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 Digital breast tomosynthesis (DBT), also called 3D mammography, was first approved by the Federal Drug Administration in 2011. The goal of 3D mammography is to improve accuracy compared to 2D digital mammography (DM), by increasing sensitivity and decreasing recall rates. To capture the broad utilization of DBT in populations receiving both screening and diagnostic imaging, this analysis investigates DBT usage over time in a longitudinal sample from 2016 through 2020 for adult women ranging from 18-74 years of age. Methods Retrospective analyses were conducted using de-identified administrative claims data from a large national U.S. health insurer. The study cohort consisted of women who were continuously enrolled in a commercial or Medicare Advantage plan from 1/2016 to 12/2020 and aged 18 to 74 years old as of 2016. All procedures were identified based on Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes. For each study year, receipt of breast cancer screening with DM (S-DM) or including DBT (S-DBT) were captured. Receipt of DM and DBT not specified for screening based on CPT code descriptions were categorized as diagnostic, D-DM and D-DBT respectively. Women that received both DBT and DM in the same year were included in the DBT group. In addition, women who received MRI and ultrasound were also captured. Rates of each procedure by study year, insurance type, and age categories that align with recommended screening guidelines (<40 years old, 40-49 years old and 50-74 years old) were examined. Results Approximately 3.8 million women met study criteria;85% were commercially insured and 15% were Medicare Advantage. Table 1 shows rates of adult women who received mammography, MRI and ultrasound over the study period. About 74% of study subjects receiving screening were 50-74 years old at the start of the study period, 25% were 40-49 years and 1% were under 40 years old. In 2020, there were fewer women (3%-13%) receiving imaging procedures compared to counts in 2019. During the 5-year study period, there was a 3.5-fold increase in the number of women who received S-DBT. In 2016, 23% of women who received a screening mammogram received S-DBT and by 2020, this percent increased to 82%. The percent of women who received a diagnostic mammogram using D-DBT compared to D-DM also increased overtime;29% of women received a D-DBT in 2016 and this increased to 77% in 2020. The number of women with receipt of ultrasound and MRI were similar in each study year. The percent diagnostic/screening tests (including DBT and DM) were in the range of 18.5%-20.2% each year. Conclusion Among this cohort of women who were continuously enrolled in the health plan throughout the 5-year study period, this analysis shows that screening and diagnostic DBT utilization rates increased from 2016 to 2020 while DM screening and diagnostic imaging utilization concomitantly decreased. The percentages of women that received S-DBT and D-DBT were highest in 2020, even though 8%-13% fewer women had evidence of mammography than in 2019, which is largely due to COVID-19 related healthcare service disruptions. The rate of diagnostic tests as a percent of screening tests did not decrease with the adoption of DBT. Further analyses investigating rates of follow-up procedures and downstream costs are warranted.