ACRIN Breast Committee

1. ACRIN Breast Committee Fall Meeting 2010 4006: Comparison of Full-Field Digital Mammography with Digital Breast Tomosynthesis Image Acquisition in Relation to Screening Call-Back Rate Emily F. Conant, MD Constantine Gatsonis, PhD ACRIN Breast Committee

2. Digital Breast Tomosynthesis • Disclosures: • GE Support (P.I. E. Conant): A Multicenter Study to Test the Non-Inferiority of Digital Breast Tomosynthesis (DBT) Compared to Full-Field Digital Mammography(FFDM) in Detecting Breast Cancer • E.Conant: Consultant to Hologic

3. Study Summary

4. Projection imaging X-rays Compression Plate Breast Detector Limitations of Mammography Tissue superimposition

5. Digital Breast Tomosynthesis Digital Breast Tomosynthesis (DBT) Multiple low dose digital mammographic images are obtain along an arc and then reconstructed into a stack of images

6. X-rays Tube Rotation Digital Breast Tomosynthesis Tomographic Imaging Compression Plate Breast Detector

7. Digital Breast Tomosynthesis • Vendors have varied approach to DBT: • Image acquisition • Angle of acquistion, number of images in arc • Continuous arc image acquisition • “Stop and shoot” image acquisition • Stand alone screening tool versus adjunct to full field digital mammography (FFDM) • Single view MLO DBT (no FFDM) • Two view DBT plus FFDM

8. Digital Breast Tomosynthesis • Preliminary experience has suggested that digital breast tomosynthesis (DBT) may provide: • Better specificity leading to reductions in recall rates • Improvements in sensitivity and the depiction of the extent of disease

9. Digital Breast Tomosynthesis • Issues? • Few published trials • Results stress specifity as measured by reduction in recall rates • Most are single institution, single vendor • Technical approach varies greatly by vendor… • Little published data on impact of tomosynthesis on sensitivity in breast cancer screening

10. Digital Breast Tomosynthesis • Multi-center trial of 1957 pts • Compared FFDM and DBT recall rates • 43% reduction in recall rate • Rafferty et al. RSNA 2007:SSG01-01 • Single institution trial of 98 pts • Compared FFDM and DBT recall rate • 40% reduction in recall rate • Poplack et al. AJR 2007;189(3):616-623 • Single institution trial of 125 selected studies • FFDM alone, DBT alone and FFDM/DBT combo • 30% decrease recall rate with combo, 10% DBT alone • Gur et al. AJR 2009;193:586-591

11. Digital Breast Tomosynthesis • Two views versus one view tomo? • Results • 22/34 (65%) both projections equal • 4/34 (12%) much better seen on MLO projection • 5/34 (15%) much better seen on CC projection • 3/34 (9%) seen only on the CC projection • Imaging in both CC and MLO positions is optimal • Rafferty et al:RSNA 2006;SSG01-04

12. Digital Breast Tomosynthesis What about calcifications in DBT? • 98 recalled cases • “image quality of tomosynthesis was inferior to diagnostic mammography” in characterization of calcs • Poplack et al. AJR 2007;189(3):616-623 • 119 DBT cases with calcifications • Approx. 50%, DBT = FFDM • Approx. 40%, DBT > FFDM • Kopans et al. RSNA 2008 SSJ01-02. • Motion artifact in DBT

13. Hypothesis • Digital breast tomography (DBT) will improve the specificity of breast cancer screening as measured by a reduction in the call-back rate while maintaining the sensitivity of cancer detection. • This improved accuracy will be achieved by the optimization of the imaging sequence and number of views obtained at a capped radiation dose in the combined DBT and 2-D screening sequence

14. Eligibility and Sample Size • Screening Group A (n=500) : • Women presenting for screening > 25 yrs • Enrichment Group B (n=50) : • Women called back from FFDM screening for diagnostic imaging • Total Accrual = 550 cases

15. Study Design • Standard of Care clinical study: • 3 view digital mammogram • Study Imaging: • 2 view tomosynthesis (MLO and CC) and low dose 2-D MLO • Sequential read of study low dose 2-D CC view. • Studies read independently therefore, • call-backs determined independently

17. Specific Aims • Primary Aim: • Compare recall rates of FFDM to limited DBT set (Group A) • Secondary Aims: • To compare sensitivity of FFDM to the limited DBT set (Groups A and B) • To assess lesion-type characterization: • To compare sensitivity and specificity by lesion-type (calc only lesions versus soft-tissue lesions, as well as lesion subgroups: masses, calcs, architectural distortions, asymmetries) in FFDM versus DBT. • To estimate the agreement of FFDM and DBT with the determination of the adjudication committee on lesion-type characterization.

18. Additional Aims • Secondary Aims, continued: • To use the sequential interpretation results [Groups A and B] to compare the two-view limited tomosynthesis set (with low-dose MLO view alone) with the tomosynthesis plus set (addition of low-dose CC view) on the basis of: • Call-back rate; • Identification of new lesion(s); • Lesion characterization; and • Triangulation • To calculate and compare the radiation dose of the FFDM and the DBT sets • To identify the determinants of participant radiation dose and clinical image quality, including factors such as kVp, mAs, target/filter combination, and breast thickness and composition

19. Recruitment • Patients to be recruited over a 1 year period • Trial scheduled to open 10/6/10 at Pennsylvania sites: • Hospital of the University of Pennsylvania • Einstein Medical Center • Limited to one industry since only one vendor in PA – Hologic

20. Future Tomosynthesis Trials? • Optimize imaging for tomosynthesis • Which combinations of 3-D and possibly 2-D images? • Decision based on risk/benefit for individual patient? • Optimization of dose based on task? • Trial powered for sensitivity? • High/intermediate risk patients (+/-MR)? • How do we best utilize tomosynthesis for diagnostic imaging?