Wetenschap­pelijk onderzoek STREAM: Digitale tomosynthese in het landelijk bevolkingsonderzoek naar borstkanker

Uw privacy

Wat gebeurt er met mijn gegevens?

Als u meedoet aan de studie, worden al uw persoonlijke en studiegegevens vertrouwelijk behandeld. In de studiedocumenten worden uw gegevens vervangen door een code. Deze code wordt apart van uw gegevens bewaard.

Alleen de onderzoekers hebben toegang tot uw gegevens in het kader van deze studie. Medewerkers van de ‘Inspectie van de Gezondheidszorg en Jeugd’ en de Gezondheidsraad kunnen hiervan gebruik maken om de veiligheid en kwaliteit van de studie te controleren.

Hoe lang worden mijn gegevens bewaard?

Uw persoonlijke en studiegegevens worden bewaakt onder de ‘Algemene Verordening Persoonsgegevens’ (AVG) en het privacyreglement van Bevolkingsonderzoek Nederland (link: www.bevolkingsonderzoek nederland.nl/privacy/).

Alle gegevens worden 20 jaar bewaard. We vragen uw toestemming deze gegevens gecodeerd op te mogen nemen in een openbare database en de gegevens te mogen gebruiken voor toekomstige studies naar borstkanker. Bij studies kunnen er ook na afsluiting nieuwe onderzoeksvragen worden gesteld. Soms is het mogelijk de nieuwe vragen te beantwoorden met behulp van de informatie die in eerdere studies is verzameld.

Researchers

ClinicalTrials.gov ID: NCT06059300

In the Netherlands, breast cancer screening is performed with digital mammography (DM), a two-dimensional (2D) imaging modality. Imaging the breast with a 2D modality requires collapsing all information into a single plane, so tissues separated only in the perpendicular direction appear in the same location in the mammogram. This results in about 25% of cancers being diagnosed as interval cancers, i.e., cancers that are not detected at screening but only within two years after screening. Furthermore, tissue superposition also results in false positive recalls for further assessment.

Digital breast tomosynthesis (DBT) is a new imaging modality similar to DM that reduces the problem of tissue superposition. DBT involves acquiring various low-dose mammograms over a limited angle. These are then processed to construct a pseudo-3D stack of slices, each separated vertically by 1 mm.

In the last decade, several large-scale European studies have shown that DBT improves the short-term outcomes for detection of breast cancer compared to mammography. DBT increases the detection rate from ~6 to ~9 cancers per 1000 women screened, while the recall rate approaches 3.5% to 4%, independent of the initial recall rate. Since its recall rate is only 2.4%, introducing DBT in the Dutch screening setting will likely generate an increase in false positives.

However, the impact of DBT screening on medium-term outcomes, in terms of reduction of interval cancers and of detection of advanced cancers, is not yet clear. Although the prospective screening trials mentioned above were considerable in size, they were powered to detect changes in cancer detection and recall rates, not in interval cancers or advanced cancers. As a result, the real impact on the latter outcomes is unknown, with up to now only disparate results being available.

In addition, a change in the imaging modality may introduce barriers in acceptance by multiple stakeholders (i.e. the eligible population, screening radiographers, and radiologists). These barriers need to be investigated and removed, when possible, to prepare the screening program for an eventual rollout of DBT screening nationwide.

Furthermore, the ~50x increase in the number of images resulting from a DBT exam compared to a DM exam doubles the reading time. For DBT screening in the Netherlands to be feasible from the economic and human resources point of view, the interpretation of these cases must be accelerated, to result in an average reading time comparable to that of reviewing DM exams.

Given all these uncertainties, it is currently impossible to determine what would be the long-term effects of transitioning to DBT screening in the Netherlands, in terms of reduction in breast cancer mortality and morbidity, and in cost-effectiveness. To determine these effects, advanced modelling is needed, which requires accurate estimation of the short- and medium-term outcomes of DBT screening, as well as an understanding of the costs of DBT screening, including acquisition and image interpretation costs.

The aim of this project, therefore, is to determine the short-, medium-, and long-term outcomes of nationwide DBT breast cancer screening in the Netherlands, when an optimal image acquisition and interpretation strategy is used. The screening program has already replaced its entire screening DM imaging infrastructure for a new, DBT-capable, one. DBT, however, will not be used until the abovementioned issues are addressed and any unforeseen challenges resolved. In this project we aim to tackle these remaining issues so that the benefits of DBT, if these exist, can be brought to the entire Dutch population of screened women.

Work Package 1

Work Package (WP) 1 will involve the introduction of DBT in 6 of the 71 screening units in the country, to screen 18,200 women for two screening rounds, and compare their results to those of another 86,400 women undergoing standard DM screening. This will allow us to identify the impact of this transition on the screen-detected cancer and recall rates, and on interval and advanced cancer rates, as well as any barriers for acceptance of DBT screening. During screening, the attendees, screening radiographers, and radiologists will be surveyed to identify any barriers that limit acceptability of this new modality. By including a second, incidence DBT round, we will be able to determine the real performance of DBT screening in the Netherlands, since subsequent screening makes up about 90% of the program. Most importantly, this study is powered to detect a combined one-third reduction in the interval and advanced cancer rates with DBT screening.

Work Package 2

In Work Package 2, we will identify the optimal DBT acquisition and reading strategy to be used in the Dutch DBT screening program so as to minimize the increase in reading time with DBT. For this, we will perform retrospective observer studies, using the images from WP1, to test eight different acquisition and reading strategies, some involving the use of cutting-edge artificial intelligence computer systems, for DBT-based screening. These strategies have been shown in initial studies, many performed by us, to result in a significant reduction in reading time, with no or minimal loss in performance. Once the optimal reading strategy is identified, it will be used to interpret the entire second round of DBT screening acquired in WP1 at the screening reading units retrospectively. In this way, we will determine its actual performance and impact on reading time in the real screening environment.

Work Package 3

Finally, in Work Package 3, we will use the results from the other two WPs to model the entire DBT screening program and therefore predict the long-term outcomes and cost-effectiveness of this new screening program. The only method possible to estimate the impact of screening on long term effects such as breast cancer mortality and morbidity, as well as cost-effectiveness, is the use of modelling. Therefore, we will use the well-validated MISCAN model with the data and results gathered, to estimate the long-term impact of DBT screening.

As a result of this project, we will have shown if breast cancer screening with DBT in the Netherlands should be implemented or not. We will also show, were it to be introduced, how it should be implemented, having addressed all the remaining questions, and having found the optimal DBT workflow specifically for a high-volume population-based screening program. 

Artsen

Studiepopulatie

De STREAM studie bestaat uit een interventiegroep met 18,200 vrouwen die een digitale borst tomosynthese (DBT) krijgen als screeningsonderzoek. Deze groep wordt vergeleken met een controlegroep bestaande uit ruim 86,000 vrouwen uit het reguliere bevolkingsonderzoek die als screeningsonderzoek een digitale mammografie (DM) krijgen.

Vrouwen worden uitgenodigd om deel te nemen aan de interventiegroep van de studie als zij, volgens de reguliere planning, worden uitgenodigd voor het bevolkingsonderzoek in een van de zes deelnemende onderzoekscentra. Vrouwen kunnen zelf kiezen of ze deelnemen aan de studie en een DBT laten maken of dat ze niet deelnemen en een regulier onderzoek met DM krijgen. De deelnemers aan de studie zullen gedurende twee opvolgende rondes van het bevolkingsonderzoek worden onderzocht met DBT. Vrouwen ouder dan 72 jaar worden niet uitgenodigd, omdat we zeker willen weten dat alle deelnemers in de interventiegroep in aanmerking komen voor twee rondes van het bevolkingsonderzoek. 

Beeldvorming

De screeningsmedewerkers in de deelnemende onderzoekscentra en de screeningsradiologen die meewerken aan de STREAM studie zijn getraind om DBT beelden te maken en beoordelen. Bij deelnemers worden per borst twee DBT afbeeldingen gemaakt (CC en MLO). Het protocol voor het maken en beoordelen van de DBT beelden is grotendeels hetzelfde als voor DM in het reguliere bevolkingsonderzoek in Nederland (dubbel lezen van CC en MLO beelden met beschikking over beschikbare beelden van eerdere rondes). Bij de DBT beelden zijn 1mm slices en synthetische 2D beelden beschikbaar voor de beoordeling door de screeningsradiologen. Deze beelden kunnen ook worden opgevraagd door het ziekenhuis in het geval van een verwijzing. 

Studieopzet

Meer informatie over de studieopzet is te vinden onder het kopje ‘researchers’.