Using AI to Select Women for Supplemental MRI in Breast Cancer Screening (ScreenTrustMRI)

• ClinicalTrials.gov Identifier: NCT04832594
• Recruitment Status: Recruiting
• First Posted: April 6, 2021
• Last Update Posted: August 19, 2022
• Sponsor: Karolinska University Hospital
• Collaborators: KTH Royal Institute of Technology; Region Stockholm; Bröstcancerförbundet, Sweden
• Information provided by (Responsible Party): Fredrik Strand, Karolinska University Hospital

Study Description

Brief Summary:

This is a prospective clinical trial aiming to determine the ability of an AI pipeline to identify women who would benefit from supplemental MRI in terms of decreasing the number of cancers having a significantly delayed detection

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Other: AI selection for supplemental breast MRI	Not Applicable

Detailed Description:

All women attending mammography screening at Karolinska University Hospital will have their mammograms analyzed by AI (Figure 1). The specific AI-implementation (AI tool) in this study is a result of AI predictions from three equally weighted component AI models analyzing mammograms: (i) masking predictor, (ii) risk predictor and (iii) cancer signs predictor (by one commercial CAD model and one in-house academic CAD model); the age of the woman is also taken into account by multiplying the score with (110-age)/70. The purpose of the age factor is to attain a relatively similar proportion of MRI exams in the lower and higher age groups. The aim of the AI tool is to identify women with the highest probability of having a delay in cancer detection, i.e., having had a false negative screening mammogram.

The specific AI tool and its settings will remain the same during the study. For each examination, the AI tool will produce an AI Joint Score and an AI Masking Score. Women having an AI Masking Score above the threshold and an AI Joint Score above the threshold will be invited to the study unless they met exclusion criteria. Women who decide to participate, will be randomized to MRI or no-MRI (standard-of-care).

A Signa Premier 3T MRI scanner from GE Healthcare will be used. The MRI protocol will contain a T2-weighted Dixon sequence and a T1-weighted dynamic contrast enhanced series, and will remain the same through the course of the study. All MRI exams will be assessed by two radiologists, where the second reader will have access to the assessment of the first reader. In case of disagreement, a consensus discussion between two radiologists will be held. The MRI exams will be assessed according to BI-RADS, and follow-up will depend on the BI-RADS category (Figure 2). Women with BI-RADS 1-2 will have no further diagnostics and will be sent a 'healthy letter'. Women with BI-RADS 3 to 5 will be recalled for 2nd look ultrasound. Women with BI-RADS 4-5 will be included in the regular process for established cancer suspicion and be discussed in a multidisciplinary team conference. For women with BI-RADS 3, the follow-up will be handled within the breast radiology unit.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 2500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: For each screening mammography examination, the AI tool will produce an AI Joint Score and an AI Masking Score. Women having an AI Masking Score above the threshold and an AI Joint Score above the threshold will be invited to the study unless they met exclusion criteria. Women who decide to participate, will be randomized to MRI or no-MRI (standard-of-care).
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Image Analysis With Artificial Intelligence to Increase Precision in Breast Cancer Screening - the ScreenTrust MRI Substudy: a Prospective Trial of AI to Select Women for Supplemental Screening MRI
• Actual Study Start Date: April 1, 2021
• Estimated Primary Completion Date: April 1, 2023
• Estimated Study Completion Date: July 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Supplemental MRI; Women randomized to MRI will be examined using a shortened MRI protocol on a Signa Premier 3T MRI scanner. The MRI examination will be reviewed by two radiologists and assigned BI-RADS score. Appropriate clinical work-up will follow according to the BI-RADS score. BI-RADS 3 or higher at initial MRI will be recalled for a second look ultrasound.	Other: AI selection for supplemental breast MRI; An AI tool will generate scores used to determine eligibility. Women randomized to MRI will be examined in an MRI scanner.
No Intervention: No MRI (standard-of-care); Standard-of-care. Both arms will have had a regular screening mammography examination prior to randomization. The "No MRI" arm will have no further intervention.

Outcome Measures

Primary Outcome Measures :

1. Significantly Delayed Breast Cancer Detection per 1000 women [ Time Frame: Until 27 months from study inclusion (includes cancer detected at subsequent screening within this time frame). Cancer detected at the initial screening mammography or MRI shall not be included. ]
   Composite end-point defined by either: 1. Interval Cancer, 2. Cancer with lymph node metastasis, 3. Cancer with invasive component larger than 15 mm

Secondary Outcome Measures :

1. MRI-detected breast cancer [ Time Frame: Diagnosis during work-up within 2 months of the initial screening MRI ]
   Breast cancer detected at the initial screening MRI for women in the Intervention arm of the study
2. Invasiveness [ Time Frame: All diagnosed breast cancer within 27 months of study inclusion ]
   In situ and/or Invasive cancer
3. Histology [ Time Frame: All diagnosed breast cancer within 27 months of study inclusion ]
   Ductal, Lobular, Mucinous, Tubular, Other
4. Lymph node metastasis [ Time Frame: All diagnosed breast cancer within 27 months of study inclusion ]
   0 nodes, 1-3 nodes, 4 or more nodes
5. Tumor size [ Time Frame: All diagnosed breast cancer within 27 months of study inclusion ]
   Size (in millimetre) for the invasive and the in situ component
6. Receptor status [ Time Frame: All diagnosed breast cancer within 27 months of study inclusion ]
   ER positive/negative, PR positive/negative, HER2 positive/negative
7. Age [ Time Frame: At study inclusion ]
   Age of the woman
8. Distribution of AI scores [ Time Frame: At study inclusion ]
   Histogram, mean, median and dispersion measures for the AI Scores
9. BI-RADS codes [ Time Frame: At study inclusion and until end of 27 month follow-up ]
   For each MRI examination, the BI-RADS code for fibroglandular volume, background enhancement and breast lesions
10. Biopsy result [ Time Frame: Diagnosis during work-up within 2 months of the MRI examination ]
    Pathology assessment of biopsy: normal tissue, benign lesion, cancer in situ, invasive cancer
11. Participant questionnaire [ Time Frame: At study inclusion ]
    Participant questionnaire replies for MRI contraindications and for Breast cancer-related history

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Complete four-view screening mammography examination

Exclusion Criteria:

• Women in surveillance program referred from the hereditary cancer unit
• Breast implants
• Prior breast cancer
• Breast feeding
• MRI contraindication requiring radiologist assessment

Contacts and Locations

Contacts

Contact: Fredrik Strand, MDPhD; +46709795511; fredrik.strand@sll.se

Locations

Sweden

Karolinska University Hospital; Recruiting

Stockholm, Sweden, 17164

Contact: Fredrik Strand, MD PhD +46851770000 fredrik.strand@ki.se

Principal Investigator: Fredrik Strand, MD PhD

Sponsors and Collaborators

Karolinska University Hospital

KTH Royal Institute of Technology

Region Stockholm

Bröstcancerförbundet, Sweden

Investigators

• Principal Investigator: Fredrik Strand, MDPhD; Karolinska University Hospital

  Study Documents (Full-Text)

Documents provided by Fredrik Strand, Karolinska University Hospital:

Study Protocol and Statistical Analysis Plan  [PDF] March 31, 2021

More Information

• Responsible Party: Fredrik Strand, Principal Investigator, Karolinska University Hospital
• ClinicalTrials.gov Identifier: NCT04832594
• Other Study ID Numbers: KSRAD001
• First Posted: April 6, 2021
• Last Update Posted: August 19, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The final trial dataset will be available for the research team of the principal investigator. Pseudonymized data can be made available for external research audit. Anonymous data may be shared with academic researchers.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Available during study time and until 2 years after publication of any manuscript resulting from the study
• Access Criteria: Data Transfer Agreement must be signed. Request must be made by an academic researcher at an internationally recognized university.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fredrik Strand, Karolinska University Hospital:

Artificial Intelligence

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases