Hologic Selenia Dimensions C-View Software Module. October 24, 2012

(1)

Hologic Selenia Dimensions C-View

Software Module

(2)

Introduction and Agenda

Peter Soltani, Ph.D.

Senior VP & GM, Breast Health Hologic, Inc.

(3)

Agenda

Technology Overview Clinical Overview

Clinical Study Design Clinical Study Results Risk/Benefit

(4)

Presenters

Peter Soltani, Ph.D.

Senior VP & GM, Breast Health Hologic, Inc.

–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Andrew Smith, Ph.D.

VP, Advanced Imaging Science Hologic, Inc.

–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Loren Niklason, Ph.D.

Director, Tomosynthesis Programs Hologic, Inc.

–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Elizabeth A. Rafferty, M.D. Director, Breast Imaging

Avon Comprehensive Breast Center Massachusetts General Hospital

(5)

Hologic and External Experts

Jay A. Stein, Ph.D.

Chief Technology Officer Hologic, Inc.

–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Zhenxue Jing, Ph.D.

Senior Vice President & Chief Science Officer Hologic, Inc.

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Arthur Friedman

Senior Vice President, RA, QA, Clinical Hologic, Inc.

––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––

Elkan Halpern, Ph.D.

Director of Statistics, Institute of Technology Assessment Statistical Consultant, Radiology, RSNA

(6)

Technology Overview

Andrew Smith, Ph.D.

Vice President, Imaging Science Hologic, Inc.

(7)

Nomenclature

Shorthand Definition

2D FFDM Conventional digital mammography

3D Tomosynthesis

2D plus 3D, Combo 2D digital mammogram and tomosynthesis images are acquired: currently approved tomosynthesis screening indication

C-View, Synthesized 2D

A projectional 2D image calculated from the 3D dataset. Does not require additional radiation exposure.

3Ds, 3D plus C-View Only tomosynthesis images are acquired, and a synthesized 2D image is created. Both are read

(8)

(9)

Tomosynthesis Screening

Current ‘combo’ mode

Imaging Reconstruct Synthesize Review

3D + Imaging 3D Imaging 2D Reconstruct Tomo Slices Review 3D + 2D

(10)

• How does it work?

– Perform a standard tomosynthesis scan (existing product)

(11)

• How does it work?

– Perform a standard tomosynthesis scan (existing product) – Reconstruct tomosynthesis slices (existing product) ~60 Tomosynthesis Slices Reconstruction Algorithm

(12)

How does it work?

– Perform a standard tomosynthesis scan (existing product) – Reconstruct tomosynthesis slices (existing product) – Synthesize 2D image (C-View) • Similar to Maximum

Intensity Projection (MIP)

as done with MRI images C-View

Image Summation

(13)

(14)

Synthesized 2D Image Usage

• C-View is part of the 3D data set

(15)

(16)

System Changes

• The synthesized 2D algorithm is a software module

• New 3D plus C-View mode is an option

(17)

Current Intended Use Statement

(The same clinical applications as the commercially available 2D and/or 3D system)

The Hologic Selenia Dimensions system generates digital mammographic images that can be used for screening and

diagnosis of breast cancer. The Selenia Dimensions (2D or 3D) system is intended for use in the same clinical applications as a 2D mammography system for screening mammograms.

Specifically, the Selenia Dimensions system can be used to acquire 2D digital mammograms and 3D mammograms.

(18)

Current Intended Use Statement (cont.)

Each view in a screening examination will consist of: • a 2D image set, or

• a 2D and 3D image set

The Selenia Dimensions system may also be used for additional diagnostic workup of the breast.

(19)

Proposed Intended Use Statement (cont.)

Each view in a screening examination will consist of: • a 2D image set, or

• a 2D and 3D image set, or

• a 3D image set in combination with a synthesized 2D image

The Selenia Dimensions system may also be used for additional diagnostic workup of the breast.

(20)

Breast Tomosynthesis: Clinical Benefit

Elizabeth A. Rafferty, M.D.

Director, Breast Imaging

(21)

Mammography

• Prompt annual mammography has shown the ability to

reduce the mortality rate from breast cancer in a population by 15% to 50%.1-3

• As many as 20% of breast cancers will be missed by mammography.

• Approximately 10% of women are recalled for additional workup and a significant portion prove to have no

(22)

Mammography Limitations

• A major factor contributing to the limited performance of

mammography is the tissue superimposition that is created by the overlap of normal breast structures in a two-dimensional mammographic projection.

• These overlapping structures can obscure a lesion making it more difficult to perceive or rendering it completely

(23)

(24)

Mammography Limitations

• A major factor contributing to the limited performance of

mammography is the tissue superimposition that is created by the overlap of normal breast structures in a two-dimensional mammographic projection.

• These overlapping structures can obscure a lesion making it more difficult to perceive or rendering it completely

mammographically occult.

• By mimicking mammographic lesions, overlapping structures can also generate false positive findings at screening, resulting in unnecessary recalls.

(25)

(26)

Anticipated Benefits of 3D

• Increased breast cancer detection

• Decreased recall rate for non-cancer cases

• Improved lesion margin visibility

(27)

(28)

(29)

RCC RCC

(30)

(31)

Benefits of 2D plus 3D

Combined digital mammography and breast tomosynthesis approved for clinical use by the FDA on February 11, 2011.

(32)

Benefits of 2D plus 3D

Study 1 – 2D plus 3D Study 1 – 2D

(33)

Benefits of 2D plus 3D

• At the 98th _{Scientific Assembly and Annual Meeting of the}

Radiological Society of North America scheduled for November of 2012:

• 9 abstracts will be presented detailing the positive benefits of combined digital mammography and breast tomosynthesis for both screening and diagnostic applications in the clinical

(34)

2D plus 3D—Dose

• While evidence of the clinical benefits of 3D are accruing, attention has also been drawn to the incremental

increase in dose over 2D FFDM.

• The imaging community is always striving to

minimize dose while maintaining quality. 0 0.5 1 1.5 2 2.5 3 2D 2D plus 3D MLO 2D plus 3D Phantom Dose (mGy)

(35)

2D plus 3D—Dose

• One strategy for reducing dose is to perform only the 3D MLO in addition to the 2D FFDM

(36)

(37)

Rationale for 3D plus C-View

• The advantage of two-view tomosynthesis suggests an alternative strategy to reducing dose while capitalizing on the benefits of 3D: elimination of the 2D mammogram.

• In interpreting the 3D study, there is value to having a 2-dimensional “summary” image available to the radiologist:

(38)

LCC

2D FFDM

(39)

LCC RCC

(40)

LMLO

2D FFDM

(41)

LMLO RMLO

(42)

Rationale for 3D plus C-View

— Assessment of side to side symmetry

(43)

(44)

(45)

Assessment of Interval Change

• The aesthetic of the C-View image may be different…

• This is commonly encountered in clinical practice

— Comparing digital mammography with analog prior imaging

— Comparing digital mammography with prior imaging from a different vendor

— Comparing digital mammography with prior imaging using different processing algorithms

(46)

Rationale for 3D plus C-View

— Assessment of interval change

(47)

Calcification Detection:

Case 1

(48)

LMLO

(49)

(50)

(51)

Calcification Detection:

Case 2

(52)

2D FFDM C-View 3D Slice

MLO

(53)

Calcification Detection:

Case 3

(54)

(55)

Calcification Detection:

Case 4

(56)

(57)

Rationale for 3D plus C-View

— Assessment of interval change

— Detection of calcifications

(58)

2D FFDM

(59)

(60)

Tomosynthesis C-View

(61)

Rationale for 3D plus C-View

• 3D plus C-View imaging provides another lower dose tomosynthesis imaging option for the radiologist.

• Our study was designed to compare the diagnostic accuracy of 3D plus C-View to the current standard: 2D FFDM.

(62)

(63)

Study Design—Image Acquisition

• Cases were accrued from 22 sites in the United States under IRB approval with written informed consent

• Subjects presented for either screening or biopsy

• Subjects underwent investigational 2D and 3D imaging (in a single compression) of both breasts in the MLO and CC views

• Screening subjects also underwent standard of care 2D FFDM imaging (SOC) on the same day

• Biopsy subjects were eligible for the study if their SOC imaging had been performed within the past 60 days.

(64)

Enrollment Exclusion Criteria

• Women with a prior excisional biopsy

• Women with an internal breast marker

• Women with breast implants

(65)

Enrollment Exclusion Criteria

(66)

Enrollment Exclusion Criteria

• Prior excisional biopsy

• Presence of an internal tissue marker

(67)

Enrollment Exclusion Criteria

(68)

Enrollment Exclusion Criteria

(69)

Enrollment Exclusion Criteria

• Breast implants

• Breasts too large to be imaged in a single

(70)

Study Design—Case Selection

Eligible collected cases were classified into one of 4 categories:

1. Malignant (biopsy-proven)

2. Benign (biopsy-proven)

3. Recalled from screening

— Based on either the reading of the SOC or investigational imaging

4. Negative

— Based on a negative interpretation of both the SOC and investigational imaging

REFERENCE STANDARD:

Malignant cases: pathology

(71)

QC Exclusion Criteria

3521 Subjects imaged 2985 Eligible cases after site exclusions 536 Excluded at site level 2299 Eligible Subjects 96

Excluded for use in a pilot study and exclusions based

on reader study criteria 590

Excluded at QC

(72)

QC Exclusion Criteria

• Entire case was excluded if any of the 8 images acquired failed to pass QC

• Acquisition protocol did not allow for repeat imaging

• Quality Control exclusions

– Patient motion

– Positioning

– Gridlines or artifacts

• Approximately 3% of images excluded

– Number of 2D FFDM and 3D exclusions rates ~ equal

• 19.8% (590/2985) cases excluded

(73)

Overview of Reader Study

• Comparison of 3Ds to 2D FFDM

• Retrospective enriched reader study (crossed design with one month delay)

• 302 cases reviewed by 15 radiologists

• Readers were MQSA qualified with a wide range of experience with 2D and 3D

• Primary Endpoint:

• Receiver-operator characteristic (ROC) area under the curve (AUC) performance for 3Ds imaging is non-inferior to that of 2D FFDM • Secondary Endpoints:

(74)

Reader Study Cohort

Calcification Cases Non-Calcification Cases All Cases Benign 24 51 75 Cancer 24 53 77 Recall 8 16 24 56 (32%) 120 (68%) 176

(75)

Reader Study Cohort

Calcification Cases Non-Calcification Cases All Cases Benign 24 51 75 Cancer 24 53 77 Recall 8 16 24 56 120 176

(76)

Study Design—Case Selection

37

117

118

30

BIRADS Density 1 BIRADS Density 2 BIRADS Density 3 BIRADS Density 4

Cases were selected to give an approximate 50/50 mix of fatty vs dense parenchymal patterns

(77)

Inherent Case Selection Bias

• The vast majority of the cancers included in the reader study came from the biopsy cohort (4 came from screening cohort) and had already been diagnosed by conventional methods prior to enrollment.

• This method of case selection biases the study against demonstrating a gain in sensitivity using 3D plus C-View

because nearly all of the cancers were detected with FFDM imaging.

• Sensitivity was not an endpoint of the study given the case selection bias.

(78)

Study Design—Readers

• 15 readers participated in the study

• All readers were MQSA qualified

• Based on their experience, readers were classified into 3 categories:

1. High volume: interprets > 5000 mammograms / year

2. Medium volume: interprets between 3000 and 5000 mammograms / year

3. Low volume: interprets 3000 mammograms / year or less Additionally, readers were asked whether they had prior clinical experience interpreting tomosynthesis imaging.

(79)

Reader Experience

Reader #

Mammography exams per year

Tomosynthesis Experience 1 1500 Y 2 9000 Y 3 3500 N 4 4000 Y 5 3500 N 6 5500 Y 7 7000 N 8 10000 N 9 3500 Y 10 10000 Y 11 5000 N

(80)

Study Design—Reader Training

• Training focused on the interpretation of 3D images:

– Normal anatomy

– Resolution of summation artifact

– Appearance of masses, architectural distortion and calcifications

• C-View images were presented with each training case reviewed

– Emphasis was placed on the use of the C-View image

functioning as an overview to guide interpretation of the 3D data set

(81)

Study Design—Reader Training

• Training focused on the interpretation of 3D images:

– Normal anatomy

– Resolution of summation artifact

– Appearance of masses, architectural distortion and calcifications

• C-View images were presented with each training case reviewed

• Readers read 2 assessment sets and performance thresholds were measured for assessment set 2

(82)

Study Design – Reader Case Review

302 cases 2D FFDM and 3Ds Data Analysis Session 2 2D FFDM (151) Session 2 3D_s (151) Session 1 3D_s(151) Session 1 2D FFDM (151) 1 month washout

(83)

Study Design—Reader Case Review

• Scoring was lesion-based

– Only lesions deemed actionable were marked

– Up to 3 lesions could be marked per case

– Lesion location was recorded for each lesion

– Lesion type (calcification, non-calcification or both) was recorded for each lesion

• Scoring:

(84)

Data Analysis

Loren Niklason, Ph.D.

Director, Tomosynthesis Programs Hologic, Inc.

(85)

Study Design—Study Endpoints

Primary Endpoint:

• ROC AUC performance for 3Ds imaging is

non-inferior to that of 2D FFDM

–

Delta 5%

–

Probability of malignancy (POM) scores used

for ROC analysis

–

p < 0.05 considered significant difference,

prospectively defined

(86)

Study Design—Study Endpoints

Primary Endpoint:

• ROC AUC performance for 3Ds imaging is

non-inferior to that of 2D FFDM

Secondary Endpoints:

• ROC AUC for subjects with dense breasts using

3Ds is non-inferior to that of 2D FFDM

–

Delta 5%

–

Probability of malignancy (POM) scores used

for ROC analysis

(87)

Study Design—Study Endpoints

Primary Endpoint:

• ROC AUC performance for 3Ds imaging is

non-inferior to that of 2D FFDM

Secondary Endpoints:

• ROC AUC for subjects with dense breasts using

3Ds is non-inferior to that of 2D FFDM

(88)

Recall Rate Analysis – Non-Cancer Cases

• Analysis of recall rate was performed for

individuals and for all readers using a

bootstrapping analysis

• Bootstrapping analysis allows determination of

confidence limits based on randomly selecting

new samples of readers and cases from the

original sample.

(89)

ROC Curves

Higher Recall Rate

Higher Cancer Detection Lower Recall Rate

(90)

System 2 System 1

ROC Curves

Area Under Curve System #1 AUC

(91)

ROC Curves

System 2 System 1

(92)

Clinical Reader Study Results

Elizabeth A. Rafferty, M.D.

Director, Breast Imaging

(93)

Results—Reader Inclusion

• Pre-determined thresholds for reader performance had been determined for 2D FFDM and 3Ds

• Application of the pre-determined thresholds resulted in

several of the radiologists not meeting criteria for inclusion in the data analysis (predominantly based on their interpretation of the 2D FFDM)

• After discussions with the FDA, it was decided to include all 15 readers in the analysis

(94)

Results—Primary Endpoint

ROC AUC performance for 3Ds imaging is non-inferior to that of 2D FFDM

(95)

Reader

ROC AUC _Difference 3D_S-2D FFDM 2D 3D_S 1 0.875 0.879 0.004 2 0.899 0.930 0.031 3 0.900 0.915 0.015 4 0.851 0.918 0.067 5 0.866 0.901 0.036 6 0.869 0.926 0.057 7 0.893 0.889 -0.004 8 0.869 0.918 0.050 9 0.858 0.888 0.030 10 0.867 0.880 0.013 11 0.851 0.919 0.068 12 0.900 0.920 0.020 13 0.827 0.905 0.078 14 0.874 0.929 0.054 15 0.809 0.887 0.078

(96)

Mean ROC curves: All Cases, All Readers

(97)

Primary Endpoint

• Using multi-reader, multi-case ROC analysis, 3Ds imaging was non-inferior to 2D FFDM

• In fact, 3Ds imaging was superior to 2D FFDM

• 14 out of 15 radiologists demonstrated improved AUC with 3Ds compared to 2D FFDM

(98)

2D FFDM

(99)

(100)

2D FFDM

(101)

(102)

3D Slice C-View

(103)

(104)

Primary Endpoint

• In fact, 3Ds imaging was superior to 2D FFDM

(105)

Secondary Endpoints

ROC AUC for subjects with dense breasts using 3Ds is non-inferior to that of 2D FFDM

(106)

ROC AUC; Dense Breast Cases, All Readers

Reader

ROC AUC Difference 3D_S

-2D FFDM 2D 3D_S 1 0.840 0.871 0.031 2 0.894 0.915 0.021 3 0.901 0.91 0.009 4 0.837 0.882 0.046 5 0.861 0.871 0.009 6 0.865 0.929 0.064 7 0.877 0.868 -0.009 8 0.854 0.913 0.059 9 0.827 0.867 0.040 10 0.836 0.859 0.023 11 0.835 0.917 0.082 12 0.870 0.917 0.047 13 0.807 0.890 0.083 14 0.844 0.906 0.063 15 0.803 0.904 0.100 Mean 0.850 0.895 0.045 One Sided 95% CI Lower Limit 0.006

(107)

Mean ROC curves; Dense Breast Cases, All

Readers

(108)

Secondary Endpoint—Dense Breasts

(109)

(110)

(111)

(112)

2D FFDM

(113)

(114)

mean POM: 46.1%

(115)

Secondary Endpoint—Dense Breasts

(116)

Secondary Endpoint—Non-cancer recall rate

The non-cancer recall rate for 3Ds is non-inferior to that of 2D FFDM

(117)

Recall Rates: Non-Cancer Cases

(Recalls, Negatives, Benign)

Reader 2D FFDM Recalls 3D_SRecalls Number Cases 2D FFDM Recall rate 3D_SRecall rate Difference 3DS-2DFFDM 1 98 82 225 43.6% 36.4% -7.2% 2 155 84 225 68.9% 37.3% -31.6% 3 79 53 225 35.1% 23.6% -11.5% 4 61 40 225 27.1% 17.8% -9.3% 5 70 53 225 31.1% 23.6% -7.5% 6 112 69 225 49.8% 30.7% -19.1% 7 124 83 225 55.1% 36.9% -18.2% 8 83 62 225 36.9% 27.6% -9.3% 9 115 76 225 51.1% 33.8% -17.3% 10 116 95 225 51.6% 42.2% -9.4% 11 119 87 225 52.9% 38.7% -14.2% 12 107 75 225 47.6% 33.3% -14.3% 13 86 50 225 38.2% 22.2% -16.0% 14 119 96 225 52.9% 42.7% -10.2% 15 107 79 225 47.6% 35.1% -12.5%

(118)

Recall Rates: Screening Cases

(Recalls, Negatives)

118 Reader 2D FFDM Recalls 3D_SRecalls Number Cases 2D FFDM Recall rate 3D_SRecall rate Difference 3DS-2DFFDM 1 48 39 150 32.0% 26.0% -6.0% 2 91 34 150 60.7% 22.7% -38.0% 3 36 15 150 24.0% 10.0% -14.0% 4 29 12 150 19.3% 8.0% -11.3% 5 34 20 150 22.7% 13.3% -9.4% 6 56 29 150 37.3% 19.3% -18.0% 7 65 36 150 43.3% 24.0% -19.3% 8 38 23 150 25.3% 15.3% -10.0% 9 59 34 150 39.3% 22.7% -16.6% 10 58 43 150 38.7% 28.7% -10.0% 11 62 41 150 41.3% 27.3% -14.0% 12 58 34 150 38.7% 22.7% -16.0% 13 44 19 150 29.3% 12.7% -16.6% 14 63 51 150 42.0% 34.0% -8.0% 15 55 38 150 36.7% 25.3% -11.4% Total/Mean 796/53 468/31 2250 35.4% 20.8% -14.6%

• On average, readers reduced the number of cases recalled using 3Ds compared to 2D FFDM by 22 cases

(119)

Secondary Endpoint—Non-cancer recall rate

• Using bootstrapping analysis, this secondary endpoint was met and 3Ds was non-inferior to 2D FFDM

• In fact, 3Ds was superior to 2D FFDM

• 15 of 15 radiologists had a statistically significant reduction in non-cancer recall rate

(120)

2D FFDM

(121)

(122)

2D FFDM

(123)

(124)

Secondary Endpoint—Non-cancer recall rate

• Using bootstrapping analysis, this secondary endpoint was met and 3Ds was non-inferior to 2D FFDM

• In fact, 3Ds was superior to 2D FFDM

• 15 of 15 radiologists had a statistically significant reduction in non-cancer recall rate

(125)

Summary of Endpoints

The primary endpoint was met

• 3Ds was shown to be superior to 2D FFDM for the primary endpoint: diagnostic accuracy for all cases

The secondary endpoints were met

• 3Ds was shown to be non-inferior to 2D FFDM for the

secondary endpoint of diagnostic accuracy in dense breast cases

(126)

(127)

Benefits of Mammography

• Clinical Trials have demonstrated that screening mammography reduces breast cancer mortality by 15% to 50%1-3

• These numbers are conservative

– 1-view vs. 2-view mammography

– Annual vs. biennial screening

– Compliance and contamination

– Limited number of screening rounds

(128)

Summary of Screening Benefits

Likely mortality reduction is at least 30% - 50%*

* EUROSCREEN Working Group. Summary of the evidence of breast cancer service screening outcomes in Europe and first estimate of the benefit and harm balance sheet. Med Screen, September 2012, Vol. 19 [Suppl 1], pp. 5-13.

(129)

Risk Analysis

Estimates of the lifetime mortality risk from annual mammography from age 40-80:

• 2D FFDM: 0.00020

(130)

ACR Phantom Dose

130 .036 .07 .04 2D FFDM 2D FFDM 2D FFDM 2D FFDM 3D + (Hologic) (MQSA*) + 3D-MLO + 3D C-View

(131)

(132)

Additional Analyses

• Calcification cases versus non-calcification cases –

ROC analysis

(133)

Mean ROC curves—All Readers

Calcification vs Non-Calcification Cases

Non-Calcification Cases

(134)

Mean ROC curves—All Readers

Calcification vs Non-Calcification Cases

Non-Calcification Cases Calcification Cases

AUC D = 0.045 p = .011 AUC D = 0.039 p = .025

(135)

(136)

3D Slice

2D FFDM C-View

(137)

Additional Analyses

• Calcification cases versus non-calcification cases –

ROC analysis

(138)

Mean ROC curves—All Readers

Fatty Breast Cases

AUC D = 0.025 p = .042

(139)

(140)

(141)

(142)

(143)

2D FFDM

(144)

2D FFDM

(145)

C-View Tomosynthesis 2D FFDM

(146)

C-View Tomosynthesis 2D FFDM

(147)

Additional Analyses

• Calcification cases versus non-calcification cases –

ROC analysis

• Fatty breasts - ROC analysis

(148)

Cancer Recalls – with Correct Location and

Lesion Type

Reader 2D FFDM Recalls 3D_SRecalls Number Cases 2D FFDM Recall rate 3D_S Recall rate Difference 3Ds-2D FFDM 1 63 61 77 81.8% 79.2% -2.6% 2 70 70 77 90.9% 90.9% 0.0% 3 65 65 77 84.4% 84.4% 0.0% 4 56 62 77 72.7% 80.5% 7.8% 5 61 62 77 79.2% 80.5% 1.3% 6 65 67 77 84.4% 87.0% 2.6% 7 68 66 77 88.3% 85.7% -2.6% 8 60 66 77 77.9% 85.7% 7.8% 9 65 65 77 84.4% 84.4% 0.0% 10 65 65 77 84.4% 84.4% 0.0% 11 62 70 77 80.5% 90.9% 10.4% 12 64 68 77 83.1% 88.3% 5.2% 13 59 62 77 76.6% 80.5% 3.9% 14 65 69 77 84.4% 89.6% 5.2% 15 63 67 77 81.8% 87.0% 5.2% Total/Mean 951/63.4 985/65.7 1155 82.3% 85.3% 3.0%

(149)

Additional Analyses

• Calcification cases versus non-calcification cases –

ROC analysis

• Fatty breasts - ROC analysis

• Cancer recall analysis

• Distribution of cases – potential for bias based on

types of cases included

(150)

Distribution of Cases

• FDA questioned the impact of case mix on the outcome of this study

• The 3Ds study has more negatives and more cancer cases than our previous 2D plus 3D PMA study

(151)

Distribution of Cases

76 76 126 Cancer Benign 51 47 138 74 Cancer Benign Recall Negatives 2D plus 3D 3Ds

(152)

Distribution of Cases

• FDA questioned the impact of case mix on the outcome of this study

• The 3Ds study has more negatives and more cancer cases than our

previous 2D plus 3D PMA study

• Analyses were done to determine if results change as a function of case distribution:

– All Cases

– Cancer + recall

– Cancer + negative

– Cancer + benign + negative

(153)

Case Distribution 2D FFDM AUC 3Ds AUC Difference 3Ds -2D FFDM Number Cases One sided 95%

CI Lower Limit p-value

All 0.867 0.907 0.040 302 0.014 0.005

Cancer + recalls 0.863 0.903 0.040 101 0.004 0.034

Cancer + negatives 0.906 0.941 0.035 201 0.013 0.005

Cancer + benign + recall 0.821 0.864 0.044 176 0.015 0.007

Cancer + benign +

negatives 0.868 0.907 0.039 278 0.014 0.006

(154)

(155)

Summary

• All primary and secondary endpoints were met or

exceeded.

• 3D plus C-View is a two-view tomosynthesis

imaging option that is superior to 2D FFDM at a

comparable dose.

(156)

LMLO

(157)

(158)

2D FFDM

(159)

(160)

C-View 3D Slice

(161)

(162)

Conclusion

• The data from our reader study has demonstrated that 3D plus C-View is effective for clinical use.

• The analysis of benefits and risk for 3D plus C-View support that it is safe for clinical use.

• 3D plus C-View provides a lower dose two-view option for tomosynthesis imaging that will help radiologists reduce recall rates and find cancers, translating to reduced

(163)