Occupational cataracts and lens opacities in interventional cardiology (O'CLOC study): are X-Rays involved? Radiation-induced cataracts and lens opacities.

International audienceBACKGROUND: The eye is well known to be sensitive to clearly high doses (>2 Gy) of ionizing radiation. In recent years, however, cataracts have been observed in populations exposed to lower doses. Interventional cardiologists are repeatedly and acutely exposed to scattered ionizing radiation (X-rays) during the diagnostic and therapeutic procedures they perform. These "low" exposures may cause damage to the lens of the eye and induce early cataracts, known as radiation-induced cataracts. The O'CLOC study (Occupational Cataracts and Lens Opacities in interventional Cardiology) was designed to test the hypothesis that interventional cardiologists, compared with an unexposed reference group of non-interventional cardiologists, have an increased risk of cataracts. METHOD/DESIGN: The O'CLOC study is a cross-sectional study that will include a total of 300 cardiologists aged at least 40 years: one group of exposed interventional cardiologists and another of non-interventional cardiologists. The groups will be matched for age and sex. Individual information, including risk factors for cataracts (age, diabetes, myopia, etc.), will be collected during a telephone interview. A specific section of the questionnaire for the exposed group focuses on occupational history, including a description of the procedures (type, frequency, radiation protection tool) used. These data will be used to classify subjects into "exposure level" groups according to cumulative dose estimates. Eye examinations for all participants will be performed to detect cataracts, even in the early stages (lens opacities, according to LOCS III, the international standard classification). The analysis will provide an estimation of the cataract risk in interventional cardiology compared with the unexposed reference group, while taking other risk factors into account. An analysis comparing the risks according to level of exposure is also planned. DISCUSSION: This epidemiological study will provide further evidence about the potential risk of radiation-induced cataracts at low doses and contribute to cardiologists' awareness of the importance of radiation protection. TRIAL REGISTRATION: NCT01061463

Association Between Cardiac Radiation Exposure and the Risk of Arrhythmia in Breast Cancer Patients Treated With Radiotherapy:A Case-Control Study

Background: Previous studies suggested that radiation therapy (RT) for breast cancer (BC) can induce cardiac arrhythmias and conduction disorders. However, the association with mean heart dose and specific cardiac substructures doses was less studied. Materials and Methods: We conducted a nested case-control study based on French BC patients, enrolled in the European MEDIRAD-BRACE study (https://clinicaltrials.gov, Identifier: NCT03211442), who underwent three-dimensional conformal radiation therapy (3D-CRT) between 2009 and 2013 and were retrospectively followed until 2019. Cases were incident cases of cardiac arrhythmia. Controls without arrhythmia were selected with propensity-scored matching by age, duration of follow-up, chemotherapy, hypertension, and diabetes (ratio 1:4 or 5). Doses to the whole heart (WH), left and right atria (LA and RA), and left and right ventricles (LV and RV) were obtained after delineation with multi-atlas-based automatic segmentation. Results: The study included 116 patients (21 cases and 95 controls). Mean age at RT was 64 ± 10 years, mean follow-up was 7.0 ± 1.3 years, and mean interval from RT to arrhythmia was 4.3 ± 2.1 years. None of the results on association between arrhythmia and cardiac doses reached statistical significance. However, the proportion of right-sided BC was higher among patients with arrhythmia than among controls (57% vs. 51%, OR = 1.18, p = 0.73). Neither mean WH dose, nor LV, RV, and LA doses were associated with an increased risk of arrhythmia (OR = 1.00, p > 0.90). In contrast, the RA dose was slightly higher for cases compared to controls [interquartile range (0.61-1.46 Gy) vs. (0.49-1.31 Gy), p = 0.44], and a non-significant trend toward a potentially higher risk of arrhythmia with increasing RA dose was observed (OR = 1.19, p = 0.60). Subanalysis according to BC laterality showed that the association with RA dose was reinforced specifically for left-sided BC (OR = 1.76, p = 0.75), while for right-sided BC, the ratio of mean RA/WH doses may better predict arrhythmia (OR = 2.39, p = 0.35). Conclusion: Despite non-significant results, our exploratory investigation on BC patients treated with RT is the first study to suggest that right-sided BC patients and the right atrium irradiation may require special attention regarding the risk of cardiac arrhythmia and conduction disorders. Further studies are needed to expand on this topic

Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study

International audienceBackground Radiotherapy (RT) for breast cancer presents a benefit in terms of reducing local recurrence and deaths resulting from breast cancer but it can lead to secondary effects due to the presence of neighboring cardiac normal tissues within the irradiation field. Breast RT has been shown to be associated with long-term increased risk of heart failure, coronary artery disease, myocardial infarction and finally cardiovascular death more than 10 years after RT. However, there is still a lack of knowledge for early cardiotoxicity induced by breast RT that can appear long before the onset of clinically significant cardiac events. Based on a 2-year follow-up prospective cohort of patients treated with breast RT, the BACCARAT (BreAst Cancer and CArdiotoxicity Induced by RAdioTherapy) study aims to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction and lesions induced by breast RT and on biological mechanisms potentially involved, based on functional and anatomical cardiac imaging combined with simultaneous assessment of multiple circulating biomarkers and accurate heart dosimetry. Methods/Design BACCARAT study consists in a monocentric prospective cohort study that will finally include 120 women treated with adjuvant 3D CRT for breast cancer, and followed for 2 years after RT. Women aged 50 to 70 years, treated for breast cancer and for whom adjuvant 3D CRT is indicated, without chemotherapy are eligible for the study. Baseline (before RT) and follow-up data include measurements of functional myocardial dysfunction including strain and strain rate based on 2D-speckle tracking echocardiography, anatomical coronary lesions including description of plaques in segments of coronary arteries based on Coronary computed tomography angiography, and a wide panel of circulating biomarkers. The absorbed dose is evaluated for the whole heart and its substructures, in particular the coronary arteries. Analysis on occurrence and evolution of subclinical cardiac lesions and biomarkers will be performed and completed with dose-response relationship. Multivariate model of normal tissue complication probability (NTCP) will also be proposed. Discussion Tools and results developed in the BACCARAT study should allow improving prediction and prevention of potential lesions to cardiac normal tissues surrounding tumors and ultimately enhance patients' care and quality of life. Trial registration ClinicalTrials.gov NCT02605512. © 2016 Jacob et al

EPI-CT: design, challenges and epidemiological methods of an international study on cancer risk after paediatric and young adult CT

Computed tomography (CT) has great clinical utility and its usage has increased dramatically over the years. Concerns have been raised, however, about health impacts of ionising radiation exposure from CTs, particularly in children, who have a higher risk for some radiation induced diseases. Direct estimation of the health impact of these exposures is needed, but the conduct of epidemiological studies of paediatric CT populations poses a number of challenges which, if not addressed, could invalidate the results. The aim of the present paper is to review the main challenges of a study on the health impact of paediatric CTs and how the protocol of the European collaborative study EPI-CT, coordinated by the International Agency for Research on Cancer (IARC), is designed to address them. The study, based on a common protocol, is being conducted in Belgium, Denmark, France, Germany, the Netherlands, Norway, Spain, Sweden and the United Kingdom and it has recruited over one million patients suitable for long-term prospective follow-up. Cohort accrual relies on records of participating hospital radiology departments. Basic demographic information and technical data on the CT procedure needed to estimate organ doses are being abstracted and passive follow-up is being conducted by linkage to population-based cancer and mortality registries. The main issues which may affect the validity of study results include missing doses from other radiological procedures, missing CTs, confounding by CT indication and socioeconomic status and dose reconstruction. Sub-studies are underway to evaluate their potential impact. By focusing on the issues which challenge the validity of risk estimates from CT exposures, EPI-CT will be able to address limitations of previous CT studies, thus providing reliable estimates of risk of solid tumours and leukaemia from paediatric CT exposures and scientific bases for the optimisation of paediatric CT protocols and patient protection

Mise en place d'une cohorte d'enfants exposés au scanner et analyse du risque de cancer radio-induit

Medical diagnostic exposure to ionizing radiation represents about 40% of the total annual radiation exposure in France. The CT scans, which represent only 5% of the total number of X-rays examinations, account for half of the total collective dose associated with medical diagnostic exposure. However, its use continues to grow, including in children, for whom the radio sensitivity is known to be greater than in adults. Several recent studies support an increased risk of leukemia and brain tumors after exposure to CT scan in childhood. A national multicenter cohort was set up at the IRSN since 2009 including 108 137 children subjected to at least one CT scans before the age of 10 during the 2000 to 2013 period in 23 French University hospital’s pediatric radiology departments. Children's exposure was assessed based on radiological protocols. It was observed high variability of doses according to the participant departments, reflecting the need for protocol optimization. Moreover, children with predisposing factor for studied cancers represented 3% of the study population, a percentage well above that observed in the general population. The linkage of the cohort with the National Register of pediatric cancers identified 106 incident cases of cancer in the cohort, 22 brain tumors and 17 leukemias. For children without predisposing factor, it was observed a non-significant excess risk of cancer according to the received dose, similar to that observed for the whole study population. For children with predisposing factor to cancer, the risk decreased without reaching significance, possibly linked to earlier non-cancer mortality in this group and then to a lower risk to develop later radiation induced cancer. The European project EPI-CT, which includes 9 national cohorts (including the French cohort), will include more than one million children and then will bring further results on this topic.L'exposition médicale diagnostique aux rayonnements ionisants représente environ 40% de l'exposition totale aux radiations en France. L'utilisation du scanner, beaucoup plus irradiant que l'imagerie conventionnelle, ne cesse de progresser, y compris chez les enfants, dont la radiosensibilité est supérieure à celle des adultes. Plusieurs études récentes sont en faveur d'une augmentation du risque de leucémie et de tumeur cérébrale après exposition au scanner dans l'enfance. Une cohorte nationale multicentrique a été mise en place à l'IRSN depuis 2009 incluant plus de 108 137 enfants soumis à un ou plusieurs scanners avant l'âge de 10 ans sur la période 2000-2010 dans 23 services de radiologie pédiatriques de CHU, répartis sur l'ensemble du territoire. L'estimation des doses reçues au niveau des principaux organes a été faite en fonction des protocoles utilisés. La grande variabilité des doses selon les services témoigne de la nécessité d'optimisation des protocoles. Près de 3% des enfants de la cohorte présentaient un facteur de prédisposition aux cancers étudiés. Le croisement de la cohorte avec le registre national des cancers pédiatriques a identifié 106 cas incidents de cancer, dont 22 tumeurs cérébrales et 17 leucémies. Chez les enfants sans facteur de prédisposition, un excès de risque positif mais non significatif était observé pour la leucémie et les tumeurs cérébrales en fonction de la dose, similaire à celui observé pour la population d'étude dans son ensemble. Chez les enfants avec un facteur de prédisposition au cancer, le risque diminuait, possiblement en lien avec une mortalité précoce augmentée entrainant un déficit de risque de cancer radio-induit à plus long terme. Le projet européen EPI-CT inclut 9 cohortes nationales, dont la cohorte française et regroupera plus d’un million d’enfants exposés au scanner. L’analyse conjointe de ces données permettra d’apporter prochainement des résultats complémentaires sur ce sujet

Setting-up of a cohort of children exposed to CT-SCAN in order to evaluate the radiation induced risk

L'exposition médicale diagnostique aux rayonnements ionisants représente environ 40% de l'exposition totale aux radiations en France. L'utilisation du scanner, beaucoup plus irradiant que l'imagerie conventionnelle, ne cesse de progresser, y compris chez les enfants, dont la radiosensibilité est supérieure à celle des adultes. Plusieurs études récentes sont en faveur d'une augmentation du risque de leucémie et de tumeur cérébrale après exposition au scanner dans l'enfance. Une cohorte nationale multicentrique a été mise en place à l'IRSN depuis 2009 incluant plus de 108 137 enfants soumis à un ou plusieurs scanners avant l'âge de 10 ans sur la période 2000-2010 dans 23 services de radiologie pédiatriques de CHU, répartis sur l'ensemble du territoire. L'estimation des doses reçues au niveau des principaux organes a été faite en fonction des protocoles utilisés. La grande variabilité des doses selon les services témoigne de la nécessité d'optimisation des protocoles. Près de 3% des enfants de la cohorte présentaient un facteur de prédisposition aux cancers étudiés. Le croisement de la cohorte avec le registre national des cancers pédiatriques a identifié 106 cas incidents de cancer, dont 22 tumeurs cérébrales et 17 leucémies. Chez les enfants sans facteur de prédisposition, un excès de risque positif mais non significatif était observé pour la leucémie et les tumeurs cérébrales en fonction de la dose, similaire à celui observé pour la population d'étude dans son ensemble. Chez les enfants avec un facteur de prédisposition au cancer, le risque diminuait, possiblement en lien avec une mortalité précoce augmentée entrainant un déficit de risque de cancer radio-induit à plus long terme. Le projet européen EPI-CT inclut 9 cohortes nationales, dont la cohorte française et regroupera plus d’un million d’enfants exposés au scanner. L’analyse conjointe de ces données permettra d’apporter prochainement des résultats complémentaires sur ce sujet.Medical diagnostic exposure to ionizing radiation represents about 40% of the total annual radiation exposure in France. The CT scans, which represent only 5% of the total number of X-rays examinations, account for half of the total collective dose associated with medical diagnostic exposure. However, its use continues to grow, including in children, for whom the radio sensitivity is known to be greater than in adults. Several recent studies support an increased risk of leukemia and brain tumors after exposure to CT scan in childhood. A national multicenter cohort was set up at the IRSN since 2009 including 108 137 children subjected to at least one CT scans before the age of 10 during the 2000 to 2013 period in 23 French University hospital’s pediatric radiology departments. Children's exposure was assessed based on radiological protocols. It was observed high variability of doses according to the participant departments, reflecting the need for protocol optimization. Moreover, children with predisposing factor for studied cancers represented 3% of the study population, a percentage well above that observed in the general population. The linkage of the cohort with the National Register of pediatric cancers identified 106 incident cases of cancer in the cohort, 22 brain tumors and 17 leukemias. For children without predisposing factor, it was observed a non-significant excess risk of cancer according to the received dose, similar to that observed for the whole study population. For children with predisposing factor to cancer, the risk decreased without reaching significance, possibly linked to earlier non-cancer mortality in this group and then to a lower risk to develop later radiation induced cancer. The European project EPI-CT, which includes 9 national cohorts (including the French cohort), will include more than one million children and then will bring further results on this topic

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

International audienceIt 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 é— 10ˆ’3 (95% CI 0.27 é— 10ˆ’3 to 1.16 é— 10ˆ’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 é— 10ˆ’3 (95% CI ˆ’ 0.19 é— 10ˆ’3 to 0.97 é— 10ˆ’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. © 2018, This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection

Mise en place d'une cohorte d'enfants exposés au scanner et analyse du risque de cancer radio-induit

Medical diagnostic exposure to ionizing radiation represents about 40% of the total annual radiation exposure in France. The CT scans, which represent only 5% of the total number of X-rays examinations, account for half of the total collective dose associated with medical diagnostic exposure. However, its use continues to grow, including in children, for whom the radio sensitivity is known to be greater than in adults. Several recent studies support an increased risk of leukemia and brain tumors after exposure to CT scan in childhood. A national multicenter cohort was set up at the IRSN since 2009 including 108 137 children subjected to at least one CT scans before the age of 10 during the 2000 to 2013 period in 23 French University hospital’s pediatric radiology departments. Children's exposure was assessed based on radiological protocols. It was observed high variability of doses according to the participant departments, reflecting the need for protocol optimization. Moreover, children with predisposing factor for studied cancers represented 3% of the study population, a percentage well above that observed in the general population. The linkage of the cohort with the National Register of pediatric cancers identified 106 incident cases of cancer in the cohort, 22 brain tumors and 17 leukemias. For children without predisposing factor, it was observed a non-significant excess risk of cancer according to the received dose, similar to that observed for the whole study population. For children with predisposing factor to cancer, the risk decreased without reaching significance, possibly linked to earlier non-cancer mortality in this group and then to a lower risk to develop later radiation induced cancer. The European project EPI-CT, which includes 9 national cohorts (including the French cohort), will include more than one million children and then will bring further results on this topic.L'exposition médicale diagnostique aux rayonnements ionisants représente environ 40% de l'exposition totale aux radiations en France. L'utilisation du scanner, beaucoup plus irradiant que l'imagerie conventionnelle, ne cesse de progresser, y compris chez les enfants, dont la radiosensibilité est supérieure à celle des adultes. Plusieurs études récentes sont en faveur d'une augmentation du risque de leucémie et de tumeur cérébrale après exposition au scanner dans l'enfance. Une cohorte nationale multicentrique a été mise en place à l'IRSN depuis 2009 incluant plus de 108 137 enfants soumis à un ou plusieurs scanners avant l'âge de 10 ans sur la période 2000-2010 dans 23 services de radiologie pédiatriques de CHU, répartis sur l'ensemble du territoire. L'estimation des doses reçues au niveau des principaux organes a été faite en fonction des protocoles utilisés. La grande variabilité des doses selon les services témoigne de la nécessité d'optimisation des protocoles. Près de 3% des enfants de la cohorte présentaient un facteur de prédisposition aux cancers étudiés. Le croisement de la cohorte avec le registre national des cancers pédiatriques a identifié 106 cas incidents de cancer, dont 22 tumeurs cérébrales et 17 leucémies. Chez les enfants sans facteur de prédisposition, un excès de risque positif mais non significatif était observé pour la leucémie et les tumeurs cérébrales en fonction de la dose, similaire à celui observé pour la population d'étude dans son ensemble. Chez les enfants avec un facteur de prédisposition au cancer, le risque diminuait, possiblement en lien avec une mortalité précoce augmentée entrainant un déficit de risque de cancer radio-induit à plus long terme. Le projet européen EPI-CT inclut 9 cohortes nationales, dont la cohorte française et regroupera plus d’un million d’enfants exposés au scanner. L’analyse conjointe de ces données permettra d’apporter prochainement des résultats complémentaires sur ce sujet

Risque de cancer radio-induit après exposition au scanner dans l’enfance : résultats de l’étude EPI-CT

International audienceObjectifDes études épidémiologiques récemment publiées ont montré une augmentation du risque de cancer radio-induit après exposition dans l'enfance ou l'adolescence aux rayonnements ionisants lors des examens tomodensitométriques (TDM). Le projet EPI-CT a pour objectif de réaliser une étude conjointe de 9 cohortes nationales européennes d’enfants et des jeunes adultes exposés à des TDMs.Matériel et méthodesLes patients exposés à au moins un scanner entre 0 et 21 ans sur la période 1977-2013 ont été inclus en Allemagne, Belgique, Danemark, Espagne, France, Grande Bretagne, Norvège, Pays-Bas, Suède. Leur exposition cumulée a été estimée à partir des données RIS, PACS et des protocoles radiologiques pour les périodes plus anciennes, avec le logiciel NCI-CT. Les cas de cancers incidents ont été obtenus après croisement avec les registres nationaux de cancer.RésultatsAu total, 948 174 patients avec un suivi > 1 an sans diagnostic de cancer ont été inclus et 1 430 454 examens TDM collectés. Un seul examen TDM a été collecté pour 75% des enfants. La durée de suivi moyenne était de 8 ans. Les analyses de risque sont en cours de finalisation et seront présentées aux JFR.ConclusionCette cohorte conjointe de près d’un million d’enfants exposés aux examens TDM dispose d’une large puissance statistique permettant d’analyser le risque de cancer radio-induit pour des faibles niveaux d’exposition aux rayonnements ionisants

Risque de cancer radio-induit après exposition au scanner dans l’enfance : résultats de l’étude EPI-CT

International audienceObjectifDes études épidémiologiques récemment publiées ont montré une augmentation du risque de cancer radio-induit après exposition dans l'enfance ou l'adolescence aux rayonnements ionisants lors des examens tomodensitométriques (TDM). Le projet EPI-CT a pour objectif de réaliser une étude conjointe de 9 cohortes nationales européennes d’enfants et des jeunes adultes exposés à des TDMs.Matériel et méthodesLes patients exposés à au moins un scanner entre 0 et 21 ans sur la période 1977-2013 ont été inclus en Allemagne, Belgique, Danemark, Espagne, France, Grande Bretagne, Norvège, Pays-Bas, Suède. Leur exposition cumulée a été estimée à partir des données RIS, PACS et des protocoles radiologiques pour les périodes plus anciennes, avec le logiciel NCI-CT. Les cas de cancers incidents ont été obtenus après croisement avec les registres nationaux de cancer.RésultatsAu total, 948 174 patients avec un suivi > 1 an sans diagnostic de cancer ont été inclus et 1 430 454 examens TDM collectés. Un seul examen TDM a été collecté pour 75% des enfants. La durée de suivi moyenne était de 8 ans. Les analyses de risque sont en cours de finalisation et seront présentées aux JFR.ConclusionCette cohorte conjointe de près d’un million d’enfants exposés aux examens TDM dispose d’une large puissance statistique permettant d’analyser le risque de cancer radio-induit pour des faibles niveaux d’exposition aux rayonnements ionisants