Search

Background:Recent epidemiological results suggested an increase of cancer risk after receiving computed tomography (CT) scans in childhood or adolescence. Their interpretation is questioned due to the lack of information about the reasons for examination. Our objective was to estimate the cancer risk related to childhood CT scans, and examine how cancer-predisposing factors (PFs) affect assessment of the radiation-related risk.Methods:The cohort included 67 274 children who had a first scan before the age of 10 years from 2000 to 2010 in 23 French departments. Cumulative X-rays doses were estimated from radiology protocols. Cancer incidence was retrieved through the national registry of childhood cancers; PF from discharge diagnoses.Results:During a mean follow-up of 4 years, 27 cases of tumours of the central nervous system, 25 of leukaemia and 21 of lymphoma were diagnosed; 32% of them among children with PF. Specific patterns of CT exposures were observed according to PFs. Adjustment for PF reduced the excess risk estimates related to cumulative doses from CT scans. No significant excess risk was observed in relation to CT exposures.Conclusions:This study suggests that the indication for examinations, whether suspected cancer or PF management, should be considered to avoid overestimation of the cancer risks associated with CT scans. [ABSTRACT FROM AUTHOR]

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 memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS)., Methods: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals., Results: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5-31.2 and RHR = 5.1, 95%CI 4.4-5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7-13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7-3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3-4.7) compared to those who did not receive radiotherapy., Conclusions: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals., (© 2024. The Author(s).)

Purpose: The dose deposited outside of the treatment field during external photon beam radiation therapy treatment, also known as out-of-field dose, is the subject of extensive study as it may be associated with a higher risk of developing a second cancer and could have deleterious effects on the immune system that compromise the efficiency of combined radio-immunotherapy treatments. Out-of-field dose estimation tools developed today in research, including Monte Carlo simulations and analytical methods, are not suited to the requirements of clinical implementation because of their lack of versatility and their cumbersome application. We propose a proof of concept based on deep learning for out-of-field dose map estimation that addresses these limitations., Methods and Materials: For this purpose, a 3D U-Net, considering as inputs the in-field dose, as computed by the treatment planning system, and the patient's anatomy, was trained to predict out-of-field dose maps. The cohort used for learning and performance evaluation included 3151 pediatric patients from the FCCSS database, treated in 5 clinical centers, whose whole-body dose maps were previously estimated with an empirical analytical method. The test set, composed of 433 patients, was split into 5 subdata sets, each containing patients treated with devices unseen during the training phase. Root mean square deviation evaluated only on nonzero voxels located in the out-of-field areas was computed as performance metric., Results: Root mean square deviations of 0.28 and 0.41 cGy/Gy were obtained for the training and validation data sets, respectively. Values of 0.27, 0.26, 0.28, 0.30, and 0.45 cGy/Gy were achieved for the 6 MV linear accelerator, 16 MV linear accelerator, Alcyon cobalt irradiator, Mobiletron cobalt irradiator, and betatron device test sets, respectively., Conclusions: This proof-of-concept approach using a convolutional neural network has demonstrated unprecedented generalizability for this task, although it remains limited, and brings us closer to an implementation compatible with clinical routine., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The evidence for the value of particle therapy (PT) is still sparse. While randomized trials remain a cornerstone for robust comparisons with photon-based radiotherapy, data registries collecting real-world data can play a crucial role in building evidence for new developments. This Perspective describes how the European Particle Therapy Network (EPTN) is actively working on establishing a prospective data registry encompassing all patients undergoing PT in European centers. Several obstacles and hurdles are discussed, for instance harmonization of nomenclature and structure of technical and dosimetric data and data protection issues. A preferred approach is the adoption of a federated data registry model with transparent and agile governance to meet European requirements for data protection, transfer, and processing. Funding of the registry, especially for operation after the initial setup process, remains a major challenge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Childhood cancer survivors, in particular those treated with radiation therapy, are at high risk of long-term iatrogenic events. The prediction of risk of such events is mainly based on the knowledge of the radiation dose received to healthy organs and tissues during treatment of childhood cancer diagnosed decades ago. We aimed to set up a standardized organ dose table to help former patients and clinicians in charge of long-term follow-up clinics., Methods and Materials: We performed whole body dosimetric reconstruction for 2646 patients from 12 European countries treated between 1941 and 2006 (median, 1976). Most plannings were 2- or 3-dimensional. A total of 46% of patients were treated using Cobalt 60, and 41%, using a linear accelerator. The median prescribed dose was 27.2 Gy (IQ1-IQ3, 17.6-40.0 Gy). A patient-specific voxel-based anthropomorphic phantom with more than 200 anatomic structures or substructures delineated as a surrogate of each subject's anatomy was used. The radiation therapy was simulated with a treatment planning system based on available treatment information. The radiation dose received by any organ of the body was estimated by extending the treatment planning system dose calculation to the whole body, by type and localization of childhood cancer., Results: The integral dose and normal tissue doses to most of the 23 considered organs increased between the 1950s and 1970s and decreased or plateaued thereafter. Whatever the organ considered, the type of childhood cancer explained most of the variability in organ dose. The country of treatment explained only a small part of the variability., Conclusions: The detailed dose estimates provide very useful information for former patients or clinicians who have only limited knowledge about radiation therapy protocols or techniques, but who know the type and site of childhood cancer, sex, age, and year of treatment. This will allow better prediction of the long-term risk of iatrogenic events and better referral to long-term follow-up clinics., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: In this Pediatric Normal Tissue Effects in the Clinic (PENTEC) vision paper, challenges and opportunities in the assessment of subsequent neoplasms (SNs) from radiation therapy (RT) are presented and discussed in the context of technology advancement., Methods and Materials: The paper discusses the current knowledge of SN risks associated with historic, contemporary, and future RT technologies. Opportunities for research and SN mitigation strategies in pediatric patients with cancer are reviewed., Results: Present experience with radiation carcinogenesis is from populations exposed during widely different scenarios. Knowledge gaps exist within clinical cohorts and follow-up; dose-response and volume effects; dose-rate and fractionation effects; radiation quality and proton/particle therapy; age considerations; susceptibility of specific tissues; and risks related to genetic predisposition. The biological mechanisms associated with local and patient-level risks are largely unknown., Conclusions: Future cancer care is expected to involve several available RT technologies, necessitating evidence and strategies to assess the performance of competing treatments. It is essential to maximize the utilization of existing follow-up while planning for prospective data collection, including standardized registration of individual treatment information with linkage across patient databases., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 incidence were calculated., Results: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50., Discussion: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms., (© 2024. The Author(s).)

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses., (© 2023. The Author(s).)

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 diagnosed between 1945 and 2000. To account for the time dependence of the occurrence of a SMN, we employed a landmark approach, considering an additive regression model for the cumulative incidence of cardiac disease. We estimated the effect of a SMN on the instantaneous risk of cardiac disease using a proportional cause-specific hazard model, considering a SMN as a time-dependent exposure. In both models, we adjusted for demographic and treatment information and considered death as a competing event., Results: In 7,670 CCS over a median follow-up of 30 years (IQR: 22-38 years), there were 378 cases of cardiac disease identified, of which 49 patients experienced a SMN. Patients who survived 25 years after their childhood cancer diagnosis and had a SMN in that time frame had a significantly increased cumulative incidence of cardiac disease, which was 3.8% (95% CI: 0.5% to 7.1%) higher compared with those without a SMN during this period. No SMN-induced excess of cardiac disease was observed at subsequent landmark times. SMNs were associated with a 2-fold increase (cause-specific HR: 2.0; 95% CI: 1.4-2.8) of cardiac disease., Conclusions: The occurrence of a SMN among CCS is associated with an increased risk of cardiac disease occurrence and risk at younger ages., Competing Interests: This work was supported and funded by the Gustave Roussy Foundation (Pediatric Program "Guérir le Cancer de l’Enfant"), the ITMO (Instituts thématiques multiorganismes) Cancer d’Aviesan Program (RadioPrediTool project no. 20CM112-00), the INCa (Institut national du cancer)/ARC (Foundation ARC for Cancer Research) foundation (CHART project), the Foundation ARC for Cancer Research (grant no. Pop-HaRC 201401208), the "START" PAIR Research Program (grant no. INCa-Fondation ARC-LNCC 11902), and the Ligue Nationale Contre le Cancer association. These funding agencies had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

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 multivariable logistic regression models. Association of attendance to a long-term follow-up (LTFU) visit with completion of an echocardiogram was estimated using a Cox regression model., Results: Among participants, 32% had an echocardiogram within the 5 previous years. Males (adjusted RR [aRR] 0.71, 95% CI 0.58-0.86), survivors aged 36-49 (aRR 0.79, 95% CI 0.64-0.98), Neuroblastoma (aRR 0.53, 95% CI 0.30-0.91) and CNS tumour survivors (aRR 0.43, 95% CI 0.21-0.89) were less likely to adhere to recommended surveillance. Attendance to an LTFU visit was associated with completion of an echocardiogram in patients who were not previously adherent to recommendations (HR 8.20, 95% CI 5.64-11.93)., Conclusions: The majority of long-term survivors at high risk of cardiomyopathy did not adhere to the recommended surveillance. Attendance to an LTFU visit greatly enhanced the completion of echocardiograms, but further interventions need to be developed to reach more survivors., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment., Materials and Methods: Organ doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al., Results: Out-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μ Sv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μ Sv (testes) and 48 μ Sv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs., Conclusion: The complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 De Saint-Hubert, Boissonnat, Schneider, Bäumer, Verbeek, Esser, Wulff, Stuckmann, Suesselbeck, Nabha, Dabin, Vasi, Radonic, Rodriguez, Simon, Journy, Timmermann, Thierry-Chef and Brualla.)

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., Results: CCSs were less likely to have obesity (9.5%; 95% CI: 8.5%-10.5%) than expected from the general French population rates (12.5%; p = 0.0001). Nevertheless, brain tumor survivors were significantly more likely to develop obesity than the general French population (p = 0.0001). Compared with patients who did not receive radiotherapy to the pituitary gland, those who received a dose >5 Gy had an increased risk of obesity: relative risk 1.9 (95% CI: 1.2-3.1), 2.5 (95% CI: 1.7-3.7), and 2.6 (95% CI: 1.6-4.3), respectively, for participants with 6 to 20 Gy, 20 to 40 Gy, and ≥40 Gy of radiation. Etoposide administration significantly increased the risk of obesity (relative risk 1.7; 95% CI: 1.1-2.6). High social deprivation index was also a risk factor, just like BMI at diagnosis., Conclusions: Long-term follow-up of CCSs should include weight follow-up during adulthood., (© 2023 The Obesity Society.)

Background: The European EPI-CT study aims to quantify cancer risks from CT examinations of children and young adults. Here, we assess the risk of brain cancer., Methods: We pooled data from nine European countries for this cohort study. Eligible participants had at least one CT examination before age 22 years documented between 1977 and 2014, had no previous diagnosis of cancer or benign brain tumour, and were alive and cancer-free at least 5 years after the first CT. Participants were identified through the Radiology Information System in 276 hospitals. Participants were linked with national or regional registries of cancer and vital status, and eligible cases were patients with brain cancers according to WHO International Classification of Diseases for Oncology. Gliomas were analysed separately to all brain cancers. Organ doses were reconstructed using historical machine settings and a large sample of CT images. Excess relative risks (ERRs) of brain cancer per 100 mGy of cumulative brain dose were calculated with linear dose-response modelling. The outcome was the first reported diagnosis of brain cancer after an exclusion period of 5 years after the first electronically recorded CT examination., Findings: We identified 948 174 individuals, of whom 658 752 (69%) were eligible for our study. 368 721 (56%) of 658 752 participants were male and 290 031 (44%) were female. During a median follow-up of 5·6 years (IQR 2·4-10·1), 165 brain cancers occurred, including 121 (73%) gliomas. Mean cumulative brain dose, lagged by 5 years, was 47·4 mGy (SD 60·9) among all individuals and 76·0 mGy (100·1) among people with brain cancer. A significant linear dose-response relationship was observed for all brain cancers (ERR per 100 mGy 1·27 [95% CI 0·51-2·69]) and for gliomas separately (ERR per 100 mGy 1·11 [0·36-2·59]). Results were robust when the start of follow-up was delayed beyond 5 years and when participants with possibly previously unreported cancers were excluded., Interpretation: The observed significant dose-response relationship between CT-related radiation exposure and brain cancer in this large, multicentre study with individual dose evaluation emphasises careful justification of paediatric CTs and use of doses as low as reasonably possible., Funding: EU FP7; Belgian Cancer Registry; La Ligue contre le Cancer, L'Institut National du Cancer, France; Ministry of Health, Labour and Welfare of Japan; German Federal Ministry of Education and Research; Worldwide Cancer Research; Dutch Cancer Society; Research Council of Norway; Consejo de Seguridad Nuclear, Generalitat de Catalunya, Spain; US National Cancer Institute; UK National Institute for Health Research; Public Health England., Competing Interests: Declaration of interests CJ reports honoraria from Pfizer, Janssen, and Astellas, and owns stocks in Y-mAbs, Novo Nordisk, Novozymes, Hansa, Zealand, Bavarian Nordic, and BioCryst Pharmaceuticals. MK reports grants from Stockholm County for clinical research within the frame of employment as a radiologist at the Karolinska University Hospital. CR reports a grant from the Dutch Cancer Society for Junior Group Leaders. All other authors declared no competing interests., (Copyright © 2023 World Health Organization. Published by Elsevier Ltd. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

In a previous systematic review and meta-analysis of studies reporting associations between hyper-/hypothyroidism and breast cancer incidence published through 29 January 2019, we identified a higher risk with diagnosed hyperthyroidism compared to euthyroidism, but no association with diagnosed hypothyroidism. This 2-year updated meta-analysis aims to investigate the role of menopause in this association and the dose-response relationship with blood levels of thyroid-stimulating hormone (TSH) and thyroid hormones. After the exclusion of studies with only mortality follow-up, with thyroid dysfunction evaluated as a cancer biomarker or after prior breast cancer diagnosis, we reviewed 25 studies that were published up to 01 December 2021 and identified in MEDLINE, the COCHRANE library, Embase, or Web of Science; of these, 9 were included in the previous meta-analysis. Risk estimates from 22 of the 25 studies were included in the meta-analysis and pooled using random-effects models. Compared to euthyroidism, hyperthyroidism and hypothyroidism diagnoses were associated with higher (pooled risk ratio (RR): 1.12, 95% CI: 1.06-1.18, 3829 exposed cases) and lower risks (RR = 0.93, 95% CI: 0.86-1.00, 5632 exposed cases) of breast cancer, respectively. The increased risk after hyperthyroidism was greater among postmenopausal women (RR = 1.19, 95% CI 1.09-1.30) and the decreased risk after hypothyroidism was more pronounced among premenopausal women (RR = 0.69, 95% CI 0.53-0.89). Among women with no prior history of thyroid disease, every 1 mIU/L increase in TSH level was associated with a 0.8% (95% CI > 0-1.5%) lower risk of breast cancer. In conclusion, this meta-analysis supports an association between thyroid hormone levels and breast cancer risk, which could be modified by menopausal status.

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 thyroid cancer from 1934 to 2005 in France, Italy and Sweden. Standardized incidence ratios (SIRs) for breast cancer were estimated by comparison with age, sex and calendar-year expected values of the general population in each country. We estimated breast cancer risk in relation to I-131 treatment using time-dependent Poisson models., Results: Of 8475 women (mean age at diagnosis: 45 years, range 2-90 years), 335 were diagnosed with breast cancer [SIR = 1.52, 95% confidence interval (CI): 1.36-1.69] during a median follow-up time of 12.7 years since diagnosis. Overall, breast cancer risk did not differ between women treated or not with I-131 (relative risk=1.07, 95% CI 0.84-1.35). However, breast cancer risk increased with increasing cumulative I-131 activity, without significant departure from linearity (excess relative risk per 100 mCi=17%, 95% CI: 2% to 38%). The higher risk associated with a cumulative I-131 activity of ≥100 mCi and ≥400 mCi was translated into 4 (95% CI -4 to 13) and 42 (95% CI -8 to 93) excess breast cancer cases per 10,000 person-years, respectively., Conclusions: An elevated risk was observed for the highest cumulative administered activity (>=400 mCi), and a significant dose-dependent association was observed among thyroid cancer survivors who were treated with I-131. However, overall, I-131 treatment might only explain partly the increase in breast cancer risk among female thyroid cancer survivors., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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 survivors of childhood cancer following radiotherapy and chemotherapy and identify possible modifying factors of radiation-associated risk., Design, Setting, and Participants: This international case-control study pooled data from 4 nested case-control studies of survivors of childhood cancer diagnosed between 1942 and 2000, followed through 2016. Cases were defined as participants diagnosed with a subsequent meningioma. Controls were matched to cases based on sex, age at first cancer diagnosis, and duration of follow-up. Data were analyzed from July 2019 to June 2022., Exposures: Radiation dose (Gy) to the meningioma site and cumulative chemotherapy doses, including intrathecal and systemic methotrexate doses., Main Outcomes and Measures: The main outcome was subsequent meningioma, assessed using odds ratios (ORs) and excess odds ratios per gray (EOR/Gy)., Results: The analysis included 273 survivors of childhood cancer who developed meningioma (cases) and 738 survivors who did not (controls), with a total of 1011 individuals (median [IQR] age at first cancer diagnosis 5.0 [3.0-9.2] years; 599 [59.2%] female). Median (IQR) time since first cancer was 21.5 (15.0-27.0) years. Increasing radiation dose was associated with increased risk of meningioma (EOR/Gy, 1.44; 95% CI, 0.62-3.61), and there was no evidence of departure from linearity (P = .90). Compared with survivors who were not exposed to radiation therapy, those who received doses of 24 Gy or more had more than 30-fold higher odds of meningioma (OR, 33.66; 95% CI, 14.10-80.31). The radiation dose-response association was significantly lower among patients treated at age 10 years or older compared with those treated before age 10 years (EOR/Gy, 0.57; 95% CI, 0.18-1.91 vs 2.20; 95% CI, 0.87-6.31; P for heterogeneity = .03). Risk associated with radiation remained significantly elevated 30 years after exposure (EOR/Gy, 3.76; 95% CI, 0.77-29.15). We found an increased risk of meningioma among children who had received methotrexate (OR, 3.43; 95% CI, 1.56-7.57), but no evidence of a dose-response association or interaction with radiation dose., Conclusions and Relevance: These findings suggest that the meninges are highly radiosensitive, especially for children treated before age 10 years. These results support the reduction in whole-brain irradiation over recent decades and the prioritization of approaches that limit radiation exposure in healthy tissue for children. The persistence of elevated risks of meningiomas for 30 years after cranial radiotherapy could help inform surveillance guidelines.

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 CCS diagnosed before the age of 21 between 1945 and 2000 by sex, birth year and region of residence to 386,073 individuals of the French general population. After linkage with the national hospital discharge database, we estimated the relative hospitalisation rate (RHR), the absolute excess risks (AERs) and the relative bed-day ratio (RBDR) during 2006-2018. We used generalised linear models to estimate associations between hospitalisation and survivor characteristics. Overall, the RHR was 2.49 (95% confidence interval [CI] 2.46-2.52) and the RBDR was 3.49 (95% CI 3.46-3.51). We found that neoplasm-related hospitalisations had the highest AER (105.8 per 1000 person-years), followed by genitourinary system diseases (34.4 per 1000 person-years) and cardiovascular diseases (19.2 per 1000 person-years). In adjusted analysis, CCS treated with chemotherapy (risk ratio [RR] 1.62, 95% CI 1.53-1.70), radiotherapy (RR 2.11, 95% CI 1.99-2.24) or both (RR 2.59, 95% CI 2.46-2.73) had a higher risk of hospitalisation than the ones who had not received any of these treatments. CCS treated during the past decades by chemotherapy and/or radiotherapy now had a higher hospitalisation risk for all main categories of diagnosis than the general population. Prevention strategies and medical surveillance programmes may promote a long-term decrease in the hospitalisation rate among CSS., (© 2022. The Author(s).)

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 second malignant neoplasms (SMNs), and 9 died. Event-free and overall survivals 20 years post HDC were 82% (95% CI = 70%-90%) and 89% (78%-95%), respectively. Compared with the French general population, the standardized mortality ratio was 19 (95% CI = 8.7-36.1; p < 0.0001) and the absolute excess risk was 37.6 (19.2-73.5). Late effects were observed in 135/145 patients (median = 3 events/patient); 103 had at least one severe event. SMNs arose at a median of 20 years post HDC and included carcinoma (n = 5), sarcoma (2), acute myeloid leukemia (2), melanoma (1), and malignant glioma (1). Non-oncologic health events included dental maldevelopment (60%), severe hearing loss (20% cumulative probability at 15 years), hepatic focal nodular hyperplasia (14%), thyroid (11%), cardiac (8%), and renal (7%) diseases and growth retardation (height-for-age z-score ≤ -2 for 21%). Gonadal insufficiency was near-universal after busulfan (40/43 females, 33/35 males). Severe late effects are frequent and progressive in HRNB survivors needing systematic very long-term follow-up., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

This study aimed to evaluate the association between thyroid dysfunction and breast cancer risk. We included 239,436 females of the UK Biobank cohort. Information on thyroid dysfunction, personal and family medical history, medications, reproductive factors, lifestyle, and socioeconomic characteristics was retrieved from baseline self-reported data and hospital inpatient databases. Breast cancer diagnoses were identified through population-based registries. We computed Cox models to estimate hazard ratios (HRs) of breast cancer incidence for thyroid dysfunction diagnosis and treatments, and examined potential confounding and effect modification by comorbidities and breast cancer risk factors. In our study, 3,227 (1.3%) and 20,762 (8.7%) women had hyper- and hypothyroidism prior to the baseline. During a median follow-up of 7.1 years, 5,326 (2.2%) women developed breast cancer. Compared to no thyroid dysfunction, there was no association between hypothyroidism and breast cancer risk overall (HR = 0.93, 95% confidence interval (CI): 0.84-1.02, 442 cases), but we found a decreased risk more than 10 years after hypothyroidism diagnosis (HR=0.85, 95%CI 0.74-0.97, 226 cases). There was no association with hyperthyroidism overall (HR=1.08, 95%CI 0.86-1.35, 79 cases) but breast cancer risk was elevated among women with treated hyperthyroidism (HR=1.38, 95%CI: 1.03-1.86, 44 cases) or aged 60 years or more at hyperthyroidism diagnosis (HR=1.74, 95%CI: 1.01-3.00, 113 cases), and 5-10 years after hyperthyroidism diagnosis (HR=1.58, 95%CI: 1.06-2.33, 25 cases). In conclusion, breast cancer risk was reduced long after hypothyroidism diagnosis, but increased among women with treated hyperthyroidism. Future studies are needed to determine whether the higher breast cancer risk observed among treated hyperthyroidism could be explained by hyperthyroidism severity, type of treatment or aetiology., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Within the European Epidemiological Study to Quantify Risks for Paediatric Computerized Tomography (EPI-CT study), a cohort was assembled comprising nearly one million children, adolescents and young adults who received over 1.4 million computed tomography (CT) examinations before 22 years of age in nine European countries from the late 1970s to 2014. Here we describe the methods used for, and the results of, organ dose estimations from CT scanning for the EPI-CT cohort members. Data on CT machine settings were obtained from national surveys, questionnaire data, and the Digital Imaging and Communications in Medicine (DICOM) headers of 437,249 individual CT scans. Exposure characteristics were reconstructed for patients within specific age groups who received scans of the same body region, based on categories of machines with common technology used over the time period in each of the 276 participating hospitals. A carefully designed method for assessing uncertainty combined with the National Cancer Institute Dosimetry System for CT (NCICT, a CT organ dose calculator), was employed to estimate absorbed dose to individual organs for each CT scan received. The two-dimensional Monte Carlo sampling method, which maintains a separation of shared and unshared error, allowed us to characterize uncertainty both on individual doses as well as for the entire cohort dose distribution. Provided here are summaries of estimated doses from CT imaging per scan and per examination, as well as the overall distribution of estimated doses in the cohort. Doses are provided for five selected tissues (active bone marrow, brain, eye lens, thyroid and female breasts), by body region (i.e., head, chest, abdomen/pelvis), patient age, and time period (1977-1990, 1991-2000, 2001-2014). Relatively high doses were received by the brain from head CTs in the early 1990s, with individual mean doses (mean of 200 simulated values) of up to 66 mGy per scan. Optimization strategies implemented since the late 1990s have resulted in an overall decrease in doses over time, especially at young ages. In chest CTs, active bone marrow doses dropped from over 15 mGy prior to 1991 to approximately 5 mGy per scan after 2001. Our findings illustrate patterns of age-specific doses and their temporal changes, and provide suitable dose estimates for radiation-induced risk estimation in epidemiological studies., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Long-term sequelae are major limitations of radiation therapy use, especially for childhood brain tumour. 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 large cohorts of patients having received radiotherapy decades ago. For the accuracy of retrospective dose reconstruction, the topographic variability of the Circle of Willis arteries is crucial. In order to improve retrospective dosimetric studies and dose-volume estimates to the typical Circle of Willis arteries, we aim to study the inter-individual topographic variability of these structures. Thirty-eight time of flight MRI sequences of children aged 2-17 years in both genders were investigated. A region growth algorithm was used for the segmentation of the cerebral arteries. A rigid registration in a common skull was performed following the anatomy of skull base foramina. The Posterior clinoid processes of the sella turcica were used as reference landmark (R0), and 5 key landmarks were chosen in each segmented Circle of Willis, then distances between the 5 landmarks and R0 were calculated for each of the 38 subjects. The distance between R0 and each landmark of the Circle of Willis followed a normal distribution, the average values ranging from 13.6 to 17.0 mm, and the standard deviations ranged from 2.6 to 3.0 mm, i.e. less than a fifth of the average value. The perimeter of the Circle of Willis was longer in older subjects, this increase being isotropic. Our study shows a remarkably low topographic variability of the typical Circle of Willis. An important result, allowing reliable anthropomorphic phantoms-based retrospective estimations of the radiation doses delivered to these arterial structures during radiotherapy treatment., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

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 reason why we undertook this study, which summarises existing information on monitoring external radiation exposure doses for the whole body, using data from medical workers on this continent. Using standard terms and combining different keyword searches for radiation dose monitoring among radiology healthcare workers in Africa, from the titles, abstracts, and full texts, we found 3139 articles in the PubMed/MEDLINE, Google Scholar and INIS databases. Two reviewers screened the retrieved publications based on predefined eligibility criteria to identify relevant studies, extract key information from each, and summarise the data in table form. A total of 20 potentially relevant articles were identified. Among these 20 articles, 15 reported the overall average annual effective dose. Studies included in this systematic review represent an inventory of the radiation protection of medical workers in various African countries, with a focus on the monitoring of occupational radiation exposure. The size of studied populations ranged between 81 and 5152 occupational exposed workers. The mean annual effective doses ranged from 0.44 to 8.20 mSv in all specialities of medical sectors, while diagnostic radiology ranged from 0.07 to 4.37 mSv. For the nuclear medicine and radiotherapy from medical groups, the mean annual effective dose varied between 0.56 and 6.30 mSv. Industrial and research/teaching sectors data varied between 0.38 to 19.40 mSv. In conclusion, more studies implemented on dosimetric monitoring in Africa are needed to get a real picture of occupational exposure in the continent., (© 2020 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

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 unhealthy behaviors in CCS., Methods: We used data from a French cohort of CCS that includes five-year survivors diagnosed between 1945 and 2000 and treated before reaching age 18, in five centers in France. A total of 2961 adult CCS answered a self-reported questionnaire pertaining to HRB. Latent class analysis was used to identify HRB profiles combining physical activity, smoking, cannabis use, and alcohol drinking. Multinomial logistic analyses examined predictors for engaging in unhealthy behaviors., Results: Three HRB patterns emerged: "Low-risk" (n = 1846, 62.3%) included CCS who exhibited the highest frequency for usual physical activity and the lowest probabilities for current smoking or cannabis use, but most drank at least moderately; "Moderate-risk behaviors" (n = 291, 9.8%), and "High-risk behaviors" (n = 824, 27.8%) for CCS who exhibited the highest frequencies for current smoking, cannabis use, and heavy drinking. The multivariable regression revealed that male CCS, less educated or not married were significantly more likely to be in the high-risk behaviors group than the low-risk group., Conclusions: As CCS remain a vulnerable population, screening for HRB should be routinized in long-term follow-up care and interventions targeting multiple HRB simultaneously among survivors should be developed., (© 2020 John Wiley & Sons Ltd.)

Purpose: To investigate the relationship between oesophagus dose-volume distribution and long-term risk of oesophageal cancer after radiation therapy for breast cancer., Materials and Methods: In a case-control study nested within a cohort of 289,748 ≥5-year survivors of female breast cancer treated in 1943-2003 in five countries, doses to the second primary cancer (D SPC ) and individual dose-volume histograms (DVH) to the entire oesophagus were reconstructed for 252 oesophageal cancer cases and 488 matched controls (median follow-up time: 13, range: 5-37 years). Using conditional logistic regression, we estimated excess odds ratios (EOR) of oesophageal cancer associated with DVH metrics. We also investigated whether DVH metrics confounded or modified D SPC -related -risk estimates., Results: Among the DVH metrics evaluated, median dose (D median ) to the entire oesophagus had the best statistical performance for estimating risk of all histological types combined (EOR/Gy = 0.071, 95% confidence interval [CI]: 0.018 to 0.206). For squamous cell carcinoma, the most common subtype, the EOR/Gy for D median increased by 31% (95% CI: 3% to 205%) for each increment of 10% of V30 (p = 0.02). Adjusting for DVH metrics did not materially change the EOR/Gy for D SPC , but there was a borderline significant positive interaction between D SPC and V30 (p = 0.07)., Conclusion: This first study investigating the relationship between oesophagus dose-volume distribution and oesophageal cancer risk showed an increased risk per Gy for D median with larger volumes irradiated at high doses. While current techniques allows better oesophagus sparing, constraints applied to D median and V30 could potentially further reduce the risk of oesophageal cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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 data from 2,965 CCS with clinical, chemo/radiotherapy data from medical records. SAH was defined as an adult height ≤ 2 standard deviation scores of control values obtained from a French population health study., Results: After exclusion of 189 CCS treated with growth hormone, 9.2% (254 of 2,776) had a SAH. Being young at the time of cancer treatment (relative risk [RR], 0.91 [95% CI, 0.88 to 0.95] by year of age), small height at diagnosis (≤ 2 standard deviation scores; RR, 6.74 [95% CI, 4.61 to 9.86]), pituitary irradiation (5-20 Gy: RR, 4.24 [95% CI, 1.98 to 9.06]; 20-40 Gy: RR, 10.16 [95% CI, 5.18 to 19.94]; and ≥ 40 Gy: RR, 19.48 [95% CI, 8.73 to 43.48]), having received busulfan (RR, 4.53 [95% CI, 2.10 to 9.77]), or > 300 mg/m 2 of lomustine (300-600 mg/m 2 : RR, 4.21 [95% CI, 1.61 to 11.01] and ≥ 600 mg/m 2 : RR, 9.12 [95% CI, 2.75 to 30.24]) were all independent risk factors for SAH. Irradiation of ≥ 7 vertebrae (≥ 15 Gy on ≥ 90% of their volume) without pituitary irradiation increased the RR of SAH by 4.62 (95% CI, 2.77 to 7.72). If patients had also received pituitary irradiation, this increased the RR by an additional factor of 1.3 to 2.4., Conclusion: CCS are at a high risk of SAH. CCS treated with radiotherapy, busulfan, or lomustine should be closely monitored for growth, puberty onset, and potential pituitary deficiency.

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) (PROSPERO: CRD42019125094). We excluded studies with thyroid dysfunction evaluated as a cancer biomarker or after prior cancer diagnosis and those considering transient thyroid dysfunction during pregnancy or severe illnesses. Risk of bias was assessed using a modified Newcastle-Ottawa scale. Risk estimates were pooled using random-effects models when ≥5 studies reported data for a specific cancer site. Twenty studies were included, of which 15 contributed to the meta-analysis. Compared to euthyroidism, hyperthyroidism was associated with higher risks of thyroid (pooled risk ratio: 4.49, 95%CI: 2.84-7.12), breast (pooled risk ratio: 1.20, 95%CI: 1.04-1.38), and prostate (pooled risk ratio: 1.35, 95%CI: 1.05-1.74), but not respiratory tract (pooled risk ratio: 1.06, 95%CI: 0.80-1.42) cancers. Hypothyroidism was associated with a higher risk of thyroid cancer within the first 10 years of follow-up only (pooled risk ratio: 3.31, 95%CI: 1.20-9.13). There was no or limited evidence of thyroid dysfunction-related risks of other cancer sites. In conclusion, thyroid dysfunction was associated with increased risks of thyroid, breast, and prostate cancers. However, it remains unclear whether these findings represent causal relationships because information on treatments and potential confounders was frequently lacking.

Background: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors., Methods: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated., Results: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs., Conclusions: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Since our previous publication of organ dose for the pediatric CT cohort in the UK, there have been questions about the magnitude of uncertainty in our dose estimates. We therefore quantified shared and unshared uncertainties in empirical CT parameters extracted from 1073 CT films (1978-2008) from 36 hospitals in the study and propagated these uncertainties into organ doses using Monte Carlo random sampling and NCICT organ dose calculator. The average of 500 median brain and marrow doses for the full cohort was 35 (95% confidence interval: 30-40) mGy and 6 (5-7) mGy, respectively. We estimated that shared uncertainty contributed ~99% of coefficient of variation of median brain doses in brain scans compared to unshared uncertainty (1% contribution). We found that the previous brain doses were slightly underestimated for <1990 and overestimated for >1990 compared to the results in the current study due to the revised CTDI models based on CT films., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)