Florent de Vathaire

• PhD
• Head of Department at French Institute of Health and Medical Research

Background Cardiac disease (CD) is a primary long-term diagnosed pathology among childhood cancer survivors. Dosiomics (radiomics extracted from the dose distribution) have received attention in the past few years to assess better the induced risk of radiotherapy (RT) than standard dosimetric features such as dose-volume indicators. Hence, using th...

Background While female survivors of Hodgkin lymphoma (HL) have an increased risk of breast cancer (BC), no BC risk prediction model is available. We developed such models incorporating mean radiation dose to the breast or breast quadrant-specific radiation doses. Methods Relative risks and age-specific incidence for BC and competing events (morta...

Purpose Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memor...

Liver cancer, a leading cause of cancer mortality, is often diagnosed by analyzing the grayscale variations in liver tissue across different computed tomography (CT) images. However, the intensity similarity can be strong, making it difficult for radiologists to visually identify hepatocellular carcinoma (HCC) and metastases. It is crucial for the...

Second malignant neoplasm (SMN) is one of the most severe long-term risks for childhood cancer survivors (CCS), significantly impacting long-term patient survival. While radiotherapy and chemotherapy are known risk factors, the observed inter-individual variability suggests a genetic component contributing to the risk of SMN. This article aims to c...

Simple Summary Liver malignancies, particularly hepatocellular carcinoma, and metastases stand as prominent contributors to cancer mortality. Within abdominal computed tomography imaging, much of data remains underused by radiologists. Radiomics uses advanced image analysis to extract quantitative features from medical scans for deeper diagnosis, t...

Background Optic pathway gliomas (OPG) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications. Methods We included patients treated at Gustave Roussy (GR) between 01.1980 and 12.2015 for OPG, before 18 years-old and alive at 5 years from diagnosis. Mortality and physical health condit...

Background Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. Methods Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940–2008), across Europe, standardized incidence ratios (SIRs) and cumulative in...

PURPOSE Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of chi...

Background Childhood cancer survivors (CCS) are at an elevated risk of developing both a second malignant neoplasm (SMN) and cardiac disease. Objectives This study sought to assess the excess of occurrence of cardiac disease after a SMN among CCS. Methods Analyses included 7,670 CCS from the French Childhood Cancer Survivors Study cohort diagnose...

Breast cancer (bc) risk is suspected to be linked to thyroid disorders, however observational studies exploring the association between bc and thyroid disorders gave conflicting results. We proposed an alternative approach by investigating the shared genetic risk factors between bc and several thyroid traits. We report a positive genetic correlatio...

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from...

Background: We aimed to study adherence to cardiac screening in long-term childhood cancer survivors (CCS) at high risk of cardiomyopathy. Methods: This study involved 976 5-year CCS at high risk for cardiomyopathy from the French Childhood Cancer Survivor Study. Determinants of adherence to recommended surveillance were studied using multivaria...

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), chr...

Background—Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after BC for RT and associations with cardiac exposure. Methods—The study included 101...

Purpose Radiation-induced lung injury (RILI) is strongly associated with various clinical conditions and dosimetric parameters. Former studies have led to reducing radiotherapy (RT) doses to the lung and have favored the discontinuation of tamoxifen during RT. However, the monocentric design and variability of dosimetric parameters chosen have limi...

Background Due to late effects, childhood cancer survivors (CCS) are more likely to have multiple chronic conditions than the general population. However, little is known about the economic burden of care of CCS in the long term. Objectives To estimate excess healthcare expenditure for long-term CCS in France compared to the general population and...

Objective: The aim of this study was to identify risk factors for obesity in childhood cancer survivors (CCSs). Methods: The study included 3199 patients of the French Childhood Cancer Survivor Study cohort, with 303 patients with obesity who had returned the self-questionnaire. Analyses were adjusted for social deprivation index and sex. Resul...

Background Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analy...

Valvular Heart Disease (VHD) is a known late complication of radiotherapy for childhood cancer (CC), and identifying high-risk survivors correctly remains a challenge. This paper focuses on the distribution of the radiation dose absorbed by heart tissues. We propose that a dosiomics signature could provide insight into the spatial characteristics o...

Purpose: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy. Methods: Twelve European countries contributed 228 c...

A growing body of scientific evidence indicates that exposure to low dose ionizing radiation (< 2 Gy) is associated with a higher risk of developing radio-induced cancer. Additionally, it has been shown to have significant impacts on both innate and adaptive immune responses. As a result, the evaluation of the low doses inevitably delivered outside...

Importance: Due to the amount of iodine 131 released in nuclear tests and its active uptake by the thyroid, differentiated thyroid carcinoma (DTC) is the most serious health risk for the population living near sites of nuclear tests. Whether low doses to the thyroid from nuclear fallout are associated with increased risk of thyroid cancer remains...

Background Mendelian randomization (MR) studies are susceptible to metadata errors (e.g. incorrect specification of the effect allele column) and other analytical issues that can introduce substantial bias into analyses. We developed a quality control (QC) pipeline for the Fatty Acids in Cancer Mendelian Randomization Collaboration (FAMRC) that can...

Simple Summary (Multi-)Morbidity shares common biological mechanisms or risk factors with breast cancer. However, the risk of breast cancer among women with (multi-)morbidity remains unclear. In this study, using data of 239,436 female participants aged 40–69 of the UK Biobank cohort, we identified five chronic disease patterns: no-predominant morb...

Background: Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective: We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify co...

This article describes the methodology used and provides a characterization of the study population in CANTO-RT (CANcer TOxicities RadioTherapy). CANTO (NCT01993498) is a prospective clinical cohort study including patients with stage I-III BC from 26 French cancer centers. Patients matching all CANTO inclusion and exclusion criteria who received R...

Background: Hospitalisation rates can be used as an indirect indicator of the burden and severity of adverse health outcomes in childhood cancer survivors. We aimed to determine the long-term risks of hospitalisation related to renal and urinary diseases. Methods: The French Childhood Cancer Survivor Study cohort was linked with data from the Fr...

Background and purpose: Valvular Heart Disease (VHD) is a known complication of childhood cancer after radiotherapy treatment. However, the dose-volume-effect relationships have not been fully explored. Materials and methods: We obtained individual heart Dose Volume Histograms (DVH) for survivors of the French Childhood Cancer Survivors Study (F...

Background Survivors of Hodgkin lymphoma (HL) are at risk of developing non‐Hodgkin lymphoma (NHL) after treatment; however, the risks of developing subsequent primary lymphomas (SPLs), including HL and NHL, after different types of childhood cancer are unknown. The authors quantified the risk of SPLs using the largest cohort of childhood cancer su...

Purpose: The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will...

Background Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risk s . Methods The PanCareSurFup cohort includes 69,460 5-year surviv...

The late effects of treatments for childhood cancers may lead to severe and multiple health conditions requiring hospitalisation. We aimed to estimate the hospitalisation rate among childhood cancer survivors (CCS) in France, to compare them with the general population and to investigate the associated factors. We matched total of 5439 5-year solid...

Background: Female thyroid cancer survivors are more likely to have a higher risk of breast cancer compared to the general population, and the underlying causes are yet to be understood. The potential role of I-131 treatment on this association remains controversial. Methods: We pooled individual data of women who were treated for differentiated t...

Importance Meningioma is the most common subsequent neoplasm following cranial irradiation among survivors of childhood cancer, but there are still uncertainties regarding the magnitude of the radiation dose-response association, potential modifiers of radiation risks, and the role of chemotherapy. Objective To evaluate meningioma risk in survivor...

In a previous systematic review and meta-analysis of studies reporting associations between hyper-/hypothyroidism and breast cancer incidence published through January 29, 2019, we identified a higher risk with diagnosed hyperthyroidism compared to euthyroidism, but no association with diagnosed hypothyroidism. This two-year updated meta-analysis a...

PURPOSE Heart failure (HF) is a potentially life-threatening complication of treatment for childhood cancer. We evaluated the risk and risk factors for HF in a large European study of long-term survivors. Little is known of the effects of low doses of treatment, which is needed to improve current treatment protocols and surveillance guidelines. ME...

Survivors of childhood cancer are at risk of anthracycline-induced cardiotoxicity, which might be prevented by dexrazoxane. However, concerns exist about the safety of dexrazoxane, and little guidance is available on its use in children. To facilitate global consensus, a working group within the International Late Effects of Childhood Cancer Guidel...

Purpose During the COVID-19 pandemic, childhood cancer survivors (CCS) may have felt more at risk of having severe consequences of COVID-19 and therefore may have been more likely to defer their health care use. We aimed to assess the risk perceptions of CCS related to COVID-19 (perceived infection risk, perceived risk of experiencing a severe illn...

Background Breast cancer (BC) risk is increased among Hodgkin lymphoma (HL) survivors treated with chest radiotherapy. Case-control studies showed a linear radiation dose-response relationship for estimated dose to the breast tumor location. However, these relative risks cannot be used for absolute risk prediction of BC anywhere in the breasts. Fur...

Background: Compared with the general population, childhood cancer survivors (CCS) could be at greater risk of psychological distress following the emergence of the COVID-19 pandemic. Purpose: This cross-sectional study assessed the psychological consequences of COVID-19 on the mental health of CCS. Design and participants: In December 2020, we int...

Background Childhood cancer survivors (CCS) may require lifelong medical care due to late effects of cancer treatments. Little is known about of their healthcare utilization and expenditures at long-term especially in publicly funded health care system. We aim to estimate and describe the health care expenditures among long-term CCS in France. Met...

Background Breast cancer is a well-recognised late adverse effect in female childhood cancer survivors (CCSs), especially after chest radiotherapy; information on subsequent male breast cancer (SMBC) is limited. We summarised the existing evidence on SMBC after childhood cancer in a systematic review and investigated the risk of SMBC among males in...

PurposeThyroid cancer is the most common endocrine cancer and its etiology is still not well understood. The aim of the present study was to assess the association between an adapted dietary inflammatory index and differentiated thyroid cancer (DTC) risk in two population-based case–control studies (CATHY and YOUNG-THYR) conducted in France.Methods...

Background: Magnetic resonance imaging (MRI) is currently considered a safe imaging technique because, unlike computed tomography, MRI does not expose patients to ionising radiation. However, conflicting literature reports possible genotoxic effects of MRI. We herein examine the chromosomal effects of repeated MRI scans by performing a longitudina...

Purpose: In this paper, we describe the methodology used, and provide a first characterization of the study population and radiotherapy (RT) data in CANTO-RT (CANcer TOxicities Radiotherapy), the largest available multicenter prospective cohort of early breast cancer (BC) patients treated with RT that aims to identify predictors of development, and...

Pre-print

Late mortality of European 5‐year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause‐specific mortality among older European survivors. PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries fr...

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, a...

Second cancers have become an increasingly important concern particularly for childhood and young adulthood cancer survivors and have become nowadays a more universal concern. We have focused this chapter on the prevalence and the risk factors for secondary cancers, and when existing we have presented the recommendations of screening for high-risk...

Intensive treatments including high-dose chemotherapy (HDC) with autologous stem cell rescue have improved high-risk neuroblastoma (HRNB) survival. We report the long-term health status of 145 HRNB survivors, alive and disease-free 5 years post HDC. Median follow-up was 15 years (range = 5–34). Six patients experienced late relapses, 11 developed s...

Background: Unhealthy behaviors among childhood cancer survivors increase the risks for cancer treatment adverse effects. We aimed to assess tobacco and cannabis use prevalence in this population and to identify factors associated with these consumptions. Methods: This study involved 2,887 5-year survivors from the French childhood cancer surviv...

The ease of prescribing radiological examinations has prompted an expansion in radiological procedures and, consequently, an increase of occupational dose to medical imaging workers. However, little is known about radiation exposure in the workplace of medical radiology professionals in many countries, and in Benin particularly. The purpose of this...

Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide e...

Background: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. Methods: Based on self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diag...

Long-term sequelae are major limitations of radiation therapy use, especially for childhood brain tumor. Circle of Willis irradiation strongly increases the long-term risk of stroke, but to establish dose-response relationship, anticipating long-term effects of new techniques, requires to perform accurate and reproducible dosimetric estimations in...

Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in...

Objective: To evaluate the potential radiological impact of atmospheric nuclear weapons tests conducted in 1966-1974 at Mururoa and Fangataufa atolls on populations in Oceania, South America and Africa. Methods: Results of measurements of total beta(β)-concentrations in filtered air and 131I activity concentrations in locally produced cow's milk...

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribu...

Purpose: After the accidents of nuclear power plants at Chernobyl and at Fukushima, huge amounts of radioactive iodine were released into the atmosphere. Methods: We reviewed data on the health consequences of these accidents with a focus on thyroid consequences. Results: Among the 2 million children who were living in highly contaminated regi...

The last decades have seen increased concern about the possible effects of low to moderate doses of ionizing radiation (IR) exposure on cognitive function. An interdisciplinary group of experts (biologists, epidemiologists, dosimetrists and clinicians) in this field gathered together in the framework of the European MELODI workshop on non-cancer ef...

With improvement in cure of childhood cancer came the responsibility to investigate the long-term morbidity and mortality associated with the treatments accountable for this increase in survival. Several large cohorts of childhood cancer survivors have been established throughout Europe and North America to facilitate research on long-term complica...

Background Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide. Methods The PanCareSurFup cohort includes 69 460 five-year survivors o...

Childhood cancer survivors are at increased risk for second primary leukemia (SPL), but there is little consensus on the magnitude of some risk factors because of the small size of previous studies. We performed a pooled analysis of all published studies with detailed treatment data, including estimated active bone marrow (ABM) dose received during...

Thyroid doses were estimated for the subjects of a population-based case-control study of thyroid cancer in a population exposed to fallout after atmospheric nuclear weapons tests conducted in French Polynesia between 1966 and 1974. Thyroid doses due to (1) intake of I and of short-lived radioiodine isotopes (I, I, I) and Te, (2) external irradiati...

Objective In this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study. Methods Eight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating i...

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. Here, we conducted a genome-wide association study (GWAS) involving 1,554 cases/1,973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from the EPITHYR consortium. O...

Objective Health risk behaviors (HRB) of childhood cancer survivors (CCS) are generally studied separately, despite the evidence suggesting that HRB are not independent. To our knowledge, few studies have examined HRB profiles in the former pediatric cancer patients. In this study, we identified HRB profiles and examined predictors engaging in unhe...

Dosimetric monitoring is useful to limit exposures to ionising radiation in medical occupational settings, and reduce subsequent health risks. Scientific literatures, such as the UNSCEAR report 2017 and International Atomic Energy Agency Report 2014b, updated information on this subject; however, few African works have been found. This is the reaso...

Context: Growth hormone (GH) deficiency is a common late effect of cranial irradiation. However, concerns have been raised that GH treatment might lead to an increased risk of second neoplasm (SN). Objective: To study the impact of GH treatment on the risk of SN in a French cohort of survivors of childhood cancer (CCS) treated before 1986. Design a...

This paper presents the results of the first comprehensive estimation of the ground deposition density of radionuclides in French Polynesia resulting from the 41 atmospheric nuclear weapons tests that were conducted between 1966 and 1974 at Mururoa and Fangataufa. For each test, the deposition density at the time of arrival of fallout was estimated...

PURPOSE Between 10% and 20% of childhood cancer survivors (CCS) experience impaired growth, leading to small adult height (SAH). Our study aimed to quantify risk factors for SAH or growth hormone deficiency among CCS. METHODS The French CCS Study holds data on 7,670 cancer survivors treated before 2001. We analyzed self-administered questionnaire...

Background and objectives: Cancer survival is improving along with an increase in the potential for adverse kidney effects from antineoplastic treatments or nephrectomy. We sought to describe recent trends in the incidence of kidney failure related to antineoplastic treatments and urinary tract cancers and evaluate patient survival and kidney tran...

In this study, we aimed to evaluate site-specific cancer risks associated with hyperthyroidism or hypothyroidism. We performed a systematic review of observational studies reporting associations between hyperthyroidism or hypothyroidism and subsequent site-specific cancer incidence, in MEDLINE and the COCHRANE library (inception-28/01/2019) (PROSPE...

Ce rapport présente les travaux du groupe d’experts réunis par l’Inserm dans le cadre de la procédure d’expertise collective pour répondre à la demande du ministère de la Défense concernant les connaissances sur les conséquences sanitaires des essais nucléaires réalisés par la France sur la population de Polynésie française. Ce travail s’appuie ess...

Background: Reconstruction of radiation doses to the thyroid for a case-control study of thyroid cancer in French Polynesians exposed to radioactive fallout from atmospheric nuclear weapons tests during childhood and adolescence faced a major limitation on very little availability of information on lifestyle of French Polynesians in the 1960s-1970...