Age-associated differences in genomic profiles among patients with pancreatic cancer undergoing next-generation sequencing.

e16422 Background: Age is frequently used to guide treatment and clinical trial eligibility in pancreatic cancer. However, limited data exist regarding age-associated differences in genomic profiles. We aimed to evaluate differences in genomic profiles between patients aged 70 years and older, and those aged 69 years and younger. Methods: We conducted a retrospective review of patients with pancreatic cancer treated at Moffitt Cancer Center in 2024. Genomic data were obtained from next-generation sequencing assays (NGS), including FoundationOne, Moffitt STAR, and germline testing platforms such as Ambry Genetics. Detected genomic alterations were recorded, including somatic and germline mutations when available. Pharmacogenomic data for DPYD and UGT1A1 metabolizer status (poor, intermediate, or normal) were also reported. Patients were stratified age into two groups: 70 years and older and 69 years and younger. Results: A total of 284 patients with available NGS were included, including 145 patients aged 69 years and younger and 139 patients aged 70 years and older. KRAS mutations were common in both groups and did not differ significantly by age (54.5% vs 58.3%, p = 0.54). CHIP-associated mutations, including DNMT3A, TET2, and ASXL1, were more frequently observed in patients aged 70 years and older compared with younger patients, although this difference was not statistically significant (15.8% vs 11.0%, p = 0.23). Similarly, the prevalence of pathogenic hereditary cancer gene mutations did not differ significantly between age groups (12.9% vs 14.5%, p = 0.69). Among KRAS-mutant tumors, older patients demonstrated higher reported variant allele frequencies (VAF) compared with younger patients by descriptive analysis. Conclusions: In this cohort of patients with NGS, no statistically significant differences in the prevalence of key genomic alterations were observed between older and younger adults. Older patients demonstrated a higher frequency of CHIP-associated mutations and KRAS VAF by descriptive analysis, while younger patients more frequently harbored pathogenic hereditary cancer gene alterations. These findings suggest that tumor genomic profiles are largely similar across age groups, supporting continued consideration of molecularly informed treatment strategies in older adults. Age-stratified genomic alterations among patients with pancreatic cancer undergoing next-generation sequencing. Feature Age ≤69 (n=145) Age ≥70 (n=139) p value KRAS-mutant tumors, n (%) 79 (54.5) 81 (58.3) 0.54 CHIP-associated mutations‡, n (%) 16 (11.0) 22 (15.8) 0.23 Hereditary cancer gene mutations§, n (%) 21 (14.5) 18 (12.9) 0.69 ‡Clonal hematopoiesis of indeterminate potential (CHIP) defined as DNMT3A, TET2, or ASXL1 mutations. §Hereditary cancer genes include ATM, BRCA1, BRCA2, and PALB2.