Genomic and sociodemographic characterization of gastrointestinal cancers in rural patients participating in the Avera Cancer Sequencing and Analytics Protocol (ASAP).

Abstract

848 Background: Rural populations remain underrepresented in large-scale sequencing initiatives, potentially limiting generalizability and widening disparities. The ASAP Study prospectively collects tumor and liquid next-generation sequencing (NGS), IHC, PGx, sociodemographic, clinical outcomes, and microbiome data to inform care in a rural setting. Here we describe the genomic landscape of various GI cancers in this cohort. Methods: We performed a retrospective analysis of 149 patients with GI malignancies enrolled in ASAP from Oct 2021 - Jul 2025. Data sources included: (1) solid and liquid biopsy NGS; (2) germline testing; (3) IHC/biomarkers (BRAF, KRAS, HER2, PD-L1, MMR, MSI, TMB); (4) PGx variants; (5) sociodemographic variables; and (6) clonal hematopoiesis variants. Concordance between liquid and solid NGSwas assessed by overlap and discordance rates. Descriptive statistics characterized clinical, molecular and socio-economic features. Results: Median age of the study cohort was 67 years; 64% were male, and 96% identified as White/Caucasian. Somatic mutation frequencies were TP53 67%, KRAS 36%, APC 33%, PIK3CA 11%, BRAF 10%, and NRAS 3%, assessed by NGS. Germline testing was performed in 57% of cases, with pathogenic or likely-pathogenic variants identified in 14% of those tested. Biomarker positivity rates were HER2 amplification 15% and MMR/MSI-dysregulation 10%. PGx panel results were completed for 99%. Clonal hematopoiesis was identified in 61% of cases. Actionable alterations (KRAS, NRAS, BRAF V600, HER2, NTRK/FGFR/RET, MSI-H/dMMR, IDH1, HRR) were found in 54% of patients. Conclusions: In this rural GI cancer cohort, over half of patients harbored actionable genomic alterations identified via solid and liquid biopsy NGS . Clonal hematopoiesis was detected in 61% of cases, highlighting the need for careful interpretation of ctDNA results. These findings illustrate both opportunities and challenges for precision oncology implementation in rural settings; prospective studies linking biomarker‐driven therapy and social determinants of health will be essential to improve care for this population. Demographics and biomarkers for GI cohort of the ASAP study. Category N (%) Colorectal Pancreas Upper GI Biliary Tract Liver >1 GI primary Total patients 149 78 30 25 9 4 3 Median age (years) 67 (60-73) 68 (63, 77) 67 (61, 77) 63 (56, 70) 61 (60, 73) 68 (67, 73) 63 (64, 71) Gender (male) 95 (64%) 44 (56%) 20 (67%) 22 (88%) 3 (33%) 4 (100%) 2 (67%) Stage IV 90 (70%) 43 (62%) 14 (74%) 17 (77%) 8 (89%) 3 (75%) 1 (33%) Race (n=114): White/Caucasian 109 (96%) - - - - - - Actionable somatic alterations (n=125) 68(54%) 39/66 (59%) 14/19 (74%) 7/24 (29%) 5/9 (56%) 1/4 (25%) 2/3 (67%) HER2 2+ISH+/3+ (n=47) 7 (15%) - - - - - - dMMR (n= 78)/MSI-H (n= 131) 8 (10%) /13 (10%) 8/9 0/1 0/1 0/2 0/0 - TMB-H (n=125) 22 (18%) 13 2 3 3 1 -