TOMOSYNTHESIS. Daniela Bernardi. U.O. Senologia Clinica e Screening mammografico APSS Trento, Italy

Transcription

1 TOMOSYNTHESIS Daniela Bernardi U.O. Senologia Clinica e Screening mammografico APSS Trento, Italy

2 BACKGROUND early detection through screening MAMMOGRAPHY is associated with reduced breast cancer morbidity and mortality (estimated values: 23% for invited women, 40% for women who attend screening mammography) EUROSCREEN Working Group, J Med Scree The Independent UK Panel on Breast Cancer Screening. Lancet Duffy SW et al. J Med Screen, 2012 Lauby-Secretan B et al. N Engl J Med 2015 not optimal sensitivity and specificity (around 70% ) high dense breast, young women Pisano E.D et al. N Engl J Med, 2006 SFM FFDM 2

3 DIGITAL BREAST TOMOSYNTHESIS (DBT) 1. Multiple low dose projections of the compressed breast during an angular movement of the X-ray tube;

4 DIGITAL BREAST TOMOSYNTHESIS (DBT) 2. A pseudo-three dimensional reconstruction of the breast using dedicated softwares Tomo slices INCREASED SENSITIVITY: reducing - masking effects related to fibro-glandular density - overlap phenomena INCREASED SPECIFICITY: reducing - overlap phenomena

5 DIAGNOSTIC TEST A BETTER DIAGNOSIS SYMPTOMATIC WOMAN: - increased diagnostic accuracy; - better and more efficient workflow (targeted ultrasound examinations, fewer additional 2D views, etc.); - fewer benign biopsies Rafferty EA, et al. Radiology 2013 Morel JC et al: Clin Radiol 2014 Gilbert F, et al: Health Technology Assessment 2015 Bansal GJ, et al. Br J Radiol PRE-OPERATIVE PLANNING: - as good as 2D in estimating lesion size; - 2D+DBT+US vs MRI: overall similar sensitivity and accuracy Fornick D, et al. Acta Radiol 2010 Timberg P, et al. Med Phys 2010 Mariscotti G, et al. Anticancer Reasearch 2014 DBT SECOND-LOOK for additional findings at pre-operatory MRI : - identified and correctly classified some of the MRI additional findings; - avoided few MRI-guided biopsy. Clauser P, et al. Eur Radiol 2015

6 SCREENING TEST A BETTER DIAGNOSIS RETROSPECTIVE EVALUATIONS IN SCREENING SETTING 2D vs 2D+DBT (before and after introduction of DBT) Skaane P. Breast Cancer Pub Year N. screens 2D vs 2D+DBT RR (%) 2D vs 2D+DB CD (%) 2D vs 2D+DB Durand , , 7.8 (s) 0.57, 0.59 Haas , , 8.4 (s) 0.52, 0.57 Lourenco , , 6.4 (s) 0.54, 0.46 McCarthy , , 8.8 (s) 0.46, 0.55 Absolute false-recall reduction(14-63%) Rose , , 5.5 (s) 0.40, 0.54 McDonald , , 7.8 (s) 0.46, 0.54 Destounis , , 4.2 (s) 0.38,0.57 (s) Greenberg , , 13.6 (s) 0.49, 0.63 (s) Friedewald , , 9.1 (s) 0.42, 0.54 (s) Cancer detection increase Conant , , 8.7 (s) 0.44, 0.59 (s)

7 A BETTER DIAGNOSIS (screening test) PROSPECTIVE POPULATION BASED SCREENING TRIALS 2D vs 2D+DBT (vs synt2d+dbt)* Study STORM Ciatto S, Lancet Oncol, 2013 OSLO* Skaane P, Eur Radiol, 2013 MALMO Lång K, Eur Radiol, 2015 STORM2* Bernardi D, Lancet Oncol, 2016 N. screens Age Design DBT Intepretation screens Prospective, paired Prospective, paired Prospective, paired Prospective, paired 2 views Double, sequential 2 views Double, independent 1 view Double, sequential 2 views Double, sequential Study CD 2D, 2D+DBT (n/1000) Aumento CD (n/1000) Diff RR 2D vs 2D+DBT (%) STORM 5.3, OSLO 6.1, MALMO 6.3, STORM2 6.3, Incremental CD RR reduction??

8 IMPLEMENTATION OF DBT implications and possible impact on the organization IMPLICATIONS Increase RR Higher x-ray dose in healthy population False-positive results are a key metric in overdiagnosis Longer reading times Management DBT detected lesions Overdiagnosis / overtreatment Cost effectiveness

9 RECALL RATE: LEARNING CURVE Lång K, Eur Radiol, 2016 N. screens 2D 2D+DBT DBT MALMO % 1.1% 1.7% LEARNING CURVE: RR decrease by the time and reading experience

10 2D 2D NO CHANGES: NO RECALL

11 2D SOUSPICIOUS DBT DISTORTION IN SYNT2D AND DBT: RECALL synt2d RADIAL SCAR DBT recalls lesions not visible/not sospicious in 2D 2015

12 FALSE POSITIVE RECALLS final RR depends by: - ratio between baseline 2D recalls and DBT recalls; - learning curve; - availability of previus DBT images for comparison

13 IMPLEMENTATION OF DBT implications and possible impact on the organization IMPLICATIONS Increase RR Higher x-ray dose in healthy population Longer reading times Management DBT detected lesions Overdiagnosis / overtreatment Cost effectiveness

14 X-RAY DOSE IN HEALTHY POPULATION Double dose using integrated 2D/DBT 2D vs 2D+DBT vs synt2d+dbt 2D 2D + DBT Combo DBT OSLO AGD per view Skaane P et al. Radiology, ± 0.61mGy 3.52 ± 1.08mGy 1.95 ± 0.58mGy STORM2 AGD per view Bernardi D, et al. Lancet Onc, ± 0.51mGy 3.22 ± 1.16mGy 1.87 ± 0.67mGy SOLUTIONS: - DBT alone aquisition - synthesized 2D images increased FPR (no comparison with priors) Lång K et al: Eur Radiol, 2015 Synthesized 2D image

15 Screening with Tomosynthesis OR standard Mammography 2 trial Bernardi D et al. Lancet Oncol, 2016 Prospective population-screening study aimed to examine the effect of screening with DBT mammography comparing different screen-readings used sequentially: - conventional 2D mammography only; - integrated 2D+DBT mammography; - integrated synt 2D+DBT mammography; ethical committee approval; resident women, aged informed consent (who declined the invitation received standard 2D); integrated 2D + DBT mammography in Combo HD mode (Selenia Dimensions 3D, Hologic) - acquired bilateral two-views (MLO and CC views); - reconstruction of synt 2D images from DBT data using C-view (Hologic)

16 READING PROTOCOL: DOUBLE, BLIND & SEQUENTIAL READING 2D+DBT RADIOLOGIST A Sequential screen-reading phase 1: report whether to recall or not based on standard 2D mammograms only RADIOLOGIST B Sequential screen-reading phase 1: report whether to recall or not based on standard 2D mammograms only Sequential screen-reading phase 2: report whether to recall or not based on 2D+3D mammograms Sequential screen-reading phase 2: report whether to recall or not based on 2D+3D mammograms

17 SCREEN READING PROTOCOL: DOUBLE BLIND & SEQUENTIAL READING synt2d+dbt RADIOLOGIST C Sequential screen-reading phase 1: report whether to recall or not based on syntetic 2D mammograms only RADIOLOGIST D Sequential screen-reading phase 1: report whether to recall or not based on syntetic 2D mammograms only Sequential screen-reading phase 2: report whether to recall or not based on synt 2D+3D mammograms Sequential screen-reading phase 2: report whether to recall or not based on synt 2D+3D mammograms Reference standard: - complete assessment outcome - excision histology Recall (positive screen) based on decision to recall by either reader (A,B,C or D) at either screen-reading phase (1 or 2) paired data were compared using McNemar s Chi-square test

18 Screening with Tomosynthesis OR standard Mammography (STORM) 2 2D vs 2D+DBT vs synt2d+dbt Bernardi D et al. Lancet Oncol, 2016 Comparison of integrated DBT vs 2D alone Partecipanti (n.9672)* N. cancri identificati CDR /1000 (95%) 2D 61/ (4.8,8.1) - p Increased CDR/1000 for integrated DBT vs 2D 2D+DBT 82/ (6.7,10.5) < (1.2,3.3) 2Dsynt+DBT 85/ (7.0,10.8) < (1.4,3.8) *analyzed for 9677 lesions Integrated synt2d+3d is not inferior to integrated 2D+3D Bernardi D et al. Lancet Oncol, 2016 Skaane P et al. Radiology, 2014

19 CHARACTERISTICS OF BREAST CANCERS DETECTED Cancers detected by 2D/synt2D/DBT Cancers detected by DBT alone N.tot 61/90 29/90 20/59 pt category ptis 15 (25%) 1 (4%) 3 (15%) pt1a 7 (11 %) 5 (17%) 0 (0%) pt1b 15 (25%) 9 (31%) 8 (40%) pt1c 18 (30%) 11 (38%) 8 (40%) pt2 6 (10%) 3 (10%)* 1 (5%) *incluso 1 pt3 STORM1 trial Cancers detected by DBT alone

20 nodal status: 10% positive tumour grade: 14% high grade

21 FALSE POSITIVE RECALLS FPRs (over n.9587)* FPRs (over n.9587)* N. of FPR 2D or 2D+3D ( ) - p Difference in FPR (%) 2Dsynt or 2Dsynt+3D ( ) ( ) *screens classified as not having BC N. of FPR FPR % (95%) 2D or 2D+DBT ( ) - p Difference in FPR (%) 2Dsynt or 2Dsynt+DBT ( ) ( ) Comparison vs 2D alone Bernardi D, Houssami N, et al. Lancet Oncol, 2016 in press 2D ( ) - 2D+DBT ( ) ( ) 2Dsynt+DBT ( ) < ( ) Bernardi D, Houssami N, et al. Lancet Oncol, 2016 Similar RR for synt2d/dbt and 2D/DBT

22 FALSE POSITIVE RECALLS FPRs (over n.9587)* N. of FPR FPR % (95%) 2D ( ) - p Difference in FPR (%) 2D+DBT ( ) ( ) 2Dsynt+DBT ( ) < ( ) STORM2 Bernardi D, Lancet Oncol, 2016 N letture 2D or 2D+3D 2Dsynt or 2Dsynt+3D tot

23 X-RAY DOSE IN HEALTHY POPULATION In screening should be considered the acquisition of DBT alone and a reconstruction of synthetic 2D images which allow: - containment radiation dose - comparison with previous images in 2D - evaluation of spatial distribution of clustered microcalcifications

24 IMPLEMENTATION OF DBT implications and possible impact on the organization IMPLICATIONS Increase RR Higher x-ray dose in healthy population Longer reading times Management DBT detected lesions Overdiagnosis / overtreatment Cost effectiveness

25 READING TIME 2D (media) 2D+DBT (media) Diff. 2D+DBT vs 2D Diff. % 2D+DBT vs 2D TRENTO STUDY* Bernardi D et al. Eur Radiol 2013 OSLO Skaane P et al. Radiology, 2013 MALMO Lång K, Eur Radiol, % % % Integrated 2D+DBT doubles the time Population-based breast screening programmes Double number of radiologists - Invitation by letter - MX double reading - Recalls for assessment

26 READING TIME learning curve; reading protocols (slabbing); CAD systems other solutions (no more double reading, single reading synt2d/dbt)

27 READING TIME: NEW STRATEGIES 2D double reading (std) vs 2D/DBT single reading vs 2D/DBT double reading Houssami N, et al. Eur J Cancer 2014 N.cancers CDR CDR p 2D, dr D+DBT, sr < D+DBT, dr <0.001 Integrated 2D+DBT single reading is Double integrated 2D+DBT reading adds more effective and efficient compared to 0.5/1000 screens (and increased FPR%) standard 2D double reading DBT single reading?

28 IMPLEMENTATION OF DBT implications and possible impact on the organization IMPLICATIONS Increase RR Higher x-ray dose in healthy population Longer reading times Management DBT detected lesions Topic of my next presentation!! Overdiagnosis / overtreatment Cost effectiveness

29 IMPLEMENTATION OF DBT implications and possible impact on the organization IMPLICATIONS Increase RR Higher x-ray dose in healthy population Longer reading times Management DBT detected lesions Overdiagnosis / overtreatment Cost effectiveness

30 SCREENING MAMMOGRAPHY: - BENEFIT: increased breast cancer detection reducing breast cancer morbidity and mortality; - HARM: increased breast cancer detection without reducing breast cancer mortality OVERDIAGNOSIS cancers detected at screening that would not have otherwise become clinically apparent in the woman's lifetime 1-10% (6,5%) EUROSCREEN Working Group, % UK Panel, 2012 DBT increased cancer detection: is it a benefit or an harm?

31 DBT & OVERDIAGNOSIS To assess incremental benefit (mortality reduction) of DBT can be used surrogate end-points, like interval cancer rates. Irwig L, et al. BMJ, 2006 Houssami N. MJA, 2013 Houssami N et al. Expert Rev. Med. Devices, 2015 INTERVAL CANCERS Negative screen Interval cancers Next screening 1 year 2 year

32 INTERVAL CANCERS 2D Screening DBT Screening screening Benefit if: - increased cancer detection - reduced interval carcinoma rates

33 DBT & INTERVAL CANCERS Interval cancers in retrospective studies (USA) STUDY 2D (n/1000) DBT (n/1000) p Upenn McDonald, JAMA 2016 PROSPR consortium Conant E, Breast Cancer Res Treat Not significative reduction None of the four prospective trials (EU) were designed (and powered) to assess interval cancer rates reduction Houssami N et al. Expert Rev. Med. Devices, 2015

34 IN THE MEANTIME. OTHER TRIALS ARE ONGOING Randomized trials (Reggio Emilia, Piemonte, Norway) end-point: evaluation of IC rates in 2D vs 2D/DBT (or synt2d/dbt in norwegian study) Pilot studies (trials) on the use of DBT in population screening programmes

35 PRIMARY OUTCOME - increased detection rate (biological cancer characteristics); - reduction of false positive recalls; - IC rates - T2+ DBT SCREEN DETECTED at the incidence round SECONDARY OUTCOME - costs for introducing DBT technology and related infrastucture (i.e. data storage) - costs for ongoing implementation (reading time, assessments, biopsies, surgeries and therapies); Gilbert FJ, et al. Clin Radiol, 2016 Houssami N et al. Expert Rev. Med. Devices, 2015

36 CONCLUSIONS: - CLINICAL MAMMOGRAPHY (symptomatic woman, screening assessment) - SCREENING MAMMOGRAPHY Increased diagnostic accuracy, Waiting regardless for results from on - overdiagnosis radiologist experience! / overtreatment - cost effectiveness Svahn TM, Macaskill P, Houssami N. The breast, 2015 YES Thank you! Daniela Bernardi Trento, ITALY dnlbernardi@gmail.com