Risk of second primary thyroid cancer after radiotherapy for a childhood cancer in a large cohort study: an update from the childhood cancer survivor study

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.     

Native American Exposure to 131Iodine from Nuclear Weapons Testing in Nevada

A great deal of work has been done to reconstruct doses from Nevada Test Site fallout, yet the unique exposures of Native American communities continue to be neglected. It is possible to estimate the exposures of these communities through a process of collaborative information gathering and analysis. This article builds on a previous exercise that demonstrated the substantial doses received through the consumption of contaminated game. The updated model includes new information on the deposition of ¹³¹iodine, an assessment of the neonatal thyroid doses received through breast milk, an exploration of the effect of population mobility on dose estimates, and estimates of thyroid cancer risk. All thyroid dose estimates from the rabbit exposure pathway are comparable in magnitude to National Cancer Institute comprehensive dose estimates that assume exposure to contaminated milk from backyard cows and goats. Dose estimates from the rabbit exposure pathway are larger than estimated doses from store-bought milk by an average factor of six. Taking historical population mobility patterns into account may result in slightly lower estimates of dose. The quantification of this exposure pathway is considered be an advance toward a more appropriate dose reconstruction for communities with diets high in wild game.     

Cancer mortality risk among workers at the Mayak nuclear complex

At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P < 0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P < 0.001) and 0.08 per gray (P < 0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.     

Shared uncertainty in measurement error problems, with application to Nevada Test Site fallout data

In radiation epidemiology, it is often necessary to use mathematical models in the absence of direct measurements of individual doses. When complex models are used as surrogates for direct measurements to estimate individual doses that occurred almost 50 years ago, dose estimates will be associated with considerable error, this error being a mixture of (a) classical measurement error due to individual data such as diet histories and (b) Berkson measurement error associated with various aspects of the dosimetry system. In the Nevada Test Site(NTS) Thyroid Disease Study, the Berkson measurement errors are correlated within strata. This article concerns the development of statistical methods for inference about risk of radiation dose on thyroid disease, methods that account for the complex error structure inherence in the problem. Bayesian methods using Markov chain Monte Carlo and Monte-Carlo expectation-maximization methods are described, with both sharing a key Metropolis-Hastings step. Regression calibration is also considered, but we show that regression calibration does not use the correlation structure of the Berkson errors. Our methods are applied to the NTS Study, where we find a strong dose-response relationship between dose and thyroiditis. We conclude that full consideration of mixtures of Berkson and classical uncertainties in reconstructed individual doses are important for quantifying the dose response and its credibility/confidence interval. Using regression calibration and expectation values for individual doses can lead to a substantial underestimation of the excess relative risk per gray and its 95% confidence intervals.     

Investigation on circular asymmetry of geographical distribution in cancer mortality of Hiroshima atomic bomb survivors based on risk maps: analysis of spatial survival data

While there is a considerable number of studies on the relationship between the risk of disease or death and direct exposure from the atomic bomb in Hiroshima, the risk for indirect exposure caused by residual radioactivity has not yet been fully evaluated. One of the reasons is that risk assessments have utilized estimated radiation doses, but that it is difficult to estimate indirect exposure. To evaluate risks for other causes, including indirect radiation exposure, as well as direct exposure, a statistical method is described here that evaluates risk with respect to individual location at the time of atomic bomb exposure instead of radiation dose. In addition, it is also considered to split the risks into separate risks due to direct exposure and other causes using radiation dose. The proposed method is applied to a cohort study of Hiroshima atomic bomb survivors. The resultant contour map suggests that the region west to the hypocenter has a higher risk compared to other areas. This in turn suggests that there exists an impact on risk that cannot be explained by direct exposure.     

Influence of the distribution of the dose on carcinogenic effects of ionizing radiations of low lineal energy transfer on the thyroid tissue]

The frequency of thyroid nodules has been studied among 396 children irradiated for a hemangioma, from 1946 to 1973. 226Ra, 192Ir, 90Y, 32P, 90Sr, as well as X-rays had been used for treatments. The doses of radiation received by the thyroid of each child have been estimated retrospectively. The irradiations have been classified in two categories based on their duration: less than 30 min., and more than 30 min. The doses received with each of these two types of irradiation were summed for each patient. The risk of thyroid nodule increased as a function of the dose to thyroid only for the dose delivered with the short duration. This study emphases the importance of the role of the dose rate in the risk of radio-induced tumour.     

Comparison of EPR occupational lifetime external dose assessments for Mayak nuclear workers and film badge dose data

The Mayak worker cohort is one of the major sources of information on health risks due to protracted exposures to plutonium and external ionizing radiation. Electron paramagnetic resonance (EPR) measurements in tooth enamel in combination with personal dose monitoring can help to improve external dose assessment for this cohort. Here, the occupational lifetime external exposure was evaluated individually for 44 nuclear workers of three plants of the Mayak Production Association by EPR measurements of absorbed doses in collected tooth enamel samples. Analysis included consideration of individual background doses in enamel and dose conversion coefficients specific for photon spectra at selected work areas. As a control, background doses were assessed for various age groups by EPR measurements on teeth from non-occupationally exposed Ozyorsk residents. Differences in occupational lifetime doses estimated from the film badges and from enamel for the Mayak workers were found to depend on the type of film badge and the selected plant. For those who worked at the radiochemical processing plant and who were monitored with IFK film badges, the dose was on average 570 mGy larger than estimated from the EPR measurements. However, the average difference was found to be only −4 and 6 mGy for those who were monitored with IFKU film badges and worked at the reactor and the isotope production plant respectively. The discrepancies observed in the dose estimates are attributed to a bias in film badge evaluation.N. El-Faramawy: On leave from Department of Physics, Faculty of Science, Ain Shams University, 65511 Abbassia, Cairo, Egypt.     

Post-Chornobyl thyroid cancers in Ukraine. Report 1: estimation of thyroid doses

About 1.8 EBq of 131I was released into the atmosphere during the Chornobyl accident that occurred in Ukraine on April 26, 1986. More than 10% of this activity was deposited on the territory of Ukraine. Beginning 4-5 years after the accident, an increase in the incidence of thyroid cancer among children, believed to be caused in part by exposure to 131I, has been observed in different regions of Ukraine. A three-level system of thyroid dose estimation was developed for the reconstruction of thyroid doses from 131I for the entire population of Ukrainian children aged 1 to 18 at the time of accident: (1) At the first level, individual doses were estimated for the approximately 99,000 children and adolescents with direct measurements of radioactivity in the thyroid (so-called direct thyroid measurements) performed in May-June of 1986; (2) at the second level, group doses by year of age and by gender were estimated for the population of 748 localities (with 208,400 children aged 1-18 in 1986) where direct thyroid measurements of good quality were performed on some of the residents; and (3) at the third level, group doses by age and by gender were estimated for the population of the localities where no thyroid measurements were made in 1986. The third-level doses were then aggregated over the population of each oblast. Data, models and procedures required for each level of thyroid dose estimation are described in the paper. At the first level, individual doses were found to range up to 27,000 mGy, with geometric and arithmetic means of 100 and 300 mGy, respectively. At the second level, group doses were found to be highest for the younger children (aged 1 to 4 years); doses for the older children (aged 16 to 18 years) were 3.5 times smaller. At the third level, average population-weighted doses were found to exceed 35 mGy in the five northern oblasts closer to the Chornobyl reactor site; to be in the 14- to 34-mGy range in seven other oblasts, Kyiv city and Crimea; and to be less than 13 mGy in all other oblasts.     

Thyroid doses in Ukraine due to 131I intake after the Chornobyl accident. Report II: dose estimates for the Ukrainian population

This paper describes the revision of the thyroid dosimetry system in Ukraine using new, recently available data on (i) revised ¹³¹I thyroid activities derived from direct thyroid measurements done in May and June 1986 in 146,425 individuals; (ii) revised estimates of ¹³¹I ground deposition density in each Ukrainian settlement; and (iii) estimates of age- and gender-specific thyroid masses for the Ukrainian population. The revised dosimetry system estimates the thyroid doses for the residents of the settlements divided into three levels depending on the availability of measurements of ¹³¹I thyroid activity among their residents. Thyroid doses due to ¹³¹I intake were estimated in this study for different age and gender groups of residents of 30,353 settlements in 24 oblasts of Ukraine, Autonomous Republic Krym, and cities of Kyiv and Sevastopol. Among them, dose estimates for 835 settlements were based on ¹³¹I thyroid activities measured in more than ten residents (the first level), for 690 settlements based on such measurements done in neighboring settlements (the second level), and for 28,828 settlements based on a purely empirical relationship between the thyroid doses due to ¹³¹I intake and the cumulative ¹³¹I ground deposition densities in settlements (the third level). The arithmetic mean of the thyroid doses due to ¹³¹I intake among 146,425 measured individuals was 0.23 Gy (median of 0.094 Gy); about 99.8% of them received doses less than 5 Gy. The highest oblast-average population-weighted thyroid doses were estimated for residents of Chernihiv (0.15 Gy for arithmetic mean and 0.060 Gy for geometric mean), Kyiv (0.13 and 0.051 Gy) and Zhytomyr (0.12 and 0.049 Gy) Oblasts followed by Rivne (0.10 and 0.039 Gy) and Cherkasy (0.088 and 0.032 Gy) Oblasts, and Kyiv City (0.076 and 0.031 Gy). The geometric mean of thyroid doses estimated in this study for the entire Ukraine essentially did not change in comparison with a previous estimate, 0.020 vs. 0.021 Gy, respectively. The ratio of geometric mean of oblast-specific thyroid doses estimated in the present study to previously calculated doses varied from 0.51 to 3.9. The highest increase in thyroid doses was found in areas remote from the Chornobyl nuclear power plant with a low level of radioactive contamination: by 3.9 times for Zakarpatska Oblast, 3.5 times for Luhansk Oblasts and 2.9 times for Ivano-Frankivsk Oblast. The developed thyroid dosimetry system is being used to revise the thyroid doses due to ¹³¹I intake for the individuals of post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort, and the Chornobyl Tissue Bank.

     

Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950-1997

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.     

Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.     

Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the chernobyl accident

The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131) doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T) and normal (N) tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N) on 64 whole genome microarrays (Agilent, 4×44 K). Associations of differential gene expression (log(2)(T/N)) with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N). The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493) were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.     

Solid cancer incidence in atomic bomb survivors: 1958-1998

This is the second general report on radiation effects on the incidence of solid cancers (cancers other than malignancies of the blood or blood-forming organs) among members of the Life Span Study (LSS) cohort of Hiroshima and Nagasaki atomic bomb survivors. The analyses were based on 17,448 first primary cancers (including non-melanoma skin cancer) diagnosed from 1958 through 1998 among 105,427 cohort members with individual dose estimates who were alive and not known to have had cancer prior to 1958. Radiation-associated relative risks and excess rates were considered for all solid cancers as a group, for 19 specific cancer sites or groups of sites, and for five histology groups. Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, how these risks vary with gender, age at exposure, and attained age, and the evidence for inter-site variation in the levels and patterns of the excess risk. For all solid cancers as a group, it was estimated that about 850 (about 11%) of the cases among cohort members with colon doses in excess of 0.005 Gy were associated with atomic bomb radiation exposure. The data were consistent with a linear dose response over the 0- to 2-Gy range, while there was some flattening of the dose response at higher doses. Furthermore, there is a statistically significant dose response when analyses were limited to cohort members with doses of 0.15 Gy or less. The excess risks for all solid cancers as a group and many individual sites exhibit significant variation with gender, attained age, and age at exposure. It was estimated that, at age 70 after exposure at age 30, solid cancer rates increase by about 35% per Gy (90% CI 28%; 43%) for men and 58% per Gy (43%; 69%) for women. For all solid cancers as a group, the excess relative risk (ERR per Gy) decreases by about 17% per decade increase in age at exposure (90% CI 7%; 25%) after allowing for attained-age effects, while the ERR decreased in proportion to attained age to the power 1.65 (90% CI 2.1; 1.2) after allowing for age at exposure. Despite the decline in the ERR with attained age, excess absolute rates appeared to increase throughout the study period, providing further evidence that radiation-associated increases in cancer rates persist throughout life regardless of age at exposure. For all solid cancers as a group, women had somewhat higher excess absolute rates than men (F:M ratio 1.4; 90% CI 1.1; 1.8), but this difference disappears when the analysis was restricted to non-gender-specific cancers. Significant radiation-associated increases in risk were seen for most sites, including oral cavity, esophagus, stomach, colon, liver, lung, non-melanoma skin, breast, ovary, bladder, nervous system and thyroid. Although there was no indication of a statistically significant dose response for cancers of the pancreas, prostate and kidney, the excess relative risks for these sites were also consistent with that for all solid cancers as a group. Dose-response estimates for cancers of the rectum, gallbladder and uterus were not statistically significant, and there were suggestions that the risks for these sites may be lower than those for all solid cancers combined. However, there was emerging evidence from the present data that exposure as a child may increase risks of cancer of the body of the uterus. Elevated risks were seen for all of the five broadly classified histological groups considered, including squamous cell carcinoma, adenocarcinoma, other epithelial cancers, sarcomas and other non-epithelial cancers. Although the data were limited, there was a significant radiation-associated increase in the risk of cancer occurring in adolescence and young adulthood. In view of the persisting increase in solid cancer risks, the LSS should continue to provide important new information on radiation exposure and solid cancer risks for at least another 15 to 20 years.     

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: objectives, design and methods

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose-response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.     

Thyroid dose and thyroid cancer incidence after the Chernobyl accident: assessments for the Zhytomyr region (Ukraine)

In the Zhytomyr region, about 52 000 measurements of the ¹³¹I activity in thyroids were performed. On the basis of these measurements, individual doses have been assessed for the people monitored and age-dependent average doses have been estimated for those settlements with more than 11 direct measurements. In order to estimate the pattern of thyroid exposure in the Zhytomyr region, these doses have been interpolated or extrapolated to population groups who were not monitored during May–June 1986. For this purpose, a model has been developed based on a correlation between thyroid dose estimates with the ¹³⁷Cs deposition and the co-ordinates of the settlements relative to Chernobyl. Collective doses of people who were born in the years 1968 to 1986 were calculated. The radiation-induced thyroid cancer incidence in the period 1991 to 1995 was assessed by subtracting the spontaneous incidence from the observed incidence. The result is considerably lower than that observed in longer periods after external exposures. Possible reasons for this difference are discussed. Received: 17 January 1997 / Accepted in revised form: 2 October 1997     

Ultrasound-detected thyroid nodule prevalence and radiation dose from fallout

Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949-1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0-0.65) and 0.31 Gy (0-9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09-3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose-response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings.     

Iodine metabolism and pathologic processes in the thyroid gland under radioiodine lesions in the regions of goitrous endemia

An existing discrepancy between the prognostic estimations and real thyroid gland sickness rate due to radiation exposure from Chernobyl is an evidence of inaccuracy of radiation doses determination. The estimation of the thyroid cancer risks is based on the assumption that the absorbed dose is uniformly distributed in the organ. But functional asynchronicity specific for iodine metabolism in thyroid may modify a space distribution of the dose. The biochemical features of the contaminated areas including iodine deficit and goitrous endemia usually are not taken into account may influence the second phase of thyroid carcinogenesis that is the promotion due to increased accumulation of some carcinogenic microelements in goitrous thyroid. In the work we consider these problems which can make significant changes in radiation risks estimation.     

Peripheral organ doses from radiotherapy for heterotopic ossification of non-hip joints: Is there a risk for radiation-induced malignancies?

Radiotherapy, used for heterotopic ossification (HO) management, may increase radiation risk to patients. This study aimed to determine the peripheral dose to radiosensitive organs and the associated cancer risks due to radiotherapy of HO in common non-hip joints. A Monte Carlo model of a medical linear accelerator combined with a mathematical phantom representing an average adult patient were employed to simulate radiotherapy for HO with standard AP and PA fields in the regions of shoulder, elbow and knee. Radiation dose to all out-of-field radiosensitive organs defined by the International Commission on Radiological Protection was calculated. Cancer induction risk was estimated using organ-specific risk coefficients. Organ dose change with increased field dimensions was also evaluated. Radiation therapy for HO with a 7 Gy target dose in the sites of shoulder, elbow and knee, resulted in the following equivalent organ dose ranges of 0.85–62 mSv, 0.28–1.6 mSv and 0.04–1.6 mSv, respectively. Respective ranges for cancer risk were 0–5.1, 0–0.6 and 0–1.3 cases per 10⁴ persons. Increasing the field size caused an average increase of peripheral doses by 15–20%. Individual organ dose increase depends upon the primary treatment site and the distance between organ of interest and treatment volume. Relatively increased risks of more than 1 case per 10,000 patients were found for skin, breast and thyroid malignancies after treatment in the region of shoulder and for skin cancer following elbow irradiation. The estimated risk for inducing any other malignant disease ranges from negligible to low.