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Radiation therapy (RT) for breast cancer (BC) can result in a broad spectrum of cardiotoxicity including subtle cardiac dysfunction that can occur early after treatment. In 2022, the first European Society of Cardiology (ESC) guidelines in cardio-oncology defined asymptomatic cancer therapy-related cardiac dysfunction (CTRCD). This newly defined event has never been studied in BC patients treated with RT. To evaluate early to mid-term asymptomatic CTRCD occurrence and to analyze the association with radiation-induced cardiac exposure. The prospective monocentric BACCARAT study included BC patients treated with RT without chemotherapy, aged 40–75 years. Conventional and 2D Speckle tracking echocardiography was performed before, 6 and 24 months after RT. The present analysis included all patients with left ventricle ejection fraction (LVEF) and global longitudinal strain (GLS) measurements available for the three-time points. Asymptomatic CTRCD, as defined in the latest ESC guidelines, combines information on LVEF and GLS decrease from baseline occurring 6 or 24 months after RT. Whole heart, left ventricle (LV), and coronary arteries dose-volume parameters were considered to evaluate the impact of cardiac exposure on CTRCD. The study included 72 BC (of 59 left-sided BC) patients with a mean age of 58 ± 8.2 years. A total of 32 (44%) patients developed any grade CTRCD during follow-up: 22 (31%) developed early dysfunction, and 14 (19%) developed midterm dysfunction with or without previous early dysfunction only in left BC patients. The cardiac doses were generally higher among patients with CTRCD rather than non-CTRCD. Significant dose-response relationships were observed between the risk of CTRCD and cardiac exposure, in particular LV exposure (OR for V2 LV dose = 1.03 (1.00–1.06) P = 0.01 and circumflex CX artery's mean dose OR = 2.44 (1.26–4.74) P = 0.008, D2 OR = 1.79 (1.13–2.85) P = 0.01 and V2 OR = 1.02 (1.01–1.04) P = 0.01. The results for the CX artery exposure were robust and significant after adjustment for classic cardiac risk factors (CVRF) and analyses according to the CTRCD grade; however, it did not remain significant for LV. Our study suggests an association between specific cardiac structures and CTRCD 2 years after BC RT. considering CVRF. However, given the limited number of patients, further research is needed to understand the early mechanisms of radiation-induced CTRCD. [ABSTRACT FROM AUTHOR]

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 regions in Belarus, Ukraine and Russia, 7000 cases of thyroid cancer had occurred in 2005. This is the most significant radiation-induced consequence of the Chernobyl accident. The increased incidence of thyroid cancer observed in adult population who lived in these highly contaminated regions is at least in major part related to screening and it is not possible to individualize among these thyroid cancers those that are potentially caused by radiation exposure. For populations who lived outside these regions at the time of the accident, there is no detectable consequence of the radiation exposure on the thyroid gland. Among children who lived nearby the Fukushima power plant in 2011, there is currently no evidence of an increased incidence of thyroid cancer. Ultrasonography screening in these individuals detected a number of thyroid cancers that are probably not related to the accident. Because thyroid cancer is frequent, studies have been carried out to distinguish radiation-induced from their sporadic counterparts, and genomic signatures might be helpful. Conclusions: The consequences of the Chernobyl accident clearly demonstrate that populations living nearby a nuclear power plant should be protected in case of accident by sheltering, food restrictions and prophylaxis of thyroid irradiation by potassium iodine administration, if the predicted estimated dose to the thyroid gland of children might be >50 mGy. These countermeasures should be applied in priority to children, adolescents and pregnant women; they are safe and effective. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. Long before the eventual occurrence of coronary radiation disease, a precise evaluation of calcified and non-calcified atheromatous plaques, quantifiable by coronary CT scan, could allow a better understanding of the early phases of radiation-induced atherosclerosis and the possible implementation of preventive measures. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after RT for BC and associations with cardiac exposure. This study included BC patients treated with 3D-CRT without chemotherapy or a history of cardiovascular disease. A contrast-enhanced coronary CT scan was performed before RT and then 2 years after RT. Plaque progression was defined at the individual level for patients with an increased number of plaques at 2-year follow-up. Dosimetric data were collected for the total heart, left ventricle, and each coronary artery (left main: LM, left anterior descending: LAD, circumflex: CX, right coronary: RC). Logistic regression models were used to assess the association between doses and risk of plaque progression with odds ratios (OR) and 95% confidence intervals (CI). This study included 101 patients (84 left and 17 right BC). The mean age at inclusion was 58.4 years. The majority of patients were free of atherosclerotic plaque at baseline and at 2-year follow-up (63% and 58%, respectively). Two years after RT, 7 patients (100% left breast) showed plaque progression: for 6 patients this progression was observed in the LAD, the most highly exposed coronary artery (Dmean = 16.0 Gy), and for 1 patient in the RC. Progression of calcified and noncalcified plaques was observed in 5 and 4 patients, respectively. The analysis of associations between dose and risk of plaque progression showed statistically significant association only for doses to the LM and CX (OR = 2.32 IC95%: 1.08–4.97; P = 0.03) and (OR = 2.27 IC95%: 1.09–4.74; P = 0.03) and positive but not significant for the other structures. Our study suggests an association between the exposure of certain coronary arteries and the risk of an increase in the number of atherosclerotic plaques 2 years after breast cancer RT, whether calcified or not. These results remain to be confirmed, however, given the very limited number of patients, further research is needed to improve the understanding of the early mechanisms of radiation-induced atherosclerosis. [ABSTRACT FROM AUTHOR]

Study Question: What are the consequences of radioactive iodine (RAI) therapy for testicular function?Summary Answer: A single activity of 3.7 GBq RAI for differentiated thyroid carcinoma (DTC) treatment in young men transiently altered Sertoli cell function and induced sperm chromosomal abnormalities.What Is Known Already: Few studies, mainly retrospective, have reported the potential impacts of RAI on endocrine and exocrine testicular function.Study Design, Size, Duration: A longitudinal prospective multi-center study on testicular function performed in DTC patients before a single 131I ablative activity of 3.7 GBq (V0) and at 3 months (V3) and 13 months (V13) after treatment.Participants/materials, Setting, Methods: Forty male patients, aged 18-55 years, with DTC participated. Hormonal analysis included FSH, LH, testosterone and inhibin B serum levels at V0, V3 and V13. Furthermore, sperm parameters, DNA fragmentation and sperm chromosomal abnormalities were evaluated at each time points. The differences in all parameters, between V0-V3, V0-V13 and V3-V13, were analyzed, using a Wilcoxon test.Main Results and the Role Of Chance: Prior to RAI administration, all patients had normal gonadal function. At V3, a statistically significant increase in FSH levels and a decrease in inhibin B levels were observed and sperm concentration, as well as the percentage of morphologically normal spermatozoa, were significantly decreased (P < 0.0001). These modifications were transient as both sperm concentration and normal morphology rate returned to baseline values at V13. However, at this later time point, FSH and inhibin B levels were still impacted by RAI administration but remained in the normal range. Although no DNA fragmentation was observed at V3 nor V13, our study revealed a statistically significant increase in the number of sperm chromosomal abnormalities both at V3 (P < 0.001) and V13 (P = 0.01).Limitations, Reasons For Caution: Among the 40 patients included in the study, only 24 had all the parameters available at all visits.Wider Implications Of the Findings: Prospective studies with longer term follow up would be helpful to determine whether the chromosome abnormalities persist. These studies would be required before sperm banking should be suggested for all patients. However, sperm preservation for DTC patients who require cumulative radioiodine activities higher than 3.7 GBq should be proposed.Study Funding/competing Interest(s): This study was supported by the Programme Hospitalier de Recherche Clinique, AP-HP (No. P040419). The authors report no conflict of interest in this work.Trial Registration Number: NCT01150318. [ABSTRACT FROM AUTHOR]

Background:Retinoblastoma is a rare childhood eye cancer caused by germline or somatic mutations in the RB1 gene. Previous studies observed elevated breast cancer risk among retinoblastoma survivors. However, there has been no research on breast cancer risk in relation to radiation (primarily scatter radiation from the primary treatment) and genetic susceptibility of retinoblastoma survivors.Methods:Two groups of retinoblastoma survivors from the US and UK were selected, and breast cancer risk analysed using a case-control methodology, nesting within the respective cohorts, matching on heritability (that is to say, having bilateral retinoblastoma or being unilateral cases with at least one relative with retinoblastoma), and using exact statistical methods. There were a total of 31 cases and 77 controls.Results:Overall there was no significant variation of breast cancer risk with dose (P>0.5). However, there was a pronounced and significant (P=0.047) increase in the risk of breast cancer with increasing radiation dose for non-heritable retinoblastoma patients and a slight and borderline significant (P=0.072) decrease in risk of breast cancer with increasing radiation dose for heritable retinoblastoma patients, implying significant (P=0.024) heterogeneity in radiation risk between the heritable and non-heritable retinoblastoma groups; this was unaffected by the blindness status. There was no significant effect of any type of alkylating-agent chemotherapy on breast cancer risk (P>0.5).Conclusions:There is significant radiation-related risk of breast cancer for non-heritable retinoblastoma survivors but no excess risk for heritable retinoblastoma survivors, and no significant risk overall. However, these results are based on very small numbers of cases; therefore, they must be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia, but their potential health effects have not previously been investigated.Methods: In a case-control study, we compared the radiation exposure of almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French Polynesian control individuals without cancer from the general population. Radiation exposures were estimated using measurements after the nuclear tests, age at time of each test, residential and dietary information.Results: The average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the cases and 3% of the controls received a dose above 10 mGy. Despite this low level of dose, and after adjusting for ethnic group, level of education, body surface area, family history of thyroid cancer and number of pregnancies for women, we observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid dose received before age of 15 years, which remained after excluding non-aggressive differentiated thyroid micro-carcinomas. This increase of risk per unit of thyroid radiation dose was higher (P=0.03) in women who later experienced four or more pregnancies than among other women.Conclusion: The risk estimate is low, but is based on limited exposure data. The release of information on exposure, currently classified, would greatly improve the reliability of the risk estimation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the long-term effects of chondroitins 4 and 6 sulfate (CS) on the radiographic progression of, and symptom changes associated with, knee osteoarthritis (OA). METHODS: We performed an international, randomized, double-blind, placebo-controlled trial in which 622 patients with knee OA were randomly assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313 patients) once daily for 2 years. Radiographs of the target knee, using the Lyon schuss view, were obtained at the time of enrollment and at 12, 18, and 24 months. The minimum joint space width (JSW) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis. The primary outcome was the loss in minimum JSW over 2 years. RESULTS: The intent-to-treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean +/- SEM -0.07 +/- 0.03 mm) as compared with the placebo group (-0.31 +/- 0.04 mm). The percentage of patients with radiographic progression >/=0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16-46%]). The number of patients needed to treat was 8 (95% confidence interval 5-17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups. CONCLUSION: The long-term combined structure-modifying and symptom-modifying effects of CS suggest that it could be a disease-modifying agent in patients with knee OA. [ABSTRACT FROM AUTHOR]

French Polynesia has one of the world's highest incidence rates of thyroid cancer. A case-control study among native residents of French Polynesia included 201 women diagnosed with differentiated thyroid cancer before the age of 56 years, between 1981 and 2004, matched to 324 population controls on date of birth. Face-to-face interviews were conducted from 2002 to 2004. Odds ratios were calculated by using conditional logistic regression and were reported in the total group and by ethnic group ('Polynesian' vs. 'mixed'). The risk of thyroid cancer increased with natural (odds ratio = 1.9) or artificial (odds ratio = 4.5) menopause compared with that associated with a premenopausal status and with number of births (p for trend = 0.03): odds ratios for one, two, three, four or five, six or seven, and eight or more births were, respectively, 0.90, 1.6, 2.3, 2.2, 2.7, and 1.7 compared with a nulliparous status. Similar results were observed for Polynesian women. No association was observed with irregular menstrual cycles, age at menopause, history of miscarriage or induced abortion, time since last birth, age at and outcome of first pregnancy, or breastfeeding. This study confirms the role of menstrual and reproductive factors in the risk of differentiated thyroid cancer in Pacific island populations. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to determine the cardiac status in children 15 years or more after adriamycin therapy for a solid tumour. Of the 447 pts, 229 pts were fully studied and 218 were not. The following cardiac evaluations were proposed to all the 447 consecutive patients (pts): (1) cardiac Doppler US by one of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-hour holter ECG; (3) (131)l-mlBG myocardial scintigraphy; (4) serum brain natriuretic peptide levels at rest; (5) an exercise test with VO(2) max measurement. The radiation doses delivered to 6 points in the heart were estimated for all patients who had received radiotherapy. Congestive heart failure was diagnosed in 24 of 229 (10%) evaluated pts, with a median interval of 15 years (0.3-24 years) from the first symptom after adriamycin treatment. Among the 205 remaining pts, 13 asymptomatic pts (6%) had severe (n=4) (FS<20%) or marked (n=9) (20< or =FS<25%) systolic dysfunction. In the 192 others, the median meridional end-systolic wall stress was 91 (53-135) and it exceeded 100 g cm(-2) in 52 pts. Using a Cox model, only the cumulative dose of adriamycin and the average radiation dose to the heart, were identified as risk factors for a pathological cardiac status. In conclusion, the risk of cardiac failure or severe abnormalities increases with adriamycin treatment, radiotherapy and time since treatment, even after a follow-up of 15 years or more. In our series, after an average follow-up of 18 years, 39% of the children had a severe cardiac dysfunction or major ventricular overload conditions. The risk increases with the dose of adriamycin and radiation received to the heart, without evidence for threshold. [ABSTRACT FROM AUTHOR]

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected. [ABSTRACT FROM AUTHOR]

In total, 281 of the 7711 women who were initially treated for breast cancer between 1954 and 1983 at the Gustave Roussy Institute developed a second malignant neoplasm (SMN) other than second primary breast cancer and nonmelanoma skin cancer at least 1 year after breast cancer treatment. We carried out a nested case-control study to determine the overall relationship between the dose of radiotherapy received at a given anatomical site and the risk of SMN at the same site. In total, 75% of the cases of SMN were previously treated by radiotherapy, as compared to 73% of the controls. In the irradiated patients, the median local dose was higher among cases (3.1?Gy) than among controls (1.3?Gy). More than 40% of the irradiated patients received a local dose of less than 1?Gy. A purely quadratic relationship was observed between the dose of radiation received at an anatomical site and the risk of SMN at this site. According to the quadratic model, the excess risk of SMN was 0.2% (95% CI 0.05-0.5%) when the target organ received 1?Gy. This risk did not differ significantly according to age at the time of radiotherapy (<40 vs ?40 years). The risk of SMN was 6.7-fold higher for doses of 25?Gy or more than in the absence of radiotherapy. No carcinogenic effect of chemotherapy was observed and a dose-effect relationship between the length of tamoxifen treatment and SMN occurrence was found. This relationship was limited to endometrial cancers and did not modify the relationship with radiation dose. Our results suggest that high radiation doses slightly increase the risk of second malignancies after breast cancer.British Journal of Cancer (2003) 89, 840-846. doi:10.1038/sj.bjc.6601138 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Objective: To describe the variations in cancer incidence in the population born in French Polynesia (FP) according to the archipelago of birth and to compare this incidence with that of Hawaiians and Maoris.Methods: Study of data from the Cancer Registry of FP, evacuation files, insurance records, hospital and pathology laboratory files.Results: The overall world standardized cancer incidence in FP during the 1985-95 period in the populations born and living in FP was 246 per 105 person-years (PY) among women and 244 per 105 PY among men. The overall cancer incidence was similar to that in Hawaiians, but 25% lower than in Maoris. Digestive tract cancer incidence was a third that of these two reference populations, whereas that of pharynx, larynx and thyroid cancers was approximately twice as high. The overall cancer incidence rate increased between the period 1985-89 and the period 1990-95 in women, but was stable in men. Colorectal cancer incidence was highest in inhabitants born on the Windward Islands. Women born on the Austral Islands had a higher thyroid and liver cancer incidence and a lower breast cancer incidence.Conclusions: Further studies are needed to elucidate the variations observed between FP archipelagos, Maoris and Hawaiians. [ABSTRACT FROM AUTHOR]

Background: Between 1966 and 1974, France performed 41 atmospheric nuclear weapon tests in the Mururoa and Fangataufa atolls in French Polynesia.Methods: We performed a geographic analysis of thyroid cancer incidence, using data from the cancer registry of French Polynesia, medical evacuation files, insurance records and hospital and pathology laboratory files.Results: A total of 153 thyroid cancers were diagnosed between 1985 and 1995 in the population born before 1976 and residing in French Polynesia. The incidence of thyroid cancer was 2-3 times larger in French Polynesia than in Maoris of New Zealand and Hawaiians of Hawaii. Based on few cases, a nonsignificant (p = 0.1) increase with decreasing distance between Mururoa and the birth place was observed in women born between 1950 and 1975 for thyroid cancer.Conclusion: Because the difference between Polynesian and reference populations was not larger for Polynesians who were children during the tests than for Polynesians born earlier; as would be expected in the case of radioiodine contamination, the high thyroid cancer rates in French Polynesia could hardly be attributed to radioiodine fallout. Nevertheless, a surveillance of the population born close to Mururoa is necessary to confirm or deny the existence of a higher risk of thyroid cancer in this population. [ABSTRACT FROM AUTHOR]

Symposium: Second malignancy after modern radiotherapy: more or less than historical precedents SP-0387: Radiotherapy and second malignancy: the facts F. De Vathaire, France. [Extracted from the article]

Objectif de l’étude Étudier les facteurs prédictifs d’une pathologie cérébrovasculaire après cancer de l’enfant. Matériel et méthode Il s’agissait d’un étude de cohorte French Childhood Cancer Survivor Study (FCCSS) : 7018 survivants à 5 ans d’un cancer de l’enfant traité avant 2001, dont 1193 pour une tumeur cérébrale, et suivis 24 ans en moyenne, par l’accès aux dossiers médicaux et aux données du Système national d’information interrégimes de l’assurance maladie (Sniiram), ainsi qu’au moyen de l’envoi d’autoquestionnaires. Les radiothérapies reçues par 4176 sujets, dont 1016, pour une tumeur cérébrale, ont été reconstituées à l’aide de fantômes anthropomorphiques, et les doses de radiation reçues au niveau des artères cérébrales et d’autres structures d’intérêt ont été estimées. Résultats Un total de 145 sujets a été atteint d’un accident vasculaire cérébral, dont 72 après une tumeur cérébrale et 134 après la radiothérapie. Le type d’accident vasculaire cérébral n’a pas pu être défini pour 24 patients, il était ischémique pour 77 et hémorragique pour 44. Il n’a pas été possible d’identifier de drogue ou de catégorie de drogue augmentant le risque d’accident vasculaire cérébral. Dans une analyse multifactorielle, celui-ci était plus important chez les sujets atteints d’une neurofibromatose de type I (NF1), et augmentait avec la dose de radiation reçue au niveau des artères cérébrales, le coefficient de risque étant plus élevé pour les accidents vasculaires cérébraux ischémiques, ainsi qu’avec la radiothérapie thoracique ou abdominale. Il n’a pas été possible de mettre en évidence de rôle de la chirurgie des tumeurs cérébrales, que ce soit propre ou par interaction avec la radiothérapie, mais seuls 206 sujets traités pour une tumeur cérébrale n’avaient pas eu de chirurgie. Les sujets qui avaient reçu de la radiothérapie, mais 30 Gy ou plus sur seulement moins de 5 % de la longueur des artères cérébrales principales avaient un risque d’accident vasculaire cérébral augmenté d’un facteur 2,8 (1,3–5,5). En revanche, il n’y avait pas d’évidence claire pour un rôle des doses faibles de rayonnements ionisants de un ou quelques Gy. Conclusion Cette étude n’a pas permis de mettre en évidence de rôle de la chimiothérapie ou de la chirurgie dans le risque de tumeur cérébrale, mais a permis de préciser et de quantifier le rôle de la radiothérapie cérébrale. [ABSTRACT FROM AUTHOR]