A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309 932 nuclear workers employed in France, the United Kingdom, and the United States were monitored for external radiation exposure. Associations of radiation with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28 089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers. Negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy = 0.65; 95% credible interval [CrI], 0.24-1.07), prostate (ERR per Gy = 0.44; 95% CrI, -0.06 to 0.91), and colon cancer (ERR per Gy = 0.53; 95% CrI, -0.07 to 1.11). The results contribute evidence regarding associations between low-dose radiation and cancer.

Objective This study aimed at investigating the relationship between occupational exposure to external ionising radiation and central nervous system (CNS) tumours mortality in healthcare workers working in France.Design and setting The Occupational Radiation-Induced Cancer in Medical staff (ORICAMs) nested case–control study was conducted based on the dosimetric records of the national register of occupational dosimetry (Système d’information de la surveillance de l’exposition aux rayonnements ionisants).Participants and methods 33 CNS tumour deaths occurred between 2002 and 2012 among the ORICAMs cohort composed of 164 015 healthcare workers. Each case was matched to five controls alive at the time of the corresponding case’s death, based on sex, year of birth, date of enrolment in the cohort and duration of follow-up. All participants were badge monitored for external radiation exposure, expressed in Hp(10). Conditional logistic regression was used to analyse the dose–response relationship between radiation dose and CNS mortality.Results Cases were exposed to a mean cumulative career radiation dose of 5.8±13.7 (max: 54.3) millisievert (mSv) compared with 4.1±15.2 (142.2) mSv for controls. No statistically significant association was found between CNS tumour mortality and cumulative whole-body career dose (OR=1.00, 95% CI 0.98 to 1.03), duration of exposure (OR=1.03; 95% CI 0.95 to 1.12) or age at first exposure (OR=0.98; 95% CI 0.91 to 1.06).Conclusion We found no evidence of an association between external radiation exposure and CNS tumour risk in healthcare workers. Limitations of the study include low statistical power and short duration of follow-up.

PURPOSE:The discovery of X-rays was followed by a variety of attempts to treat infectious diseases and various other non-cancer diseases with ionizing radiation, in addition to cancer. There has been a recent resurgence of interest in the use of such radiotherapy for non-cancer diseases. Non-cancer diseases for which use of radiotherapy has currently been proposed include refractory ventricular tachycardia, neurodegenerative diseases (e.g. Alzheimer's disease and dementia), and Coronavirus Disease 2019 (COVID-19) pneumonia, all with ongoing clinical studies that deliver radiation doses of 0.5-25 Gy in a single fraction or in multiple daily fractions. In addition to such non-cancer effects, historical indications predominantly used in some countries (e.g. Germany) include osteoarthritis and degenerative diseases of the bones and joints. This narrative review gives an overview of the biological rationale and ongoing preclinical and clinical studies for radiotherapy proposed for various non-cancer diseases, discusses the plausibility of the proposed biological rationale, and considers the long-term radiation risks of cancer and non-cancer diseases. CONCLUSIONS:A growing body of evidence has suggested that radiation represents a double-edged sword, not only for cancer, but also for non-cancer diseases. At present, clinical evidence has shown some beneficial effects of radiotherapy for ventricular tachycardia, but there is little or no such evidence of radiotherapy for other newly proposed non-cancer diseases (e.g. Alzheimer's disease, COVID-19 pneumonia). Patients with ventricular tachycardia and COVID-19 pneumonia have thus far been treated with radiotherapy when they are an urgent life threat with no efficient alternative treatment, but some survivors may encounter a paradoxical situation where patients were rescued by radiotherapy but then get harmed by radiotherapy. Further studies are needed to justify the clinical use of radiotherapy for non-cancer diseases, and optimize dose to diseased tissue while minimizing dose to healthy tissue.

The International Nuclear Workers Study (INWORKS) contributes knowledge on the dose-response association between predominantly low dose, low dose rate occupational exposures to penetrating forms of ionizing radiation and cause-specific mortality. By extending follow-up of 309,932 radiation workers from France (1968–2014), the United Kingdom (1955–2012), and the United States (1944–2016) we increased support for analyses of temporal variation in radiation-cancer mortality associations. Here, we examine whether age at exposure, time since exposure, or attained age separately modify associations between radiation and mortality from all solid cancers, solid cancers excluding lung cancer, lung cancer, and lymphohematopoietic cancers. Multivariable Poisson regression was used to fit general relative rate models that describe modification of the linear excess relative rate per unit organ absorbed dose. Given indication of greater risk per unit dose for solid cancer mortality among workers hired in more recent calendar years, sensitivity analyses considering the impact of year of hire on results were performed. Findings were reasonably compatible with those from previous pooled and country-specific analyses within INWORKS showing temporal patterns of effect measure modification that varied among cancers, with evidence of persistent radiation-associated excess cancer risk decades after exposure, although statistically significant temporal modification of the radiation effect was not observed. Analyses stratified by hire period (< 1958, 1958+) showed temporal patterns that varied; however, these analyses did not suggest that this was due to differences in distribution of these effect measure modifiers by hire year.

Background A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. Methods We assembled a cohort of 309 932 radiation-monitored workers (269 487 [87%] males and 40 445 [13%] females) employed for at least 1 year by a nuclear facility in France (60 697 workers), the UK (147 872 workers), and the USA (101363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 1072 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes ofleukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. Findings The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 268, 90% CI 113 to 455, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (957, 400 to 1791, n=122) and myelodysplastic syndromes alone (319, 035 to 733, n=163) or combined with acute myeloid leukaemia (155, 005 to 342, n=598). No significant association was observed for acute lymphoblastic leukaemia (425, -419 to 1932, n=49) or CLL (020, -181 to 221, n=242). A positive association was observed between radiation dose and multiple myeloma (162, 006 to 364, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (027, -061 to 139, n=1146) or Hodgkin lymphoma (060, -364 to 483, n=122) mortality. Interpretation This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10 000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. Funding National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de S & ucirc;ret & eacute; Nucl & eacute;aire, Orano, Electricit & eacute; de France, UK Health Security Agency. Copyright (c) 2024. World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved.

INTRODUCTION:Between 2019-2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. METHODS:The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use. RESULTS:After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. DISCUSSION:Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.

Le modèle linéaire sans seuil (LNT) a été introduit dans le système de radioprotection il y a environ 60 ans, mais ce modèle et son utilisation en radioprotection sont encore débattus aujourd’hui. Cet article résume les résultats en radiobiologie et en épidémiologie accumulés au cours de la dernière décennie sur les effets d’une exposition aux rayonnements ionisants à faible Transfert d’Énergie Linéique (TEL) et discute de leur impact sur l’utilisation du modèle LNT dans l’évaluation des risques de cancer par rayonnement à faibles doses. Les connaissances acquises au cours des 10 dernières années, tant en radiobiologie qu’en épidémiologie, ont renforcé les fondements scientifiques sur les risques de cancer à faibles doses. En radiobiologie, bien que certains mécanismes ne soient pas linéaires avec la dose, les premiers stades de la cancérogenèse composés d’événements mutationnels, qui jouent un rôle clé dans la cancérogenèse, montrent des réponses linéaires à des doses aussi faibles que 10 mGy. L’impact des mécanismes non mutationnels sur le risque de cancer associé aux rayonnements à faibles doses est actuellement difficile à évaluer. En épidémiologie, les résultats montrent un excès de risques de cancer à des niveaux de dose de 100 mGy ou moins. Bien que certains résultats récents indiquent des relations non linéaires avec la dose pour certains types de cancers, le modèle LNT ne surestime pas substantiellement globalement les risques à faibles doses. Les résultats actuels, en radiobiologie ou en épidémiologie, ne démontrent pas l’existence d’un seuil de dose en dessous duquel le risque de cancer associé aux rayonnements serait nul. Des incertitudes persistent mais un tel seuil de dose, s’il existe, ne pourrait être supérieur à quelques dizaines de mGy. L’IRSN considère que les connaissances scientifiques actuellement disponibles ne remettent pas en cause l’utilisation du modèle LNT pour l’évaluation des risques de cancers radio-induits en appui au système de radioprotection. L’utilisation de ce modèle semble raisonnable d’un point de vue scientifique, et aucune autre relation dose-réponse ne semble plus adaptée ou justifiée à des fins de radioprotection.

Le modele lineaire sans seuil (LNT) a ete introduit dans le systeme de radioprotection il y a environ 60ans, mais ce modele et son utilisation en radioprotection sont encore debattus aujourd'hui. Cet article resume les resultats en radiobiologie et en epidemiologie accumules au cours de la derniere decennie sur les effets d'une exposition aux rayonnements ionisants a faible Transfert d'Energie Lineique (TEL) et discute de leur impact sur l'utilisation du modele LNT dans l'evaluation des risques de cancer par rayonnement a faibles doses. Les connaissances acquises au cours des 10 dernieres annees, tant en radiobiologie qu'en epidemiologie, ont renforce les fondements scientifiques sur les risques de cancer a faibles doses. En radiobiologie, bien que certains mecanismes ne soient pas lineaires avec la dose, les premiers stades de la cancerogenese composes d'evenements mutationnels, qui jouent un role cle dans la cancerogenese, montrent des reponses lineaires a des doses aussi faibles que 10mGy. L'impact des mecanismes non mutationnels sur le risque de cancer associe aux rayonnements a faibles doses est actuellement difficile a evaluer. En epidemiologie, les resultats montrent un exces de risques de cancer a des niveaux de dose de 100mGy ou moins. Bien que certains resultats recents indiquent des relations non lineaires avec la dose pour certains types de cancers, le modele LNT ne surestime pas substantiellement globalement les risques a faibles doses. Les resultats actuels, en radiobiologie ou en epidemiologie, ne demontrent pas l'existence d'un seuil de dose en dessous duquel le risque de cancer associe aux rayonnements serait nul. Des incertitudes persistent mais un tel seuil de dose, s'il existe, ne pourrait etre superieur a quelques dizaines de mGy. L'IRSN considere que les connaissances scientifiques actuellement disponibles ne remettent pas en cause l'utilisation du modele LNT pour l'evaluation des risques de cancers radio-induits en appui au systeme de radioprotection. L'utilisation de ce modele semble raisonnable d'un point de vue scientifique, et aucune autre relation dose-reponse ne semble plus adaptee ou justifiee a des fins de radioprotection.

Introduction Ionizing radiation is an established carcinogen. Previously, the International Nuclear Workers Study (INWORKS), a pooled cohort of 308,297 workers from the United States (US), the United Kingdom (UK), and France followed 1944–2005, yielded an estimated excess relative rate of 0.51 per Gy (90% CI = 0.23, 0.82) for cancer mortality (19,748 deaths). Prior analyses suggested potential for healthy worker survivor bias and modification by age-at-exposure and time-since-exposure. Material and Methods We reanalyzed INWORKS data using the parametric g-formula, which can address healthy worker survivor bias. We estimated impacts of 2 hypothetical interventions: 1) reduce historical standards of worker equivalent doses to 5 mSv/year; and, 2) exposure to constant levels of 20 mGy/year vs. 5 mGy/year while at work. This approach requires models for exposure, employment and cause-specific mortality. Mortality models allow variation in the radiation-mortality association with age-at-exposure and time-since-exposure. Results Conditional on prior exposure and covariates, employment in the prior year was inversely associated with mortality among French workers but positively associated in US and UK workers. Associations between dose and cancer mortality were largest for doses received after age 45, lagged 30+ years. Approximately 224 cancer deaths per 1,000 workers were expected by age 90 in the pooled cohort. Relative to historical exposure levels (10% of working-years > 5 mGy/year), we estimated that a hypothetical standard at 5 mGy/year would result in 6.9 (95% CI = -5.7, 19) fewer cancer deaths per 1,000 workers by age 90. A constant exposure at 5 mGy/year (relative to 20 mGy/year) would have resulted in 13 (95% CI = -1.1, 27) fewer deaths. Conclusion Our results suggest that confounding by employment status was present, suggesting healthy worker survivor bias. The importance of doses at older ages and long times-since-exposure suggest continued need to assess potential impacts of occupational ionizing radiation exposures.

Objective To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer. Design Multinational cohort study. Setting Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). Participants 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. Main outcome measures Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer. Results The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos. Conclusions This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world’s most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings.

Cohorts of nuclear workers are particularly relevant to study the health effects of protracted exposures to low doses at low dose-rates of ionizing radiation (IR). In France, a cohort of nuclear workers badge-monitored for external IR exposure has been followed-up for several decades. Its size and follow-up period have recently been extended. The present paper focuses on mortality from both cancer and non-cancer diseases in this cohort. The SELTINE cohort of nuclear workers employed by CEA, Orano, and EDF companies was followed-up for mortality from 1968 to 2014. Mortality in the cohort was compared to that in the French general population. Poisson regression methods were used to estimate excess relative rates of mortality per unit of cumulative dose of IR, adjusted for calendar year, age, company, duration of employment, and socioeconomic status. The cohort included 80,348 workers. At the end of the follow-up, the mean attained age was 63 years, and 15,695 deaths were observed. A strong healthy worker effect was observed overall. A significant excess of pleural cancer mortality was observed but not associated with IR dose. Death from solid cancers was positively but non-significantly associated with radiation. Death from leukaemia (excluding chronic lymphocytic leukaemia), dementia, and Alzheimer’s disease were positively and significantly associated with IR dose. Estimated dose–risk relationships were consistent with those from other nuclear worker studies for all solid cancers and leukaemia but remained associated with large uncertainty. The association between IR dose and dementia mortality risk should be interpreted with caution and requires further investigation by other studies.

The linear no-threshold (LNT) model was introduced into the radiological protection system about 60 years ago, but this model and its use in radiation protection are still debated today. This article presents an overview of results on effects of exposure to low linear-energy-transfer radiation in radiobiology and epidemiology accumulated over the last decade and discusses their impact on the use of the LNT model in the assessment of radiation-related cancer risks at low doses. The knowledge acquired over the past 10 years, both in radiobiology and epidemiology, has reinforced scientific knowledge about cancer risks at low doses. In radiobiology, although certain mechanisms do not support linearity, the early stages of carcinogenesis comprised of mutational events, which are assumed to play a key role in carcinogenesis, show linear responses to doses from as low as 10 mGy. The impact of non-mutational mechanisms on the risk of radiation-related cancer at low doses is currently difficult to assess. In epidemiology, the results show excess cancer risks at dose levels of 100 mGy or less. While some recent results indicate non-linear dose relationships for some cancers, overall, the LNT model does not substantially overestimate the risks at low doses. Recent results, in radiobiology or in epidemiology, suggest that a dose threshold, if any, could not be greater than a few tens of mGy. The scientific knowledge currently available does not contradict the use of the LNT model for the assessment of radiation-related cancer risks within the radiological protection system, and no other dose-risk relationship seems more appropriate for radiological protection purposes.

Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in several national cohorts, no study has been conducted in France to date. The ORICAMs (Occupational Radiation Induced Cancer in Medical staff) cohort is a nationwide French longitudinal cohort of medical workers exposed to ionizing radiation aiming to investigate the risk of radiation-associated cancer and non-cancer mortality. The ORICAMs cohort was set up in 2011 and includes all medical personnel monitored for ionizing radiation exposure with at least one dosimetric record in the SISERI database (the national registry for monitoring ionizing radiation exposure in workers) over the period 2002-2012. Causes of death were abstracted from death certificates and coded according to ICD-10. The follow-up ended on 31/12/2013. Standardized mortality ratios (SMRs) were calculated by cause of death to compare the mortality in the cohort to that in the French population, by gender, age group and calendar period. Among the 164,015 workers included in the cohort (60% women) a total of 1,358 deaths (892 in male and 466 in female) were reported. The observed number of all-cause deaths was significantly lower than expected based on national rates in both male (SMR = 0.35; 95% CI: 0.33, 0.38; n(deaths) = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; n(deaths) = 466). This analysis leads to the conclusion that mortality in French workers exposed to medical radiation is significantly lower than the national reference rates. However, these results based on a comparative analysis with national rates may be impacted by the healthy worker effect towards low SMRs, and do not enable to establish a potential relationship between occupational exposure and mortality risk, even if we may suspect an impact of high SES of these professionals on the observed decreased mortality. Thus, further dose-response analyses based on individual ionizing radiation exposure and job's type will be conducted to characterize correlation between risk of cancer mortality and occupational exposure.

This article summarizes a Symposium on 'Radiation risks of the central nervous system' held virtually at the 67th Annual Meeting of the Radiation Research Society, 3-6 October 2021. Repeated low-dose radiation exposure over a certain period could lead to reduced neuronal proliferation, altered neurogenesis, neuroinflammation and various neurological complications, including psychological consequences, necessitating further research in these areas. Four speakers from radiation biology, genetics and epidemiology presented the latest data from their studies seeking insights into this important topic. This symposium highlighted new and important directions for further research on mental health disorders, neurodegenerative conditions and cognitive impairment. Future studies will examine risks of mental and behavioral disorders and neurodegenerative diseases following protracted radiation exposures to better understand risks of occupational exposures as well as provide insights into risks from exposures to galactic cosmic rays. The Million Person Study of Low-Dose Health Effects (MPS) is evaluating the risk of cognitive dysfunction and dementia following intakes of radionuclides and after low-LET external radiation in the workplace. A recent study of Mayak workers in Russia suggested a link with Parkinson's disease following low-LET radiation. High-LET radiation from galactic cosmic ray simulations have reported the potential to accelerate the development of Alzheimer's disease, dementia and anxiety disorders in experimental studies. To date, seven MPS cohorts have evaluated Parkinson's disease at the level of mortality among 515,857 workers and veterans. The excess relative risks (ERR) per 100 mGy dose to brain was estimated for nuclear power plant workers (NPP), industrial radiographers (IR), medical radiation workers (MRW), nuclear weapons test participants and former DOE workers at Mallinckrodt Chemical Works, Mound facility in Ohio, and Los Alamos National Laboratory. There was a general tendency for the risk of Parkinson's disease to increase with increasing estimates of radiation dose to brain. The pooled ERR per 100 mGy for the combined NPP + IR + MRW cohorts was 0.30 (95% CI 0.08, 0.56). Confirmation of these associations are being sought from ongoing studies of an additional 300,000 workers and from linkages within the Centers for Medicare & Medicaid Services (CMS) databases for incidence data on Parkinson's disease for 600,000 workers. Further, a wide range of nonfatal conditions related to dementia and depression are being identified, as are cognitive impairment scores among 600,000 cohort workers alive in 1999 when the CMS data systems became available. Neuroinflammation and synaptic loss have been implicated in cognitive dysfunction seen after brain radiation exposure. Based on evidence that elements of the complement cascade are critical for synaptic pruning by microglia during development and are upregulated in neurodegenerative diseases and aging where synapse density is reduced, we previously demonstrated that deletion of complement receptor 3 (CR3), which is expressed on microglia, protected male mice from dendritic spine loss in the molecular layer of the hippocampus after radiation exposure. Using Thy1-eYFP mice with or without the CR3 receptor, we also found a clear correlation between microglial activation, spine loss and cognitive dysfunction 30 d after 10 Gy cranial irradiation, only in male mice, that is dependent on CR3 expression. Moreover, treatment with leukadherin-1 (LA1), which engages the CR3 receptor, prevents spine loss and cognitive dysfunction due to radiation exposure. To guide application of potential therapeutic interventions, we carried out time course analyses of synaptic density, microglial activation and complement deposition and found that these processes are initiated in the first few days following radiation exposure, suggesting a relatively acute response with long-lasting consequences.

Increased risks of central nervous system (CNS) tumors and leukemia associated with computed tomography (CT) exposure during childhood have been reported in recent epidemiological studies. However, no evidence of increased risks was suggested in a previous analysis of the French CT cohort. This study benefits from an updated cohort with a longer follow-up and a larger sample size of patients. The patients were followed from the date of their first CT (between 2000 and 2011) until their date of cohort exit defined as the earliest among the following: 31 December 2016, date of death, date of first cancer diagnosis or date of their 18th birthday. Cancer incidence, vital status, cancer predisposing factors (PFs), and additional CT scans were collected via external national databases. Hazard ratios (HRs) associated to cumulative organ doses and sex were estimated from Cox models. At the end of follow-up, mean cumulative doses were 27.7 and 10.3 mGy for the brain and the red bone marrow (RBM), respectively. In patients without PFs, an HR per 10 mGy of 1.05 (95% CI: 1.01–1.09) for CNS tumors, 1.17 (95% CI: 1.09–1.26) for leukemia, and 0.96 (95% CI: 0.63–1.45) for lymphoma was estimated. These estimates were not modified by the inclusion of CT scans performed outside the participating hospitals or after the inclusion period. This study shows statistically significant dose-response relationships for CNS tumors and leukemia for patients without PFs. • Computed tomography is the most important contributor to the collective dose for diagnostic imaging to the French population. • Concerns have been raised about possible cancer risks, particularly after exposure to CT in childhood, due to the greater radiation sensitivity of children and to their longer life expectancy. • Analysis of the updated French CT cohort shows statistically significant dose-response relationships for CNS tumors and leukemia.

Le personnel médical constitue actuellement le plus grand groupe de travailleurs exposés professionnellement à des sources artificielles de rayonnements ionisants (RI). Le risque de maladie associé à ces expositions chroniques à de faibles doses fait encore l'objet de débats chez ces professionnels. L'objectif était d’évaluer le risque de mortalité toutes causes confondues et par cause spécifique chez les travailleurs du secteur médical exposés aux RI en France au sein de la cohorte ORICAMS (« Occupational Radiation Induced Cancer in Medical Staff ») par rapport à la population générale. ORICAMS a été mise en place en 2011 par l'Institut de radioprotection et de sûreté nucléaire et inclut le personnel de santé suivi pour une exposition aux RI avec au moins une dosimétrie enregistrée dans le Système d'information de la surveillance des expositions aux RI sur la période 2002-2012. Les causes de décès ont été extraites des certificats de décès et codées selon la CIM-10. Le suivi s'est terminé le 31/12/2017. Des ratios standardisés de mortalité (SMR) ont été calculés par causes de décès pour comparer la mortalité de la cohorte à celle de la population française. Au total, 126 960 travailleurs ont été inclus dans la cohorte (62 % de femmes et 38 % d'hommes), parmi lesquels 2386 décès ont été enregistrés. Par rapport à la population générale, une baisse significative de la mortalité, toutes causes confondues, a été observée, ce qui est cohérent avec « l'effet du travailleur sain ». Cependant, des excès de décès pour certaines causes sont suspectés. Ces résultats préliminaires seront détaillés par cause de décès, par tranche d’âge, et par sexe lors du congrès. Des analyses dose-réponse basées sur l'exposition professionnelle individuelle cumulée aux RI permettront de caractériser plus précisément les risques radio-induits de cancer dans le cadre d'une exposition professionnelle. Les auteurs déclarent ne pas avoir de liens d'intérêts.

Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate IR exposure in adulthood and to assess the risk of non-cancerous CNS diseases. Methods: A systematic literature search of four electronic databases was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled standardized mortality ratios, relative risks, and excess relative risks (ERR) were estimated with a random effect model. Results: Forty-five publications were included in the systematic review, including thirty-three in the quantitative meta-analysis. The following sources of IR-exposure were considered: atomic bomb, occupational, environmental, and medical exposure. Increased dose-risk relationships were found for cerebrovascular diseases incidence and mortality (ERRpooled per 100 mGy = 0.04; 95% CI: 0.03–0.05; ERRpooled at 100 mGy = 0.01; 95% CI: −0.00–0.02, respectively) and for Parkinson’s disease (ERRpooled at 100 mGy = 0.11; 95% CI: 0.06–0.16); Conclusions: Our findings suggest that adult low-to-moderate IR exposure may have effects on non-cancerous CNS diseases. Further research addressing inherent variation issues is encouraged.

BACKGROUND Despite being a recognized carcinogen, public exposure to ionizing radiation has increased in recent decades. An update to the International Nuclear Workers Study (INWORKS) is being undertaken to strengthen direct assessments of the risks from low dose, low dose rate exposure to penetrating forms of ionizing radiation. Follow-up has been extended by 10 or more years in each partner country. METHODS We are conducting a pooled analysis of cohort mortality studies of nuclear industry workers in the United Kingdom, France, and the United States of America. Individual annual estimates of whole-body dose due to external exposure to penetrating radiation are derived from personal occupational exposure monitoring data. Vital status has been ascertained through 2012, 2014, and 2016 for workers in the United Kingdom, France, and the United States of America, respectively. RESULTS The updated pooled study includes 309,932 workers and 10.7 million person-years of observation. Over the period of follow-up, there have been 103,553 deaths observed, of which 31,009 are deaths due to cancer. CONCLUSIONS This presentation will describe the motivation for an update of the INWORKS study, the major aims of the project, and the progress that we have made to-date. We will report on a major update of this highly-influential study; the person-time in INWORKS increases by a factor of 1.3 and the number of cancer deaths increases by a factor of 1.6. The updated INWORKS analyses will provide some of the most informative direct estimates of low dose radiation risks reported to-date.