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Article ; Online: Biomarkers of Genotoxicity in Medical Workers Exposed to Low-Dose Ionizing Radiation

Clémence Baudin / Marie-Odile Bernier / Dmitry Klokov / Maria Grazia Andreassi

International Journal of Molecular Sciences, Vol 22, Iss 7504, p

Systematic Review and Meta-Analyses

2021 Volume 7504

Abstract: Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the ... ...

Abstract	Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θ pooled = 3.19, 95% CI 1.46–4.93; and θ pooled = 1.41, 95% CI 0.97–1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.
Keywords	systematic review ; meta-analysis ; medical workers ; ionizing radiation ; cytogenetic biomarkers ; DNA integrity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cohort profile

Julie Lopes / Clémence Baudin / Juliette Feuardent / Hervé Roy / Sylvaine Caër-Lorho / Klervi Leuraud / Marie-Odile Bernier

PLoS ONE, Vol 18, Iss

ORICAMs, a French cohort of medical workers exposed to low-dose ionizing radiation

2023 Volume 6

Abstract: 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 ... ...

Abstract	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; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 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 ...
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cohort profile

Julie Lopes / Clémence Baudin / Juliette Feuardent / Hervé Roy / Sylvaine Caër-Lorho / Klervi Leuraud / Marie-Odile Bernier

PLoS ONE, Vol 18, Iss 6, p e

ORICAMs, a French cohort of medical workers exposed to low-dose ionizing radiation.

2023 Volume 0286910

Abstract	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; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 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 ...
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Myocardial deformation after radiotherapy

Valentin Walker / Olivier Lairez / Olivier Fondard / Gaëlle Jimenez / Jérémy Camilleri / Loïc Panh / David Broggio / Marie-Odile Bernier / Dominique Laurier / Jean Ferrières / Sophie Jacob

Radiation Oncology, Vol 15, Iss 1, Pp 1-

a layer-specific and territorial longitudinal strain analysis in a cohort of left-sided breast cancer patients (BACCARAT study)

2020 Volume 10

Abstract: Abstract Background Radiotherapy for breast cancer (BC) and its resulting cardiac exposure are associated with subclinical left ventricular dysfunction characterized by early decrease of global longitudinal strain (LS) measurement based on 2D speckle- ... ...

Abstract	Abstract Background Radiotherapy for breast cancer (BC) and its resulting cardiac exposure are associated with subclinical left ventricular dysfunction characterized by early decrease of global longitudinal strain (LS) measurement based on 2D speckle-tracking echocardiography. Recent software allows multi-layer and segmental analysis of strain, which may be of interest to quantify and locate the impact of cardiac exposure on myocardial function and potentially increase the early detection of radiation-induced cardiotoxicity. The aim of the study was to evaluate whether decrease in LS 6 months after radiotherapy is layer-specific and if it varies according to the left ventricular regional level and the coronary arterial territories. Methods LS was measured at baseline before radiotherapy and 6 months post-radiotherapy. The LS was obtained for each myocardial layer (endocardial, mid-myocardial, epicardial), left ventricular regional level (basal, mid, apical) and coronary artery territory (left anterior descending artery (LAD), circumflex artery, right coronary artery). Results The study included 64 left-sided BC patients. Mean age was 58 years, mean doses to the heart, the left ventricle and the LAD were respectively 3.0, 6.7 and 16.4 Gy. The absolute decrease of LS was significant for the three layers (endocardial: − 20.0 ± 3.2% to − 18.8 ± 3.8%; mid-myocardial: − 16.0 ± 2.7% to − 15.0 ± 3.1%; epicardial: − 12.3 ± 2.5% to − 11.4 ± 2.8%, all p = 0.02), but only the relative decrease of LS in the endocardial layer was close to be significant (− 4.7%, p = 0.05). More precisely, the LS of the endocardial layer was significantly decreased for the most exposed parts of the left ventricle corresponding to the apical level (− 26.3 ± 6.0% vs. -24.2 ± 7.1%, p = 0.03) and LAD territory (− 22.8 ± 4.0% vs. -21.4 ± 4.8%, p = 0.03). Conclusion Six months post-radiotherapy, LS decreased predominantly in the endocardial layer of the most exposed part of the left ventricle. For precise evaluation of radiotherapy-induced ...
Keywords	Radiation therapy ; Cardiac toxicity ; Echocardiography ; Multilayer strain ; Coronary arteries ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exposure to low-dose ionising radiation from cardiac catheterisation and risk of cancer

BMJ Open, Vol 11, Iss

the COCCINELLE study cohort profile

2021 Volume 8

Abstract: Purpose The COCCINELLE study is a nationwide retrospective French cohort set up to evaluate the risk of cancer in patients who undergone cardiac catheterisation (CC) procedures for diagnosis or treatment of congenital heart disease during childhood ... ...

Abstract	Purpose The COCCINELLE study is a nationwide retrospective French cohort set up to evaluate the risk of cancer in patients who undergone cardiac catheterisation (CC) procedures for diagnosis or treatment of congenital heart disease during childhood.Participants Children who undergone CC procedures from 1 January 2000 to 31 December 2013, before the age of 16 in one of the 15 paediatric cardiology departments which perform paediatric CC in mainland France were included. The follow-up started at the date of the first recorded CC procedure until the exit date, that is, the date of death, the date of first cancer diagnosis, the date of the 18th birthday or the 31 December 2015, whichever occurred first. The cohort was linked to the National Childhood Cancer Registry to identify patients diagnosed with cancer and with the French National Directory for the Identification of Natural Persons to retrieve the patients’ vital status.Findings to date A total of 17 104 children were included in the cohort and followed for 110 335 person-years, with 22 227 CC procedures collected. Among the patients, 81.6% received only one procedure. Fifty-nine cancer cases were observed in the cohort. Standardised incidence ratios (SIRs) were increased for all-cancer (SIR=3.8, 95% CI: 2.9 to 4.9), leukaemia (SIR=3.3, 95% CI: 2.0 to 5.4), lymphoma (SIR=14.9, 95% CI: 9.9 to 22.5) and solid cancers excluding central nervous system (CNS) tumours (SIR=3.3, 95% CI: 2.0 to 5.5) compared with the general population.Future plans Dose reconstruction is currently underway to estimate individual cumulative doses absorbed to relevant organs, including red bone marrow and brain for respectively haematologic disorders and CNS tumours risk estimation. A dose–response analysis will be conducted with consideration to confounding factors such as age at exposure, gender, predisposing factors to cancer and other sources of medical diagnostic low-dose ionising radiation.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Is mean heart dose a relevant surrogate parameter of left ventricle and coronary arteries exposure during breast cancer radiotherapy

Sophie Jacob / Jérémy Camilleri / Sylvie Derreumaux / Valentin Walker / Olivier Lairez / Mathieu Lapeyre / Eric Bruguière / Atul Pathak / Marie-Odile Bernier / Dominique Laurier / Jean Ferrieres / Olivier Gallocher / Igor Latorzeff / Baptiste Pinel / Denis Franck / Christian Chevelle / Gaëlle Jimenez / David Broggio

Radiation Oncology, Vol 14, Iss 1, Pp 1-

a dosimetric evaluation based on individually-determined radiation dose (BACCARAT study)

2019 Volume 10

Abstract: Abstract Background Intra-individual heterogeneity of cardiac exposure is an issue in breast cancer (BC) radiotherapy that was poorly considered in previous cardiotoxicity studies mainly based on mean heart dose (MHD). This dosimetric study analyzes the ... ...

Abstract	Abstract Background Intra-individual heterogeneity of cardiac exposure is an issue in breast cancer (BC) radiotherapy that was poorly considered in previous cardiotoxicity studies mainly based on mean heart dose (MHD). This dosimetric study analyzes the distribution of individually-determined radiation doses to the heart and its substructures including coronary arteries and evaluate whether MHD is a relevant surrogate parameter of dose for these substructures. Methods Data were collected from the BACCARAT prospective study that included left or right unilateral BC patients treated with 3D-Conformal Radiotherapy (RT) between 2015 and 2017 and followed-up for 2 years with repeated cardiac imaging examinations. A coronary computed tomography angiography (CCTA) was performed before RT for all patients. Registration of the planning CT and CCTA images allowed delineation of the coronary arteries on the planning CT images. Using the 3D dose matrix generated during treatment planning and the added coronary contours, dose distributions were generated for whole heart and the following substructures: left ventricle (LV), left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA). A descriptive analysis of the physical doses in Gray (Gy) was performed, Dmean was the volume-weighted mean dose. Results Dose distributions were generated for 89 left-sided BC patients (MHD = 2.9 ± 1.5 Gy, Dmean_LAD = 15.7 ± 3.1 Gy) and 15 right-sided BC patients (MHD = 0.5 ± 0.1 Gy; Dmean_RCA = 1.2 ± 0.4 Gy). For left-sided BC patients, the ratio Dmean_LAD/MHD was around 5. Pearson correlation coefficients between MHD and Dmean for delineated substructures were all statistically significant. However, for all substructures, the coefficient of determination R2 indicated that the proportion of the variance in Dmean of the substructure predictable from MHD was moderate to low (in particular R2 = 0.45 for LAD). Among left-sided BC patients with MHD < 3Gy, 56% of patients could nevertheless receive LAD doses above 40Gy (V40 > 0). Conclusion Our study illustrates that MHD is not enough to predict with confidence individual patient dose to the LV and coronary arteries, in particular the LAD. For precise radiotherapy-induced cardiotoxicity studies it would be necessary to consider the distribution of doses within these cardiac substructures rather than just the MHD. Trial registration ClinicalTrials.gov: NCT02605512, Registered 6 November 2015 - Retrospectively registered.
Keywords	Breast cancer ; Radiotherapy ; Heterogeneity in cardiac exposure ; Mean heart dose ; Coronary arteries doses ; Cardiotoxicity ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	610
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Early detection of subclinical left ventricular dysfunction after breast cancer radiation therapy using speckle-tracking echocardiography

Valentin Walker / Olivier Lairez / Olivier Fondard / Atul Pathak / Baptiste Pinel / Christian Chevelle / Denis Franck / Gaëlle Jimenez / Jérémy Camilleri / Loïc Panh / David Broggio / Sylvie Derreumaux / Marie-Odile Bernier / Dominique Laurier / Jean Ferrières / Sophie Jacob

Radiation Oncology, Vol 14, Iss 1, Pp 1-

association between cardiac exposure and longitudinal strain reduction (BACCARAT study)

2019 Volume 11

Abstract: Abstract Background Breast cancer (BC) radiotherapy (RT) can induce cardiotoxicity, with adverse events often observed many years after BC RT. Subclinical left ventricular (LV) dysfunction can be detected early after BC RT with global longitudinal strain ...

Abstract	Abstract Background Breast cancer (BC) radiotherapy (RT) can induce cardiotoxicity, with adverse events often observed many years after BC RT. Subclinical left ventricular (LV) dysfunction can be detected early after BC RT with global longitudinal strain (GLS) measurement based on 2D speckle-tracking echocardiography. This 6-month follow-up analysis from the BACCARAT prospective study aimed to investigate the association between cardiac radiation doses and subclinical LV dysfunction based on GLS reduction. Methods The patient study group consisted of 79 BC patients (64 left-sided BC, 15 right-sided BC) treated with RT without chemotherapy. Echocardiographic parameters, including GLS, were measured before RT and 6 months post-RT. The association between subclinical LV dysfunction, defined as GLS reduction > 10%, and radiation doses to whole heart and the LV were performed based on logistic regressions. Non-radiation factors associated with subclinical LV dysfunction including age, BMI, hypertension, hypercholesterolemia and endocrine therapy were considered for multivariate analyses. Results A mean decrease of 6% in GLS was observed (− 15.1% ± 3.2% at 6 months vs. − 16.1% ± 2.7% before RT, p = 0.01). For left-sided patients, mean heart and LV doses were 3.1 ± 1.3 Gy and 6.7 ± 3.4 Gy respectively. For right-sided patients, mean heart dose was 0.7 ± 0.5 Gy and median LV dose was 0.1 Gy. Associations between GLS reduction > 10% (37 patients) and mean doses to the heart and the LV as well as the V20 were observed in univariate analysis (Odds Ratio = 1.37[1.01–1.86], p = 0.04 for Dmean Heart; OR = 1.14 [1.01–1.28], p = 0.03 for Dmean LV; OR = 1.08 [1.01–1.14], p = 0.02 for LV V20). In multivariate analysis, these associations did not remain significant after adjustment for non-radiation factors. Further exploratory analysis allowed identifying a subgroup of patients (LV V20 > 15%) for whom a significant association with subclinical LV dysfunction was found (adjusted OR = 3.97 [1.01–15.70], p = 0.048). ...
Keywords	Breast Cancer ; 3D conformal radiation therapy ; Cardiac dysfunction ; Strain imaging ; Cardiac Dosimetry ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	616 ; 610
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Occupational radiation exposure and glaucoma and macular degeneration in the US radiologic technologists

Mark P. Little / Cari M. Kitahara / Elizabeth K. Cahoon / Marie-Odile Bernier / Raquel Velazquez-Kronen / Michele M. Doody / David Borrego / Jeremy S. Miller / Bruce H. Alexander / Steven L. Simon / Dale L. Preston / Craig Meyer / Martha S. Linet / Nobuyuki Hamada

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 9

Abstract: Abstract There are well-documented associations of glaucoma with high-dose radiation exposure, but only a single study suggesting risk of glaucoma, and less conclusively macular degeneration, associated with moderate-dose exposure. We assessed risk of ... ...

Abstract	Abstract There are well-documented associations of glaucoma with high-dose radiation exposure, but only a single study suggesting risk of glaucoma, and less conclusively macular degeneration, associated with moderate-dose exposure. We assessed risk of glaucoma and macular degeneration associated with occupational eye-lens radiation dose, using participants from the US Radiologic Technologists Study, followed from the date of surveys in 1994–1998, 2003–2005 to the earliest of diagnosis of glaucoma or macular degeneration, cancer other than non-melanoma skin cancer, or date of last survey (2012–2014). We excluded those with baseline disease or previous radiotherapy history. Cox proportional hazards models with age as timescale were used. There were 1631 cases of newly self-reported doctor-diagnosed cases of glaucoma and 1331 of macular degeneration among 69,568 and 69,969 eligible subjects, respectively. Estimated mean cumulative eye-lens absorbed dose from occupational radiation exposures was 0.058 Gy. The excess relative risk/Gy for glaucoma was −0.57 (95% CI −1.46, 0.60, p = 0.304) and for macular degeneration was 0.32 (95% CI −0.32, 1.27, p = 0.381), suggesting that there is no appreciable risk for either endpoint associated with low-dose and low dose-rate radiation exposure. Since this is the first examination of glaucoma and macular degeneration associated with low-dose radiation exposure, this result needs to be replicated in other low-dose studies.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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