Abstract 1301: Real-world analysis of NSCLC variant-level frequencies from liquid biopsy testing in diverse U.S. populations.

Abstract Non-small cell lung cancer (NSCLC) is a highly prevalent and genetically heterogeneous disease, making molecular profiling critical for guiding targeted therapy decisions. However, establishing on-site testing can be complex and costly and thus represents an unmet need in the community. The advent of liquid biopsy has increased accessibility of testing in rural and underrepresented groups in the United States, catalyzing large scale molecular profiling analyses. Data surrounding variant-level mutation frequencies across diverse U.S. populations remain limited, particularly from real-world settings in the community. This study evaluated more than 350,000 tests and 20 ethnically diverse groups for variant level frequencies of actionable molecular markers across the four major mutation classes (Single Nucleotide Variants/INDELs, Fusions, Amplifications, and Exon Skipping) in NSCLC, as identified from send-out liquid biopsy amplicon-based NGS and ddPCR testing over the past 10 years. The overall ddPCR positivity rate over the testing period was 1.5%. Among positive ddPCR results, KRAS G12C was the most frequent mutation (3.9%). NGS testing showed a 46% positivity rate for SNV/INDEL variants, with TP53 as the most frequently mutated gene (34%). NGS fusion positivity was 15%, with EML4-ALK.E6aA20.AB374361 being the most prevalent (12.95%). A disproportionate burden of NSCLC mutations was observed in African American patients, highlighting disparities in lung cancer prevalence. Geographically, the highest positive variant distributions were concentrated in the Southeastern U.S. region. These findings emphasize the utility of centralized molecular testing and the importance of including underrepresented populations in molecular profiling studies. Together, this data may help guide treatment decisions in the community setting. Citation Format: Emma K. Longshore, Ubaradka G. Sathyanarayana, Reis Pestano, Brittany D'Alessio, Theo Petropolis, Colin Cochran, Matthew Sowada, Adam Stephen, Zachariah Velasco, Alex Corral, Sam Cotten, Pauline Galvin, Gunnar Johnson, Leisa Jackson, Amanda Weaver, Gary A. Pestano. Real-world analysis of NSCLC variant-level frequencies from liquid biopsy testing in diverse U.S. populations abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1301.