Survival adjusted cancer risks attributable to radiation exposure from cardiac catheterisations in children.

OBJECTIVES: To estimate the risk of developing cancer in relation to the typical radiation doses received from a range of X-ray guided cardiac catheterisations in children, taking variable survival into account. METHODS: Radiation doses were estimated for 2749 procedures undertaken at five UK hospitals using Monte Carlo simulations. The lifetime attributable risk (LAR) of cancer incidence was estimated using models developed by the Biological Effects of Ionising Radiation committee, based on both normal life expectancy, and as a function of attained age, from 20 to 80 years, to take reduced life expectancy into account. RESULTS: The radiation-related risks from these procedures are dominated by lung and breast cancer (for females). Assuming normal life expectancy, central LAR estimates for cancer incidence, based on median doses, ranged from <1 in 2000 for atrial septal defect occlusions to as high as 1 in 150 for valve replacements. For a reduced life expectancy of 50 years, estimated risks are lower by a factor of around 7. For conditions with especially poor survival (age 20 years), such as hypoplastic left heart syndrome, estimated cancer risks attributable to radiation were <1 in 20 000. CONCLUSIONS: Based on recent UK radiation dose levels, the risk of cancer following cardiac catheterisations is relatively low and strongly modified by survival and the type of procedure. The risk of breast cancer, especially following pulmonary artery angioplasty and valve replacements, is the greatest concern.

Radiological Risk Assessment by Convergence Methodology Model in RDD Scenarios.

A radiological dispersal device (RDD) is a simple weapon capable of causing human harm, environmental contamination, disruption, area denial, and economic cost. It can affect small, large, or long areas depending on atmospheric stability. The risk of developing a radio-induced cancer depends on exposure, and an effective response depends upon available timely guidance. This article proposes and demonstrates a convergence of three different capabilities to assess risk and support rapid safe resource efficient response. The three capabilities that are integrated are Hotspot for dispersion, RERF for epidemiological risk, and RESRAD-RDD for response guidance. The combined methodology supports decisions on risk reduction and resource allocation through work schedules, the designation and composition of response teams, and siting for operations. In the illustrative RDD scenario, the contamination area for sheltering, evacuation, and long-term public concern was greatest for calm atmospheric conditions, whilst close-quarter responders faced highest dose rates for neutral atmospheric conditions. Generally, the risks to women responders were found to be significantly greater than for men, and the risks to 20-year-old responders were three times that of their 60-year-old counterparts for similar exposure.

Impact of uncertainties in exposure assessment on estimates of thyroid cancer risk among Ukrainian children and adolescents exposed from the Chernobyl accident.

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy(-1) (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy(-1) (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy(-1) (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p = 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment.

Assessment of organ dose reduction and secondary cancer risk associated with the use of proton beam therapy and intensity modulated radiation therapy in treatment of neuroblastomas.

BACKGROUND: To compare proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT) with conformal radiation therapy (CRT) in terms of their organ doses and ability to cause secondary cancer in normal organs. METHODS: Five patients (median age, 4 years; range, 2-11 years) who underwent PBT for retroperitoneal neuroblastoma were selected for treatment planning simulation. Four patients had stage 4 tumors and one had stage 2A tumor, according to the International Neuroblastoma Staging System. Two patients received 36 Gy, two received 21.6 Gy, and one received 41.4 Gy of radiation. The volume structures of these patients were used for simulations of CRT and IMRT treatment. Dose-volume analyses of liver, stomach, colon, small intestine, pancreas, and bone were performed for the simulations. Secondary cancer risks in these organs were calculated using the organ equivalent dose (OED) model, which took into account the rates of cell killing, repopulation, and the neutron dose from the treatment machine. RESULTS: In all evaluated organs, the mean dose in PBT was 20-80% of that in CRT. IMRT also showed lower mean doses than CRT for two organs (20% and 65%), but higher mean doses for the other four organs (110-120%). The risk of secondary cancer in PBT was 24-83% of that in CRT for five organs, but 121% of that in CRT for pancreas. The risk of secondary cancer in IMRT was equal to or higher than CRT for four organs (range 100-124%). CONCLUSION: Low radiation doses in normal organs are more frequently observed in PBT than in IMRT. Assessments of secondary cancer risk showed that PBT reduces the risk of secondary cancer in most organs, whereas IMRT is associated with a higher risk than CRT.

Imaging doses and secondary cancer risk from kilovoltage cone-beam CT in radiation therapy.

The authors assessed the radiation-induced cancer risk due to organ doses from kilovoltage (kV) cone beam computed tomography (CBCT), a verification technique in image-guided radiotherapy (IGRT). CBCTs were performed for three different treatment sites: the head and neck, chest, and pelvis. Using a glass dosimeter, primary doses versus depth were measured inside a homemade phantom, and organ doses were measured at various locations inside an anthropomorphic phantom. The excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) for cancer induction were estimated using the BEIR VII models based on dose measurement. The average primary (i.e., in-field) doses at the center of the phantom for standard imaging options were 1.9, 5.1, and 16.7 cGy for the head and neck, chest, and pelvis, respectively. The average secondary dose per scan for the pelvis measured 20-50 cm from the isocenter and ranged from 0.67-0.02 cGy, whereas the secondary dose per scan for the head and neck ranged from 0.07-0.003 cGy, indicating that CBCT for treatment of the head and neck is associated with a smaller secondary radiation dose than CBCT for treatment of the pelvis. The estimation of LAR from CBCT in IGRT indicated that the lifetime cancer risk for major organs can reach approximately 400 per 10,000 persons if 30 CBCT scans are performed to position a patient during radiation treatment of the pelvis site.

Radiation-related cancer risk associated with surveillance imaging for metastasis from choroidal melanoma.

OBJECTIVE: To estimate the lifetime attributable risk of cancer associated with whole-body positron emission tomography (PET)/computed tomography (CT) and with CT of the chest, abdomen, and pelvis if performed at various frequencies and for different durations for surveillance of patients with primary choroidal or ciliary body melanoma for distant metastasis. METHODS: Effective radiation doses for whole-body CT and for CT of the chest, abdomen, and pelvis were calculated using Monte Carlo simulation studies. The effective dose of the PET scan was estimated by multiplying fludeoxyglucose F18 radioactivity with dose coefficients. Lifetime attributable risks of cancer were calculated using the approach described in the Biological Effects of Ionizing Radiation VII report. RESULTS: For a 50-year-old patient, an annual CT of the chest, abdomen, and pelvis for 10 years carries an estimated lifetime attributable risk of cancer of 0.9% for male patients and 1.3% for female patients, whereas an annual PET/CT each year for 10 years carries an estimated lifetime attributable risk of cancer of 1.6% for male patients and 1.9% for female patients. Lifetime risk was found to be higher in younger, female patients. The lifetime attributable risk of cancer was estimated to be as high as 7.9% for a 20-year-old female patient receiving a PET/CT scan every 6 months for 10 years. CONCLUSIONS: Aggressive surveillance protocols incorporating CT scanning or PET/CT scanning for detection of metastasis from primary choroidal or ciliary body melanoma appear to confer a significant substantial risk of a secondary malignant tumor in patients who do not succumb to metastatic melanoma within the first few posttreatment years.

Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient.

Pediatric patients who received radiation therapy are at risk of developing side effects such as radiogenic second cancer. We compared proton and photon therapies in terms of the predicted risk of second cancers for a 4 year old medulloblastoma patient receiving craniospinal irradiation (CSI). Two CSI treatment plans with 23.4 Gy or Gy (RBE) prescribed dose were computed: a three-field 6 MV photon therapy plan and a four-field proton therapy plan. The primary doses for both plans were determined using a commercial treatment planning system. Stray radiation doses for proton therapy were determined from Monte Carlo simulations, and stray radiation doses for photon therapy were determined from measured data. Dose-risk models based on the Biological Effects of Ionization Radiation VII report were used to estimate the risk of second cancer in eight tissues/organs. Baseline predictions of the relative risk for each organ were always less for proton CSI than for photon CSI at all attained ages. The total lifetime attributable risk of the incidence of second cancer considered after proton CSI was much lower than that after photon CSI, and the ratio of lifetime risk was 0.18. Uncertainty analysis revealed that the qualitative findings of this study were insensitive to any plausible changes of dose-risk models and mean radiation weighting factor for neutrons. Proton therapy confers lower predicted risk of second cancer than photon therapy for the pediatric medulloblastoma patient.

Role of low-cost thyroid follow-up in children treated with radiotherapy for primary tumors at high risk of developing a second thyroid tumor.

AIM: Differentiated thyroid cancer (DTC) is uncommon in childhood and data on its prevalence as a second malignant neoplasm (SNM) after radiotherapy (RT) for malignancies are limited. We evaluated: 1) the incidence DTC in pediatric-oncologic patients treated with RT; 2) the relationship between DTC, RT and the features of the first malignancy; 3) the usefulness of thyroid follow-up in irradiated oncological patients. METHODS: We have followed up 252 patients treated with RT out of 966 oncologic pediatric patients. Thyroid follow-up included TSH level evaluation and neck ultrasonography. In the presence of thyroid nodule/s ≥1 cm and/or with ultrasonography suspicious for malignancy, fine needle aspiration biopsy (FNAB) was performed. When papillary/follicular lesions were detected by cytology, thyroidectomy was performed. If DTC was confirmed, patients underwent radioactive iodine (RAI) treatment. RESULTS: At least one thyroid nodule was detected in 106 irradiated patients (42%): 45 patients underwent FNAB and 27 underwent thyroidectomy. Seventeen DTC (6.7%) were found on histology. A higher incidence of DTC was seen in patients with neuroblastoma (38%) or Wilms' tumor (18%). One third of DTC showed capsule invasion, and one fourth node involvement. Eleven patients, treated with a single RAI treatment, showed undetectable thyroglobulin levels after rh-TSH-stimulation. Five patients underwent at least two RAI treatments: four patients showed complete remission and one patient partial remission. CONCLUSION: A high rate of DTC, often with invasive features, was observed in children treated with RT for primary tumors. This finding underlines the usefulness of thorough low-cost thyroid follow-up in this high-risk population.

[Role of French hospital claims databases from care units in epidemiological studies: the example of the "Cohorte Enfant Scanner" study]. / Utilisation des données du programme de médicalisation des systèmes d'information (PMSI) dans les études épidémiologiques : application à la Cohorte Enfant Scanner.

BACKGROUND: The "Cohorte Enfant Scanner", a study designed to investigate the risk of radiation-induced cancer after childhood exposure to CT (computed tomography) examinations, used clinical information contained in the "programme de médicalisation des systèmes d'information" (PMSI) database, the French hospital activities national program based upon diagnosis related groups (DRG). However, the quality and adequacy of the data for the specific needs of the study should be verified. The aim of our work was to estimate the percentage of the cohort's children identified in the PMSI database and to develop an algorithm to individualize the children with a cancer or a disease at risk of cancer from medical diagnoses provided by the DRGs database. METHODS: Of the 1519 children from the "Cohorte Enfant Scanner", who had had a CT scan in the radiology department of a university hospital in 2002, a cross linkage was performed with the DRGs database. All hospitalizations over the period 2002-2009 were taken into account. An algorithm was constructed for the items "cancer" and "disease at risk for cancer" on a sample of 150 children. The algorithm was then tested on the entire population. RESULTS: Overall, 74% of our population was identified in the DRGs database. The algorithm individualized cancer diagnoses with 91% sensitivity (95% confidence interval [95%CI]: 86%; 97%) and 98% specificity (95%CI: 97%; 99%) and 86% positive predictive value (95%CI: 80%; 93%). For the diagnosis of disease at risk for cancer, the sensitivity, specificity and positive predictive value were respectively 91% (95%CI: 84%; 98%), 94% (95%CI: 92%; 95%) and 52% (95%CI: 43%; 61%). CONCLUSION: The DRG database identified with excellent sensitivity and specificity children with diagnoses of cancer or disease at risk for cancer. Hence, potential confounding factors related to the disease of the child can be taken into account for analyses performed with the cohort.

Effectiveness of skin cancer screening for individuals age 14 to 34 years.

BACKGROUND: Approximately 15 % of all cases of melanoma are diagnosed before age 35 years. In Germany, individuals ≥ 35 years are eligible for the national skin cancer screening program. The effectiveness of a population-based skin cancer screening in general and in particular for young adults is unclear. OBJECTIVES: Assessment of the effectiveness of a skin cancer screening program and of risk factors for detection of a melanoma/atypical nevus in the setting of a screening for the age group 14 to 34 years. METHODS: A total of 12,187 individuals age 14 to 34 years were screened in Saxony for skin cancer by a dermatologist in the program "Haut-Check 14-34 Jahre" of the AOK PLUS, a large German health insurance, between January and July 2009. Demographic, clinical and histopathological data and UV-exposure data were collected from each participant. Multivariate logistic regression models were used to assess risk factors for the detection of a (histopathologically confirmed) melanoma or atypical nevus. RESULTS: 2.8 % of the eligible individuals participated in the skin cancer screening program with women being more likely to do so. In 1 072 individuals (8.8 %) screening included at least one excision of a skin lesion leading to the diagnosis of melanoma in two participants, melanoma in situ in four persons, and atypical nevus in 641 persons. Use of tanning beds, higher age, number of nevi, and previous cutaneous excision were independent risk factors for the detection of a melanoma or atypical nevus. CONCLUSIONS: In 5.5 % of all cases skin cancer screening resulted in the excision of a malignant or atypical melanocytic lesion. It remains unclear what proportion of these cases would have been detected in routine care. The rate of excisions per newly diagnosed melanoma was 179 : 1. Further investigations are necessary to explore the reasons for this low diagnostic specificity. This study highlights the possibilities and limitations of routine data to evaluate screening programs and indicates the need to collect additional information on healthcare utilization behaviour.

New models for evaluation of radiation-induced lifetime cancer risk and its uncertainty employed in the UNSCEAR 2006 report.

Generalized relative and absolute risk models are fitted to the latest Japanese atomic bomb survivor solid cancer and leukemia mortality data (through 2000), with the latest (DS02) dosimetry, by classical (regression calibration) and Bayesian techniques, taking account of errors in dose estimates and other uncertainties. Linear-quadratic and linear-quadratic-exponential models are fitted and used to assess risks for contemporary populations of China, Japan, Puerto Rico, the U.S. and the UK. Many of these models are the same as or very similar to models used in the UNSCEAR 2006 report. For a test dose of 0.1 Sv, the solid cancer mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 5.4% Sv(-1) [90% Bayesian credible interval (BCI) 3.1, 8.0]. At 0.1 Sv, leukemia mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 0.50% Sv(-1) (90% BCI 0.11, 0.97). Risk estimates varied little between populations; at 0.1 Sv the central estimates ranged from 3.7 to 5.4% Sv(-1) for solid cancers and from 0.4 to 0.6% Sv(-1) for leukemia. Analyses using regression calibration techniques yield central estimates of risk very similar to those for the Bayesian approach. The central estimates of population risk were similar for the generalized absolute risk model and the relative risk model. Linear-quadratic-exponential models predict lower risks (at least at low test doses) and appear to fit as well, although for other (theoretical) reasons we favor the simpler linear-quadratic models.

Assessment of induction of secondary tumours due to various radiotherapy modalities.

One of the objectives of the European Sixth Framework integrated project MAESTRO is to perform an assessment of risk due to various radiotherapy modalities, regarding secondary tumour induction. Initially, the study will focus on cancer of the prostate and the present work represents the first step towards that goal. One of the intended tools, to be used in the assessment, is the Monte Carlo radiation transport code ORANGE. A validation of the ORANGE code's capability to tally dose on a grid superimposed on an existing MCNP geometry is given. Preliminary results on the dose distribution due to conventional radiotherapy treatment of prostate cancer are discussed. Two mathematical models of the patient are proposed and the clinical relevance of the ADAM phantom is investigated. A problem in comparing average doses provided by commercial treatment planning systems and those calculated with Monte Carlo is noticed. The two proposed models are shown to receive a lower dose and average energy deposition than a 'real' patient.

Use of risk projection models to estimate mortality and incidence from radiation-induced breast cancer in screening programs.

The authors report on a method to calculate radiological risks, applicable to breast screening programs and other controlled medical exposures to ionizing radiation. In particular, it has been applied to make a risk assessment in the Valencian Breast Cancer Early Detection Program (VBCEDP) in Spain. This method is based on a parametric approach, through Markov processes, of hazard functions for radio-induced breast cancer incidence and mortality, with mean glandular breast dose, attained age and age-at-exposure as covariates. Excess relative risk functions of breast cancer mortality have been obtained from two different case-control studies exposed to ionizing radiation, with different follow-up time: the Canadian Fluoroscopy Cohort Study (1950--1987) and the Life Span Study (1950--1985 and 1950--1990), whereas relative risk functions for incidence have been obtained from the Life Span Study (1958--1993), the Massachusetts tuberculosis cohorts (1926--1985 and 1970--1985), the New York post-partum mastitis patients (1930--1981) and the Swedish benign breast disease cohort (1958--1987). Relative risks from these cohorts have been transported to the target population undergoing screening in the Valencian Community, a region in Spain with about four and a half million inhabitants. The SCREENRISK software has been developed to estimate radiological detriments in breast screening. Some hypotheses corresponding to different screening conditions have been considered in order to estimate the total risk associated with a woman who takes part in all screening rounds. In the case of the VBCEDP, the total radio-induced risk probability for fatal breast cancer is in a range between [5 x 10(-6), 6 x 10(-4)] versus the natural rate of dying from breast cancer in the Valencian Community which is 9.2 x 10(-3). The results show that these indicators could be included in quality control tests and could be adequate for making comparisons between several screening programs.

[Skin cancer and occupational disease]. / Hautkrebs und Berufserkrankung.

Although it is universally accepted that UV light exposure can cause malignant skin tumors, UV-induced skin cancers are not recognized as an occupational disease in Germany. Exposure to natural or artificial UV light occurs in many work places, so that the induction of occupational skin cancers is certainly plausible. In recent years, a special clause in the occupational disability rules has recognized some cases of UV-induced skin cancers. We discuss the nature of occupational UV exposure, explore preventative measures and review the data regarding occupational UV-induced skin tumors. After evaluating recent publications, we conclude that for squamous cell carcinoma the epidemiological proof of an at least doubled risk (RR >2) due to occupational UV radiation can be given. The clear dose response relationship supports these epidemiological findings. For the individual risk assessment, an attributive UV radiation >40% due to occupational factors must exist. Under those circumstances, squamous cell carcinoma should be recognized and compensated as an occupational disease.