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Importance: Chest irradiation for childhood cancer is associated with increases in breast cancer risk. Growing evidence suggests that anthracyclines increase this risk, but the outcome of combined anthracycline use and radiotherapy has not been studied., Objectives: To evaluate breast cancer risk in childhood cancer survivors following radiotherapy and chemotherapy and assess whether risks varied by estrogen receptor (ER) status., Design, Setting, and Participants: In a North American hospital-based nested case-control study, a retrospective cohort of 14 358 five-year survivors of childhood cancer, diagnosed from 1970 to 1986 and followed up through December 31, 2016, was analyzed. Cases (n = 271) were defined as women with subsequent breast cancer. Controls (n = 1044) were matched 4:1 to cases by age at first cancer and duration of follow-up (± 2 years). Data analysis was conducted from September 2017 to July 2018., Exposures: Radiation dose to breast tumor site and ovaries and cumulative chemotherapy doses, including anthracyclines and alkylating agents., Main Outcomes and Measures: Odds ratios (ORs) for subsequent breast cancer by ER status., Results: A total of 271 women served as breast cancer cases (median age at first cancer diagnosis, 15 years [range, 3-20]; median age at breast cancer diagnosis, 39 years [range, 20-57]): 201 invasive (113 ER positive [ER+], 41 ER negative [ER-], and 47 unknown) and 70 in situ breast cancers. The OR for breast cancer increased with increasing radiation dose to the breast (OR per 10 Gy, 3.9; 95% CI, 2.5-6.5) and was similar for ER+ (OR per 10 Gy, 5.5; 95% CI, 2.8-12.6) and ER- (OR per 10 Gy, 4.8; 95% CI, 1.7-22.3) cancers. For women who received ovarian doses less than 1 Gy, the OR per 10 Gy to the breast was higher (OR, 6.8; 95% CI, 3.9-12.5) than for women who received ovarian doses greater than or equal to 15 Gy (OR, 1.4; 95% CI, 1.0-6.4). The OR for breast cancer increased with cumulative anthracycline dose (OR per 100 mg/m2, 1.23; 95% CI, 1.09-1.39; P < .01 for trend), and was 1.49 (95% CI, 1.21-1.83) for ER+ cancer vs 1.10 (95% CI, 0.84-1.45) for ER- cancers (P value for heterogeneity = .47). There was an additive interaction between radiotherapy and anthracycline treatment (P = .04) with the OR for the combined association between anthracycline therapy and breast radiation dose of 10 Gy or more (compared with 0 to less than 1 Gy) of 19.1 (95% CI, 7.6-48.0) vs 9.6 (95% CI, 4.4-20.7) without anthracycline use., Conclusions and Relevance: This study provides the first evidence to date that the combination of anthracyclines and radiotherapy may increase breast cancer risks compared with use of neither treatment with a similar radiation dose response for ER+ and ER- cancers and possibly higher anthracycline risks for ER+ cancers. These results might help inform surveillance guidelines for childhood cancer survivors.

While the patterns and trends of computed tomography (CT) are well documented in developed countries, relatively little is known about CT usage in developing countries, including Brazil. We evaluated CT usage among outpatients from the public healthcare system in Brazil (SUS), which is the unique healthcare provider to about 75% of the Brazilian population. We collected the annual number of CT procedures and type of CT examinations performed in SUS for the period 2001-2011. Age at examination was evaluated for 2008-2011. CT usage in Brazil has more than tripled during the study period, but the most striking annual increase (17.5%) was observed over the years 2008-2011. Head was the most frequently examined region for all age groups, but a decreasing trend of proportional contribution of head CT, with a simultaneous increase of abdomen/pelvis and chest CT over time was observed. CT examination for pediatric and young adult patients was about 13% of all CTs (9% if we considered age-standardized CT rates). CT usage has grown rapidly in Brazil and may still be increasing. Increased CT usage may certainly be associated with improved patient care. However, given the high frequency of pediatric and young adult CT procedures and the suggested associated cancer risk, efforts need to be undertaken to reduce unwarranted CT scans in Brazil.

Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

With therapeutic successes and improved survival after a cancer diagnosis in childhood, increasing numbers of cancer survivors are at risk of subsequent treatment-related morbidities, including cataracts. While it is well known that the lens of the eye is one of the most radiosensitive tissues in the human body, the risks associated with radiation doses less than 2 Gy are less understood, as are the long- and short-term cataract risks from exposure to ionizing radiation at a young age. In this study, we followed 13,902 five-year survivors of childhood cancer in the Childhood Cancer Survivor Study cohort an average of 21.4 years from the date of first cancer diagnosis. For patients receiving radiotherapy, lens dose (mean: 2.2 Gy; range: 0-66 Gy) was estimated based on radiotherapy records. We used unconditional multivariable logistic regression models to evaluate prevalence of self-reported cataract in relationship to cumulative radiation dose both at five years after the initial cancer diagnosis and at the end of follow-up. We modeled the radiation effect in terms of the excess odds ratio (EOR) per Gy. We also analyzed cataract incidence starting from five years after initial cancer diagnosis to the end of follow-up using Cox regression. A total of 483 (3.5%) cataract cases were identified, including 200 (1.4%) diagnosed during the first five years of follow-up. In a multivariable logistic regression model, cataract prevalence at the end of follow-up was positively associated with lens dose in a manner consistent with a linear dose-response relationship (EOR per Gy = 0.92; 95% CI: 0.65-1.20). The odds ratio for doses between 0.5 and 1.5 Gy was elevated significantly relative to doses <0.5 Gy (OR = 2.2; 95% CI: 1.3-3.7). The results from this study indicate a strong association between ocular exposure to ionizing radiation and long-term risk of pre-senile cataract. The risk of cataract increased with increasing exposure, beginning at lens doses as low as 0.5 Gy. Our findings are in agreement with a growing body of evidence of an elevated risk for lens opacities in populations exposed to doses of ionizing radiation below the previously suggested threshold level of 2 Gy.

Recently, the idea of generating radon map of Brazil has emerged. First attempts of coordinating radon surveys--carried out by different groups across the country--and initial discussions on how to proceed on a larger scale were made at the First Brazilian Radon Seminary, Natal, September 2012. Conventionally, it is believed that indoor radon is no major problem in Brazil, because the overall benign climate usually allows high ventilation rates. Nevertheless, scattered measurements have shown that moderately high indoor radon concentrations (up to a few hundred Bq m⁻³) do occur regionally. Brazilian geology is very diverse and there are regions where an elevated geogenic radon potential exists or is expected to exist. Therefore, a Brazilian Radon Survey is expected to be a challenge, although it appears an important issue, given the rising concern of the public about the quality of its environment., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Thyroid cancer incidence has risen steadily over the last few decades in most of the developed world, but information on incidence trends in developing countries is limited. Sao Paulo, Brazil, has one of the highest rates of thyroid cancer worldwide, higher than in the United States. We examined thyroid cancer incidence patterns using data from the Sao Paulo Cancer Registry (SPCR) in Brazil and the National Cancer Institute's Surveillance Epidemiology End Results (SEER) program in the United States., Methods: Data on thyroid cancer cases diagnosed during 1997-2008 were obtained from SPCR (n=15,892) and SEER (n=42,717). Age-adjusted and age-specific rates were calculated by sex and histology and temporal patterns were compared between the two populations., Results: Overall incidence rates increased over time in both populations and were higher in Sao Paulo than in the United States among females (SPCR/SEER incidence rate ratio [IRR]=1.65) and males (IRR=1.23). Papillary was the most common histology in both populations, followed by follicular and medullary carcinomas. Incidence rates by histology were consistently higher in Sao Paulo than in the United States, with the greatest differences for follicular (IRR=2.44) and medullary (IRR=3.29) carcinomas among females. The overall female/male IRR was higher in Sao Paulo (IRR=4.17) than in SEER (IRR=3.10) and did not change over time. Papillary rates rose over time more rapidly in Sao Paulo (annual percentage change=10.3% among females and 9.6% among males) than in the United States (6.9% and 5.7%, respectively). Regardless of sex, rates rose faster among younger people (<50 years) in Sao Paulo, but among older people (≥50 years) in the United States. The papillary to follicular carcinoma ratio rose from <3 to >8 among both Sao Paulo males and females, in contrast to increases from 9 to 12 and from 6 to 7 among U.S.males and females, respectively., Conclusions: Increased diagnostic activity may be contributing to the notable rise in incidence, mainly for papillary type, in both populations, but it is not likely to be the only reason. Differences in iodine nutrition status between Sao Paulo and the U.S. SEER population might have affected the observed incidence patterns.

Purpose: We developed three absolute risk models for second primary thyroid cancer to assist with long-term clinical monitoring of childhood cancer survivors., Patients and Methods: We used data from the Childhood Cancer Survivor Study (CCSS) and two nested case-control studies (Nordic CCSS; Late Effects Study Group). Model M1 included self-reported risk factors, model M2 added basic radiation and chemotherapy treatment information abstracted from medical records, and model M3 refined M2 by incorporating reconstructed radiation absorbed dose to the thyroid. All models were validated in an independent cohort of French childhood cancer survivors., Results: M1 included birth year, initial cancer type, age at diagnosis, sex, and past thyroid nodule diagnosis. M2 added radiation (yes/no), radiation to the neck (yes/no), and alkylating agent (yes/no). Past thyroid nodule was consistently the strongest risk factor (M1 relative risk [RR], 10.8; M2 RR, 6.8; M3 RR, 8.2). In the validation cohort, 20-year absolute risk predictions for second primary thyroid cancer ranged from 0.04% to 7.4% for M2. Expected events agreed well with observed events for each model, indicating good calibration. All models had good discriminatory ability (M1 area under the receiver operating characteristics curve [AUC], 0.71; 95% CI, 0.64 to 0.77; M2 AUC, 0.80; 95% CI, 0.73 to 0.86; M3 AUC, 0.75; 95% CI, 0.69 to 0.82)., Conclusion: We developed and validated three absolute risk models for second primary thyroid cancer. Model M2, with basic prior treatment information, could be useful for monitoring thyroid cancer risk in childhood cancer survivors.

Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors.

Risk projection methods allow for timely assessment of the potential magnitude of radiation-related cancer risks following low-dose radiation exposures. The estimation of such risks directly through observational studies would generally require infeasibly large studies and long-term follow-up to achieve reasonable statistical power. We developed an online radiation risk assessment tool (RadRAT) which can be used to estimate the lifetime risk of radiation-related cancer with uncertainty intervals following a user-specified exposure history (https://irep.nci.nih.gov/radrat). The uncertainty intervals constitute a key component of the program because of the various assumptions that are involved in such calculations. The risk models used in RadRAT are broadly based on those developed by the BEIR VII committee for estimating lifetime risk following low-dose radiation exposure of the US population for eleven site-specific cancers. We developed new risk models for seven additional cancer sites, oral, oesophagus, gallbladder, pancreas, rectum, kidney and brain/central nervous system (CNS) cancers, using data from Japanese atomic bomb survivors. The lifetime risk estimates are slightly higher for RadRAT than for BEIR VII across all exposure ages mostly because the weighting of the excess relative risk and excess absolute risk models was conducted on an arithmetic rather than a logarithmic scale. The calculator can be used to estimate lifetime cancer risk from both uniform and non-uniform doses that are acute or chronic. It is most appropriate for low-LET radiation doses < 1 Gy, and for individuals with life-expectancy and cancer rates similar to the general population in the US.

Background: Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy., Methods: The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose., Results: Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P(trend) = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy., Conclusions: Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing., Impact: Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.

Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose-response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8-31.5). At thyroid radiation doses >20 Gy, a downturn in the dose-response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P  =  0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.

The first Brazilian historical mortality cohort study on miners was conducted. The cohort consisted of 3224 workers in the underground coal mining industry in southern Brazil. This industry has been operating since 1942 without compliance with any regulatory standards, since there were no relevant national regulations. Over almost 60 years, about 5000 workers were exposed to high levels of radiation. However, later radiation exposure was significantly reduced, particularly that due to radon exposure. Recent radon concentration measurements indicated an average annual exposure to radon progeny of 2.1 WLM, ranging from 0.2 to 7.2 WLM. As radon exposure in the past was unknown, it can be suggested that mine workers have not been working safely as regards the health hazard related to radon and radon progeny exposure. The cohort inclusion criteria are as follows: (a) all male employees who had worked for at least one year at the coal mine; (b) workers with complete workplace information (underground and surface); (c) employment hiring between 1945 and 1997 and (d) the worker must have been alive on 1 January 1979. Through multiple strategies of search it was possible to follow up the members of the cohort with a success rate of 92%. This paper presents the characteristics of the study population and provides information about the feasibility of conducting a retrospective mortality study in Brazil, taking into account the methodological and logistical difficulties of conducting such a study in a developing country.

An epidemiological investigation was launched in several cities in southern Minas Gerais State, Brazil, considering the possibility of increased cancer incidence due to high exposure to natural radiation. First, the cancer mortality patterns were assessed to determine whether there was an increase in cancer deaths and to discuss the possible risk factors related to such an increase. The study proposed the use of a screening methodology based on standardized mortality ratio (SMR) in order to classify priority areas for future studies. Cities considered high priority for further investigation were: Andradas, for lung cancer in men (SMR = 208 (106-310)) and liver cancer in women (SMR = 403 (104-701)); Poços de Caldas, leukemia in men and women (SMR = 284 (156-412)) and SMR = 211 (111-312), respectively); Pouso Alegre, leukemia in men (SMR = 333 (127-540)) and hematological cancers in women (SMR = 257 (188-396)). Epidemiological studies are necessary to evaluate the role of radiation and other risk factors in these cancers and thus to support future preventive and control measures.

Recently a high radon concentration was detected in the underground coal mine of Figueira, located in the south of Brazil. This coal mine has been operating since 1942 without taking cognizance of the high radon environment. In order to assess possible radon-related health effects on the workers, a retrospective (1979-2002) mortality study of 2,856 Brazilian coal miners was conducted, with 2,024 underground workers potentially exposed to radon daughters. Standard mortality ratio (SMR) analysis hints at lower mortality from all causes for both underground (SMR = 88, 95% CI = 78-98) and surface workers (SMR = 96, 95% CI = 80-114). A high statistically significant SMR for lung cancer mortality was observed only in the underground miners (SMR = 173, 95% CI = 102-292), with a statistically significant trend reflecting the duration of underground work. High statistically significant SMRs were observed for pneumonia as a cause of death between both surface (SMR = 304, 95% CI = 126-730) and underground miners (SMR = 253, 95% CI = 140-457). Because mortality from smoking-related cancers other than lung cancer was not found elevated in underground workers and because diesel equipments were not used in this mine, it can be concluded that the enhanced lung cancer mortality observed for underground miners is associated with exposure to radon and radon daughters, rather than other confounding risk factors.

The main source of radiation exposure in most underground mining operations is radon and radon decay products. The situation of radon exposure in underground mining in Brazil is still unknown, since there has been no national regulation regarding this exposure. A preliminary radiological survey in nonuranium mines in Brazil indicated that an underground coal mine in the south of Brazil had high radon concentration and needed to be better evaluated. This paper intends to present an assessment of radon and radon decay product exposure in the underground environment of this coal mining industry and to estimate the annual exposure to the workers. As a product of this assessment, it was found that average radon concentrations at all sampling campaign and excavation sites were above the action level range for workplaces of 500-1500 Bq m(-3) recommended by the International Commission on Radiological Protection--ICRP 65. The average effective dose estimated for the workers was almost 30 times higher than the world average dose for coal miners.

This paper aims to present an assessment of the environmental radiological exposure at a Brazilian area of high natural radiation and discusses the indoor radon exposure risk. A survey of inhabitant exposures arising from the inhalation of radon progeny and external gamma exposure was conducted in urban and rural areas of the Poços de Caldas Plateau, which is recognized worldwide as a high natural radiation region. The results of this survey indicated that highest radiation exposure was restricted to the rural area of Poços de Caldas. The radiation exposure in urban locations was quite similar to the values observed in normal background areas in some Brazilian counties. By the application of a constant relative risk model, an additional 20% in the lifetime risk of lung cancer mortality due to the exposure to radon progeny was estimated at Poços de Caldas. It was also estimated that 16% of all lung cancer deaths at Poços de Caldas county could be attributable to radon exposure.

The Jacarepaguá lagoon receives the waste from 239 industries and domestic sewage. Bottom sediment analysis revealed that metal pollution is not spread over the lagoons but restricted to the discharge areas of the main metal-carrier rivers. Metal concentrations in superficial water showed the following concentrations values in ng/ml: Zn, 9.63+/-3.59; Pb, 0.61+/-0.43; Cu, 0.94+/-0.45; Mn, 12.7+/-8.0. Metal concentration in fish (average of seven different species) presented the following results, in mg/kg wet weight: Cr, 0.08+/-0.01; Cu, 0.4+/-0.15; Zn, 4.6+/-3.4; Fe, 2.4+/-1.3; Mn, 0.4+/-0.3. These results imply, considering fish consumption rate and the RfD (USEPA Reference Dose), that the local population is not exposed to undue health risks. Metal concentrations in the water may, however, increase due to their dissolution induced by pH and redox changes in the sediments.