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1.  Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies 
Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose–response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34–90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1–3, respectively (overall mean = 33.5, range 0–303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.
doi:10.1007/s00411-010-0307-z
PMCID: PMC3075914  PMID: 20602108
2.  Increased Frequency of Chromosome Translocations Associated with Diagnostic X-Ray Examinations 
Radiation research  2008;170(2):149-155.
Informative studies of cancer risks associated with medical radiation are difficult to conduct owing to low radiation doses, poor recall of diagnostic X rays, and long intervals before cancers occur. Chromosome aberrations have been associated with increased cancer risk and translocations are a known radiation biomarker. Seventy-nine U.S. radiologic technologists were selected for blood collection, and translocations were enumerated by whole chromosome painting. We developed a dose score to the red bone marrow for medical radiation exposure from X-ray examinations reported by the technologists that they received as patients. Using Poisson regression, we analyzed translocations in relation to the dose scores. Each dose score unit approximated 1 mGy. The estimated mean cumulative red bone marrow radiation dose score was 42 (range 1–265). After adjustment for age, occupational radiation, and radiotherapy for benign conditions, translocation frequencies significantly increased with increasing red bone marrow dose score with an estimate of 0.007 translocations per 100 CEs per score unit (95% CI, 0.002 to 0.013; P = 0.01). Chromosome damage has been linked with elevated cancer risk, and we found that cumulative radiation exposure from medical X-ray examinations was associated with increased numbers of chromosome translocations.
doi:10.1667/RR1422.1
PMCID: PMC2766815  PMID: 18666821
3.  ORGAN-SPECIFIC EXTERNAL DOSE COEFFICIENTS AND PROTECTIVE APRON TRANSMISSION FACTORS FOR HISTORICAL DOSE RECONSTRUCTION FOR MEDICAL PERSONNEL 
Health physics  2011;101(1):13-27.
While radiation absorbed dose (Gy) to the skin or other organs is sometimes estimated for patients from diagnostic radiologic examinations or therapeutic procedures, rarely is occupationally-received radiation absorbed dose to individual organs/tissues estimated for medical personnel, e.g., radiologic technologists or radiologists. Generally, for medical personnel, equivalent or effective radiation doses are estimated for compliance purposes. In the very few cases when organ doses to medical personnel are reconstructed, the data is usually for the purpose of epidemiologic studies, e.g., a study of historical doses and risks to a cohort of about 110,000 radiologic technologists presently underway at the U.S. National Cancer Institute. While ICRP and ICRU have published organ-specific external dose conversion coefficients (DCCs), i.e., absorbed dose to organs and tissues per unit air kerma and dose equivalent per unit air kerma, those factors have been primarily published for mono-energetic photons at selected energies. This presents two related problems for historical dose reconstruction, both of which are addressed here. It is necessary to derive conversion factors values for (i) continuous distributions of energy typical of diagnostic medical x rays (bremsstrahlung radiation), and (ii) for energies of particular radioisotopes used in medical procedures, neither of which are presented in published tables. For derivation of DCCs for bremsstrahlung radiation, combinations of x-ray tube potentials and filtrations were derived for different time periods based on a review of relevant literature. Three peak tube potentials (70 kV, 80 kV, and 90 kV) with four different amounts of beam filtration were determined to be applicable for historic dose reconstruction. The probability of these machine settings were assigned to each of the four time periods (earlier than 1949, 1949-1954, 1955-1968, and after 1968). Continuous functions were fit to each set of discrete values of the ICRP/ICRU mono-energetic DCCs and the functions integrated over the air-kerma weighted photon fluence of the 12 defined x-ray spectra. The air kerma-weighted DCCs in this work were developed specifically for an irradiation geometry of anterior to posterior (AP) and for the following tissues: thyroid, breast, ovary, lens of eye, lung, colon, testes, heart, skin (anterior side only), red bone marrow (RBM), heart, and brain. In addition, a series of functional relationships to predict DT per Ka values for RBM dependent on body mass index [BMI (kg m−2) ≡ weight per height2] and average photon energy were derived from a published analysis. Factors to account for attenuation of radiation by protective lead aprons were also developed. Because lead protective aprons often worn by radiology personnel not only reduce the intensity of x-ray exposure but also appreciably harden the transmitted fluence of bremsstrahlung x rays, DCCs were separately calculated for organs possibly protected by lead aprons by considering three cases: no apron, 0.25 mm Pb apron, and 0.5 mm Pb apron. For estimation of organ doses from conducting procedures with radioisotopes, continuous functions of the reported mono-energetic values were developed and DCCs were derived by estimation of the function at relevant energies. By considering the temporal changes in primary exposure-related parameters, e.g., energy distribution, the derived DCCs and transmission factors presented here allow for more realistic historical dose reconstructions for medical personnel when monitoring badge readings are the primary data on which estimation of an individual's organ doses are based.
doi:10.1097/HP.0b013e318204a60a
PMCID: PMC3964780  PMID: 21617389
4.  POLYMORPHISMS IN ESTROGEN BIOSYNTHESIS AND METABOLISM-RELATED GENES, IONIZING RADIATION EXPOSURE, AND RISK OF BREAST CANCER AMONG U.S. RADIOLOGIC TECHNOLOGISTS 
Ionizing radiation-associated breast cancer risk appears to be modified by timing of reproductive events such as age at radiation exposure, parity, age at first live birth, and age at menopause. However, potential breast cancer risk modification of low- to moderate radiation dose by polymorphic estrogen metabolism-related gene variants has not been routinely investigated. We assessed breast cancer risk of 12 candidate variants in 12 genes involved in steroid metabolism, catabolism, binding, or receptor functions in a study of 859 cases and 1083 controls within the US Radiologic Technologists (USRT) cohort. Using cumulative breast dose estimates from a detailed assessment of occupational and personal diagnostic ionizing radiation exposure, we investigated the joint effects of genotype on the risk of breast cancer. In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the CYP3A4 M445T minor allele (rs4986910, OR=0.3; 95% CI 0.1–0.9). We found a borderline increased breast cancer risk with having both minor alleles of CYP1B1 V432L (rs1056836, CC vs. GG, OR=1.2; 95% CI 0.9–1.6). Assuming a recessive model, the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic x-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose (pinteraction=0.03) and had a similar joint effect for cumulative occupational radiation dose adjusted for personal diagnostic x-ray exposure (pinteraction=0.06). We found suggestive evidence that common variants in selected estrogen metabolizing genes may modify the association between ionizing radiation exposure and breast cancer risk.
doi:10.1007/s10549-009-0307-3
PMCID: PMC2860373  PMID: 19214745
5.  Increased frequency of chromosome translocations in airline pilots with long-term flying experience 
Background
Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience.
Methods
We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromo-some painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying.
Results
There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33).
Conclusions
This data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.
doi:10.1136/oem.2008.038901
PMCID: PMC2608721  PMID: 19074211
6.  Incidence of haematopoietic malignancies in US radiologic technologists 
Background: There are limited data on risks of haematopoietic malignancies associated with protracted low-to-moderate dose radiation.
Aims: To contribute the first incidence risk estimates for haematopoietic malignancies in relation to work history, procedures, practices, and protective measures in a large population of mostly female medical radiation workers.
Methods: The investigators followed up 71 894 (77.9% female) US radiologic technologists, first certified during 1926–80, from completion of a baseline questionnaire (1983–89) to return of a second questionnaire (1994–98), diagnosis of a first cancer, death, or 31 August 1998 (731 306 person-years), whichever occurred first. Cox proportional hazards regression was used to compute risks.
Results: Relative risks (RR) for leukaemias other than chronic lymphocytic leukaemia (non-CLL, 41 cases) were increased among technologists working five or more years before 1950 (RR = 6.6, 95% CI 1.0 to 41.9, based on seven cases) or holding patients 50 or more times for x ray examination (RR = 2.6, 95% CI 1.3 to 5.4). Risks of non-CLL leukaemias were not significantly related to the number of years subjects worked in more recent periods, the year or age first worked, the total years worked, specific procedures or equipment used, or personal radiotherapy. Working as a radiologic technologist was not significantly linked with risk of multiple myeloma (28 cases), non-Hodgkin's lymphoma (118 cases), Hodgkin's lymphoma (31 cases), or chronic lymphocytic leukaemia (23 cases).
Conclusion: Similar to results for single acute dose and fractionated high dose radiation exposures, there was increased risk for non-CLL leukaemias decades after initial protracted radiation exposure that likely cumulated to low-to-moderate doses.
doi:10.1136/oem.2005.020826
PMCID: PMC1740936  PMID: 16299095
7.  Chromosomal aberrations in human lymphocytes and fibroblasts after exposure to very low doses of high-LET radiation 
Journal of Radiation Research  2014;55(Suppl 1):i50-i51.
Purpose: The relationship between biological effects and low doses of radiation is still uncertain, especially for high-LET radiation exposures. Estimates of risk from exposure to low doses and low dose rates are often extrapolated from the Japanese atomic bomb survivor data using either linear or linear-quadratic models fitted to dose–response data. In this study, we determined the dose–response for chromosome damage after exposure to very low doses of high-LET radiation and assessed the radiation qualities of Fe, Si and Oxygen ions.
Materials and methods: Chromosomal aberrations (CA) were measured in human peripheral blood lymphocytes and normal skin fibroblasts after exposure to very low doses (0.01–0.20 Gy) of 77-MeV/u oxygen (LET = 55 keV/µm), 170-MeV/u 28Si (LET = 99 keV/µm), or 56Fe ions with energies of 600- or 450-MeV/u (LET = 180 or 195 keV/µm). These exposures included doses that, on average, produce fewer than one in five direct ion traversals per cell nucleus. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and CA were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving more than two breaks in two or more chromosomes). The frequencies of CA in the painted chromosome(s) were evaluated as the ratio between aberrations scored and total cells analyzed. The dose–response for simple exchanges was assessed using a generalized linear model assuming binomial errors per number of chromosomes scored. The model coefficients were extrapolated to whole-genome equivalents. The linear dose–response denoted as the targete effects (TE) model considered the mean number of radiation tracks per cell. Two different non-targeted effect (NTE) models, P = P0 + αT + κ × I (NTE1), and P = P0 + αT (1 − e−T) + κe−T × I (NTE2), were compared with the simple linear model, P = P0 + αT. Akaike information criteria (AIC) and Bayes information criteria (BIC) were used to compare TE and NTE models for fitting chromosome aberrations in low dose range.
Results: Doses that on average produce more than one ion traversal per cell nucleus showed a linear dose–response for CA in both lymphocytes and fibroblasts. However, for doses that produce fewer than one tracks per cell in fibroblasts, O, Si and Fe particles showed a dose-independent response for CA that was significantly elevated relative to background frequencies. For fibroblasts the NTE model 2, P = P0 + αT (1 − e−T) + κe−T × I, showed improved fit to CA in low dose range compared with TE model or NTE1 model. For lymphocytes, tests of the various models were less clear with TE model optimal for Si and Fe while the NTE2 model optimal for O particles. When low-dose exposures were fractionated with 2-h intervals, increased frequencies of both simple and complex exchanges were observed. Nitric oxide scavenger reduced CA induced by low doses of high-LET irradiation. Inhibition of transforming growth factor-β receptor-1 reduced the frequency of simple exchanges.
Conclusions: The results show a non-linear dose–response for CA in fibroblasts after very low doses of high-LET exposure. Possible explanations for this could involve non-targeted effects due to aberrant cell signaling [ 1], perhaps involving nitric oxide and TGF-β, or could be due to delta-ray dose fluctuations [ 2] where CA are induced in cells that receive a significant dose from delta-rays emanating from the multiple ion tracks that do not directly traverse cell nuclei.
doi:10.1093/jrr/rrt212
PMCID: PMC3941494
low dose; heavy ion; chromosome aberrations
8.  Radiation awareness among radiology residents, technologists, fellows and staff: where do we stand? 
Insights into Imaging  2014;6(1):133-139.
Objectives
To investigate and compare the knowledge of radiation dose and risk incurred in common radiology examinations among radiology residents, fellows, staff radiologists and technologists.
Methods
A questionnaire containing 17 multiple choice questions was administered to all residents, technologists, fellows and staff radiologists of the department of medical imaging through the hospital group mailing list.
Results
A total of 92 responses was received. Mean score was 8.5 out of 17. Only 48 % of all participants scored more than 50 % correct answers. Only 23 % were aware of dose from both single-view and two-view chest X-ray; 50–70 % underestimated dose from common studies; 50–75 % underestimated the risk of fatal cancer. Awareness about radiation exposure in pregnancy is variable and particularly poor among technologists. A statistically significant comparative knowledge gap was found among technologists.
Conclusions
Our results show a variable level of knowledge about radiation dose and risk among radiology residents, fellows, staff radiologists and technologists, but overall knowledge is inadequate in all groups. There is significant underestimation of dosage and cancer risk from common examinations, which could potentially lead to suboptimal risk assessment and excessive or unwarranted studies posing significant radiation hazard to the patient and radiology workers.
Main Messages
• Knowledge of radiation dose and risk is poor among all radiology workers.
• Significant knowledge gap among technologists compared to residents, fellows and staff radiologists.
• Significant underestimation of radiation dose and cancer risk from common examinations.
doi:10.1007/s13244-014-0365-x
PMCID: PMC4330233  PMID: 25412827
Radiation dose; Radiation risk; Residents; Technologists; Cancer risk; Questionnaire
9.  Risk of Cataract after Exposure to Low Doses of Ionizing Radiation: A 20-Year Prospective Cohort Study among US Radiologic Technologists 
American Journal of Epidemiology  2008;168(6):620-631.
The study aim was to determine the risk of cataract among radiologic technologists with respect to occupational and nonoccupational exposures to ionizing radiation and to personal characteristics. A prospective cohort of 35,705 cataract-free US radiologic technologists aged 24–44 years was followed for nearly 20 years (1983–2004) by using two follow-up questionnaires. During the study period, 2,382 cataracts and 647 cataract extractions were reported. Cigarette smoking for ≥5 pack-years; body mass index of ≥25 kg/m2; and history of diabetes, hypertension, hypercholesterolemia, or arthritis at baseline were significantly (p ≤ 0.05) associated with increased risk of cataract. In multivariate models, self-report of ≥3 x-rays to the face/neck was associated with a hazard ratio of cataract of 1.25 (95% confidence interval: 1.06, 1.47). For workers in the highest category (mean, 60 mGy) versus lowest category (mean, 5 mGy) of occupational dose to the lens of the eye, the adjusted hazard ratio of cataract was 1.18 (95% confidence interval: 0.99, 1.40). Findings challenge the National Council on Radiation Protection and International Commission on Radiological Protection assumptions that the lowest cumulative ionizing radiation dose to the lens of the eye that can produce a progressive cataract is approximately 2 Gy, and they support the hypothesis that the lowest cataractogenic dose in humans is substantially less than previously thought.
doi:10.1093/aje/kwn171
PMCID: PMC2727195  PMID: 18664497
cataract; radiation; technology, radiologic; x-rays
10.  A Prospective Study of Medical Diagnostic Radiography and Risk of Thyroid Cancer 
American Journal of Epidemiology  2013;177(8):800-809.
Although diagnostic x-ray procedures provide important medical benefits, cancer risks associated with their exposure are also possible, but not well characterized. The US Radiologic Technologists Study (1983–2006) is a nationwide, prospective cohort study with extensive questionnaire data on history of personal diagnostic imaging procedures collected prior to cancer diagnosis. We used Cox proportional hazard regressions to estimate thyroid cancer risks related to the number and type of selected procedures. We assessed potential modifying effects of age and calendar year of the first x-ray procedure in each category of procedures. Incident thyroid cancers (n = 251) were diagnosed among 75,494 technologists (1.3 million person-years; mean follow-up = 17 years). Overall, there was no clear evidence of thyroid cancer risk associated with diagnostic x-rays except for dental x-rays. We observed a 13% increase in thyroid cancer risk for every 10 reported dental radiographs (hazard ratio = 1.13, 95% confidence interval: 1.01, 1.26), which was driven by dental x-rays first received before 1970, but we found no evidence that the relationship between dental x-rays and thyroid cancer was associated with childhood or adolescent exposures as would have been anticipated. The lack of association of thyroid cancer with x-ray procedures that expose the thyroid to higher radiation doses than do dental x-rays underscores the need to conduct a detailed radiation exposure assessment to enable quantitative evaluation of risk.
doi:10.1093/aje/kws315
PMCID: PMC3668423  PMID: 23529772
radiation; radiography; thyroid gland; thyroid neoplasms; x-rays
11.  Childhood cancer in the offspring born in 1921–1984 to US radiologic technologists 
British Journal of Cancer  2008;99(3):545-550.
We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921–1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2–1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (⩾82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7–4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.
doi:10.1038/sj.bjc.6604516
PMCID: PMC2527813  PMID: 18665174
radiation; in utero; preconception; malignancy; aetiology; risk factors
12.  Historical Review of Cancer Risks in Medical Radiation Workers 
Radiation research  2010;174(6):793-808.
Epidemiologic studies of medical radiation workers have found excess risks of leukemia, skin and female breast cancer in those employed before 1950, but little consistent evidence of cancer risk increases subsequently. Occupational radiation-related dose-response, risk estimates for recent years, and lifetime cancer risk data are limited for radiologists and radiologic technologists and lacking for physicians and technologists performing or assisting with fluoroscopically-guided procedures. Based on data from 80 mostly small studies of cardiologists and substantially fewer studies of physicians in other specialties, estimated effective doses to physicians per interventional procedure vary by more than an order of magnitude. There is an urgent need to expand the limited base of information on average annual occupational radiation exposures and time-trends in doses received by medical radiation workers, to assess lifetime cancer risks of radiologists and radiologic technologists in the existing cohorts, and to initiate long-term follow-up studies of cancer and other radiation-associated disease risks in physicians and technologists performing or assisting with interventional procedures. Such studies will help to optimize standardized protocols for radiologic procedures, determine if current radiation protection measures are adequate, provide guidance on cancer screening needs, and yield valuable insights on cancer risks associated with chronic radiation exposure.
doi:10.1667/RR2014.1
PMCID: PMC4098897  PMID: 21128805
radiologists; interventional radiologists; radiologic technologists; interventional cardiologists; neoplasms; reviews
13.  Is there a place for quantitative risk assessment? 
The use of ionising radiations is so well established, especially in the practice of medicine, that it is impossible to imagine contemporary life without them. At the same time, ionising radiations are a known and proven human carcinogen. Exposure to radiation in some contexts elicits fear and alarm (nuclear power for example) while in other situations, until recently at least, it was accepted with alacrity (diagnostic x-rays for example).
This non-uniform reaction to the potential hazards of radiation highlights the importance of quantitative risk estimates, which are necessary to help put things into perspective. Three areas will be discussed where quantitative risk estimates are needed and where uncertainties and limitations are a problem.
First, the question of diagnostic x-rays. CT usage over the past quarter of a century has increased about 12 fold in the UK and more than 20 fold in the US. In both countries, more than 90% of the collective population dose from diagnostic x-rays comes from the few high dose procedures, such as interventional radiology, CT scans, lumbar spine x-rays and barium enemas. These all involve doses close to the lower limit at which there are credible epidemiological data for an excess cancer incidence. This is a critical question; what is the lowest dose at which there is good evidence of an elevated cancer incidence? Without low dose risk estimates the risk–benefit ratio of diagnostic procedures cannot be assessed.
Second, the use of new techniques in radiation oncology. IMRT is widely used to obtain a more conformal dose distribution, particularly in children. It results in a larger total body dose, due to an increased number of monitor units and to the application of more radiation fields. The Linacs used today were not designed for IMRT and are based on leakage standards that were decided decades ago. It will be difficult and costly to reduce leakage from treatment machines, and a necessary first step is to refine the available radiation risks at the fractionated high doses characteristic of radiotherapy. The dose response for carcinogenesis is known for single doses up to about 2 Sv from the A-bomb data, but the shape at higher fractionated doses is uncertain.
Third, the proliferation of proton facilities. The improved dose distribution made possible by charged particle beams has created great interest and led to the design and building of many expensive proton centres. However, due to technical problems, most facilities use passive scattering, rather than spot scanning, to spread the pencil beam to cover realistic target volumes. This process, together with the methods used of final collimation, results in substantial total body doses of neutrons. The relative biological effectiveness of these neutrons is not well known, and the risk estimates are therefore uncertain. Unless and until the risks are known with more certainty, it is difficult to know how much effort and cost should be directed towards reducing, or eliminating, the neutron doses. These three examples, where uncertainties in quantitative risk estimates result in important practical problems, will be discussed.
doi:10.1088/0952-4746/29/2A/S12
PMCID: PMC3684965  PMID: 19454800
14.  Childhood cancer after prenatal exposure to diagnostic X-ray examinations in Britain. 
British Journal of Cancer  1990;62(1):152-168.
Detailed data were provided by the Oxford Survey of Childhood Cancer OSCC on deaths from childhood cancer in Britain after irradiation of the fetus during diagnostic radiology of the mother. In each age group at death, 0-5, 6-9 and 10-15 years, excess cancer deaths decreased suddenly for births in and after 1958. A major factor was concerted action initiated in 1956 to reduce radiation exposure of fetal gonads for fear of genetic hazards. Dose reduction was achieved during 1957 and early 1958 by reducing the rising rate of obstetric radiography and by virtually abandoning pelvimetry as that had been understood. In the 1970s the rate of X-raying increased again and so did cancer risk but not significantly. Direct evidence that diagnostic X-rays can cause childhood cancer is the similar excess rate per X-ray in twins and singleton births when X-raying rate is 5-6 times higher in twins. In the past a dose-response for cancer in OSCC data based on number of films per X-ray examination was taken to be evidence for causation but dose per film varies with kind of X-ray examination. Fixed values for dose per film were mistakenly assumed by UNSCEAR (1972) and used by it and others when deriving risk co-efficients. In updated OSCC data cancer risk is independent of film number. The odds ratio for childhood cancer deaths after X-raying in birth years 1958-61 (1.23 with 95% confidence intervals CI 1.04-1.48) and the mean fetal whole body dose from obstetric radiography in 1958 (0.6 cGy) can each be derived from nationwide surveys in Britain. The corresponding risk coefficient for irradiation in the third trimester for childhood cancer deaths at ages 0-15 years = 4-5 x 10(-4) per cGy fetal whole body dose (95% CI 0.8-9.5 x 10(-4) per cGy). It is the same for cancer incidence and mortality. A lower risk in bomb survivors exposed in utero is not incompatible since its CI are wide. There is no dependable evidence that radiosensitivity is greater in early pregnancy. A significantly raised cancer rate after diagnostic X-raying supports the hypothesis that carcinogenesis by ionising radiation has no threshold.
PMCID: PMC1971756  PMID: 2202420
15.  Major Radiodiagnostic Imaging in Pregnancy and the Risk of Childhood Malignancy: A Population-Based Cohort Study in Ontario 
PLoS Medicine  2010;7(9):e1000337.
In a record-linkage study, Joel Ray and colleagues examine the association between diagnostic imaging during pregnancy and later childhood cancers.
Background
The association between fetal exposure to major radiodiagnostic testing in pregnancy—computed tomography (CT) and radionuclide imaging—and the risk of childhood cancer is not established.
Methods and Findings
We completed a population-based study of 1.8 million maternal-child pairs in the province of Ontario, from 1991 to 2008. We used Ontario's universal health care–linked administrative databases to identify all term obstetrical deliveries and newborn records, inpatient and outpatient major radiodiagnostic services, as well as all children with a malignancy after birth. There were 5,590 mothers exposed to major radiodiagnostic testing in pregnancy (3.0 per 1,000) and 1,829,927 mothers not exposed. The rate of radiodiagnostic testing increased from 1.1 to 6.3 per 1,000 pregnancies over the study period; about 73% of tests were CT scans. After a median duration of follow-up of 8.9 years, four childhood cancers arose in the exposed group (1.13 per 10,000 person-years) and 2,539 cancers in the unexposed group (1.56 per 10,000 person-years), a crude hazard ratio of 0.69 (95% confidence interval 0.26–1.82). After adjusting for maternal age, income quintile, urban status, and maternal cancer, as well as infant sex, chromosomal or congenital anomalies, and major radiodiagnostic test exposure after birth, the risk was essentially unchanged (hazard ratio 0.68, 95% confidence interval 0.25–1.80).
Conclusions
Although major radiodiagnostic testing is now performed in about 1 in 160 pregnancies in Ontario, the absolute annual risk of childhood malignancy following exposure in utero remains about 1 in 10,000. Since the upper confidence limit of the relative risk of malignancy may be as high as 1.8 times that of an unexposed pregnancy, we cannot exclude the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In industrialized countries, childhood cancer (any form of cancer in a child aged 14 years or under) remains a major cause of death. With the exception of a few known risk factors, such as acquired genetic predisposition to cancer, which accounts for about 10% of all childhood cancers, the etiology of most childhood cancer remains unknown. There is thought to be an association between exposure to ionizing radiation in pregnancy and the subsequent risk of development of cancer in the exposed mother's child, but the evidence base to support this association is conflicting. For example, studies examining maternal exposure to plain radiographs in pregnancy and subsequent childhood cancer are inconsistent. Furthermore, although their use has dramatically increased over the past two decades, little is known about the cancer risk related to certain types of radiodiagnostic tests, such as CT and radionuclide imaging, both of which expose the fetus to considerably higher doses of radiation than plain radiographs administered at the same anatomical level.
Why Was This Study Done?
Many women could be exposed to major radiodiagnostic tests, such as those used in emergency situations, before they are aware that they are pregnant, as almost 50% of pregnancies are unplanned. This situation means that it is important to determine the subsequent cancer risk to any child exposed to maternal radiodiagnostic tests before birth.
What Did the Researchers Do and Find?
The researchers conducted a retrospective population-based cohort study of women who delivered a live infant in Ontario, Canada between April 1, 1992 and March 31, 2008. The basis of the research was an anonymized database for the whole province of Ontario, where universal health care, including prenatal care and radiodiagnostic testing, is available to all residents. Database characteristics allowed the researchers to link maternal radiation exposure (a major radiodiagnostic test performed on the mother up to one day before her delivery date) in a specific (index) pregnancy to a subsequent malignancy in the child. After birth, maternal-infant pairs were only followed up if the infant was delivered at term, weighed 2,500 g or more, and survived for at least 30 days.
The researchers were able to follow up 1,835,517 maternal-child pairs. The overall rate of exposure to major radiodiagnostic testing in pregnancy was 3.0 per 1,000 and occurred at an estimated mean gestational age of 15.7 weeks. A total of four childhood cancers occurred in the exposed group and 2,539 cancers in the unexposed group corresponding to a crude hazard ratio of 0.69, which did not significantly change after adjustments were made for potential confounding factors, such as maternal age, sex, and the presence of any chromosomal or congenital anomalies in the infant. The overall prevalence of childhood cancer following exposure to CT or radionuclide imaging in pregnancy is under 0.07%, giving an incidence rate of 1.13 per 10,000 person-years.
What Do These Findings Mean?
These findings can help inform clinicians and mothers about the risk of childhood malignancy following major radiodiagnostic testing in pregnancy. The absolute risk appears to be low, while the relative risk is not materially higher than that of unexposed controls. However, as the upper confidence limit of the relative risk of malignancy may be a maximum of 1.8 times that of an unexposed pregnancy, the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic cannot be excluded. Because this finding means that a very slight risk may exist, beta hCG testing should continue to be done in all potentially pregnant women before undergoing major radiodiagnostic testing, and lead apron shielding used in all women of reproductive age, whether or not known to be pregnant. In addition, nonradiation-emitting imaging, such as MRI and ultrasonography, should be considered first, when clinically appropriate. However, some pregnant women will still be faced with the decision to undergo CT or nuclear imaging because the test is clinically warranted. The findings of this study suggest that when clinically indicated, major radiodiagnostic testing in pregnancy should be performed, along with brief counseling to help lessen the anxiety experienced by an expectant mother before and after the birth of her child.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000337.
For information for patients and caregivers on radiodiagnostic testing, see The Royal College of Radiologists
The National Cancer Institute provides information about childhood cancer
CureSearch for Children's Cancer provides additional information about research into childhood cancer
doi:10.1371/journal.pmed.1000337
PMCID: PMC2935460  PMID: 20838660
16.  A prospective follow-up study of the association of radiation exposure with fatal and non-fatal stroke among atomic bomb survivors in Hiroshima and Nagasaki (1980–2003) 
BMJ Open  2012;2(1):e000654.
Objective
Use of medical radiotherapy has increased markedly in recent decades. Whether the consequence includes an increased risk of cardiovascular disease remains to be determined. The purpose of this study was to examine the association between radiation exposure and the incidence of stroke among Japanese atomic bomb survivors.
Design
A prospective follow-up study.
Setting and participants
Radiation exposure from the atomic bombing was assessed in 9515 subjects (34.8% men) with 24-year follow-up from 1980. Subjects were free of prevalent stroke when follow-up began.
Outcome measures
Stroke events and the underlying cause of death were reviewed to confirm the first-ever stroke. Subtypes (ischaemic and haemorrhagic events) were categorised based on established criteria according to the definitions of typical/atypical stroke symptoms.
Results
Overall mean radiation dose (±SD) in units of gray (Gy) was 0.38±0.58 (range: 0–3.5). During the study period, 235 haemorrhagic and 607 ischaemic events were identified. For men, after adjusting for age and concomitant risk factors, the risk of haemorrhagic stroke rose consistently from 11.6 to 29.1 per 10 000 person-years as doses increased from <0.05 to ≥2 Gy (p=0.009). Incidence also rose within the dose range <1 Gy (p=0.004) with no dose threshold. In women, the risk of haemorrhagic stroke rose with increasing radiation exposure but not until doses reached a threshold of 1.3 Gy (95% CI 0.5 to 2.3). Among women, for doses <1.3 Gy, differences in stroke risk were modest (13.5 per 10 000 person-years), while it increased to 20.3 per 10 000 person-years for doses that ranged from 1.3 to <2.2 Gy and to 48.6 per 10 000 person-years for doses that were higher (p=0.002). In both sexes, dose was unrelated to ischaemic stroke.
Conclusion
While the risk of haemorrhagic stroke increases with rising radiation exposure for both sexes, effects in women are less apparent until doses exceed a threshold at 1.3 Gy.
Article summary
Article focus
Use of medical radiotherapy has increased in recent decades.
Whether the consequence includes an increased risk of cardiovascular disease is unknown.
Our purpose was to examine the association between radiation exposure and the incidence of stroke among atomic bomb survivors in Japan.
Key messages
Risk of haemorrhagic stroke increased with rising radiation exposure for both sexes, although effects in women were less apparent until doses exceeded a threshold at 1.3 Gy.
Radiation exposure was unrelated to ischaemic stroke.
Strengths and limitations of this study
This report provides information on the incidence of stroke using data from clinical examinations and mortality records following a structured research protocol.
Measurement of radiation exposure adheres to a precise system of quantification.
While best attempts were made to properly classify strokes outcomes, diagnostic uncertainties persist.
doi:10.1136/bmjopen-2011-000654
PMCID: PMC3274709  PMID: 22307102
17.  The Radiation Issue in Cardiology: the time for action is now 
The "radiation issue" is the need to consider possible deterministic effects (e.g., skin injuries) and long-term cancer risks due to ionizing radiation in the risk-benefit assessment of diagnostic or therapeutic testing. Although there are currently no data showing that high-dose medical studies have actually increased the incidence of cancer, the "linear-no threshold" model in radioprotection assumes that no safe dose exists; all doses add up in determining cancer risks; and the risk increases linearly with increasing radiation dose. The possibility of deterministic effects should also be considered when skin or lens doses may be over the threshold. Cardiologists have a special mission to avoid unjustified or non-optimized use of radiation, since they are responsible for 45% of the entire cumulative effective dose of 3.0 mSv (similar to the radiological risk of 150 chest x-rays) per head per year to the US population from all medical sources except radiotherapy. In addition, interventional cardiologists have an exposure per head per year two to three times higher than that of radiologists. The most active and experienced interventional cardiologists in high volume cath labs have an annual exposure equivalent to around 5 mSv per head and a professional lifetime attributable to excess cancer risk on the order of magnitude of 1 in 100. Cardiologists are the contemporary radiologists but sometimes imperfectly aware of the radiological dose of the examination they prescribe or practice, which can range from the equivalent of 1-60 mSv around a reference dose average of 10-15 mSv for a percutaneous coronary intervention, a cardiac radiofrequency ablation, a multi-detector coronary angiography, or a myocardial perfusion imaging scintigraphy. A good cardiologist cannot be afraid of life-saving radiation, but must be afraid of radiation unawareness and negligence.
doi:10.1186/1476-7120-9-35
PMCID: PMC3256101  PMID: 22104562
cancer; cardiology; imaging; risk
18.  Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study 
Lancet  2012;380(9840):499-505.
Summary
Background
Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults.
Methods
In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT.
Findings
During follow-up, 74 of 178 604 patients were diagnosed with leukaemia and 135 of 176 587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005–0·120; p=0·0097) and brain tumours (0·023, 0·010–0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46–6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50–74 mGy (mean dose 60·42 mGy) was 2·82 (1·33–6·03).
Interpretation
Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10 000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate.
Funding
US National Cancer Institute and UK Department of Health.
doi:10.1016/S0140-6736(12)60815-0
PMCID: PMC3418594  PMID: 22681860
19.  Comparison of RBE values of high- LET α-particles for the induction of DNA-DSBs, chromosome aberrations and cell reproductive death 
Background
Various types of radiation effects in mammalian cells have been studied with the aim to predict the radiosensitivity of tumours and normal tissues, e.g. DNA double strand breaks (DSB), chromosome aberrations and cell reproductive inactivation. However, variation in correlations with clinical results has reduced general application. An additional type of information is required for the increasing application of high-LET radiation in cancer therapy: the Relative Biological Effectiveness (RBE) for effects in tumours and normal tissues. Relevant information on RBE values might be derived from studies on cells in culture.
Methods
To evaluate relationships between DNA-DSB, chromosome aberrations and the clinically most relevant effect of cell reproductive death, for ionizing radiations of different LET, dose-effect relationships were determined for the induction of these effects in cultured SW-1573 cells irradiated with gamma-rays from a Cs-137 source or with α-particles from an Am-241 source. RBE values were derived for these effects. Ionizing radiation induced foci (IRIF) of DNA repair related proteins, indicative of DSB, were assessed by counting gamma-H2AX foci. Chromosome aberration frequencies were determined by scoring fragments and translocations using premature chromosome condensation. Cell survival was measured by colony formation assay. Analysis of dose-effect relations was based on the linear-quadratic model.
Results
Our results show that, although both investigated radiation types induce similar numbers of IRIF per absorbed dose, only a small fraction of the DSB induced by the low-LET gamma-rays result in chromosome rearrangements and cell reproductive death, while this fraction is considerably enhanced for the high-LET alpha-radiation. Calculated RBE values derived for the linear components of dose-effect relations for gamma-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0 ± 0.3, 14.7 ± 5.1, 15.3 ± 5.9 and 13.3 ± 6.0 respectively.
Conclusions
These results indicate that RBE values for IRIF (DNA-DSB) induction provide little valid information on other biologically-relevant end points in cells exposed to high-LET radiations. Furthermore, the RBE values for the induction of the two types of chromosome aberrations are similar to those established for cell reproductive death. This suggests that assays of these aberrations might yield relevant information on the biological effectiveness in high-LET radiotherapy.
doi:10.1186/1748-717X-6-64
PMCID: PMC3127784  PMID: 21651780
20.  A meta-analysis of leukaemia risk from protracted exposure to low-dose gamma radiation 
Context
More than 400 000 workers annually receive a measurable radiation dose and may be at increased risk of radiation-induced leukaemia. It is unclear whether leukaemia risk is elevated with protracted, low-dose exposure.
Objective
We conducted a meta-analysis examining the relationship between protracted low-dose ionising radiation exposure and leukaemia.
Data sources
Reviews by the National Academies and United Nations provided a summary of informative studies published before 2005. PubMed and Embase databases were searched for additional occupational and environmental studies published between 2005 and 2009.
Study selection
We selected 23 studies that: (1) examined the association between protracted exposures to ionising radiation and leukaemia excluding chronic lymphocytic subtype; (2) were a cohort or nested case–control design without major bias; (3) reported quantitative estimates of exposure; and (4) conducted exposure–response analyses using relative or excess RR per unit exposure.
Methods
Studies were further screened to reduce information overlap. Random effects models were developed to summarise between-study variance and obtain an aggregate estimate of the excess RR at 100 mGy. Publication bias was assessed by trim and fill and Rosenthal's file drawer methods.
Results
We found an ERR at 100 mGy of 0.19 (95% CI 0.07 to 0.32) by modelling results from 10 studies and adjusting for publication bias. Between-study variance was not evident (p=0.99).
Conclusions
Protracted exposure to low-dose gamma radiation is significantly associated with leukaemia. Our estimate agreed well with the leukaemia risk observed among exposed adults in the Life Span Study (LSS) of atomic bomb survivors, providing increased confidence in the current understanding of leukaemia risk from ionising radiation. However, unlike the estimates obtained from the LSS, our model provides a precise, quantitative summary of the direct estimates of excess risk from studies of protracted radiation exposures.
doi:10.1136/oem.2009.054684
PMCID: PMC3095477  PMID: 20935290
Epidemiology; leukaemia; radiation; health and safety; meta-analysis
21.  Use of non-steroidal anti-inflammatory drugs and risk of basal cell carcinoma in the United States Radiologic Technologists study 
Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of colorectal and other cancers, but the association with basal cell carcinoma (BCC) is unclear. Previous epidemiological studies have been small in size, conducted in especially vulnerable populations, or have not accounted for solar UV exposure, a major risk factor for BCC. In the United States Radiologic Technologists cohort, we followed subjects to assess NSAID use on risk of first incident BCC. We included Caucasian participants who responded to both second and third questionnaires (administered from 1994–1998 and 2003–2005, respectively) and who reported no cancer at the time of the second questionnaire, N=58,213. BCC, constituent risk factors (e.g., eye color, complexion, hair color) and sun exposure history were assessed through self-administered survey. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Of the 58,213 people in the study population, 2,291 went on to develop BCC. Any NSAID use was not associated with subsequent incidence of BCC (HR = 1.04, 95% CI: 0.92–1.16) after adjusting for age, sex, and estimated lifetime summer sun exposure. No association was observed when stratified by NSAID type (aspirin and other NSAIDs), nor did dose-response patterns emerge by frequency of use (average days per month). Further analyses did not reveal interaction with sex, birth cohort, smoking, alcohol consumption, sun exposure, occupational radiation exposure, or personal risk factors for BCC. In this large nationwide study, we observed no association between NSAID use and subsequent BCC risk.
doi:10.1002/ijc.26286
PMCID: PMC3262887  PMID: 21780102
non-steroidal anti-inflammatory drugs; basal cell carcinoma; ultraviolet radiation Article category: Epidemiology
22.  Polymorphisms in oxidative stress and inflammation pathway genes, low-dose ionizing radiation, and the risk of breast cancer among US radiologic technologists 
Cancer causes & control : CCC  2010;21(11):1857-1866.
Objective
Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk.
Methods
We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose–response across genotypes.
Results
There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2–12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0–3.8) and EOR/Gy < 0 (95%CI < 0–14.8) for the GC and CC genotypes, respectively, (pinteraction = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined.
Conclusions
This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.
doi:10.1007/s10552-010-9613-7
PMCID: PMC3076104  PMID: 20711808
PTGS2; COX-2; Inflammation; Breast cancer; Radiation
23.  Radiation as a Risk Factor for Cardiovascular Disease 
Antioxidants & Redox Signaling  2011;15(7):1945-1956.
Abstract
Humans are continually exposed to ionizing radiation from terrestrial sources. The two major contributors to radiation exposure of the U.S. population are ubiquitous background radiation and medical exposure of patients. From the early 1980s to 2006, the average dose per individual in the United States for all sources of radiation increased by a factor of 1.7–6.2 mSv, with this increase due to the growth of medical imaging procedures. Radiation can place individuals at an increased risk of developing cardiovascular disease. Excess risk of cardiovascular disease occurs a long time after exposure to lower doses of radiation as demonstrated in Japanese atomic bomb survivors. This review examines sources of radiation (atomic bombs, radiation accidents, radiological terrorism, cancer treatment, space exploration, radiosurgery for cardiac arrhythmia, and computed tomography) and the risk for developing cardiovascular disease. The evidence presented suggests an association between cardiovascular disease and exposure to low-to-moderate levels of radiation, as well as the well-known association at high doses. Studies are needed to define the extent that diagnostic and therapeutic radiation results in increased risk factors for cardiovascular disease, to understand the mechanisms involved, and to develop strategies to mitigate or treat radiation-induced cardiovascular disease. Antioxid. Redox Signal. 15, 1945–1956.
doi:10.1089/ars.2010.3742
PMCID: PMC3159113  PMID: 21091078
24.  Real practice radiation dose and dosimetric impact of radiological staff training in body CT examinations 
Insights into Imaging  2013;4(2):239-244.
Objectives
To evaluate the radiation dose of the main body CT examinations performed routinely in four regional diagnostic centres, the specific contribution of radiologists and technologists in determining CT dose levels, and the role of radiological staff training in reducing radiation doses.
Methods
We retrospectively evaluated the radiation dose in terms of dose-length product (DLP) values of 2,016 adult CT examinations (chest, abdomen-pelvis, and whole body) collected in four different centres in our region. DLP values for contrast-unenhanced and contrast-enhanced CT examinations performed at each centre were compared for each anatomical area. DLP values for CT examinations performed before and after radiological staff training were also compared.
Results
DLP values for the same CT examinations varied among centres depending on radiologists’ preferences, variable training of technologists, and diversified CT image acquisition protocols. A specific training programme designed for the radiological staff led to a significant overall reduction of DLP values, along with a significant reduction of DLP variability.
Conclusions
Training of both radiologists and technologists plays a key role in optimising CT acquisition procedures and lowering the radiation dose delivered to patients.
Main messages
• The effective dose for similar CT examinations varies significantly among radiological centres.
• Staff training can significantly reduce and harmonise the radiation dose.
• Training of radiologists and technologists is key to optimise CT acquisition protocols.
doi:10.1007/s13244-013-0241-0
PMCID: PMC3609953  PMID: 23494878
Multidetector computed tomography; Radiation dose; Radiation protection; Staff training
25.  Screening Mammography for Women Aged 40 to 49 Years at Average Risk for Breast Cancer 
Executive Summary
Objective
The aim of this review was to determine the effectiveness of screening mammography in women aged 40 to 49 years at average risk for breast cancer.
Clinical Need
The effectiveness of screening mammography in women aged over 50 years has been established, yet the issue of screening in women aged 40 to 49 years is still unsettled. The Canadian Task Force of Preventive Services, which sets guidelines for screening mammography for all provinces, supports neither the inclusion nor the exclusion of this screening procedure for 40- to 49-year-old women from the periodic health examination. In addition to this, 2 separate reviews, one conducted in Quebec in 2005 and the other in Alberta in 2000, each concluded that there is an absence of convincing evidence on the effectiveness of screening mammography for women in this age group who are at average risk for breast cancer.
In the United States, there is disagreement among organizations on whether population-based mammography should begin at the age of 40 or 50 years. The National Institutes of Health, the American Association for Cancer Research, and the American Academy of Family Physicians recommend against screening women in their 40s, whereas the United States Preventive Services Task Force, the National Cancer Institute, the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists recommend screening mammograms for women aged 40 to 49 years. Furthermore, in comparing screening guidelines between Canada and the United States, it is also important to recognize that “standard care” within a socialized medical system such as Canada’s differs from that of the United States. The National Breast Screening Study (NBSS-1), a randomized screening trial conducted in multiple centres across Canada, has shown there is no benefit in mortality from breast cancer from annual mammograms in women randomized between the ages of 40 and 49, relative to standard care (i.e. physical exam and teaching of breast-self examination on entry to the study, with usual community care thereafter).
At present, organized screening programs in Canada systematically screen women starting at 50 years of age, although with a physician’s referral, a screening mammogram is an insured service in Ontario for women under 50 years of age.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined, whereas mortality is decreasing, though at a slower rate. These decreasing mortality rates may be attributed to screening and advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the SEER cancer registry in the United States indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20-year period (from 2.7 to 25 per 100,000).
The incidence of breast cancer is lower in women aged 40 to 49 years than in women aged 50 to 69 years (about 140 per 100,000 versus 500 per 100,000 women, respectively), as is the sensitivity (about 75% versus 85% for women aged under and over 50, respectively) and specificity of mammography (about 80% versus 90% for women aged under and over 50, respectively). The increased density of breast tissue in younger women is mainly responsible for the lower accuracy of this procedure in this age group. In addition, as the proportion of breast cancers that occur before the age of 50 are more likely to be associated with genetic predisposition as compared with those diagnosed in women after the age of 50, mammography may not be an optimal screening method for younger women.
Treatment options vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy, and/or radiotherapy.
Surgery is the first-line intervention for biopsy confirmed tumours. The subsequent use of radiation, chemotherapy, or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is noninvasive.
With such controversy as to the effectiveness of mammography and the potential risk associated with women being overtreated or actual cancers being missed, and the increased risk of breast cancer associated with exposure to annual mammograms over a 10-year period, the Ontario Health Technology Advisory Committee requested this review of screening mammography in women aged 40 to 49 years at average risk for breast cancer. This review is the first of 2 parts and concentrates on the effectiveness of screening mammography (i.e., film mammography, FM) for women at average risk aged 40 to 49 years. The second part will be an evaluation of screening by either magnetic resonance imaging or digital mammography, with the objective of determining the optimal screening modality in these younger women.
Review Strategy
The following questions were asked:
Does screening mammography for women aged 40 to 49 years who are at average risk for breast cancer reduce breast cancer mortality?
What is the sensitivity and specificity of mammography for this age group?
What are the risks associated with annual screening from ages 40 to 49?
What are the risks associated with false positive and false negative mammography results?
What are the economic considerations if evidence for effectiveness is established?
The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the International Network of Agencies for Health Technology Assessment.
Keywords used in the search were breast cancer, breast neoplasms, mass screening, and mammography.
In total, the search yielded 6,359 articles specific to breast cancer screening and mammography. This did not include reports on diagnostic mammograms. The search was further restricted to English-language randomized controlled trials (RCTs), systematic reviews, and meta-analyses published between 1995 and 2005. Excluded were case reports, comments, editorials, and letters, which narrowed the results to 516 articles and previous health technology policy assessments.
These were examined against the criteria outlined below. This resulted in the inclusion of 5 health technology assessments, the Canadian Preventive Services Task Force report, the United States Preventive Services Task Force report, 1 Cochrane review, and 8 RCTs.
Inclusion Criteria
English-language articles, and English and French-language health technology policy assessments, conducted by other organizations, from 1995 to 2005
Articles specific to RCTs of screening mammography of women at average risk for breast cancer that included results for women randomized to studies between the ages of 40 and 49 years
Studies in which women were randomized to screening with or without mammography, although women may have had clinical breast examinations and/or may have been conducting breast self-examination.
UK Age Trial results published in December 2006.
Exclusion Criteria
Observational studies, including those nested within RCTs
RCTs that do not include results on women between the ages of 40 and 49 at randomization
Studies in which mammography was compared with other radiologic screening modalities, for example, digital mammography, magnetic resonance imaging or ultrasound.
Studies in which women randomized had a personal history of breast cancer.
Intervention
Film mammography
Comparators
Within RCTs, the comparison group would have been women randomized to not undergo screening mammography, although they may have had clinical breast examinations and/or have been conducting breast self-examination.
Outcomes of Interest
Breast cancer mortality
Summary of Findings
There is Level 1 Canadian evidence that screening women between the ages of 40 and 49 years who are at average risk for breast cancer is not effective, and that the absence of a benefit is sustained over a maximum follow-up period of 16 years.
All remaining studies that reported on women aged under 50 years were based on subset analyses. They provide additional evidence that, when all these RCTs are taken into account, there is no significant reduction in breast cancer mortality associated with screening mammography in women aged 40 to 49 years.
Conclusions
There is Level 1 evidence that screening mammography in women aged 40 to 49 years at average risk for breast cancer is not effective in reducing mortality.
Moreover, risks associated with exposure to mammographic radiation, the increased risk of missed cancers due to lower mammographic sensitivity, and the psychological impact of false positives, are not inconsequential.
The UK Age Trial results published in December 2006 did not change these conclusions.
PMCID: PMC3377515  PMID: 23074501

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