Breast Cancer
Conditions
Brief summary
Controlled, blinded, multi-reader, multi-case study
Detailed description
The Imagio Feasibility Reader Study-01 Study is intended to evaluate if a subsequent pivotal study can be implemented to test prospective hypotheses for pre-specified effectiveness endpoints with an acceptable sample size. The Feasibility Study will be based on ITD masses from the PIONEER (NCT01943916) Pivotal study to simultaneously reflect the distributions with and without mammograms as well as site CDU BI-RADS scores within benign and malignant masses as strata. The study population will be split into 3 cohorts - Cohort 1, the 120 patient ITD Population used to run the primary/ secondary analyses. Cohort 2, 30 patients used to run exploratory analyses on false negative rate and Cohort 3, 5 patients used to run exploratory analyses on specific mass types
Interventions
DEVICEImagio (IUS+OA)
The Imagio ultrasound and opto-acoustic images to be reviewed as part of the reader study
DEVICEImagio Ultrasound
Imagio ultrasound images to be reviewed as part of the reader study
DEVICEMammography
Mammography images as available per standard of care
Sponsors
American College of Radiology
Seno Medical Instruments Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
Independent Readers blinded to mass diagnosis
Intervention model description
This will be a controlled, blinded, multi-reader, multi-case (MRMC) study using a sequential design. The study will include 5-12 independent readers depending on qualifications and availability. Imagio (IUS+OA) Training to be completed prior to any reads taking place. Read 1 is immediately followed by Read 2 within the same read session. Read 1 (Control): Mammogram (if available) + History + IUS (stills and videos provided), IUS Probability of Malignancy (POM) and BI-RADS scored and the data form locked. Read 2 (Test): Mammogram (if available) + History + IUS (stills and videos provided), and Imagio (IUS+OA) (stills and videos provided). An interim IUS POM and BI-RADS is recorded as well as a combined Imagio (IUS+OA) POM and BIRADS Pre and Post SenoGram on separate data forms.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Female subjects participating in the PIONEER-0 Study of the Imagio Breast Imaging System with known clinical status
Exclusion criteria
\- Female subjects who did not have known clinical status in the PIONEER-0 Study of the Imagio Breast Imaging System with known clinical status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | Baseline to 12 month follow-up | Primary effectiveness endpoint was the specificity of Imagio \[IUS+OA\] compared to IUS alone at fixed 95-99% sensitivity (fSp) interpolated from the area under the curve (AUC) of receiver operating characteristic (ROC) curves, averaged across all 10 independent readers. Both imaging modalities (IUS alone and IUS+OA) were read for each subject (subject as own control). Results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Receiver Operating Characteristic (ROC) Area Under the Curve (pAUC), Cohort 1 | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months) | pAUC considers only the region of the ROC space that corresponds to clinically relevant values of sensitivity defined as 95% to 99% for Imagio \[IUS+OA\] vs. IUS alone; averaged across 10 readers. |
| BiRads [Breast Imaging Reporting and Data System] Downgrades and Upgrades- Cohort 1 | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months | The cumulative effect of downgrades and upgrades for benign masses expressed as the net gain of True Negative reads |
| The Negative Likelihood Ratio (NLR) for IUS vs. Imagio® (IUS+OA), Cohort 1 | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months) | NLR (Imagio \[IUS+OA\] vs. IUS alone); averaged across 10 readers (all readers). |
| SenoGram Usage Cohort 1 for Imagio (IUS+OA) Only | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months | SenoGram Utilization by number of readers using the SenoGram reported by the readers. SenoGram is not used for Imagio IUS Arm only Imagio (IUS+OA) |
| SenoGram Performance | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months | Sensitivity of SenoGram estimated from cross-validation - Cohort 1 |
Countries
United States
Participant flow
Recruitment details
New Independent Reader Feasibility Study (new readers re-reading a sub-set of randomly selected images acquired during PIONEER-01 Study (NCT01943916); Reader-01 study execution dates: 13 Nov 2018 to 6 Dec 2018
Pre-assignment details
Breast mass images were acquired during PIONEER-01 study. The Reader-01 study-single arm, sequentially read (IUS vs. Imagio \[IUS+OA\]), controlled, blinded, multi-reader, multi-case (MRMC) feasibility study. New readers recruited; NO new subjects were recruited. Subject baseline, demographic and safety data comes from PIONEER-01 subjects who were randomly selected for Reader-01 study. Outcome measures compared IUS vs. IUS+OA. Truth based on biopsy diagnosis or 12 Mo F/U truth panel decision.
Participants by arm
| Arm | Count |
|---|---|
| Overall (Subjects Randomly Selected From PIONEER-01 Study) Each subject had one mass that was read by all readers. Each subject served as her own control, with imaging of each mass by both IUS and IUS+OA modalities. Therefore, baseline data are for overall population only. | 155 |
| Total | 155 |
Baseline characteristics
| Characteristic | Overall (Subjects Randomly Selected From PIONEER-01 Study) |
|---|---|
| Age, Continuous | 51.2 Years STANDARD_DEVIATION 14.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 130 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Mass Diagnosis Subjects: Benign (includes benign + Truth Panel Benign [TPB]) (Cohort 1) | 75 Participants |
| Mass Diagnosis Subjects: Malignant atypical (Cohort 3) | 5 Participants |
| Mass Diagnosis Subjects: Malignant (Cohort 1) | 45 Participants |
| Mass Diagnosis Subjects: Malignant false negative in PIONEER-01 (Cohort 2) | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 117 Participants |
| Region of Enrollment United States | 155 Participants |
| Sex: Female, Male Female | 155 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 155 |
| other Total, other adverse events | 0 / 155 |
| serious Total, serious adverse events | 0 / 155 |
Outcome results
Primary
The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1
Primary effectiveness endpoint was the specificity of Imagio \[IUS+OA\] compared to IUS alone at fixed 95-99% sensitivity (fSp) interpolated from the area under the curve (AUC) of receiver operating characteristic (ROC) curves, averaged across all 10 independent readers. Both imaging modalities (IUS alone and IUS+OA) were read for each subject (subject as own control). Results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth).
Time frame: Baseline to 12 month follow-up
Population: 120 patients/masses were included in Cohort 1-the Intent-to-diagnose (ITD) population used to run the analysis to set the sample size for the future pivotal Reader-02 Study, 30 masses Cohort 2 to assess False negative rate, and 5 Cohort 3 DCIS, lymphoma, etc. masses to assess how readers scored. 155 masses in total across all cohorts analyzed for the Safety population analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| IUS Alone | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (95.0%) | 80.9 Percent of correct benign masses |
| IUS Alone | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (96.0%) | 78.7 Percent of correct benign masses |
| IUS Alone | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (97.0%) | 75.8 Percent of correct benign masses |
| IUS Alone | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (97.5%) | 74 Percent of correct benign masses |
| IUS Alone | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (98.0%) | 71.8 Percent of correct benign masses |
| IUS Alone | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (99.0%) | 65.2 Percent of correct benign masses |
| Imagio (IUS+OA) | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (98.0%) | 58.9 Percent of correct benign masses |
| Imagio (IUS+OA) | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (95.0%) | 75.4 Percent of correct benign masses |
| Imagio (IUS+OA) | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (97.5%) | 62.8 Percent of correct benign masses |
| Imagio (IUS+OA) | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (96.0%) | 71.4 Percent of correct benign masses |
| Imagio (IUS+OA) | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (99.0%) | 47.7 Percent of correct benign masses |
| Imagio (IUS+OA) | The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | fSp (97.0%) | 66.1 Percent of correct benign masses |
Secondary
BiRads [Breast Imaging Reporting and Data System] Downgrades and Upgrades- Cohort 1
The cumulative effect of downgrades and upgrades for benign masses expressed as the net gain of True Negative reads
Time frame: Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months
Population: ITD Population- Number of Subjects/Masses 120
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IUS Alone | BiRads [Breast Imaging Reporting and Data System] Downgrades and Upgrades- Cohort 1 | 38.5 % of correctly identified benign masses |
| Imagio (IUS+OA) | BiRads [Breast Imaging Reporting and Data System] Downgrades and Upgrades- Cohort 1 | 49.1 % of correctly identified benign masses |
Secondary
Partial Receiver Operating Characteristic (ROC) Area Under the Curve (pAUC), Cohort 1
pAUC considers only the region of the ROC space that corresponds to clinically relevant values of sensitivity defined as 95% to 99% for Imagio \[IUS+OA\] vs. IUS alone; averaged across 10 readers.
Time frame: Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months)
Population: Cohort 1, pAUC considers only the region of the ROC space that corresponds to clinically relevant values of sensitivity defined as 95% to 99% for Imagio \[IUS+OA\] vs. IUS alone; averaged across 10 readers.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IUS Alone | Partial Receiver Operating Characteristic (ROC) Area Under the Curve (pAUC), Cohort 1 | 2.6 Probability as percentage |
| Imagio (IUS+OA) | Partial Receiver Operating Characteristic (ROC) Area Under the Curve (pAUC), Cohort 1 | 3.0 Probability as percentage |
Secondary
SenoGram Performance
Specificity of SenoGram estimated from cross-validation
Time frame: Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months
Population: ITD Population - Cohort 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IUS Alone | SenoGram Performance | NA Percent |
| Imagio (IUS+OA) | SenoGram Performance | 62.2 Percent |
Secondary
SenoGram Performance
Sensitivity of SenoGram estimated from cross-validation - Cohort 1
Time frame: Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months
Population: ITD Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IUS Alone | SenoGram Performance | NA Percent |
| Imagio (IUS+OA) | SenoGram Performance | 98.0 Percent |
Secondary
SenoGram Usage Cohort 1 for Imagio (IUS+OA) Only
SenoGram Utilization by number of readers using the SenoGram reported by the readers. SenoGram is not used for Imagio IUS Arm only Imagio (IUS+OA)
Time frame: Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months
Population: Cohort 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IUS Alone | SenoGram Usage Cohort 1 for Imagio (IUS+OA) Only | NA participants |
| Imagio (IUS+OA) | SenoGram Usage Cohort 1 for Imagio (IUS+OA) Only | 111 participants |
Secondary
The Negative Likelihood Ratio (NLR) for IUS vs. Imagio® (IUS+OA), Cohort 1
NLR (Imagio \[IUS+OA\] vs. IUS alone); averaged across 10 readers (all readers).
Time frame: Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months)
Population: Cohort 1 - 120
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IUS Alone | The Negative Likelihood Ratio (NLR) for IUS vs. Imagio® (IUS+OA), Cohort 1 | .049 Ratio |
| Imagio (IUS+OA) | The Negative Likelihood Ratio (NLR) for IUS vs. Imagio® (IUS+OA), Cohort 1 | .094 Ratio |