Digital Tomosynthesis for the Diagnosis of Breast Cancer

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; ALCARAZ, A.; GLUJOVSKY, D.; LOPEZ, A.; REY-ARES, L.; BARDACH, A.; CIAPPONI, A; COMANDE, D

Documento de Evaluación de tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Breast cancer is a public health problem worldwide due to its high incidence and related mortality. Argentina is among the countries with higher rates of incidence and mortality due to malignant breast tumors. Every year, approximately 17,000 new cases are diagnosed and 5,400 women die, which represents an incidence and mortality rate of 74 and 20.1 every 100,000 people. Consequently, it is the first cause of mortality among women.Most breast cancers are diagnosed after an abnormal mammography, however, their diagnostic confirmation requires other imaging studies that will determine the need of biopsy.Digital Breast Tomosynthesis (DBT) or 3D mammography is an imaging diagnostic technology that might allow a better definition and location of the lesions by eliminating image overlapping and consequently a lower rate of diagnostic doubts.TechnologyDBT is an imaging diagnostic technique based on a modification of the digital mammography. This system consists in a rotational system fitted with an X-ray tube that rotates along an angle set between 15º and 50º. By processing the images, it is possible to get thin 1 mm slices in different planes thus allowing reconstructing the breast in three dimensions (3D).PurposeTo assess the available evidence on the efficacy, safety and coverage related aspects regarding DBT use for the diagnosis of breast cancer.MethodsIn April 2013, a bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsNineteen publications from 17 primary cross-sectional studies reporting data on the DBT performance were selected. Ten of these studies estimated the operating characteristics of mammography and DBT in diagnosing breast cancer in women with clinically or imaging (recalls) breast cancer suspicion; four of them described issues related with imaging reading, assessing the level of consistency between radiologists and the tumor size and five of them evaluated the addition DBT to mammography, two of them for screening and two of them in the population with suspected breast cancer. Additionally, two health technology assessments (Spain and Australia), four coverage policies and protocol of a multicenter retrospective study sponsored by the NHS (United Kingdom´s National Health System) were identified.Studies assessing the operating characteristics of mammography vs. DBTSix out of 10 studies that compared the operating characteristics of mammography versus DBT in patients with suspected breast cancer, did not find significant differences among them.Three out of four that did find statistically significant differences, observed a higher area under the ROC curve for DBT. One study conducted on 220 women only observed this difference using two projection DBT images for pathological images in general (0.86 vs. 0.80) and for masses (0.84 vs. 0.76) and calcifications (0.87 vs. 0.79). Another one, that included 185 women found an average area under ROC curve value for DBT of 0.860 and 0.766 for mammography. The third study conducted on a population of 206 women showed area under the ROC curve values of 0.87 vs. 0.83; the authors also found a significant reduction in the rate of false positives from 57% to 48% in images classified as BI-RADS 4 or 5.The fourth study that found significant differences included 144 women and observed a higher sensitivity of 88.4% vs. 73.3 and a negative predictive value (NPV) of 81.8 vs. 66.2.Studies assessing consistency in image readingOne study tried to compare lesion visibility in mammography and DBT; it was conducted in 129 women and found that after assessing DBT images on deferred basis, biopsy was indicated in four women whom their mammography images did not indicate this need. In two of the women, the biopsy was positive and in two, negative. When simultaneously observing the mammography and the DBT images, radiologists considered that the visibility of malignant lesions was higher with DBT.A second study including 98 patients found that the quality of DBT images was equivalent to that of mammography in 52% of the cases, however it proved to be higher (68%) in terms of mass evaluation and lower (73%) in calcification visualization.Another study comparing mammography, DBT and ultrasound found that the three techniques underestimated the tumor size when compared with the size resulting from anatomopathology. As regards staging, 79% of the tumors were adequately staged by DBT, 52% by mammography and 73%, by ultrasound, with a statistically significant difference between mammography and DBT, while the latter behaved analogous to ultrasound.The fourth study assessing the tumor visibility in 36 patients found that 17.5% of tumors were not visualized by mammography and 12.5%, with DBT.Studies assessing the operating characteristics of mammography vs. mammography + DBTThree studies were carried out on a population of women with suspected breast cancer, one of them found that sensitivity (91.9% vs. 73.3%) and NPV (86% vs. 66.2%) were statistically higher and another one also found a significant increase in the area under the ROC (0.97 vs. 0.89). The third study did not find statistically significant differences in terms of operating characteristics but did find differences in image reading (correct image location).Finally, two studies carried out in a screened population, one on 12,631 women and the other one on 1,192 were found. The former showed that the mixed screening strategy increased the rate of cancer detection from 6.1 to 8 every 1,000 screened women and reduced the rate of false positive by 13% (61.1% to 53.1%), in the latter, two groups of radiologists assessed different sets of images, both groups found an increase in the area under the ROC curve (0.894 vs. 0.821; p<0.001 in group 1 and 0.895 vs. 0.828; p<0.001 in group 2) when adding DBT to mammography.In a report, the Adelaide´s Health Technology Assessment department describes that although DBT may be used as a supplement of digital mammography, it is unlikely that it´s use becomes widespread in Australia due to the current deployment of digital mammography and it is likely that DBT becomes the next generation of technology used to screen breast cancer; but this will take place once the digital mammography equipment becomes naturally obsolete. An assessment from Andalusia´s Health Technology Assessment Agency concludes that the evidence found is not enough to be able to assess the effectiveness of DBT as screening test in the general population. In terms of breast cancer diagnosis, they consider that the evidence suggests that DBT might be useful and might become an intermediate step between mammography and biopsy, without defining what population will benefit from it. As regards coverage policies, five US private health sponsors consulted do not cover DBT because they consider it experimental.ConclusionsThe available evidence is of moderate methodological quality.As regards breast cancer diagnosis in the population with clinical or imaging suspicion, the studies assessed that included few patients suggest that DBT might be as effective as mammography. Specifically, the studies that measured the operating characteristics of DBT found that its performance was comparable to that of mammography, however, it should be considered that the only comparator assessed was mammography; therefore, the value of ultrasound and MRI has not been taken into account as diagnostic ancillary method.Adding DBT to diagnostic mammography proved, also in small studies, to increase the sensitivity, negative predictive value and area under the curve in a population with clinical or imaging suspected breast cancer. In terms of screening strategies in the general population, no studies assessing DBT as a single procedure have been found. Two studies showed an increase in the rate of cancer detection and area under the ROC curve and a decrease in the rate of false positives when adding DBT to mammography. However, the current evidence is not good enough to recommend general changes in the screening strategy or to support the use of DBT routinely for breast cancer diagnosis. There are also other barriers for the use of DBT as screening strategy that include its high cost and exposure to higher questionable radiation levels for screening population. DBT might be eventually considered as an intermediate step between diagnostic mammography and biopsy in certain selected cases, although there is still no clear consensus on what the definite role of DBT might be in the diagnostic process of patients who are being evaluated due to suspected lesions.Although DBT has shown excellent operating characteristics and might be a promising technology to continue under evaluation, most clinical practice guidelines and coverage policies do not consider DBT as an integral part of the screening process or pathological image evaluation yet; however this could be modified in the next few years as scientific evidence becomes available.Since mammography and ultrasound equipment are widely available, the conduct of studies of very strict methodology quality and with a large number of patients is considered highly required together with cost-effectiveness studies prior to widely adopting this new technology.