TMIST—the first randomized controlled trial (RCT) to identify patients for whom breast tomosynthesis bests digital mammography (DM) in reducing the development of advanced breast cancer—is now underway and accruing patients.

Not only is TMIST seeking practices that are willing to operationalize the necessary steps to enroll, implement trial protocols, and follow patients, it provides financial subsidies for both insured and uninsured patients, offering the ability to underwrite trial operations and reduce care disparities in communities.

TMIST, short for Tomosynthesis Mammographic Imaging Screening Trial, also is an opportunity to support imaging science that has the potential to improve patient care and impact coverage policy. The primary objective of the study is to compare proportions of participants in the tomosynthesis mammography (TM) and DM study arms that experience an advanced breast cancer (as defined by study protocols) at any time during the 4.5 years from randomization, including during active screening and clinical follow-up after last screen.

“In the everyday clinical setting, not all patients get their imaging performed at a large academic site,” said Etta Pisano, MD, FACR, chief research officer, American College of Radiology, in an email exchange with Hub. “Engaging more private practices is part of an effort to ensure that the results of large-scale clinical trials may better reflect the state of care across care settings. It also may provide a more reasonable expectation that patients in various geographic areas may uniformly experience any demonstrated patient benefit resulting from the trial.”

Goal: 165,000 Enrollees

While T-Mist is already underway with 50 sites up and running, Pisano is seeking 80 additional sites to help enroll 165,000 women who are already planning to get routine mammography.

Participating sites receive the following financial support:

·      $500 for data submission for each insured and uninsured patient enrolled

·      $150 for each subsequent screening exam for patients with private insurance, Medicare, or Medicaid—in addition to insurance payment

·      additional payment for biopsy, blood and buccal smear samples

·      $288 per screening exam ($138.17 for exam, $150 for data submission) for uninsured who qualify for charity care.

Patients will be screened either annually or biennially. To receive annual screening, patients must meet the following criteria:

1. Premenopausal or postmenopausal and age 45 to 69 with any of the following risk factors

•       Dense breasts (BIRADS c or d)

•       Known deleterious breast cancer genetic mutation

•       First degree relative with breast cancer or whose family history of breast cancer is unknown

•       Currently on hormone replacement therapy

2. Aged 70-74 with dense breasts or currently on hormone replacement therapy

3. Aged 45 to 74, with at least one LCIS or atypia of any kind.

All women aged 45 to 74 not meeting criteria for annual screening are eligible to participate in biennial screening in the trial.

While the enrollment process is carefully protocoled, the daily expectations for enrollment are modest, at 1-3 patients per day. “Enrolling one to three patients per day equates to enrolling approximately 600 to 1,800 participants total over a 3-year period,” Pisano said. “Many sites have hired a research assistant to serve as an on-site coordinator. This allows the site to handle the administrative duties for the trial without requiring a significant increase in added responsibility from previously existing staff. The added reimbursement, over time, can more than pay for the cost of this added position.”

The TMIST screening examinations will occur within the first five years after randomization, and the site will collect and submit the clinical and imaging data regarding screening, diagnosis, and treatment of breast cancer. After the study-specific exams are completed, a long-term follow-up period of from 8 years or until the end of the study in 2025 commences.

Private Practice Pathways

All TMIST sites must either be a part of a National Community Oncology Research Program or be a member of a National Clinical Trials Network Research Group, such as ECOG-ACRIN. In addition, sites must complete the following five qualifying steps:

•       IRB approval

•       Credentialing phantom image submission

•       Online trial training

•       Physics/IT survey completion

•       Sample mammography reports submission.

Pisano identified two pathways for participating in TMIST for radiology private practices:

1.       Participate through an existing National Clinical Trials Network group affiliation (ECOG-ACRIN, SWOG, NRG, or  Alliance) under one of the hospitals you cover.  “Under this scenario, research agreement negotiations would probably be necessary between the hospital and your private practice governing research staffing support, funding, and regulatory oversight for imaging-based NCTN run clinical trials,” Pisano explained.

2.      Establish one or more of your outpatient imaging centers as an enrolling research facility with CTEP and join the ECOG-ACRIN as a special participant member.  “You will also be required to  become a member institution of the NCI Central IRB unless you are affiliated with a  local IRB that is already a member of the NCI Central IRB,” she added.

Private practices—and their patients—will reap multiple benefits by getting wired into the research process through membership in a National Clinical Trials Network Research Group such as ECOG-ACRIN, according to Pisano.

“ECOG-ACRIN membership allows private practice facilities to participate in a variety of imaging and image-guided procedure clinical trials conducted via the NCTN network,” she said. “This enables facilities to help inform future imaging practice to benefit patients, empowers site investigators to co-author resulting papers in major medical journals, allows for additional revenue through clinical trial per-patient reimbursement, and particular to TMIST, special reimbursement enables facilities to offer free care to the underserved in their communities.”     

For further guidance, visit the TMIST site. Direct general questions to TMIST@acr.org.