ABSTRACT
Background: The ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST), which opened in 2017, is a randomized trial designed to assess whether Tomosynthesis Mammography (TM) should replace Digital Mammography (DM) for breast cancer screening. It is hypothesized that women assigned to TM for 3-5 screening rounds will have fewer advanced breast cancers than the women assigned to DM. Advanced cancers are those that have distant metastases or positive nodes, are invasive tumors greater than or equal to 2.0 cm in size, or are invasive tumors greater than 1.0 cm in size that are triple negative or HER 2+. The initially planned enrollment of 164,946 women was due to be completed by the end of 2020, with follow-up concluded by 2025. There were substantial challenges in meeting this timeline, including the organizational and funding structure of the NCI National Clinical Trials Network which is dependent upon sites using their existing staffing resources (not always readily available at the time of study activation). This led to longer than anticipated start of enrollment for most interested sites and lower than anticipated annual enrollment per participating site based ultimately on the staffing support that could be allocated to manage TMIST. In addition, research staffing shortages and periodic research operations closures due to COVID-19 have also impacted enrolling TMIST sites, though unevenly, since the start of the pandemic. Enrollment plateaued at approximately 2,100 subjects per month by the end of 2020. With that accrual rate expected, the trial design was modified to reduce the sample size so that the study could be completed by 2027. Methods: With the approval of the NCI CIRB, we changed how the primary endpoint measure for TMIST is assessed from the number of advanced cancers that occur by 4.5 years after randomization to the time from randomization to occurrence of advanced cancers. All advanced cancers occurring within 7 years of randomization are now included and all participants followed for at least three years. In addition, the power of the study of the study was modified from 0.9 to 0.85, while the originally assumed effect size at 4.5 years was retained These changes allowed a reduction of sample size to 128,905, with subject recruitment projected to end in 2024. As of February 14, 2022, there are 125 sites open, 114 in the U.S. and 11 in other countries, with an additional 31 sites planning to open. As of February 14, 2022, a total of 63,845 women have been enrolled in the trial worldwide at 115 sites, with 20% of US participants self-identifying as belonging to minority racial and ethnic groups and 70% consenting to optional blood and/or buccal cell collection.
ABSTRACT
Background: ECOG-ACRIN launched the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) through the National Cancer Institute's National Clinical Trials Network (NCTN) - a network of academic medical centers, community hospitals, and private clinical practices that are committed to participating in NCI-funded clinical trials. The NCI NCTN was developed to support rapid trial start-up of NCI-funded cancer control/prevention, cancer treatment, and nontherapeutic clinical trials that occur within the institution through centralized institutional administration and shared clinical resource allocation (personnel, lab services). TMIST is a randomized clinical trial assessing two breast cancer screening imaging modalities, tomosynthesis and digital mammography, in the population of women presenting for screening mammography and therefore requires active involvement of radiology. Methods: TMIST seeks to enroll 164,946 women, ages 45 to 74 years who present for screening mammography. Because the population under evaluation are women already scheduled for screening mammography, the mammography clinic is critical to successful recruitment as well as adherence to imaging randomization assignments over a 5-year period and therefore must be actively engaged in this trial with a breast imaging radiologist championing the trial within this service. To get active engagement of breast imaging radiologists, we needed to first make them aware of TMIST. Breast imaging radiologists that were already actively involved in the NCTN received notification of the trial through the NCTN email lists. So our goal was to come up with a strategy to reach out to breast imaging radiologists that were not active members in the NCTN. This was achieved through in-person informational sessions to introduce the trial at national and international breast imaging meetings, introduction of the trial and the workings of the NCTN network to the radiology community through articles placed in American College of Radiology (ACR) newsletters, ads promoting TMIST on ACR social media platforms, and direct email by the TMIST study chair to key radiology stakeholders. As of February 15, 2021, there are 115 sites open: 106 in the U.S. and 9 internationally with an additional 54 sites planning to open. A total of 39,366 women are enrolled in the trial with twothirds also consenting to optional blood and/or buccal cell collection. Minority populations' participation in the trial is over 20%. A significant drop in enrollment occurred in Spring 2020 coinciding with the suspension of mammography services globally due to COVID-19 beginning mid- March 2020. Enrollment and follow-up screening visits for TMIST restarted in May 2020 and gradually ramped back up to pre-COVID totals in September 2020. Our highest monthly accrual so far occurred in November 2020 with 2,148 subjects enrolled.