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.

Technical note: Realization and uncertainty analysis for an adjustable 3D structured breast phantom in digital breast tomosynthesis.

BACKGROUND: Projection imaging phantoms are often optimized for 2-dimensional image characteristics in homogeneous backgrounds. Therefore, evaluation of image quality in tomosynthesis (DBT) lacks accepted and established phantoms. PURPOSE: We describe a 3D breast phantom with a structured, variable background. The phantom is an adaptable and advanced version of the L1 phantom by Cockmartin et al. Phantom design and its use for quality assurance measurements for DBT devices are described. Four phantoms were compared to assess the objectivity. METHODS: The container size was increased to a diameter of 24 cm and a total height of 53.5 mm. Spiculated masses were replaced by five additional non-spiculated masses for higher granularity in threshold diameter resolution. These patterns are adjustable to the imaging device. The masses were printed in one session with a base layer using two-component 3D printing. New materials compared to the L1 phantom improved the attenuation difference between the lesion models and the background. Four phantoms were built and intra-human observer, inter-human observer and inter-phantom variations were determined. The latter assess the reproducibility of the phantom production. Coefficients of variance (V) were calculated for all three variations. RESULTS: The difference of the attenuation coefficients between the lesion models and the background was 0.20 cm-1 (with W/Al at 32 kV, equivalent to 19-20 keV effective energy) compared to 0.21 cm-1 for 50/50 glandular/adipose breast tissue and cancerous lesions. PMMA equivalent thickness of the phantom was 47.0 mm for the Siemens Mammomat Revelation. For the masses, the V i n t r a $V_{intra}$ for the intra-observer variation was 0.248, the averaged inter-observer variation, V ¯ i n t e r $\overline{V}_{inter}$ was 0.383. V p h a n t o m $V_{phantom}$ for phantom variance was 0.321. For the micro-calcifications, V i n t r a $V_{intra}$ was 0.0429, V ¯ i n t e r = $\overline{V}_{inter}=$ 0.0731 and V p h a n t o m = $V_{phantom}=$ 0.0759. CONCLUSIONS: Position, orientation and shape of the masses are reproducible and attenuation differences appropriate. The phantom presented proved to be a candidate test object for quality control.

Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial.

BACKGROUND: Two dimensional (2D) full-field digital mammography is the current standard of breast cancer screening. Digital breast tomosynthesis generates pseudo-three dimensional datasets of the breast from which synthesised 2D (s2D) mammograms can be reconstructed. This innovative approach reduces the likelihood of overlapping breast tissues that can conceal features of malignancy. We aimed to compare digital breast tomosynthesis plus s2D mammography with digital screening mammography for the detection of invasive breast cancer. METHODS: TOSYMA was a randomised, open-label, superiority trial done at 17 screening units in two federal states of Germany. Eligible participants were women aged 50-69 years who had been invited to participate in a population-wide, quality-controlled mammography screening programme. Women were randomly assigned (1:1) to digital breast tomosynthesis plus s2D mammography or digital mammography alone using block randomisation (block size of 32), stratified by site. The primary endpoints were the detection rate of invasive breast cancer and invasive interval cancer rate at 24 months, analysed in the modified full analysis set, which included all randomly assigned participants who underwent either type of screening examination. Ten examinations, corresponding to a second study participation, were excluded. Analyses were done according to the intention-to-treat principle. Interval cancer rates will be reported in the follow-up study. Safety was assessed in the as-treated population, which included all participants who were randomly assigned. This trial is registered with ClinicalTrials.gov, NCT03377036, and is closed to accrual. FINDINGS: Between July 5, 2018, and Dec 30, 2020, 99 689 women were randomly assigned to digital breast tomosynthesis plus s2D mammography (n=49 804) or digital mammography (n=49 830). Invasive breast cancers were detected in 354 of 49 715 women with evaluable primary endpoint data in the digital breast tomosynthesis plus s2D group (detection rate 7·1 cases per 1000 women screened) and in 240 of 49 762 women in the digital mammography group (4·8 cases per 1000 women screened; odds ratio 1·48 [95% CI 1·25-1·75]; p<0·0001). Adverse events and device deficiencies were rare (six adverse events in each group; 23 device deficiencies in the digital breast tomosynthesis plus s2D group vs five device deficiencies in the digital mammography group) and no serious adverse events were reported. INTERPRETATION: The results from this study indicate that the detection rate for invasive breast cancer was significantly higher with digital breast tomosynthesis plus s2D mammography than digital mammography alone. Evaluation of interval cancer rates in the follow-up study will further help to investigate incremental long-term benefits of digital breast tomosynthesis screening. FUNDING: Deutsche Forschungsgemeinschaft (German Research Foundation).

Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial.

INTRODUCTION: Development of digital breast tomosynthesis (DBT) provides a technology that generates three-dimensional data sets, thus reducing the pitfalls of overlapping breast tissue. Observational studies suggest that the combination of two-dimensional (2D) digital mammography and DBT increases diagnostic accuracy. However, because of duplicate exposure, this comes at the cost of an augmented radiation dose. This undesired adverse impact can be avoided by using synthesised 2D images reconstructed from the DBT data (s2D).We designed a diagnostic superiority trial on a high level of evidence with the aim of providing a comparison of screening efficacy parameters resulting from DBT+s2D versus the current screening standard 2D full-field digital mammography (FFDM) in a multicentre and multivendor setting on the basis of the quality-controlled, population-based, biennial mammography screening programme in Germany. METHODS AND ANALYSIS: 80 000 women in the eligible age 50-69 years attending the routine mammography screening programme and willing to participate in the TOSYMA trial will be assigned by 1:1 randomisation to either the intervention arm (DBT+s2D) or the control arm (FFDM) during a 12-month recruitment period in screening units of North Rhine-Westphalia and Lower Saxony. State cancer registries will provide the follow-up of interval cancers.Primary endpoints are the detection rate of invasive breast cancers at screening examination and the cumulative incidence of interval cancers in the 2 years after a negative examination. Secondary endpoints are the detection rate of ductal carcinoma in situ and of tumour size T1, the recall rate for assessment, the positive predictive value of recall and the cumulative 12-month incidence of interval cancers. An adaptive statistical design with one interim analysis provides the option to modify the design. ETHICS AND DISSEMINATION: This protocol has been approved by the local medical ethical committee (2016-132-f-S). Results will be submitted to international peer-reviewed journals. TRIAL REGISTRATION: NCT03377036; Pre-results.

Detection Rates of Ductal Carcinoma in Situ with Biennial Digital Mammography Screening: Radiologic Findings Support Pathologic Model of Tumor Progression.

Purpose To compare detection rates of ductal carcinoma in situ (DCIS), classified according to nuclear grade, between the prevalence round (baseline screening) and two subsequent screening rounds of a population-based digital mammography screening program, to assess differences over time. Materials and Methods The cancer registry provided data for 1970 graded pure DCIS cases from 16 screening regions of the prevalence round (baseline screening, from 2005 to 2008), first subsequent round, and second subsequent round; the interval between all screening rounds was 22-30 months. Age-adjusted logistic regression analysis was performed to compare the grade-specific detection rates between the prevalence round (reference) and subsequent screening rounds. Results Over all screening rounds, cancer detection rates were lowest for low-grade DCIS (range, 0.11 [58 of 508 817 patients] to 0.25 [178 of 713 867 patients] per 1000 women screened) and highest for high-grade DCIS (range, 0.53[271 of 508 817 patients] to 0.59 [237 of 398 944 patients] per 1000 women screened). Detection rates for low-grade DCIS were significantly lower in the first (odds ratio [OR] = 0.45, P < .001) and second (OR = 0.57, P < .001) subsequent screening rounds compared with that in the prevalence round; the relative reduction of detection rates of intermediate-grade DCIS was less pronounced (OR = 0.79, P = .006 and OR = 0.76, P = .003, respectively). Conversely, the detection rate of high-grade DCIS remained at the high level found in the prevalence screening (OR = 0.89, P = .143 and OR = 0.97, P = .700, respectively). Conclusion The findings demonstrate persistently high detection rates of high-grade DCIS in two consecutive subsequent screening rounds compared with the prevalence round; conversely, rates of low-grade DCIS and, less markedly, intermediate-grade DCIS decreased in subsequent rounds. Grade-related changes of DCIS detection are suggestive of distinct dynamics of lesion progression. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on November 10, 2017.

Digital mammography screening with photon-counting technique: can a high diagnostic performance be realized at low mean glandular dose?

PURPOSE: To assess screening performance of a direct radiography (DR) photon-counting system versus statewide screening units with different digital technologies. MATERIALS AND METHODS: The local ethics board approved retrospective study of prospectively acquired data from the North Rhine-Westphalian mammography screening program (2009-2010). Informed consent was waived. Examinations in 13 312 women with a DR photon-counting system and statewide digital screening examinations in 993 822 women were included (37 computed radiography mammography systems and 55 DR systems). Diagnostic performance was assessed with cancer detection rate, recall rate, and proportion of small invasive cancers and ductal carcinoma in situ (DCIS). Mean glandular dose was calculated for DR photon counting and for a conventional DR subgroup. Differences were tested with χ(2) and t tests (P < .05). RESULTS: The cancer detection rate for subsequent screenings was higher for DR photon counting than statewide rates (0.76% [67 of 8842] vs 0.59% [3108 of 527 194], P = .05) at a higher recall rate (5.4% [475 of 8842] vs 3.3% [17 656 of 527 194], P = .001). Detection of invasive cancers up to 10 mm for DR photon counting was high for initial (40% [14 of 35]) and subsequent (42% [19 of 45]) screenings but not significantly different from statewide rates (initial, 31.6% [942 of 2979], P = .50; subsequent, 32.5% [765 of 2353], P = .25). The DCIS subsequent screening rate was higher for DR photon counting than statewide screening (0.23% [20 of 8842] vs 0.12% [616 of 527 194], P = .01) and the conventional DR subgroup (0.23% [20 of 8842] vs 0.12% [65 of 52 813], P = .025). Mean glandular dose for DR photon counting was significantly lower than that for conventional DR (0.60 mGy ± 0.20 vs 1.67 mGy ± 0.47 [craniocaudal views], 0.64 mGy ± 0.23 vs 1.79 mGy ± 0.53 [mediolateral oblique views], both P = .0001). CONCLUSION: Digital mammography screening with dose-efficient photon counting enables desirable detection rates of small invasive cancers and DCIS. Higher detection rates compared with statewide performance occurred with subsequent screening but had higher recall rates.

Contrast-to-noise ratios of different elements in digital mammography: evaluation of their potential as new contrast agents.

PURPOSE: To determine the contrast-to-noise ratios (CNRs) of different elements at different energies using various anode/filter combinations currently employed in digital mammography. The elements investigated included not only elements already used in conventional contrast agents such as gadolinium and iodine but also other elements to investigate their potential as mammographic contrast agents. MATERIALS AND METHODS: The CNRs of 20 mmol/L bismuth (Bi), gadolinium (Gd), ytterbium (Yb), dysprosium (Dy), and iodine (I) were determined at different slice thicknesses (0.25, 0.5, and 1 cm) of the element solution with an additional 4-cm Plexiglas in relation to water (to simulate dense glandular tissue), oil, and air. The following anode/filter combinations were used: Mo/Mo in the range of 22-34 kVp, Mo/Rh in the range of 36-40 kVp, Rh/Rh in the range of 42-46 kVp, and Mo/Cu in the range of 47-49 kVp. In the range of 22-46 kVp, the mAs were chosen to achieve a fairly uniform dose range (of 4.38-4.71 mGy). Doses were measured using the PTW DIADOS diagnostic dosimeter. The element solutions were examined with a GE Senographe 2000D. RESULTS: Bismuth showed the best CNR for all energies investigated and in relation to both water and oil. In the energy range below 46 kVp, bismuth (CNR at 30 kVp/50 mAs and 1/0.5/0.25 cm slice thickness: 9.9/6.1/3.4) was followed by Yb (5.9/3.5/2.0), Dy (5.3/3.2/1.9), Gd (4.2/2.5/1.6), and iodine (2.4/1.8/1.5). Bismuth had the best CNR relative to both water (values given above) and oil (Bi: 20.7/11.2/5; Yb: 16.9/8.6/3.6; Dy: 16.6/8.4/3.5; Gd: 15.21/7.5/3.2; I: 13.8/6.3/3.2). The CNR of Bi was also superior to that of the other elements investigated at high energy in combination with copper filters (eg, CNR at 49 kVp Mo/Cu at slice thicknesses of 1/0.5/0.25 cm, relative to water: 9.6/6.0/4.0) but now followed by iodine (7.9/5.3/3.5), Yb (5.8/4.0/2.9), Dy (5.4/3.7/2.8), and Gd (4.7/3.2/2.7). Iodine was the only element of those investigated whose contrast-to-noise ratio was improved with the use of a copper filter at high energies based on its K-edge (increase in CNR from 2.9 to 7.9 from 40 to 49 kVp at 1-cm slice thickness). Nevertheless, the improved CNR of iodine was below that of Bi at low energies and for Mo/Mo or Mo/Rh filters. The contrast of water/fat tended to decrease slightly at higher energies (CNR of water/air at 42 kVp: 33.9, at 48 kVp: 25.6; CNR of oil/air at 42 kVp: 23.8, at 48 kVp: 21.9). CONCLUSION: Copper filters and higher energies are useful for visualizing iodine-based contrast agents in contrast-enhanced mammography because they markedly improve the CNR relative to water. This technique further benefits from the fact that the CNR of water and fat relative to air markedly decreases at higher energies and with the use of copper filters. Bismuth was found to have a much better CNR than iodine for all energies investigated including the low energy ranges typically used in mammography. These results suggest that bismuth is a potential candidate for a specific mammographic contrast agent.