Utility of Plasma Circulating Tumor DNA (ctDNA) in Asymptomatic Subjects for the Detection of Neoplastic Disease

The objectives of this study are to obtain human blood samples from asymptomatic subjects who have never been diagnosed with cancer, but who may be at increased risk for cancer due to heredity, exposures, age, or family history to assess the validity of screening healthy but at risk patients for cancer via analysis of ctDNA.

Specifically, the blood specimens will be collected from individuals who have responded to a self-administered health questionnaire that screens for higher risk of contracting cancer. Each participant will be asked to provide a 30 ml blood sample to be drawn by a primary care provider (PCP) or licensed phlebotomist. The specimens collected during the study may also be used in the research and development of new or modified molecular genetics assays. The results of these studies will be used to further the understanding of the use of ctDNA for the detection and monitoring of cancer in humans.

The blood samples are collected in blood collection tubes (BCT) called Cell-Free DNA BCT® manufactured by Streck and intended for collection, stabilization and transportation of cell-free plasma DNA. This device also stabilizes and preserves cellular genomic DNA present in nucleated blood cells and circulating epithelial cells (tumor cells) found in whole blood. This product has not been cleared by the U.S. Food and Drug Administration for In Vitro Diagnostic use and is labeled by Streck for research use only. Under the Clinical Laboratory Improvement Amendments (CLIA) regulations, laboratories are authorized to validate and use, as part of a laboratory-developed test (LDT), devices that have not been cleared or approved by the FDA. Pathway Genomics validated the CancerInterceptTM Detect molecular analysis system with the Streck tubes, in accordance with CLIA.

Once the specimen has been collected and sent to Pathway by the physician or the phlebotomist who collects the samples, all other processing and testing are conducted by Pathway laboratory personnel. The analysis begins with the separation of the plasma from the rest of the blood sample. cfDNA will then be isolated from each sample. The quantity of cfDNA is measured and then the sample is amplified via PCR for next generation sequencing. The results of the sequencing will then be analyzed for the presence of one or more of the 96 mutations analyzed in this assay. The data are then reviewed and a report will be generated.

Inclusion criteria

• strong family history of cancer
• known carrier of a pathogenic variant in a gene indicating an increased risk of cancer, for example, in the BRCA1 or TP53 genes.
• exposure to environmental toxins, carcinogens, or mutagens, including but not limited to tobacco, radiation, asbestos, long-time industrial chemical exposure
• age equal to or over 50 years

Exclusion criteria

• prior diagnosis of cancer except basal cell carcinoma
• no risk factors that place the individual at high risk
• age under 18 years
• individuals unwilling to sign the IRB-approved consent form