J. C. Burton1, F. De Asis1, S. Mekonnen1, M. Stewart-McLellan2, D. Potts1, T. Howard1, and N. Nabavizadeh1; 1Oregon Health and Science University, Portland, OR, 2Midwestern University, Glendale, AZ
Purpose/Objective(s):Cancer screening continues to be a major challenge, with reliable tests only being available for very few cancers. Multi-cancer early detection (MCED) genomic tests are being developed that allow for blood-based screening for up to 50 cancers simultaneously. The PATHFINDER study was a multi-institution prospective cohort study in healthy participants over the age of 50 years (no cancer history, or history of treated cancer > 3 years prior), investigating the feasibility of the Galleri (GRAIL, LLC) ctDNA methylation MCED blood test. For participants in which the Galleri MCED test revealed methylation signatures indicative of cancer, predicted cancer signal origins were provided to the clinicians to assist with further diagnostic workup. Our institution was the highest accruing site nationally. Here, we describe our institutional test performance. Materials/
Methods: Under IRB approval, a retrospective chart review of participants enrolled in the PATHFINDER study was performed. Cancer risk factors, outcomes of tests and studies performed due to MCED signal positive, time to diagnostic resolution, and treatment outcomes were obtained. Results: From Jan 2020 to Dec 2020, our institution enrolled 1735 participants (26% of total study enrollment), 27 of which returned a signal positive for cancer suspicion (1.6%), and ultimately 12 diagnosed cancers (true positives) for a positive predictive value of 44%. Four of 12 were recurrent cancers in participants > 3 years from cancer therapy. There were 15 signal positives without cancer diagnoses (false positives), with one patient receiving extensive work-up for possible uterus, breast or lung cancer origin. Six of 15 false positive results correlated to monoclonal B-cell lymphocytosis (CLL precursor).During the course of 12-month follow-up for signal negatives, 19 participants were diagnosed with a cancer (sensitivity: 39%, specificity: 99.1%). Conclusion: Our institutional experience demonstrates the feasibility of MCED testing. Additional prospective randomized clinical trials are needed before widespread adoption.
