The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme--a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone.

BACKGROUND: Digital breast tomosynthesis (DBT) is a three-dimensional mammography technique with the potential to improve accuracy by improving differentiation between malignant and non-malignant lesions. OBJECTIVES: The objectives of the study were to compare the diagnostic accuracy of DBT in conjunction with two-dimensional (2D) mammography or synthetic 2D mammography, against standard 2D mammography and to determine if DBT improves the accuracy of detection of different types of lesions. STUDY POPULATION: Women (aged 47-73 years) recalled for further assessment after routine breast screening and women (aged 40-49 years) with moderate/high of risk of developing breast cancer attending annual mammography screening were recruited after giving written informed consent. INTERVENTION: All participants underwent a two-view 2D mammography of both breasts and two-view DBT imaging. Image-processing software generated a synthetic 2D mammogram from the DBT data sets. RETROSPECTIVE READING STUDY: In an independent blinded retrospective study, readers reviewed (1) 2D or (2) 2D + DBT or (3) synthetic 2D + DBT images for each case without access to original screening mammograms or prior examinations. Sensitivities and specificities were calculated for each reading arm and by subgroup analyses. RESULTS: Data were available for 7060 subjects comprising 6020 (1158 cancers) assessment cases and 1040 (two cancers) family history screening cases. Overall sensitivity was 87% [95% confidence interval (CI) 85% to 89%] for 2D only, 89% (95% CI 87% to 91%) for 2D + DBT and 88% (95% CI 86% to 90%) for synthetic 2D + DBT. The difference in sensitivity between 2D and 2D + DBT was of borderline significance (p = 0.07) and for synthetic 2D + DBT there was no significant difference (p = 0.6). Specificity was 58% (95% CI 56% to 60%) for 2D, 69% (95% CI 67% to 71%) for 2D + DBT and 71% (95% CI 69% to 73%) for synthetic 2D + DBT. Specificity was significantly higher in both DBT reading arms for all subgroups of age, density and dominant radiological feature (p < 0.001 all cases). In all reading arms, specificity tended to be lower for microcalcifications and higher for distortion/asymmetry. Comparing 2D + DBT to 2D alone, sensitivity was significantly higher: 93% versus 86% (p < 0.001) for invasive tumours of size 11-20 mm. Similarly, for breast density 50% or more, sensitivities were 93% versus 86% (p = 0.03); for grade 2 invasive tumours, sensitivities were 91% versus 87% (p = 0.01); where the dominant radiological feature was a mass, sensitivities were 92% and 89% (p = 0.04) For synthetic 2D + DBT, there was significantly (p = 0.006) higher sensitivity than 2D alone in invasive cancers of size 11-20 mm, with a sensitivity of 91%. CONCLUSIONS: The specificity of DBT and 2D was better than 2D alone but there was only marginal improvement in sensitivity. The performance of synthetic 2D appeared to be comparable to standard 2D. If these results were observed with screening cases, DBT and 2D mammography could benefit to the screening programme by reducing the number of women recalled unnecessarily, especially if a synthetic 2D mammogram were used to minimise radiation exposure. Further research is required into the feasibility of implementing DBT in a screening setting, prognostic modelling on outcomes and mortality, and comparison of 2D and synthetic 2D for different lesion types. STUDY REGISTRATION: Current Controlled Trials ISRCTN73467396. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA programme website for further project information.This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA programme website for further project information.Gilbert FJ, Tucker L, Gillan MGC, Willsher P, Cooke J, Duncan KA, et al. The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme – a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone. Health Technol Assess 2015;19(4). © Queen’s Printer and Controller of HMSO 2015. This work was produced by Gilbert et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Digital Breast Tomosynthesis : - the future screening tool for breast cancer?

Bakgrunn: Brystkreft er den vanligste kreftformen blant kvinner og en av de hyppigste årsakene til kreftdødsfall i Norge og globalt. Målsettingen med mammografiscreening er å oppdage brystkreft i et tidlig stadium og redusere dødeligheten av sykdommen. Studier har vist høyere deteksjon av screeningoppdagede krefttilfeller med digital brysttomosyntese som inkluderer ~200-250 bilder sammenlignet med standard digital mammografi (DM) med fire bilder. Vi utførte en randomisert kontrollert studie (RCT), Tomosyntese-studien i Bergen (To-Be1). Målsettingen med studien var å sammenligne tidligindikatorer i screening ved bruk av digital brysttomosyntese i kombinasjon med syntetiske 2D-bilder (DBT) versus standard DM. Avhandlingen inkluderer tre studier med følgende mål: Studie 1: Å sammenligne lesetid, stråledose, konsensus og tilbakekalling ved bruk av DBT og DM etter det første året av To-Be1. Studie 2: Å sammenligne tilbakekalling, falske positive screeningsresultater og screeningoppdaget kreft for kvinner med ulik mammografisk tetthet målt automatisk (Volpara tetthetsgrad, VDG 1-4) og med ulike screeningteknikker (DBT versus DM). Studie 3: Å undersøke fordeling av mammografiske funn hos kvinner tilbakekalt etter screening med DBT versus DM og analysere sammenhenger mellom mammografiske funn og det endelige resultatet av screeningundersøkelsen. Metode: Alle kvinner som deltok i screening utført i Bergen i løpet av 2016-2017 som en del av Mammografiprogrammet (n=32 976) ble invitert til å delta i To-Be1. Totalt aksepterte 89,3 % av kvinnene invitasjonen og ble randomisert til DBT eller DM. Etter uavhengig dobbelttyding med konsensus ble resultater etter DBT sammenlignet med DM. Mammografisk tetthet ble oppgitt som VDG 1-4, som er analog til kategoriene i BI-RADS´ 5. utgave. Radiologene klassifiserte mammografiske funn hos etterinnkalte kvinner etter en modifisert BI-RADS skala. Vi brukte deskriptive analyser og t-test for å sammenligne gjennomsnittsverdier, samt kji-kvadrat-test med tilhørende 95% konfidensintervall (KI) for å sammenligne kategorier. Log-binominale regresjonsmodeller ble brukt for å estimere relativ risiko. En p-verdi lavere enn 0,05 ble definert som statistisk signifikant. Vi brukte statistikkprogrammet STATA. Resultater: Studie 1: Gjennomsnittlig lesetid var 1:11 min:sek for DBT og 0:41 min:sek for DM i det første året av To-Be1. Det var ingen statistiske forskjeller i gjennomsnittlig stråledose for noen av tetthetskategoriene for DBT (2,96 mGy) versus DM (2,95 mGy). Tilbakekallingen var 3,0 % for DBT og 3,6 % for DM etter det første året med To-Be1. Studie 2: Etterundersøkelsesraten for kvinner med VDG 1 var 2,1% for DBT og 3,3% for DM, mens den var 3,2% for DBT og 4,3% for DM for de med VDG 2. Raten av falske positive screening resultater var 1,6% for DBT og 2,8% for DM for kvinner med VDG 1. For kvinner med VDG 2 var den 2,4% for DBT og 3,6 for DM. Ingen statistiske forskjeller i screeningoppdaget kreft ble funnet mellom DBT og DM for noen av tetthetskategoriene. Justert relativ risiko for tilbakekalling, falskt positivt screeningsresultat og screeningoppdaget kreft økte med VDG i DBT, mens det ikke ble funnet forskjeller i DM. Studie 3: Studien inkluderte 182 screeningdetekterte krefttilfeller (n=95 for DBT og n=87 for DM). Blant disse var 36,8% spikulerte masser for DBT mens det var 18,4% for DM. Kalk var det hyppigste mammografiske funnet for brystkrefttilfeller for de som var screenet med DM (23%). For DBT var andelen på 13,7%. Asymmetri, uskarp og skjult masse var mindre hyppig hos kvinner med et falsk positiv screening resultat etter screening med DBT versus DM. Konklusjon: Resultater fra To-Be1 indikerte at DBT var minst like god som DM når det gjelder etterundersøkelser og deteksjon av brystkreft, som betyr at DBT er trygt å bruke i screening. DBT var bedre egnet enn DM for kvinner med VDG 1 og 2 med hensyn til etterundersøkelsesrate og falske positive, mens deteksjon av brystkreft ikke var forskjellig. Det tok lengre tid å lese DBT enn DM bilder, og konsensus tok lengre tid med DBT. Mer kunnskap om forskjeller i mammografiske funn og sammenheng med screeningsresultater for DBT versus DM kan bidra til å ytterligere forbedre fordelene med DBT som et screeningverktøy.Background: Breast cancer is the most common cancer and one of the leading causes of cancer deaths in Norway and globally. Mammographic screening aims for early detection of breast cancer and reduced mortality from the disease. Studies have shown higher rates of screen-detected cancers for digital breast tomosynthesis including ~200-250 images compared to standard digital mammography (DM) including four images. We performed a randomized controlled trial (RCT), the Tomosynthesis trial in Bergen (To-Be1), were the aim was to compare early performance measures for digital breast tomosynthesis including synthesised 2D images (DBT) versus DM in screening. This thesis includes three studies with the following aims: Study 1: To compare preliminary results of reading time, radiation dose, consensus and recall for DBT and DM after the first year of To-Be1. Study 2: To compare recall, false positive screening results and screen-detected cancers by automated mammographic density (Volpara density grade, VDG 1-4) and screening technique (DBT versus DM). Study 3: To investigate distribution of mammographic features in women recalled after screening with DBT versus DM and assess associations between mammographic features and final outcome of the screening examination. Method: All women who attended the screening unit in Bergen during 2016-2017 as part of BreastScreen Norway (n=32 976) were invited to participate in To-Be1. In total, 89.3% of the women accepted the invitation and were randomized to undergo either DBT or DM. After independent double reading with consensus, results for DBT were compared with DM. Mammographic density were described by VDG 1-4 which are analogue to the categories in the BI-RADS 5th edition. The radiologists classified the mammographic features of recalled women according to a modified BI-RADS scale. We presented descriptive results and used t-tests to test for means, and chi-squared tests for categories with corresponding 95% confidence intervals (CI). Log-binominal regression models were used to estimate relative risks. A p-value lower than 0.05 was defined as statistically significant. We used STATA software. Results: Study 1: Mean reading time was 1:11 min:sec for DBT versus 0:41 min:sec for DM in the first year of To-Be1. Mean glandular dose did not differ statistically for women screened with DBT (2.96 mGy) versus DM (2.95 mGy). Recall was 3.0% for DBT and 3.6% for DM in the first year of To-Be1. Study 2: Recall rate for women with VDG 1 was 2.1% for DBT and 3.3% for DM, while it was 3.2% for DBT and 4.3% for DM for women with VDG 2. The rate of false positive screening results was 1.6% for DBT and 2.8% for DM for women with VDG 1. For women with VDG 2 it was 2.4% for DBT and 3.6% for DM. No statistical difference in screen-detected cancers was observed between DBT and DM in any density categories. Adjusted relative risk of recall, false positives and screen-detected cancers increased with VDG for DBT. No difference was found for DM. Study 3: The study included 182 screen detected cancers (n=95 DBT and n= 87 DM). 36.8% of those detected with DBT was spiculated mass, while it was 18.4 % for DM. Calcifications was the most frequent feature for breast cancer among those screened with DM (23.0%), which did not differ statistically from the 13.7% for DBT. Asymmetry, indistinct and obscured mass was less frequent in women with a false positive screening result after screening with DBT versus DM. Conclusion: Results from To-Be1 indicated DBT to be as least as good as DM in terms of recall and cancer detection, which means that DBT is safe for the women. DBT was superior to DM in women with VDG 1 and 2 (lower recall, fewer false positives, no difference in cancer detection). However, time spent on initial screen reading and on consensus was longer for DBT compared with DM. More knowledge of the differences in distribution of mammographic features and their association with screening outcome, might contribute to further improve the benefits of DBT as a screening tool for breast cancer.Doktorgradsavhandlin

Enhanced Digital Breast Tomosynthesis diagnosis using 3D visualization and automatic classification of lesions

Breast cancer represents the main cause of cancer-related deaths in women. Nonetheless, the mortality rate of this disease has been decreasing over the last three decades, largely due to the screening programs for early detection. For many years, both screening and clinical diagnosis were mostly done through Digital Mammography (DM). Approved in 2011, Digital Breast Tomosynthesis (DBT) is similar to DM but it allows a 3D reconstruction of the breast tissue, which helps the diagnosis by reducing the tissue overlap. Currently, DBT is firmly established and is approved as a stand-alone modality to replace DM. The main objective of this thesis is to develop computational tools to improve the visualization and interpretation of DBT data. Several methods for an enhanced visualization of DBT data through volume rendering were studied and developed. Firstly, important rendering parameters were considered. A new approach for automatic generation of transfer functions was implemented and two other parameters that highly affect the quality of volume rendered images were explored: voxel size in Z direction and sampling distance. Next, new image processing methods that improve the rendering quality by considering the noise regularization and the reduction of out-of-plane artifacts were developed. The interpretation of DBT data with automatic detection of lesions was approached through artificial intelligence methods. Several deep learning Convolutional Neural Networks (CNNs) were implemented and trained to classify a complete DBT image for the presence or absence of microcalcification clusters (MCs). Then, a faster R-CNN (region-based CNN) was trained to detect and accurately locate the MCs in the DBT images. The detected MCs were rendered with the developed 3D rendering software, which provided an enhanced visualization of the volume of interest. The combination of volume visualization with lesion detection may, in the future, improve both diagnostic accuracy and also reduce analysis time. This thesis promotes the development of new computational imaging methods to increase the diagnostic value of DBT, with the aim of assisting radiologists in their task of analyzing DBT volumes and diagnosing breast cancer

Mammographic breast density: comparison of methods for quantitative evaluation.

PURPOSE: To evaluate the results from two software tools for measurement of mammographic breast density and compare them with observer-based scores in a large cohort of women. MATERIALS AND METHODS: Following written informed consent, a data set of 36 281 mammograms from 8867 women were collected from six United Kingdom centers in an ethically approved trial. Breast density was assessed by one of 26 readers on a visual analog scale and with two automated density tools. Mean differences were calculated as the mean of all the individual percentage differences between each measurement for each case (woman). Agreement in total breast volume, fibroglandular volume, and percentage density was assessed with the Bland-Altman method. Association with observer's scores was calculated by using the Pearson correlation coefficient (r). RESULTS: Correlation between the Quantra and Volpara outputs for total breast volume was r = 0.97 (P < .001), with a mean difference of 43.5 cm(3) for all cases representing 5.0% of the mean total breast volume. Correlation of the two measures was lower for fibroglandular volume (r = 0.86, P < .001). The mean difference was 30.3 cm(3) for all cases representing 21.2% of the mean fibroglandular tissue volume result. Quantra gave the larger value and the difference tended to increase with volume. For the two measures of percentage volume density, the mean difference was 1.61 percentage points (r = 0.78, P < .001). Comparison of observer's scores with the area-based density given by Quantra yielded a low correlation (r = 0.55, P < .001). Correlations of observer's scores with the volumetric density results gave r values of 0.60 (P < .001) and 0.63 (P < .001) for Quantra and Volpara, respectively. CONCLUSION: Automated techniques for measuring breast density show good correlation, but these are poorly correlated with observer's scores. However automated techniques do give different results that should be considered when informing patient personalized imaging. (©) RSNA, 2015 Clinical trial registration no. ISRCTN 73467396.Supported by the National Institute for Health Research’s Health Technology Assessment Programme.This is the final version of the article. It first appeared at http://pubs.rsna.org/doi/full/10.1148/radiol.1414150

Measurement of Tumor Extent and Effects of Breast Compression in Digital Mammography and Breast Tomosynthesis

Breast cancer is the most common form of cancer affecting women in the western countries. Today x-ray digital mammography (DM) of the breast is commonly used for early detection of breast cancer. However, the sensitivity of mammography is limited, mainly due to the fact that a 3D volume is projected down to a 2D image. This problem can be partially solved by a tomographic technique. Breast tomosynthesis (BT) reduces the detrimental effect of the projected anatomy. Tumor size is an important predictor of prognosis and treatment effect. We hypothesized that the tumor outline would be better defined in BT and therefore tumor measurement in BT would be more accurate compared with DM. The results showed that breast tumor size measured on BT correlated better with the size measured by the pathologists on the surgical specimens compared with measurement on DM. Breast compression is important in mammography both to improve image quality and to reduce the radiation dose to the breast, but it also has a negative consequence as some women refrain from mammography due to the pain associated with the examination. Since BT is a 3D technique, it was hypothesized that less breast compression force can be applied. The results indicated that less compression force is possible without significantly compromising the diagnostic quality of the image and that the patient comfort was improved. An applied breast compression force as used in mammography results in a pressure distribution over the breast. The pressure distribution was assessed using thin pressure sensors attached to the compression plate. The results showed that the pressure distribution was heterogeneous in appearance and varied widely between different breasts. In almost half of the subjects most of the pressure was over the juxtathoracic part of the breast and the pectoral muscle with little or no pressure over the rest of the breast. Another concern regarding breast compression is the question whether the resulting pressure might damage tumors, causing a shedding of malignant cells into the blood system. Peripheral venous blood samples were drawn before and after breast compression and analyzed for circulating tumor cells. The study found no elevated number of circulating cancer cells in peripheral blood after breast compression. Future analysis of samples from veins draining the breast are needed to study if circulating tumor cells are being trapped in the lung capillaries

Full-Field Digital Mammography for Breast Cancer Screening: An Example of Evidence, Lost in Translation

Screening mammography is the gold standard for early breast cancer detection and a cornerstone of preventive medicine. Traditional mammography is currently being replaced by newer, more eloquent digital technology. Clinical trials have not proven that digital mammography reduces breast cancer mortality or burden of suffering. Nevertheless, the technology has spread according to Everett Roger's Diffusion of Innovation pattern. The purpose of this Master's Paper is closely to examine the process by which breast cancer screening in the United States has evolved from screen film mammography to full-field digital mammography. This is a qualitative, iterative analysis that triangulates analyses of the medical literature, elite interview responses, and media coverage to cultivate a storyline about the development and dissemination of digital mammography. The technology has spread because of our national hunger for computers and innovation, our eagerness to support the war on cancer, public perceptions about the technology's theoretical advantages, and ongoing efforts of advocacy groups to maintain health care equality. Although digital mammography is significantly more expensive than is screen film mammography, cost-effectiveness considerations have been deferred by many health care leaders. Regulating technologies such as digital mammography, which are extremely expensive but do not confer better public health outcomes, is a necessary component of fixing our health care system.Master of Public Healt