Outline. Digital Breast Tomosynthesis: Update and Pearls for Implementation. Tomosynthesis Dataset: 2D/3D (Hologic Combo Acquisition)

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1 Outline Digital Breast Tomosynthesis (DBT) the new standard of care Digital Breast Tomosynthesis: Update and Pearls for Implementation Emily F. Conant, M.D. Professor, Chief of Breast Imaging Department of Radiology Hospital of the University of Pennsylvania Philadelphia, PA Breast cancer screening outcomes with DBT: Population level Patient level Outcomes by age Outcomes by density Issues of xray dose synthetic imaging Limitation of DBT Tomosynthesis Dataset: D/3D ( Combo Acquisition) Arc of motion of x ray tube, showing individual exposures Tomosynthesis Acquisition Arc of motion of x ray tube, showing individual exposures 1

2 3D Dataset Tomosynthesis Dataset: D/3D ( Combo Acquisition) Projections reconstructed into 1 mm thick slices Projection Images 15 images/15 0 arc Reconstructed Tomosynthesis Slices D Dose Mammogram Projection Images 15 images/15 0 arc Reconstructed Tomo Slices Reconstructed Synthetic D Digital Breast Tomosynthesis The new, better mammogram: Recall reduction (-15-37%) Increased invasive cancer detection (up to 50%) No increase in situ detection (? overdiagnosis) DBT Screening Outcomes

3 Summary of DBT Screening Studies Summary of DBT Screening Studies Prospective Retrospective Author (Year) Industry Skaane (013) Ciatto (013) Lang (015) Siemens single view only Friedewald (014) Greenberg (014) McCarthy (014) Lourenco (015) Volumes DM versus DBT Recall Rate (%) Cancer Rate (per/1000) 1,631 multi reads 6.1 to 5.3% 6.1 to % reduction 7% increase 4.5 to 3.5% 5.3 to 8.1/1000 7,9 DM then DBT 17.% conditional reduction (cancers overall not by pt) 5.8% increase 7,500.6 to 3.8% 6.3 to 8.9% 46% increase (to 3.8%) 43% increase 454, to to 5.4 (DM: 81,187 15% reduction 4% increase Increase in DBT: 173,663) Decrease in Recall of Cancer Detection up 59, to 13.6% 4.9 to 6.6 (DM: 38,674 16% up reduction to 31% 35% to increase 53% DBT: 0,943) (p<0.0001) (p=0.035) 6, to 8.8% 4.6 to 5.5 (DM: 10,78 15% reduction 19.6% increase DBT: 15,571) (p=0.3) 5, to 6.4% 5.4 to 4.6 (DM: 1,577 31% reduction 15% decrease DBT: 1,91) (p< ) (P =0.44) Prospective Retrospective Author (Year) Industry Skaane (013) Ciatto (013) Lang (015) Siemens single view only Friedewald (014) Greenberg (014) McCarthy (014) Lourenco (015) Volumes DM versus DBT Recall Rate (%) Cancer Rate (per/1000) 1,631 multi reads 6.1 to 5.3% 6.1 to % reduction 7% increase 4.5 to 3.5% 5.3 to 8.1/1000 7,9 DM then DBT 17.% conditional reduction (cancers overall not by pt) 5.8% increase 7,500.6 to 3.8% 46% increase (to 3.8%) 454,850 (DM: 81,187 DBT: 173,663) 59,617 (DM: 38,674 DBT: 0,943) 6,99 (DM: 10,78 DBT: 15,571) 5,99 (DM: 1,577 DBT: 1,91) 6.3 to 8.9% 43% increase The improvement in outcomes achieved with DBT directly address the 10.7 to to 5.4 major 15% reduction concerns regarding screening 4% increase for breast cancer with mammography: 16. to 13.6% 4.9 to % reduction 35% increase (p<0.0001) (p=0.035) Too many false positives (low specificity) Too 10.4 few to cancers 8.8% detected (low sensitivity) 4.6 to % reduction 19.6% increase Over diagnosis (esp. DCIS) (p=0.3) 9.3 to 6.4% 5.4 to % reduction 15% decrease (p< ) (P =0.44) Conant (016) 198,881 (DM: 14,883 DBT:55,998) 10.4 to 8.7 % 16.3% reduction (p <.0001) 4.4 to % increase (p=0.006) Conant (016) 198,881 (DM: 14,883 DBT:55,998) 10.4 to 8.7 % 16.3% reduction (p <.0001) 4.4 to % increase (p=0.006) Sub populations reported in Friedewald, et al. Sub populations reported in Friedewald, et al. DBT reduces false positive call backs: 47yr old presents for screening, focal asymmetry, left lateral on CC Recall Reduction Tomosynthesis imaging shows no abnormality. (Tissue superimposition present on D) 3

4 DBT reduces false positive call backs: 43yr old presents for baseline screening. Architectural distortion? On sequential DBT slices, each component of lesion is a separate structure (note localizer positions). No recall needed! 46 year old woman presents for screening Improved Cancer Detection A case 4

5 D DBT US 6 cm Invasive Lobular Carcinoma Teaching point: it s not all about density MRI Cancer detected on DBT alone: 68 year old woman presenting for screening Findings: Architectural distortion, irregular mass in UOQ, best on DBT. Work up was directly to US. The D mammogram was interpreted as negative Pathology: Invasive lobular carcinoma 5

6 Limitations of early trials Most studies first, prevalent round screening Only 3 studies were prospective (Oslo, STORM, Malmo) Majority of retrospective studies had concurrent DM screening potential for bias in screened cohorts There has been little data on false negatives. University of Pennsylvania Data Method: Three consecutive years DBT screening Population level analysis (each year of screening) Patient level analysis (each round of screening) Comparison with cancer registry data for false negatives McDonald EM et al. JAMA Oncol. 016;(6): 1 7 Results from Penn consecutive years of DBT screening Metric Year 0DM Year 1 DBT Year DBT Year 3 DBT Recall rate (%) Cancer rate/ PPV Interval CA/ Population level Cancer and Biopsy rates, PPV1 by year Cancer/ Invasive cancer/ Interval cancer/ Biopsy % PPV yr 0 (DM) DBT yr 1 DBT yr DBT yr 3 McDonald EM et al. JAMA Oncol. 016;(6): 1 7 McDonald EM et al. JAMA Oncol. 016;(6): 1 7 6

7 What about first round, Prevalence Effect? Breast Cancer Research and Treatment on line 3/1/16 14 Patient level Outcomes for Consecutive Years of Screening DM with priors One DBT Screen with Two DBT Screens (n= priors (n= 1395) 9316) Three DBT Screens (n=303) Recall rate % Cancer/1000 PPV1 % PROSPR consortium (BWH-D, UVt, UPenn) DM and DBT cases (14,883 DM and 55,998 DBT studies) Patient level data Reduction in recall (8.7% vs 10.4% p<0.0001) Increase in cancer detection (5.9 vs 4.4/1000, p= 0.006), 34% increase in cancers overall 7% invasive cancers Trend in decrease in false negatives (0.46 vs 0.6/1000) McDonald EM et al. JAMA Oncol. 016;(6): 1 7 Conant EF et al. BCR&T 016; on line 3/1/16 Cancer Detection (per 1000) by Age 9 Tomosynthesis Outcomes by Density Category Cancer Detection per BCSC DM DBT Change in Cancer Author Year Mean Age Number of Dense Detection Rate Patients (per 1000) Change in Recall Rate (per 1000) Prospective Trials Ciatto , Lang , Bernardi , Tagliafico ,31 +4 Retrospective Trials >70 Rose , McCarthy , Conant ,65 (1,133) Rafferty , Derived from unpublished data: Friedewald, et al. JAMA 014;311(4): Adapted from Houssami N, Turner RM. Breast 016:

8 Cancer Detection (per 1000) by Density Category Cancer Detection per BCSC DM DBT What about False Negatives? 1 0 Fat Scattered Hetero Extreme Derived from unpublished data: Friedewald, et al. JAMA 014;311(4): False negative DBT: Not all cancers visible with DBT. 4 yo with lump in left breast. 54 yo with pain, thickening of the right breast DBT MLO Views MIP Right MIP Left (Normal) Invasive Ductal CA (TNeg) Diagnostic mammogram (013), ultrasound for rt pain, thickening negative. DM DBT MRI extensive asymmetric NMLE enhancement rt breast. Invasive ductal carcinoma. 8

9 Comparison of DBT Dose What about Dose?? DBT has dose boost at > 50mm Siemens DBT dose higher than DM for all thicknesses GE DBT dose same as DM (uses grid for both modes) Siemens GE Courtesy of Andrew Maidment, PhD Overview of sd Reconstruction Tomo Stack Synthetic D Imaging DBT image data used to create both 1mm slices for tomo stack and sd images sd Mammo Multiple, low dose images obtained and then reconstruction 9

10 Synthetic D is about more than just dose! Skaane (RSNA 014): Detection Sensitivities Synthetic D versus DM Need D images for interpretative tasks essential to improved performance of DM/DBT screening: Global assessment of breasts BI RADS density assessment Comparison with prior images Assessment of lesions esp. calcs, asymmetries, etc. Efficient, high volume screening Synthetic D DM D p value Non calc lesions* (n=73) Observer % (54/73) 7.6% (53/73) Observer 83.6% (61/73) 83.6% (61/73) Observer % (6/73) 83.6% (61/73) Calcified lesions* (n=14) Observer 1 9.9% (13/14) 85.7% (1/14) Observer 9.9% (13/14) 100% (14/14) Observer 3 9.9% (13/14) 9.9% (13/14) *Analysis performed on 87 cancers seen on either synthetic D or digital (DM) D Gilbert et al (online Radiol 7/17/15): Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial) Arch. Distortion only on sd and DBT 51 yo architectural distortion seen only on sd/dbt Pathology: invasive ductal carcinoma. Multicenter/reader, retrospective study Dataset of 7060 cases D mammo D plus DBT (DBT) sd plus DBT (sdbt) Sensitivity: 87% D 89% D + DBT 88% sdbt Specificity 57% D 70% D + DBT 7% sdbt sd + DBT and D + DBT had better sensitivity for depicting 11 0 mm inv CA than D alone. However sd + DBT was inferior to both D alone and D + DBT in depicting microcalcs and 11 0mm DCIS. DM DBT sd 10

11 Synthetic D with Tomosynthesis Synthetic D with Tomosynthesis D C View 3D Slice Pathology: Ductal Carcinoma in situ (DCIS) DM Pathology: Ductal Carcinoma in situ (DCIS) sd Synthetic Imaging: False Positive Calcifications 56 yo at screening. Synthetic D (sd) use at Penn Penn: Integrated sd over 4 mos. (9/14-1/14) Screening: Jan 7 th, 015 began screening all pts with sd-dbt sd RCC Possible calcifications? DM Magnification: No definite calcifications Magnification at recall demonstrates no calcifications. sd reconstruction algorithm may make normal ligaments appear like calcifications. Performance outcomes measured Recall rate (by lesion type, cancer detecton, PPV1) Cancer detection PPV1, 3 Zuckerman S, et al. Radiology

12 Performance metrics with sd? Modality Overall Calcs Masses Asym. Arch dist Technical Recall DM 10.4% 1.8%.4% 6.1% 0.7% 0.44% DM+DBT 8.8% 1.6%.7% 4.5% 1.0% 0.% sd+dbt 7.1% 1.1%.4% 3.% 1.1% 0.1% p value (DM/DBT vs sd/dbt) < < DBT screening dose reduced by 39% Maintained low recall rate (actually continues to decrease) Significant changes in calcs, asymmetries and technical recalls Zuckerman S, et al. Radiology, 016 sd Performance metrics continued Metric DM/DBT sd/dbt p value Biopsy rate (%) Cancers/ in situ invasive PPV1 (%) PPV3 (%) sd maintains benefits of DBT: Increased number of cancers detected per recall (PPV1) Sensitivity and specificity similar, thus far Slight decrease in detection of in situ cancers to be monitored See RSNA 015 Zuckerman scientific S, et exhibit al. Radiology, RC UPenn Data with sd as 4 th consecutive year Population level Cancer and Biopsy rates, PPV1 by year *Screening with sd/dbt Cancer/1000 Invasive cancer/1000 Interval cancer/1000 Biopsy % PPV1 Aujero et al (017): More on Synthetic D/DBT DM n=3,076 DM/DBT n=30,561 sd/dbt n=16,173 Recall rate (%) Cancer detection/ Invasive In situ Biopsy rate (%) PPV1 (%) PPV yr 0 (DM) DBT yr 1 DBT yr DBT yr 3 sd yr 4 Are we missing in situ cancers? Is this ok (decreasing overdx) or bad (increasing interval cancers?) *sd data is based on initial 6 months of data not powered for cancer detection Zuckerman S, et al. Radiol 016 Aujero MP, et al. Radiology on line Feb 3 1

13 DBT is the better mammogram Additional outcome data is needed Modality based: DBT versus Ultrasound, abbreviated MR, Molecular Breast Imaging, Contrast mammography (D or DBT) Larger populations for subgroup analyses: Age, density, screening intervals, etc. Biology, biology, biology Are additional DBT cancers biologically more aggressive? Surrogate for mortality reduction? Perelman Center for Advanced Medicine University of Pennsylvania Medical Center Thank you! 13