Moderne mammadiagnostikk hvor står vi og hvor går vi?

Transcription

1 NBCG Oslo 15. juni 2018 Moderne mammadiagnostikk hvor står vi og hvor går vi? Professor dr.med. emeritus Per Skaane Oslo University Hospital Ullevaal Breast Imaging Center Oslo / Norway PERSKA@ous-hf.no 25 min.

2 Mammographic techniques * Conventional mammography: - Screen-film mammography (SFM) - Xeromammography - Computed radiography CR (CR-mammo) - Full-field digital mammography (FFDM) - Standard views (cc, mlo, lat) - Supplemental views (mag - cone view) - Ductography (galactography) (today:mri!) - Mammography-guided biopsy Advanced mammographic techniques: - Digital breast tomosynthesis (DBT) - Contrast-enhanced spectral mammography (CESM) * Projection images using X-ray (i.e., «MR mammography», «Ultrasound mammography» «Dedicated breast CT» and other modalities should not be included in «mammographic techniques»!)

3 A) Klinisk mamma-diagnostikk : Hvor står vi og Hvor går vi? Today: Assessment of palpable and non-palpable breast abnormalities Conventional mammography - incl. supplemental views, mx-guided biopsy Ultrasonography - (Doppler imaging) - (Elastography) - US-guided biopsy MRI - incl. several sequences (T1, T2, CE-MRI, DWI) - MRI-guided biopsy

4 Tomorrow: Assessment of palpable and non-palpable breast abnormalities Mammography - incl. supplemental views, mx-guided biopsy - Advanced mammographic techniques: - Digital breast tomosynthesis (DBT) - Contrast-enhanced spectral mammography (CESM) - Spectral imaging (mammography) Ultrasonography - Conventional B-mode - Doppler imaging plus advanced techniques MRI - incl. several sequences (T1, T2, CE-MRI, DWI) - «ABB-MRI» (screening?!) Isotope scanning (molecular breast imaging - PEM) Diffuse Optical Tomography (DOT) Computed tomography (dedicated breast CT) Fusion (hybrid) techniques (FDG-PET and others)

5 Digital Breast Tomosynthesis (DBT) Overlapping structures (cancer) can hide in 2D, but are clearly seen in a DBT (3D) slice DBT System by Manufacturer Scan angle Range, º Pixel size Range, µ Projections Range, 9-25 Scan time Range, 4-25 s Tube motion - Step-and-shoot - Continuous Preibsch H: Radiologe 2015;55:59-69 Reconstruct. FBP / Iterative FBP: Filtered back projection

6 Contrast-enhanced mammography: a) Temporal Subtraction Approach Mask image taken Several Post-contrast images taken at certain time intervals Log Subtraction: (Each Post-contrast image) (Mast image) (1) (2) (3) (4) (5) time Non-ionic contrast agent injected into the patient Works in Progress. Not cleared by the FDA for use in the US. Contrast uptake Uptake and Washout of Cancer time Mask Image (Post-contrast image at 5-min) (Mask image) Images Courtesy of Martin Yaffe PhD, Sunnybrook

7 b) Dual Energy Subtraction Approach ( Dual-energy: Contrast-Enhanced Spectral Mammography CESM )

8 Eur J Radiol 2015 a)

9 Spectral mammography («spectral imaging»): Is it possible to distinguish cysts from tumors on screening mammograms? The Philips MicroDose Mammography system Cases where LCT works CIST_00084: Cyst P cyst = 70% Left: Philips MicroDose Mammography system Right: The spectral image receptor and electronics Slide courtesy: Sectra - Philips, Stockholm

10 Breast US Primary tumor features : Shape Axial orientation Contour (margin) Echotexture Echogenicity Transmission Surrounding 98% Advanced applications : Higher frequencies Color Doppler Power Doppler Compound scanning Harmonic imaging Contrast-enhanced US Increased specificity («down-grading») Influence on decision making? Skaane P et al.: Am J Roentgenol 1998;170:109

11 Jung HK et al. B-mode PDI AngioPLUS «ROC (AUC) showed that AngioPLUS was superior to power Doppler US in differentiating benign from malignant breast masses, but the difference was not statistically significant» B-mode US CDI PDI SMI Park AY et al.

12 MacDonald L: J Nucl Med 2009;50:1666

13 Computed tomography: Dedicated breast CT O Connell A et al.: AJR 2010;195:496 Canon cone beam breast CT skanner: X-ray tube rotates 360 degrees around the breast (placed into a cup); not regulated for commercial use.

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15 Hybrid techniques: Work in progress (experimental): Dual-Modality Tomosynthesis (DMT) Combined optical and tomosynthesis imaging Invasive ductal carcinoma 25 mm Hybrid scanning: Tomosynthesis and 99m sestamibi gamma imaging Fang Q et al.: Radiology 2011;258:89-97 Williams MB et al.: Radiology 2010;255:181

16 Morphological («qualitative») imaging tests: «Conventional imaging» such as mammography, US, DBT Functional («quantitative») imaging techniques: «Advanced imaging» such as MRI, CESM, PET/CT

17 A) PET/MRI: Complete response after NAC Pretreatment After 1. NAC cycle Cho N et al. Pretreatment MRI MRI after 1. NAC cycle Preop. MRI after 8 NAC cycle: No enhancement; histo: No residual tumor B) PET/MRI: Incomplete response after NAC Pretreatment After 1. NAC cycle Pretreatment MRI MRI after 1. NAC cycle Preop. MRI after 8 NAC cycle: Enhancing mass; histo: 3.6-cm IDC grade 3

18 B) Mammografi screening: Hvor står vi og Hvor går vi? JAMA 1961 Bassett LW et a.: Diagnosis of Diseases of the Breast. Elsevier Saunders, 2005

19 Sensitivity The «gold standard» of breast cancer screening today is conventional Full-Field Digital Mammography (FFDM) Conventional mammography has two serious inherent limitations: 1. Low sensitivity (cancer detection rate) in women with dense breast parenchyma due to superimposed tissue ( masking effect ) Mammography: Sensitivity (%) and breast density I II II IV BI - RADS Density BI-RADS (ACR) density category Low specificity (false positive interpretations) due to summation of normal parenchyma ( pseudotumors ) Breast cancer screening in the future might require a better diagnostic test!

20 Breast MRI: The highest sensitivity for breast cancer Screening: CE: Lump + (?) MX neg / US neg / FNAC neg Multifocal invasive ductal carcinoma (IDC)

21 Acquisition time of «Abb-MRI» (and «Short first-pass MRI» of the breast) is only about 3 to 4 minutes and reading time for MIP images very short Hall FH The Rise and Impending Decline of Screening Mammography Radiology 2008; 247: : I believe that mammography is going to be replaced by magnetic resonance (MR) imaging, not only in high-risk women but increasingly in those at average risk. However: Two main challenges (problems) regarding implementation of «ABB-MRI» for women at average risk in population-based screening remain: 1.Costs 2.Availability

22 Tomosynthesis (DBT) in breast cancer screening: Pros and «Cons» A) DBT pros: Reduced summation simulating masses («pseudotumors») (i.e., increased specificity and lower recall rates) Replacement of supplemental views for non-calcified lesions (i.e., increased specificity and lower recall rates) Increased cancer conspicuity and visibility (i.e., increased cancer detection rates) B) DBT cons («challenges»): One- vs. two-view DBT, radiation dose, and synthetic 2D Microcalcifications: syn2d and DBT vs. FFDM The (very) dense breast Lesions seen only on DBT («tomo-only lesions») Increased work-load / interpretation time Overdiagnosis («length-time bias») Cost-effectiveness

23 DBT pros: Increased specificity (reduced recall rate) Lcc: Syn2D Lcc: DBT? Indeterminate / suspicious finding on FFDM A) Excluding the presence of a mass B) Confirming the presence of a benign mass Circumscribed mass: Cyst or tumor? Ultrasound!

24 DBT pros in breast cancer screening: Replacement of supplementary mammographic views for non-calcified lesions Lcc: FFDM (2D) Assessment: Lcc 1. and 2. cone-mag views?? Lcc: 3D (Tomo)? OTST: IDC G2, 4.5 mm

25 DBT pros: Increased cancer conspicuity and visibility (i.e., increased sensitivity) a) Increased cancer conspicuity FFDM R mlo TOMO R mlo Tubular carcinoma 6 mm b) Increased cancer visibility FFDM R cc TOMO R cc IDC G2, 14mm (+ DCIS G3, 24 mm)

26 Retrospective US screening studies comparing 2D+3D (FFDM+DBT) vs. 2D (FFDM) alone Study Popul - 2D - 3D Recall % Sign CDR n Sign Study Popul - 2D - 3D Recall % Sign CDR n Sign Yale Uni, New Haven, CT Haas BM: Radiology D 3D ns Newark, DE, USA 2D Aujero MP: Radiology D ns TOPS, Houston, TX Rose SL: AJR ns PROSPR consortium, US Conant EF: BCRT US Comm. Practice, MD-VA Greenberg JS: AJR Uni Utah, Salt Lake City, UT Freer PE: BCRT ns E. Wende Breast Care, NY Destounis S: J Clin Imag Sci NA Dpt. Radiology, Brigham, MA Giess CS: AJR ns Pennsylvania, Philadelphia, PA McCarthy AM: JNCI ns Pennsylvania, Philadelphia, PA McDonald ES: JAMA Onc 2016* ns Yale Uni, New Haven, CT Durand MA: Radiology ns Ohio State Uni, Columbus, OH Powell JL: Acad Radiol ns Brown Uni, Providence, RI Lourenco AP: Radiology ns Significant US multicenter study Friedewald SM: JAMA 2014 Harvard Med Sch, Boston, MA Sharpe RE: Radiology 2016 Pennsylvania, Philadelphia, PA McDonald ES: AJR ns FFDM: Full-Field Digital Mammography DBT: Digital Breast Tomosynthesis Popul: Study population CDR: Cancer Detection Rate ns: Non-significant NA: Non applicable (not given) * Year 1 DBT cohort

27 Prospective population-based European studies comparing 2D (FFDM)+3D (DBT) vs 2D alone Study Design Reading STORM (Italy) 1) OTST (Norway) 2) MBTST (Sweden) 3) STORM-2 (Italy) 4) Cordoba (Spain) 5) OTST (Norway) 6) OVVV (Norway) 7) Prosp. paired Prosp. paired Prosp. paired Prosp. paired Prosp. paired Prosp. historical Prosp. geographic Double sequent. Double parallel Double sequent. Double sequent. Double Sequent. Double parallel Double Population ( n ) 2D: 7,292 3D: 7,292 2D: 12,621 3D: 12,621 2D: 7,500 3D: 7,500 2D: 9,677 3D: 9,677 2D: 16,067 3D: 16,067** 2D: 59,877 3D: 24,301 2D: 61,742 3D: 37,185** Recall: (%) Difference 2D: 5.2 3D: 4.3 a - 17% 2D: D: 8.5 b - 18% 2D: 2.6 3D: 3.8 c + 43% 2D: 3.4 3D: 4.0 d + 13% 2D: 5.0 3D: 4.4 e - 13% 2D: 4.2 f 3D: % 2D: 3.3 g 3D: % * Cancer detection: n / 1000 exams ** syn2d+dbt 1) STORM (Trento-Verona): Ciatto S et al. Lancet Oncol 2013;14:583 [ a) conditional recall ] 2) OTST (Oslo): Skaane P et al. Eur Radiol 2013;23:2061 [ b) false positive rate ] 3) MBTST (Malmø): Lång K et al. Eur Radiol 2016;26:184 [ c) single-view DBT ] 4) STORM-2 (Trento): Bernardi D et al. Lancet Oncol 2016;17:1105 [ d) results 2D+3D only ] 5) Cordoba (Cordoba): Romero Martin S et al. Eur Radiol 2018; doi [ e) synthetic 2D+DBT ] 6) OTST (Oslo): Skaane P et al. Breast Cancer Res Treat 2018;169:489 [ f) Historical 2D control ] 7) OVVV (Oslo-Drammen-Tønsber): Radiology 2018; doi [ g) Geographical 2D control] ns Cancer detection* Cancer increase + 51% + 34% + 43% + 34% + 17% + 47% + 54% Significant: - DBT favour - DBT disfavour - ns : non-sign.

28 DBT and the (very) dense breast R mlo: FFDM (2D) R mlo: TOMO (3D) Reader (Arm) A B C D Score (NBCSP) Ultrasound: a) Confirming the presence of a mass in the very dense breast b) Differentiation tumor cyst if circumscribed mass at DBT

29 Limitations of Hand-Held UltraSonography (HHUS) in breast cancer screening Automated Breast UltraSound (ABUS) A) IDC G 2, 15 mm Hand-Held US (HHUS) B) IDC G 1, 4 mm (screening high risk woman) - Images often not reproducible - Limited documentation - Comparison with priors difficult - Time-consuming - Double reading not possible - US as stand-alone: low specificity

30 Rafferty EA et al.: JAMA 2016;315:1784 In near future: Automated breast density assessment in population-based screening: Suppl. US screening (single visit) in women with very dense breasts using ABUS!? ABUS

31 DBT screening: Do we need 2D? DBT challenge: One- vs. two-view DBT, radiation dose, and synthetic 2D Images to be included: One view TOMO (mlo) only? One view TOMO + one view 2D? One view TOMO + two view 2D? Two view TOMO only? Two view TOMO + one view 2D? Two view TOMO + two view 2D? Why do we need 2D (+ TOMO): 2D maximize mc detection? (TOMO: Thin-slice-effect ) Comparison with prior exams Comparison right-left breast Externals may request current 2D Experience from clinical studies : Two view 2D (FFDM: MLO + CC) plus two view TOMO (MLO + CC) seems to offer highest clinical performance. However: This means a double radiation dose! Synthetic 2D may substitute for FFDM images (when combined with tomosynthesis) without additional radiation dose!!

32 Synthetic 2D image Rmlo: Conv FFDM (2D) Rmlo: Synthetic 2D Rmlo: Tomo (3D) Invasive lobular carcinoma (ILC) 12 mm, G1 (+ DCIS G3 )

33 Radiology 2017

34 Tomosynthesis: «Overdiagnosis» and prevalent DBT screening! 2006 * Non-attender R MLO: FFDM R MLO: FFDM R MLO: FFDM R MLO: Synthetic 2D * Reader score: 1-1 Reader score: 1-1 Reader score: 1-1 Reader score: year-old-woman Screening-detected cancer 2014: Histology: Radial scar + DCIS G1

35 Tomosynthesis and detection of early preclinical invasive cancer FFDM Lcc TOMO Lcc TOMO Lcc FFDM 2011 TOMO 2011 TOMO 2015 Reader (Arm) 2011 A B C D Score (NBCSP) : Invasive ductal carcinoma IDC: G2, 15 mm (pt1c, pn1)

36 «Overdiagnosis» is an epidemiological concept! Acad Radiol 2015;22:961 «The recent development of tomosynthesis has increased breast cancer detection while reducing false recalls. Because the greatest harm of overdiagnosis is overtreatment, the key goal should not be less diagnosis but better treatment decision tools»

37 Tomosynthesis screening: «Cost-effectiveness studies «Studies confirm that DBT-screening is cost-effective compared with 2D alone BUT: Differences between countries (recalls, work-up, reimbursement etc.); i.e.; Each program (country) needs its own analysis! Of most importance for healthcare providers and policymakers

38 Challenge: Optimize balance between benefit and harms of BC screening: Improving benefits while reducing harms of breast cancer screening might require moving from «one-size-fits-all» mammography paradigm to a «personalized» (individualized) multimodality approach (strategy) Today: «One-size-fits-all» Two-view mammography screening for all Tomorrow: «Personalized screening» Based on: Age Breast density Risk models Supplemental imaging techniques / modalities But: Is «personalized» high-volume (population-based) screening possible??

39 Today Tomorrow? Gold standard Alternatives for supplemental screening Digital Breast Tomosynthesis has the potential to overcome the limitations of conventional mammography (low specificity and low sensitivity in dense breasts) DBT: The best solution for personalized high-volume (population-based) screening!

40 Potential improvements of breast cancer screening for women with dense breasts New techniques / modalities Tomosynthesis US SFM MRI CESM Short first-pass MRI: MIP acquired in 4:35 min FFDM CT PET Tomo High(er) cost Implementation: Low(er) cost - New equipment (not CESM) - Existing equipment - More manpower - Existing manpower - Re-organization - Existing program Thank you very much for your time! DBT: A better mammogram!