TMIST A Bridge to Personalized Screening. Canadian Society of Breast Imaging April 26, 2018

Transcription

1 TMIST A Bridge to Personalized Screening Canadian Society of Breast Imaging April 26, 2018

2 Topics 1. Overview of TMIST Aims and Methods 2. Status of the Study (4/13/18) 3. How your site (in Canada) can participate 2

3 Should Tomosynthesis replace Digital Mammography for breast cancer screening? 3

4 TMIST Scientific Rationale 1. We have not had a breast cancer screening trial since the 1980s 4

5 TMIST Scientific Rationale 1. We have not had a breast cancer screening trial since the 1980s 2. More recent screening technologies (tomosynthesis (TM), US, MRI) find more cancers than the current standard of care, digital mammography (DM), but also have more false positives 5

6 TMIST Scientific Rationale 1. We have not had a breast cancer screening trial since the 1980s 2. More recent screening technologies (tomosynthesis (TM), US, MRI) find more cancers than the current standard of care, digital mammography (DM), but also have more false positives 3. TM is generally done with greater radiation to patient (up to 2X), costs more and takes more time to interpret than digital mammography 6

7 How TM is currently used in the US 1. ~30% of available mammography systems. 2. Many systems are being used in the same centers where DM is also being used patients assigned somewhat randomly to the next available machine. 3. Most systems require both TM images PLUS DM images. 4. Synthetic 2D images are possible with many systems, but are not widely utilized. 5. Cost for machines is higher for TM than DM. 6. Time to interpret is ~ 2X for TM. 7

8 Literature on Hologic TM (TM+DM v DM) 1. Diagnostic accuracy (AUC) trends better for TM+DM vs. DM. 2. Screening recall rates trend lower for TM+DM vs DM (though results are mixed). 3. Cancer detection rate trends higher for TM+DM vs DM. 4. Lesion Characterization trends better for TM+DM vs. DM. 5. Average glandular dose is significantly higher for TM+DM vs. DM (~2X)

9 TMIST Scientific Rationale Equipoise Question: Does TM find life-threatening cancers? 9

10 TMIST Scientific Rationale Equipoise Question: Does TM find life-threatening cancers? Randomized clinical trials with mortality endpoints are very expensive and impractically long (10-30 years) 10

11 TMIST Scientific Rationale Equipoise Question: Does TM find life-threatening cancers? Randomized clinical trials with mortality endpoints are very expensive and impractically long (10-30 years) TMIST primary endpoint measures the difference in potentially lifethreatening cancers in women screened with DM versus TM. 11

12 TMIST Scientific Rationale Equipoise Question: Does TM find life-threatening cancers? Randomized clinical trials with mortality endpoints are very expensive and impractically long (10-30 years) TMIST primary endpoint measures the difference in potentially lifethreatening cancers in women screened with DM versus TM If there are fewer life-threatening cancers in women screened with TM over 4.5 years of screening, TM should replace DM for breast cancer screening 12

13 In order to reduce mortality, an effective screening test should REDUCE the number of advanced breast cancers in the population screened, over time. 13

14 Screening Detects Cancer Preclinical Extended life Normal Cancer Symptomatic Disease Cancer Death Lead Time Death from other causes

15 Screening/Prevention Prevent Cancer from Winning! Stroke Heart Disease Breast

16 What we don t know 1. How do Tomosynthesis and Digital Mammography compare in reducing advanced breast cancer in the population being screened? 2. How does Tomosynthesis affect breast cancer mortality compared with DM? 3. What is the rate of overdiagnosis? 16

17 What we don t know 1. Do ALL Tomosynthesis systems perform at the same diagnostic accuracy, sensitivity and specificity in the North American population? 2. Should all DM systems be replaced by TM or would some women be equally well served by DM? 3. How genetic, demographic and other information can be used to tailor individual screening strategies? 17

18 1. Compare the number of advanced cancers detected using TM vs. DM With advanced cancers defined as- 1) Those with metastases. 2) Those with positive nodes. 3) All invasive cancers > 2.0 cm. in size. TMIST Primary Aim 4) All invasive cancers that are > 1 cm. in size and which have prognostic markers that suggest aggressive behavior, (ie triple negative or her2+). 18

19 TMIST Study Design 1. Study Type: Randomized Clinical Trial. 2. Patient Population: Asymptomatic women presenting for screening mammography, ages No prior breast cancer, implants. Can t be pregnant or lactating. 3. Number of Women: 164,946 women (82,473 per arm) 4. Randomization Assignments: Breast Tomosynthesis (TM) or Digital Mammography (DM). 19

20 1. Frequency of Screening- Annual for Premenopausal women TMIST Study Design Annual for Postmenopausal women ages who either have dense breasts, OR are on hormone therapy OR have a family history of breast cancer OR have a known deleterious breast cancer mutation. Annual for Postmenopausal women over age 70 who either have dense breasts or have a known deleterious breast cancer mutation or are on hormone therapy. Biennial for all other postmenopausal women.* *Miglioretti, JAMA Oncology 2015,

21 TMIST Methods 1. Annual screening will take place at entry and 1, 2,3 and 4 years after entry. (5 screens) 2. Biennial screening will take place at entry and 2 and 4 years after entry (3 screens). 3. Truth on breast cancer status will be determined by biopsies and follow-up information. 4. Total numbers of advanced cancers will be compared 4.5 years after randomization in both study populations (TM vs DM). 21

22 Definitions 1. Postmenopausal- No periods for 12 months or longer or s/p hysterectomy with oophorectomy or s/p hysterectomy without oophorectomy over age Dense breasts: Two densest BIRADS categories. If baseline mammogram, assigned after mammogram read by the study radiologist. 3. Positive Family History: First degree relative (mother/father, sister/brother, daughter/son) with breast cancer. 22

23 TMIST Secondary Aims 1. Patient-Centered Aim To compare the recall and biopsy rates due to abnormal screening examinations for TM versus DM 2. Imaging Aims To compare diagnostic accuracy of TM versus DM To compare interval cancer rates. 23

24 3. Biological Aims TMIST Secondary Aims To determine correlates of TM/DM findings, pathology and genetic analysis, and other patient characteristics with long-term patient outcomes, including interval cancer rate. To assess and compare the characteristics (e.g. stage, grade, cell subtype) of cancers detected from screening by TM and DM. To ascertain potential biomarkers for aggressive tumors and/or poor outcomes via blood DNA/RNA/protein analysis. 24

25 TMIST Physics Aims (Martin Yaffe, PhD, Sunnybrook) 1. To assess temporal and site-to site variations in image quality, breast radiation dose, and other quality control parameters in TM vs. DM. 2. To refine and implement task-based measures of image quality to assess the effects of technical parameters, including machine type, and detector spatial and contrast resolution on measures of diagnostic accuracy for TM. 3. To evaluate which QC tests are useful for determination of image quality and those that are predictive of device failure, in order to recommend an optimal QC program for TM. TMIST Training Module 25

26 Timeline 1. Accrue all 164,946 women over months (July 2018-June 2021). 2. Image women for 4 years after randomization, so that the final round of imaging will take place Follow women annually through at least 8 years after recruitment. So, follow-up information will take place from the present (for patients already enrolled in Canada) through early We will seek funding for follow-up to mortality endpoints. 26

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28 Progress (4/13/2018) 1. ~130 sites will be participating sites are open and accruing. Accrual to date: 1084 (+~3000 women st 4 sites in Canadian lead-in study) more sites fully qualified and ready to open soon. 4. Odette Cancer Centre/Sunnybrook Health Sciences Centre has recruited 17 women. 5. Ottawa Hospital and Cancer Centre has recruited 78 women. 6. Another 42 sites are actively working on opening this winter/early spring. 7. The other ~51+ sites should open by summer/early fall. 8. Other sites approved to open in Canada: Princess Margaret Hospital, Vancouver Cancer Center. 28

29 WE ARE STILL SEEKING CANADIAN SITES TO PARTICIPATE IN TMIST! 29

30 Canadian Sites Specific Requirements Canadian Cancer Trials Group (CCTG) membership* is required for your institution to participate in TMIST Contact Dora Baczyk, for CCTG membership confirmation Your local Regulatory Ethics Board project review and approval is required. Your local REB Approval notification and approved documents (consent forms, patient materials) are to be submitted to CCTG for their review/approval and submission to CTSU *CCTG membership is typically established through Cancer Centers or Oncology Departments. Radiology departments should establish inter-institutional agreements with the department that maintains CCTG membership within your institution if required.

31 Canadian Sites Specific TMIST Documents CCTG approved TMIST documents are posted to the CCTG website under protocol TMIST MAC22 Consent template and other documents Canadian sites that should be used in obtaining REB approval are posted on CCTG website. ticeofcentralactivation.pdf

32 ACRIN Requirements To activate the study, all sites must- Submit sample mammography reports by to Elodia Cole Submit physics/it survey online: Submit phantom credentialing images using TRIAD (NCI Oncology Domain) for research: Complete training webinar by lead radiologist and lead research associate at

33 Individual CTEP Credentials TMIST uses the NCI Cancer Trials Support Unit (CTSU) to manage user access to information systems that are used in the trial. CTEP IAM accounts are required for Lead Radiologist/PI at each site (Investigator Credentials) Non-Physician Staff (Associate Plus Credentials) responsible for any of the following TMIST study tasks : Enrollment/Randomization of Subjects Entry of electronic case report forms data Communication of Data Queries to sites and collection of query responses from sites Entry of information in STS tracking system of biospecimen samples submissions Submission of images through TRIAD Your CTEP IAM account needs to be associated with your site s CTSU personnel Roster for CCTG recognized CTEP Site ID Instructions for obtaining CTEP IAM accounts can be found:

34 Contact Us TMIST General Project Management help (any questions) Physics QC Help Desk (physics quality assurance testing questions) TRIAD Support Help Desk(image transfer software questions) ECOG-ACRIN Central Biorepository and Pathology Facility (biospecimen questions)

35 Questions? Comments? 35