Radiation exposure and screening yield by digital breast tomosynthesis compared to mammography: results of the TOSYMA Trial breast density related.

OBJECTIVES: The randomized TOmosynthesis plus SYnthesized MAmmography (TOSYMA) screening trial has shown that digital breast tomosynthesis plus synthesized mammography (DBT + SM) is superior to digital mammography (DM) in invasive breast cancer detection varying with breast density. On the other hand, the overall average glandular dose (AGD) of DBT is higher than that of DM. Comparing the DBT + SM and DM trial arm, we analyzed here the mean AGD and their determinants per breast density category and related them to the respective invasive cancer detection rates (iCDR). METHODS: TOSYMA screened 99,689 women aged 50 to 69 years. Compression force, resulting breast thickness, the calculated AGD obtained from each mammography device, and previously published iCDR were used for comparisons across breast density categories in the two trial arms. RESULTS: There were 196,622 exposures of 49,227 women (DBT + SM) and 197,037 exposures of 49,132 women (DM) available for analyses. Mean breast thicknesses declined from breast density category A (fatty) to D (extremely dense) in both trial arms. However, while the mean AGD in the DBT + SM arm declined concomitantly from category A (2.41 mGy) to D (1.89 mGy), it remained almost unchanged in the DM arm (1.46 and 1.51 mGy, respectively). In relative terms, the AGD elevation in the DBT + SM arm (64.4% (A), by 44.5% (B), 27.8% (C), and 26.0% (D)) was lowest in dense breasts where, however, the highest iCDR were observed. CONCLUSION: Women with dense breasts may specifically benefit from DBT + SM screening as high cancer detection is achieved with only moderate AGD elevations. CLINICAL RELEVANCE STATEMENT: TOSYMA suggests a favorable constellation for screening with digital breast tomosynthesis plus synthesized mammography (DBT + SM) in dense breasts when weighing average glandular dose elevation against raised invasive breast cancer detection rates. There is potential for density-, i.e., risk-adapted population-wide breast cancer screening with DBT + SM. KEY POINTS: Breast thickness declines with visually increasing density in digital mammography (DM) and digital breast tomosynthesis (DBT). Average glandular doses of DBT decrease with increasing density; digital mammography shows lower and more constant values. With the smallest average glandular dose difference in dense breasts, DBT plus SM had the highest difference in invasive breast cancer detection rates.

Radiation risk and protection of patients in clinical SPECT/CT.

Clinical studies have demonstrated that hybrid single photon emission computed tomography (SPECT)/CT for various diagnostic issues has an added value as compared to SPECT alone. However, the combined acquisition of functional and anatomical images can substantially increase radiation exposure to patients, in particular when using a hybrid system with diagnostic CT capabilities. It is, therefore, essential to carefully balance the diagnostic needs and radiation protection requirements. To this end, the evidence on health effects induced by ionizing radiation is outlined. In addition, the essential concepts for estimating radiation doses and lifetime attributable cancer risks associated with SPECT/CT examinations are presented taking into account both the new recommendations of the International Commission on Radiological Protection (ICRP) as well as the most recent radiation risk models. Representative values of effective dose and lifetime attributable risk are reported for ten frequently used SPECT radiopharmaceuticals and five fully diagnostic partial-body CT examinations. A diagnostic CT scan acquired as part of a combined SPECT/CT examination contributes considerably to, and for some applications even dominates, the total patient exposure. For the common SPECT and CT examinations considered in this study, the lifetime attributable risk of developing a radiation-related cancer is less than 0.27 %/0.37 % for men/women older than 16 years, respectively, and decreases markedly with increasing age at exposure. Since there is no clinical indication for a SPECT/CT examination unless an emission scan has been indicated, the issue on justification comes down to the question of whether it is necessary to additionally acquire a low-dose CT for attenuation correction and anatomical localization of tracer uptake or even a fully diagnostic CT. In any case, SPECT/CT studies have to be optimized, e.g. by adapting dose reduction measures from state-of-the-art CT practice, and exposure levels should not exceed the national diagnostic reference levels for standard situations.

Lung Cancer Screening with Low-Dose CT: Radiation Risk and Benefit-Risk Assessment for Different Screening Scenarios.

Lung cancer is a severe disease that affects predominantly smokers and represents a leading cause of cancer death in Europe. Recent meta-analyses of randomized controlled trials (RCTs) have yielded that low-dose computed tomography (LDCT) screening can significantly reduce lung cancer mortality in heavy smokers or ex-smokers by about 20% compared to a control group of persons who did not receive LDCT. This benefit must be weighed against adverse health effects associated with LDCT lung screening, in particular radiation risks. For this purpose, representative organ doses were determined for a volume CT dose index of 1 mGy that can be achieved on modern devices. Using these values, radiation risks were estimated for different screening scenarios by means of sex-, organ-, and age-dependent radio-epidemiologic models. In particular, the approach was adjusted to a Western European population. For an annual LDCT screening of (ex-)smokers aged between 50 and 75 years, the estimated radiation-related lifetime attributable risk to develop cancer is below 0.25% for women and about 0.1% for men. Assuming a mortality reduction of about 20% and taking only radiation risks into account, this screening scenario results in a benefit-risk ratio of about 10 for women and about 25 for men. These benefit-risk ratio estimates are based on the results of RCTs of the highest evidence level. To ensure that the benefit outweighs the radiation risk even in standard healthcare, strict conditions and requirements must be established for the entire screening process to achieve a quality level at least as high as that of the considered RCTs.

Early Detection of Diseases by Radiological Imaging: New Legal Situation and Evaluation of Service Offers using CT Examinations as an Example. / Früherkennung von Krankheiten mittels radiologischer Bildgebung: Neue Rechtslage und Bewertung von Leistungsangeboten am Beispiel von CT-Untersuchungen.

BACKGROUND: Radiological imaging offers promising prospects for the early detection of diseases. In Germany, the legal framework for such examinations was created by the Radiation Protection Law, which entered into force on December 31, 2018. Under this law, each specific type of radiodiagnostic screening of non-communicable diseases needs an approval on a generic level (permission) by a federal statutory ordinance, defining the specific requirements and conditions. It is the aim of the present paper, (i) to present in detail the new legal situation and (ii) to assess actual service offers for the screening of asymptomatic persons using CT examinations as an example. METHOD: In February 2019, radiology institutions in Germany illegally offering on the Internet CT examinations for the screening of lung and colon cancer or coronary artery disease were identified. For each type of examination, 50 pertinent websites were evaluated particularly regarding the general information on the offered screening examination and the concrete procedure. RESULTS: In the vast majority of cases, the information provided on the websites was inadequate and disproportionately emphasized the benefits over the risks of the screening examination. Moreover, the offers differed substantially with respect to the age and risks factors of potential participants, the frequency of examinations, the screening procedure, and the diagnostic workup. CONCLUSION: The evaluated service offers strongly substantiate the need to define requirements and conditions regarding radiological screening examinations by statutory ordinances, in order to ensure an informed decision of potential screening participants as well as the benefit versus the risks of the procedures. KEY POINTS: · High-evidence studies prove the benefit of radiological screening for some diseases.. · In Germany, screening examinations are only permissible when stated in a federal statutory ordinance.. · At present, only mammography screening for breast cancer is permitted in Germany.. · CT screening examinations currently being conducted in Germany do not fulfill the legal and professional requirements.. · A review process has been initiated regarding possible generic approval of lung cancer screening.. CITATION FORMAT: · Brix G, Nekolla EA, Griebel J. Early Detection of Diseases by Radiological Imaging: New Legal Situation and Evaluation of Service Offers using CT Examinations as an Example. Fortschr Röntgenstr 2020; 192: 139 - 148.

COPD Imaging on a 3rd Generation Dual-Source CT: Acquisition of Paired Inspiratory-Expiratory Chest Scans at an Overall Reduced Radiation Risk.

As stated by the Fleischner Society, an additional computed tomography (CT) scan in expiration is beneficial in patients with chronic obstructive pulmonary disease (COPD). It was thus the aim of this study to evaluate the radiation risk of a state-of-the-art paired inspiratory-expiratory chest scan compared to inspiration-only examinations. Radiation doses to 28 organs were determined for 824 COPD patients undergoing routine chest examinations at three different CT systems-a conventional multi-slice CT (MSCT), a 2nd generation (2nd-DSCT), and 3rd generation dual-source CT (3rd-DSCT). Patients examined at the 3rd-DSCT received a paired inspiratory-expiratory scan. Organ doses, effective doses, and lifetime attributable cancer risks (LAR) were calculated. All organ and effective doses were significantly lower for the paired inspiratory-expiratory protocol (effective doses: 4.3 ± 1.5 mSv (MSCT), 3.0 ± 1.2 mSv (2nd-DSCT), and 2.0 ± 0.8 mSv (3rd-DSCT)). Accordingly, LAR was lowest for the paired protocol with an estimate of 0.025 % and 0.013% for female and male patients (50 years) respectively. Image quality was not compromised. Paired inspiratory-expiratory scans can be acquired on 3rd-DSCT systems at substantially lower dose and risk levels when compared to inspiration-only scans at conventional CT systems, offering promising prospects for improved COPD diagnosis.

[Long-term investigation of the risk of malignant diseases following intravenous radium-224 treatment for ankylosing spondylitis]. / Langzeituntersuchung zum Risiko maligner Erkrankungen nach intravenöser Behandlung des Morbus Bechterew mit Radium-224.

BACKGROUND AND PURPOSE: In German-speaking countries, the intravenous treatment of ankylosing spondylitis (AS) with radium-224 ((224)Ra) was common between the late 1940s and 2005. In this long-term investigation, the risk of malignant diseases following intravenous (224)Ra treatment for AS was assessed. PATIENTS AND METHODS: In a prospective long-term study, 1,471 patients with AS who were treated with (224)Ra between 1948 and 1975 have been followed together with a control group of 1,324 AS patients treated neither with radioactive drugs nor with X-rays. Standardized questionnaires to evaluate the patients' health status were used. Observed numbers of malignant diseases were compared with those of the control group as well as with expected numbers for a normal population. RESULTS: After 26 years of follow-up, causes of death have been certified for 1,006 patients of the exposure group (control group: 1,072 patients). Significantly increased rates of myeloid leukemia (12 cases observed vs. 2.9 expected; p < 0.001), kidney cancer (18 vs. 9.1; p < 0.01), thyroid cancer (4 vs. 1.2; p = 0.03) and borderline significantly increased rates of cancer of female genital organs (10 vs. 5.6; p = 0.06) were found in the exposure group in contrast to no significant increases of these diseases in the control group. Rates of pulmonary and gastrointestinal malignancies were not increased. Lymphatic leukemia (exposure group: 8 vs. 2.7; p < 0.01; control group: 7 vs. 3; p = 0.03) was significantly elevated due to a high rate of chronic lymphatic leukemia in both, the exposure as well as the control group. CONCLUSION: Treatment of AS with (224)Ra led to increased incidences of myeloid leukemia and malignancies of kidneys, thyroid and female genital organs. Although this kind of therapy is now abandoned, there is a need for close follow-up of patients who received it.

Risks and safety aspects related to PET/MR examinations.

INTRODUCTION: The introduction of positron emission tomography (PET)/magnetic resonance (MR) systems into medical practice in the foreseeable future may not only lead to a gain in clinical diagnosis compared to PET/computed tomography (CT) imaging due to the superior soft-tissue contrast of the MR technology but can also substantially reduce exposure of patients to ionizing radiation. On the other hand, there are also risks and health effects associated with the use of diagnostic MR devices that have to be considered carefully. OBJECTIVES: This review article summarizes biophysical and biological aspects, which are of relevance for the assessment of health effects related to the exposure of patients to both ionizing radiation in PET and magnetic and electromagnetic fields in MR. On this basis, some considerations concerning the justification and optimization of PET/MR examinations are presented--as far as this is possible at this very early stage. DISCUSSION: Current safety standards do not take into account synergistic effects of ionizing radiation and magnetic and electromagnetic fields. In the light of the developing PET/MR technology, there is an urgent need to investigate this aspect in more detail for exposure levels that will occur at PET/MR systems.

[Radiation risk associated with mammography screening examinations for women younger than 50 years of age]. / Strahlenrisiko infolge von Mammographie-Screening-Untersu- chungen für Frauen unter 50 Jahren.

The target group of the German mammography screening program, conducted according to the European guidelines, is clearly defined: all women aged 50 to 69 years without evidence of breast cancer are invited to screening mammography every two years. In the present study the question was raised whether breast cancer screening by means of mammography is--from the point of view of radiation hygiene--justified also for women under 50 years of age. Based on current radio-epidemiological breast cancer studies, the excess lifetime risk (ELR) to incur or die from breast cancer of a 40, 45 and 50 year old woman was assessed. Different risk models were used to estimate the radiation risk, e.g. models given for the "Life Span Study" of the atomic bomb survivors and the risk model given in the recent Biological Effects of Ionizing Radiation (BEIR) VII report. The benefit risk ratio was defined as the ratio of the number of "saved lives" due to screening to the number of deaths due to "radiation induced breast cancer". All estimations were based on the assumption that screening is taking place up to the age of 69 years, with screening examinations being performed annually up to the age of 50 and every two years from the age of 50 onwards. The glandular dose per two-view mammography investigation was assumed to be 4 mGy. The benefit due to mammography screening was assumed to be 25% for all age groups. Assuming screening from the age of 40 or 45 years, the ELR of breast cancer is on average about 3.5 or 2 times as high compared to the ELR associated with screening starting from the age of 50 years. In comparison to the benefit risk ratio, which results for women participating in a mammography screening from the age of 50 years, the benefit risk ratio for women starting with screening already from the age of 40 or 45 years is reduced by a factor of 3 or 2. With the present data--with regard to both, the benefit and the radiation risk--it appears not to be justified to expose women from the age of 40 years to the additional radiation exposure associated with a mammography screening.

Cumulative radiation exposure from imaging procedures and associated lifetime cancer risk for patients with lymphoma.

The aim of this study was to systematically evaluate the cumulative radiation exposure and the associated lifetime-cancer-risk from diagnostic imaging in patients with Hodgkin-lymphoma-(HL) or diffuse-large-B-cell-lymphoma (DLBCL). 99 consecutive patients (53-males) diagnosed with HL or DLBCL were included in the study and followed. Based on the imaging reports, organ and effective-doses-(ED) were calculated individually for each patient and the excess lifetime risks were estimated. The average ED in the first year after diagnosis was significantly different for men (59 ± 33 mSv) and women (74 ± 33 mSv)-(p < 0.05). The mean cumulative ED in each of the following 5 years was 16 ± 16 mSv without significant differences between men and women-(p > 0.05). Over all years, more than 90% of the ED resulted from CT. The average cumulative radiation risk estimated for the first year was significantly lower for men (0.76 ± 0.41%) as compared to women (1.28 ± 0.54%)-(p < 0.05). The same was found for each of the subsequent 5-years (men-0.18 ± 0.17%; women-0.28 ± 0.25%)-(p < 0.05). In conclusion, for HL and DLBCL patients investigated in this study, a cumulative radiation risk of about 1 excess cancer per 100 patients is estimated for diagnostic imaging procedures performed during both the first year after diagnosis and a follow-up period of 5 years.

Radiation protection issues in dynamic contrast-enhanced (perfusion) computed tomography.

Dynamic contrast-enhanced (DCE) CT studies are increasingly used in both medical care and clinical trials to improve diagnosis and therapy management of the most common life-threatening diseases: stroke, coronary artery disease and cancer. It is thus the aim of this review to briefly summarize the current knowledge on deterministic and stochastic radiation effects relevant for patient protection, to present the essential concepts for determining radiation doses and risks associated with DCE-CT studies as well as representative results, and to discuss relevant aspects to be considered in the process of justification and optimization of these studies. For three default DCE-CT protocols implemented at a latest-generation CT system for cerebral, myocardial and cancer perfusion imaging, absorbed doses were measured by thermoluminescent dosimeters at an anthropomorphic body phantom and compared with thresholds for harmful (deterministic) tissue reactions. To characterize stochastic radiation risks of patients from these studies, life-time attributable cancer risks (LAR) were estimated using sex-, age-, and organ-specific risk models based on the hypothesis of a linear non-threshold dose-response relationship. For the brain, heart and pelvic cancer studies considered, local absorbed doses in the imaging field were about 100-190 mGy (total CTDI(vol), 200 mGy), 15-30 mGy (16 mGy) and 80-270 mGy (140 mGy), respectively. According to a recent publication of the International Commission on Radiological Protection (ICRP Publication 118, 2012), harmful tissue reactions of the cerebro- and cardiovascular systems as well as of the lenses of the eye become increasingly important at radiation doses of more than 0.5 Gy. The LARs estimated for the investigated cerebral and myocardial DCE-CT scenarios are less than 0.07% for males and 0.1% for females at an age of exposure of 40 years. For the considered tumor location and protocol, the corresponding LARs are more than 6 times as high. Stochastic radiation risks decrease substantially with age and are markedly higher for females than for males. To balance the diagnostic needs and patient protection, DCE-CT studies have to be strictly justified and carefully optimized in due consideration of the various aspects discussed in some detail in this review.

Cumulative radiation exposure and cancer risk of patients with ischemic heart diseases from diagnostic and therapeutic imaging procedures.

OBJECTIVES: To present a detailed analysis of the cumulative radiation exposure and cancer risk of patients with ischemic heart diseases (IHD) from diagnostic and therapeutic imaging. METHODS: For 1219 IHD patients, personal and examination data were retrieved from the information systems of a university hospital. For each patient, cumulative organ doses and the corresponding effective dose (E) resulting from all imaging procedures performed within 3 months before and 12 months after the date of the diagnosis were calculated. The cumulative lifetime attributable risk (LAR) of the patients to be diseased by radiation-related cancer was estimated using sex-, age-, and organ-specific risk models. RESULTS: Among the 3870 procedures performed in the IHD patients, the most frequent were radiographic examinations (52.4%) followed by coronary catheter angiographies and percutaneous cardiac interventions (41.3%), CT scans (3.9%), and perfusion SPECT (2.3%). 87% of patient exposure resulted from heart catheter procedures. E and LAR were significantly higher in males than females (average, 13.3 vs. 10.3 mSv and 0.09 vs. 0.07%, respectively). Contrary to the effective dose, the cancer risk decreased markedly for both sexes with increasing age. CONCLUSIONS: Although IHD patients were partially exposed to considerable amounts of radiation, estimated LARs were small as compared to their baseline risk to develop cancer in the remaining life.

Incidence of malignant diseases in humans injected with radium-224.

The "Spiess study" follows the health of 899 persons who received multiple injections of the short-lived alpha-particle emitter (224)Ra mainly between 1945 and 1955 for the treatment of tuberculosis, ankylosing spondylitis and some other diseases. In December 2007, 124 persons were still alive. The most striking health effect, observed shortly after (224)Ra injections, was a temporal wave of 57 malignant bone tumors. During the two most recent decades of observation, a significant excess of non-skeletal malignant diseases has become evident. Expected numbers of cases were computed from the age, gender and calendar year distribution of person years at risk and incidence rates from the German Saarland Cancer Registry. Poisson statistics were applied to test for statistical significance of the standardized incidence ratios. Up to the end of December 2007, the total number of observed malignant non-skeletal diseases was 270 (248 specified cases of non-skeletal solid cancers and 22 other malignant diseases, among these 16 malignant neoplasms of lymphatic and hematopoietic tissue, six without specification of site) compared to 192 expected cases. Accounting for a 5-year minimum latent period and excluding 13 cases of non-melanoma skin cancer, 231 non-skeletal solid cancers were observed compared to 151 expected cases. Significantly increased cancer rates were observed for breast (32 compared to 9.7), soft and connective tissue (11 compared to 1.0), thyroid (7 compared to 1.0), liver (10 compared to 2.4), kidney (13 compared to 5.0), pancreas (9 compared to 4.1), bladder (16 compared to 8.0), and female genital organs (15 compared to 7.8).

Radiation exposures of cancer patients from medical X-rays: how relevant are they for individual patients and population exposure?

X-ray procedures have a substantial impact not only on patient care but also on man-made radiation exposure. Since a reliable risk-benefit analysis of medical X-rays can only be performed for diagnosis-related groups of patients, we determined specific exposure data for patients with the ten most common types of cancer. For all patients with the considered cancers undergoing medical X-ray procedures in a maximum-care hospital between 2000 and 2005, patient- and examination-specific data were retrieved from the hospital/radiology information system. From this data, the cumulative 5-year effective dose was estimated for each patient as well as the mean annual effective dose per patient and the mean patient observation time for each cancer site. In total, 151,439 radiographic, fluoroscopic, and CT procedures, carried out in 15,866 cancer patients (age, 62+/-13 years), were evaluated. The mean 5-year cumulative dose varied between 8.6 mSv (prostate cancer) and 68.8 mSv (pancreas cancer). Due to an increasing use of CT scans, the mean annual effective dose per patient increased from 13.6 to 18.2 mSv during the 6-year period. Combining the results obtained in this study for a particular hospital with cancer incidence data for Germany, we estimated that cancer patients having X-ray studies constitute at least 1% of the population but receive more than 10% of the total effective dose related to all medical X-ray procedures performed nationwide per year. A large fraction of this dose is radiobiologically ineffective due to the reduced life expectancy of cancer patients.

Risk coefficient for gamma-rays with regard to solid cancer.

A previous investigation has uncoupled the solid cancer risk coefficient for neutrons from the low dose estimates of the relative biological effectiveness (RBE) of neutrons and the photon risk coefficient, and has related it to two more tangible quantities, the excess relative risk (ERR1) due to an intermediate reference dose D1 = 1 Gy of gamma-rays and the RBE of neutrons, R1, against this reference dose. With tentatively assumed RBE values between 20 and 50 and in terms of organ-averaged doses--rather than the usually invoked colon doses--the neutron risk factor was seen to be in general agreement with the current risk estimate of the International Commission on Radiation Protection (ICRP). The present assessment of the risk coefficient for gamma-rays incorporates--in terms of the unchanged A-bomb dosimetry system, DS86--this treatment of the neutrons, but is otherwise largely analogous to the evaluation of the A-bomb data for the ICRP report and for the recent report of the United Nations Scientific Committee on the effects of ionizing radiation, UNSCEAR. The resulting central estimate of the lifetime attributable risk (LAR) for solid cancer mortality is 0.043/Gy for a working population (ages 25-65), and is nearly the same whether the age at exposure or the attained age model is used for risk projection. For a population of all ages 0.042/Gy is obtained with the attained age model and 0.068/Gy with the age at exposure model. The values do not include a dose and dose rate effectiveness factor (DDREF), and they are only half as large as the new UNSCEAR estimates of 0.082/Gy (attained age model and all ages) and 0.13/Gy (age at exposure model and all ages). The difference is only partly due to the more explicit treatment of the neutrons. It reflects also the fact that UNSCEAR has converted ERR into LAR in a way that differs from the ICRP procedure, and that it has summed the overall risk coefficient for solid tumor mortality and incidence from separate estimates for eight solid tumor categories, whereas the present study employs a combined computation for all solid tumors and uses the ICRP procedure for the conversion of ERR into LAR. The appendix gives results for the solid cancer incidence data.