Real-world data and clinical experience from over 100,000 multi-cancer early detection tests
Marc Matrana, Vershalee Shukla, Dallas Kingsbury, Martin Poliak, Jordan Lipton, Matthew McMillin, Louis B. Malinow, Oliver Venn, John F. Beausang, Geoff Stanley, Earl Hubbell, Kathryn N. Kurtzman, Jeffrey M. Venstrom, Rita Shaknovich, Candace Westgate
Abstract
Blood-based multi-cancer early detection (MCED) has the potential to simultaneously screen for multiple deadly cancers with high positive predictive value. To assess real-world performance, we evaluated the Galleri® MCED test (GRAIL, Inc.) across 111,080 individuals (median age 58 years, 55.5% males). This MCED test analyzes methylation patterns of cell-free DNA to detect presence of a cancer signal and predict the anatomical cancer signal origin (CSO) to facilitate diagnostic evaluation. Cancer signal detection rate was 0.91% (1011/111,080), consistent with clinical studies and independent modeled values. Providers reported clinical outcome for 459 of 1011 individuals with cancer signal detected MCED tests. Of these, 258 had an invasive cancer diagnosis, spanning 32 cancer types. The MCED test correctly predicted the CSO in 87% of cases with a reported cancer type, consistent with previous clinical studies. CSO enabled efficient workup in most patients, with a median 39.5 days from result receipt to cancer diagnosis. The Galleri MCED cfDNA test is designed to screen for cancer signal in asymptomatic individuals. Here, the authors analyse the real-world performance of the test in over 100,000 individuals. In agreement with clinical validation studies, they observe a 49.4% empirical positive predictive value, with 87% accuracy for cancer signal localization in the body.