHODS: The Task Group is reviewing relevant literature since Publication 90 'Biological effects after prenatal irradiation (embryo and fetus)' (2003) and will include radiation-related effects on future generations in humans, animals, and plants. This review will be conducted to account for the health effects on offspring and subsequent generations in the current system of radiological protection. Radiation detriment calculation will also be reviewed. Finally, preliminary recommendations will be made to update the integration of health effects in offspring and next generations in the system of radiological protection. RESULTS: A Workshop, jointly organized by ICRP Task Group 121 and European Radiation Protection Research Platforms MELODI and ALLIANCE was held in Budapest, Hungary, from 31st May to 2nd June 2022. Participants discussed four important topics: (1) hereditary and epigenetic effects due to exposure of the germ cell line (preconceptional exposure), (2) effects arising from exposure of the embryo and fetus (intrauterine exposure), (3) transgenerational effects on biota, and (4) its potential impact on the system of radiological protection. CONCLUSIONS: Based on the discussions and presentations during the breakout sessions, newer publications, and gaps on the current scientific literature were identified. For instance, there are some ongoing systematic reviews and radiation epidemiology reviews of intrauterine effects. There are newer methods of Monte Carlo simulation for fetal dosimetry, and advances in radiation genetics, epigenetics, and radiobiology studies. While the current impact of hereditary effects on the global detriment was reported as small, the questions surrounding the effects of radiation exposure on offspring and the next generation are crucial, recurring, and with a major focus on exposed populations. This article summarizes the workshop discussions, presentations, and conclusions of each topic and introduces the special issue of the International Journal of Radiation Biology resulting from the discussions of the meeting.

An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood.

BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards. DISCUSSION: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.

Effective doses and risks from medical diagnostic x-ray examinations for male and female patients from childhood to old age.

The consideration of risks from medical diagnostic x-ray examinations and their justification commonly relies on estimates of effective dose, although the quantity is actually a health-detriment-weighted summation of organ/tissue-absorbed doses rather than a measure of risk. In its 2007 Recommendations, the International Commission on Radiological Protection (ICRP) defines effective dose in relation to a nominal value of stochastic detriment following low-level exposure of 5.7 × 10-2Sv-1, as an average over both sexes, all ages, and two fixed composite populations (Asian and Euro-American). Effective dose represents the overall (whole-body) dose received by a person from a particular exposure, which can be used for the purposes of radiological protection as set out by ICRP, but it does not provide a measure that is specific to the characteristics of the exposed individual. However, the cancer incidence risk models used by ICRP can be used to provide estimates of risk separately for males and females, as a function of age-at-exposure, and for the two composite populations. Here, these organ/tissue-specific risk models are applied to estimates of organ/tissue-specific absorbed doses from a range of diagnostic procedures to derive lifetime excess cancer incidence risk estimates; the degree of heterogeneity in the distribution of absorbed doses between organs/tissues will depend on the procedure. Depending on the organs/tissues exposed, risks are generally higher in females and notably higher for younger ages-at-exposure. Comparing lifetime cancer incidence risks per Sv effective dose from the different procedures shows that overall risks are higher by about a factor of two to three for the youngest age-at-exposure group, 0-9 yr, than for 30-39 yr adults, and lower by a similar factor for an age-at-exposure of 60-69 yr. Taking into account these differences in risk per Sv, and noting the substantial uncertainties associated with risk estimates, effective dose as currently formulated provides a reasonable basis for assessing the potential risks from medical diagnostic examinations.

Summary of Radiation Research Society Online 67th Annual Meeting, Symposium on "Radiation and Circulatory Effects".

PURPOSE: This article summarizes a number of presentations from a session on "Radiation and Circulatory Effects" held during the Radiation Research Society Online 67th Annual Meeting, October 3-6 2021. MATERIALS AND METHODS: Different epidemiological cohorts were analyzed with various statistical means common in epidemiology. The cohorts included the one from the U.S. Million Person Study and the Canadian Fluoroscopy Cohort Study. In addition, one of the contributions in our article relies on results from analyses of the Japanese atomic bomb survivors, Russian emergency and recovery workers and cohorts of nuclear workers. The Canadian Fluoroscopy Cohort Study data were analyzed with a larger series of linear and nonlinear dose-response models in addition to the linear no-threshold (LNT) model. RESULTS AND CONCLUSIONS: The talks in this symposium showed that low/moderate acute doses at low/moderate dose rates can be associated with an increased risk of CVD, although some of the epidemiological results for occupational cohorts are equivocal. The usually only limited availability of information on well-known risk factors for circulatory disease (e.g. smoking, obesity, hypertension, diabetes, physical activity) is an important limiting factor that may bias any observed association between radiation exposure and detrimental health outcome, especially at low doses. Additional follow-up and careful dosimetric and outcome assessment are necessary and more epidemiological and experimental research is required. Obtaining reliable information on other risk factors is especially important.

Radiation dose rate effects: what is new and what is needed?

Despite decades of research to understand the biological effects of ionising radiation, there is still much uncertainty over the role of dose rate. Motivated by a virtual workshop on the "Effects of spatial and temporal variation in dose delivery" organised in November 2020 by the Multidisciplinary Low Dose Initiative (MELODI), here, we review studies to date exploring dose rate effects, highlighting significant findings, recent advances and to provide perspective and recommendations for requirements and direction of future work. A comprehensive range of studies is considered, including molecular, cellular, animal, and human studies, with a focus on low linear-energy-transfer radiation exposure. Limits and advantages of each type of study are discussed, and a focus is made on future research needs.

The risk of cancer following high, and very high, doses of ionising radiation.

It is established that moderate-to-high doses of ionising radiation increase the risk of subsequent cancer in the exposed individual, but the question arises as to the risk of cancer from higher doses, such as those delivered during radiotherapy, accidents, or deliberate acts of malice. In general, the cumulative dose received during a course of radiation treatment is sufficiently high that it would kill a person if delivered as a single dose to the whole body, but therapeutic doses are carefully fractionated and high/very high doses are generally limited to a small tissue volume under controlled conditions. The very high cumulative doses delivered as fractions during radiation treatment are designed to inactivate diseased cells, but inevitably some healthy cells will also receive high/very high doses. How the doses (ranging from <1 Gy to tens of Gy) received by healthy tissues during radiotherapy affect the risk of second primary cancer is an increasingly important issue to address as more cancer patients survive the disease. Studies show that, except for a turndown for thyroid cancer, a linear dose-response for second primary solid cancers seems to exist over a cumulative gamma radiation dose range of tens of gray, but with a gradient of excess relative risk per Gy that varies with the type of second cancer, and which is notably shallower than that found in the Japanese atomic bomb survivors receiving a single moderate-to-high acute dose. The risk of second primary cancer consequent to high/very high doses of radiation is likely to be due to repopulation of heavily irradiated tissues by surviving stem cells, some of which will have been malignantly transformed by radiation exposure, although the exact mechanism is not known, and various models have been proposed. It is important to understand the mechanisms that lead to the raised risk of second primary cancers consequent to the receipt of high/very high doses, in particular so that the risks associated with novel radiation treatment regimens-for example, intensity modulated radiotherapy and volumetric modulated arc therapy that deliver high doses to the target volume while exposing relatively large volumes of healthy tissue to low/moderate doses, and treatments using protons or heavy ions rather than photons-may be properly assessed.

Cancer risks among studies of medical diagnostic radiation exposure in early life without quantitative estimates of dose.

BACKGROUND: There is accumulating evidence of excess risk of cancer in various populations exposed at acute doses below several tens of mSv or doses received over a protracted period. There is also evidence that relative risks are generally higher after radiation exposures in utero or in childhood. METHODS AND FINDINGS: We reviewed and summarised evidence from 89 studies of cancer following medical diagnostic exposure in utero or in childhood, in which no direct estimates of radiation dose are available. In all of the populations studied exposure was to sparsely ionizing radiation (X-rays). Several of the early studies of in utero exposure exhibit modest but statistically significant excess risks of several types of childhood cancer. There is a highly significant (p < 0.0005) negative trend of odds ratio with calendar period of study, so that more recent studies tend to exhibit reduced excess risk. There is no significant inter-study heterogeneity (p > 0.3). In relation to postnatal exposure there are significant excess risks of leukaemia, brain and solid cancers, with indications of variations in risk by cancer type (p = 0.07) and type of exposure (p = 0.02), with fluoroscopy and computed tomography scans associated with the highest excess risk. However, there is highly significant inter-study heterogeneity (p < 0.01) for all cancer endpoints and all but one type of exposure, although no significant risk trend with calendar period of study. CONCLUSIONS: Overall, this large body of data relating to medical diagnostic radiation exposure in utero provides support for an associated excess risk of childhood cancer. However, the pronounced heterogeneity in studies of postnatal diagnostic exposure, the implied uncertainty as to the meaning of summary measures, and the distinct possibilities of bias, substantially reduce the strength of the evidence from the associations we observe between radiation imaging in childhood and the subsequent risk of cancer being causally related to radiation exposure.

Review of the risk of cancer following low and moderate doses of sparsely ionising radiation received in early life in groups with individually estimated doses.

BACKGROUND: The detrimental health effects associated with the receipt of moderate (0.1-1 Gy) and high (>1 Gy) acute doses of sparsely ionising radiation are well established from human epidemiological studies. There is accumulating direct evidence of excess risk of cancer in a number of populations exposed at lower acute doses or doses received over a protracted period. There is evidence that relative risks are generally higher after radiation exposures in utero or in childhood. METHODS AND FINDINGS: We reviewed and summarised evidence from 60 studies of cancer or benign neoplasms following low- or moderate-level exposure in utero or in childhood from medical and environmental sources. In most of the populations studied the exposure was predominantly to sparsely ionising radiation, such as X-rays and gamma-rays. There were significant (p < 0.001) excess risks for all cancers, and particularly large excess relative risks were observed for brain/CNS tumours, thyroid cancer (including nodules) and leukaemia. CONCLUSIONS: Overall, the totality of this large body of data relating to in utero and childhood exposure provides support for the existence of excess cancer and benign neoplasm risk associated with radiation doses < 0.1 Gy, and for certain groups exposed to natural background radiation, to fallout and medical X-rays in utero, at about 0.02 Gy.

Quantitative Bias Analysis of the Association between Occupational Radiation Exposure and Ischemic Heart Disease Mortality in UK Nuclear Workers.

The scientific question of whether protracted low-dose or low-dose-rate exposure to external radiation is causally related to the risk of circulatory disease continues to be an important issue for radiation protection. Previous analyses of a matched case-control dataset nested in a large cohort of UK nuclear fuel cycle workers indicated that there was little evidence that observed associations between external radiation dose and ischemic heart disease (IHD) mortality risk [OR = 1.35 (95% CI: 0.99-1.84) for 15-year-lagged exposure] could alternatively be explained by confounding from pre-employment tobacco smoking, BMI or blood pressure, or from socioeconomic status or occupational exposure to excessive noise or shiftwork. To improve causal inference about the observed external radiation dose and IHD mortality association, we estimated the potential magnitude and direction of non-random errors, incorporated sensitivity analyses and simulated bias effects under plausible scenarios. We conducted quantitative bias analyses of plausible scenarios based on 1,000 Monte Carlo samples to explore the impact of exposure measurement error, missing information on tobacco smoking, and unmeasured confounding, and assessed whether observed associations were reliant on the inclusion of specific matched pairs using bootstrapping with 10% of matched pairs randomly excluded in 1,000 samples. We further explored the plausibility that having been monitored for internal exposure, which was an important confounding factor in the case-control analysis for which models were adjusted, was indeed a confounding factor or whether it might have been the result of some form of selection bias. Consistent with the broader epidemiological evidence-base, these analyses provide further evidence that the dose-response association between cumulative external radiation exposure and IHD mortality is non-linear in that it has a linear shape plateauing at an excess risk of 43% (95% CI: 7-92%) on reaching 390 mSv. Analyses of plausible scenarios of patterns of missing data for tobacco smoking at start of employment indicated that this resulted in relatively little bias towards the null in the original analysis. An unmeasured confounder would have had to have been highly correlated (rp > 0.60) with cumulative external radiation dose to importantly bias observed associations. The confounding effect of "having been monitored for internal dose" was unlikely to have been a true confounder in a biological sense, but instead may have been some unknown factor related to differences over time and between sites in selection criteria for internal monitoring, possibly resulting in collider bias. Plausible patterns of exposure measurement error negatively biased associations regardless of the modeled scenario, but did not importantly change the shape of the observed dose-response associations. These analyses provide additional support for the hypothesis that the observed association between external radiation exposure and IHD mortality may be causal.

Overview of epidemiological studies of nuclear workers: opportunities, expectations, and limitations.

Epidemiological studies of those exposed occupationally to ionising radiation offer an important opportunity to directly check the assumptions underlying the international system of radiological protection against low-level radiation exposures. Recent nuclear worker studies, notably the International Nuclear Workers Study (INWORKS) and studies of the Mayak workforce in Russia, provide powerful investigations of a wide range of cumulative photon doses received at a low dose-rate over protracted periods, and broadly confirm radiation-related excess risks of leukaemia and solid cancers at around the levels predicted by standard risk models derived mainly from the experience of the Japanese atomic-bomb survivors acutely exposed principally to gamma radiation. However, the slope of the dose-response for solid cancers expressed in terms of the excess relative risk per unit dose, ERR/Gy, differs between INWORKS and Mayak, such that when compared with the slope derived from the atomic-bomb survivors, INWORKS does not provide obvious support for the use in radiological protection of a dose and dose-rate effectiveness factor greater than one whereas the Mayak workforce apparently does. This difference could be a chance effect, but it could also point to potential problems with these worker studies. Of particular concern is the adequacy of recorded doses received in the early years of operations at older nuclear installations, such as the potential for 'missed' photon doses. A further issue is how baseline cancer rates may influence radiation-related excess risks. There is scope for a considerable increase in the statistical power of worker studies, with longer follow-up capturing more deaths and incident cases of cancer, and further workforces being included in collaborative studies, but the difficulties posed by dosimetry questions should not be ignored and need to be the subject of detailed scrutiny.

Lymphoma and multiple myeloma in cohorts of persons exposed to ionising radiation at a young age.

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted. Years of entry spanned 1916-1981. At the end of follow-up (mean 42.1 years) there were 593 lymphoma (422 non-Hodgkin (NHL), 107 Hodgkin (HL), 64 uncertain subtype), 66 chronic lymphocytic leukaemia (CLL) and 122 multiple myeloma (MM) deaths and incident cases among 143,136 persons, with mean ABM dose 0.14 Gy (range 0-5.95 Gy) and mean age at first exposure 6.93 years. Excess relative risk (ERR) was not significantly increased for lymphoma (ERR/Gy = -0.001; 95% CI: -0.255, 0.279), HL (ERR/Gy = -0.113; 95% CI: -0.669, 0.709), NHL + CLL (ERR/Gy = 0.099; 95% CI: -0.149, 0.433), NHL (ERR/Gy = 0.068; 95% CI: -0.253, 0.421), CLL (ERR/Gy = 0.320; 95% CI: -0.678, 1.712), or MM (ERR/Gy = 0.149; 95% CI: -0.513, 1.063) (all p-trend > 0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues.