The purpose of this study is to further understand the clinical impact and follow-up steps that may be required based on using whole-body Magnetic Resonance Imaging (MRI) or whole-body ultrasound and blood tests to detect multiple cancers in firefighters.

This study involves an investigational test (cancer blood test) that has not been approved by the U.S. Food and Drug Administration (FDA).

Whole-body MRI and whole-body ultrasound are approved by the U.S. Food and Drug Administration (FDA) to be used in the diagnosis of some cancers and is approved for adults and children who present other signs of potential disease. In this study, however, the whole-body MRI and the whole-body ultrasound are considered investigational devices because they are not yet approved for use in healthy adults with no other cancer indications.

In July 2022, a Working Group of the International Agency for Research on Cancer (IARC) concluded that occupational work as a firefighter is carcinogenic to humans (Group 1) based on a comprehensive review of the scientific literature. Given the established higher risk of multiple cancer types in firefighters, an emphasis on evaluating and delivering evidence-based preventive health services including screening for early detection of cancer in this population is imperative. Evidence-based recommendations on the optimal screening approach for firefighters at higher risk of cancer and greater understanding of the risks and benefits of investigational screening modalities that firefighters are currently receiving in real-world practice are needed. As part of a multidisciplinary cancer screening program for firefighters that is being conducted by the Saville Cancer Screening and Prevention Center and Department of Occupational Health within the Inova Health System, the purpose of this research study is to generate preliminary data on the clinical impact of investigational cancer screening modalities in 800 career and volunteer firefighters age ≥ 35 years old with at least 10 cumulative years of employment as a firefighter. Participating firefighters will be randomized equally to one of two whole-body imaging screening arms (1. whole body MRI, 2. whole body ultrasound) and all participants will further be screened with a multi-cancer detection assay. Aims include evaluating the clinical impact and performance of each tool in detecting cancer, the diagnostic follow-up and healthcare utilization prompted by use of each investigational tool, and assessments of anxiety and feasibility of implementation related to the screening protocols in participants. It is anticipated that results from this pilot will support the development of future firefighter cancer screening programs and serve as a research framework that can be adopted and tested within other health systems in partnership with the local fire jurisdictions in their catchment area, with the ultimate goal of identifying the risks and benefits of these tools for early cancer detection in the firefighter population.

All whole-body MRI examinations will be conducted without contrast using 1.5T (T is a unit of measure for magnetic field strength) (Tesla) MRI systems (Philips Healthcare Clinical Systems, Amsterdam, Netherlands). Scans will be obtained at an outpatient MRI facility with the images subsequently reviewed and reported by the imaging center radiologists specialized in the practice of preventive healthcare screening using whole-body MRI. The scan protocol that will be used for this research study is designed to be consistent with the protocol that has been implemented at external imaging centers such as Prenuvo where firefighters are already being screened. The resulting whole-body MRI report and images will be sent to the Saville clinical team who will use the report from the consulting radiologist to determine the follow-up diagnostic plan, as appropriate. The imaging report will include an interpretation of findings from each organ system with an assessment based on the Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) along with any applicable clinical notes from the reviewing radiologist.

Whole-Body Ultrasound:

All whole-body ultrasound examinations will be conducted by a vendor that specializes in ultrasound diagnostics using the Mindray Z60 ultrasound technology with site-specific presets. The procedure will include scans of the liver, spleen, gallbladder, kidneys, thyroid (scanning of the right and left lobes of the gland to evaluate any nodules or echotexture changes), heart, and bladder. For female patients, further evaluation of the reproductive system including the uterus and ovaries will be assessed transabdominally while the urinary bladder is at its fullest capacity. For male patients, imaging of the testicles and surrounding region will also be performed. Any abnormality detected during the scan will be imaged multiple times with and without color (color imaging is used to show vascularity in the region where an abnormality is noted). Identical protocols and procedures for this scan will be used for all participants randomized to receive wholebody ultrasound and will be performed by the same imaging company. Unified Diagnostic Services (UDS), the ultrasound vendor, will provide the mobile ultrasounds at a location convenient to the participants, which could include the Saville Cancer Screening and Prevention Center, an Inova Occupational Health location, or directly at the firehouse or other convenient community location of a participating jurisdiction.

Multiple Cancer Detection (MCD) Test:

Blood samples collected from all participants for this assay (Cancerguard EXTM) will be shipped to and analyzed at the central laboratory of the collaborating MCD company. Blood draws will be collected either at the Saville Cancer Screening and Prevention Center by clinical research staff, or using mobile phlebotomy at a location outside of the Saville Center that is convenient for the firefighter (e.g., Inova Occupational Health location, firehouse at the participating jurisdiction). The assay may include whole or targeted genetic sequencing to sequence healthy DNA or abnormal DNA. A study report indicating whether a cancer signal has been detected from analysis of the blood sample will be issued to the Saville Center clinical investigators. For participants that do not have a cancer signal detected, no further diagnostic evaluations will be scheduled based on this particular screening test. Participants who do have a cancer signal detected will undergo diagnostic follow-up as clinically appropriate. In rare cases, there may be an invalid test results due to sample collection and/or processing errors. Participants with and invalid test results will have the option to undergo a repeat blood draw. If a participant declines the repeat blood draw, the invalid test result will not terminate the participant from the study.

Inclusion Criteria:

• Age ≥ 35 years old
• at least 10 cumulative years working as a firefighter
• Actively serving as a firefighter (active or volunteer) with completion of NFPA physical examination within the past 6 months
• Ability to understand and willing to sign informed consent
• Ability to understand and willing to sign the Health Insurance Portability and Accountability Act (HIPAA) Authorization
• Additional eligibility criteria in protocol

Exclusion Criteria:

• No prior history of any invasive cancer within the previous 5 years (non-melanoma skin cancer and in situ carcinoma would still be eligible) and no current diagnostic workup for suspicion of cancer
• Received a whole-body MRI, whole-body ultrasound, or been tested with a MCD within the past 1-year
• For women of childbearing potential, pregnancy and no plans for pregnancy for the duration of the study
• Additional exclusion criteria in protocol

All data and records generated during this study will be kept confidential in accordance with Inova Health System institutional policies and HIPAA on participant privacy. The Investigator and other site personnel will not use such data and records for any purpose other than conducting the study. No identifiable data will be shared with anyone outside of the authorized Investigators and clinical research staff involved in the study. It is possible that aggregate data results from the project may be shared with other researchers in the future to facilitate pooled analyses or meta-analyses. Individual patient-level data will not be shared.