Institutional disparities in actionable mutation detection in pancreatic ductal adenocarcinoma: An AACR Project GENIE analysis.

Abstract

e16378 Background: The identification of actionable mutations in pancreatic ductal adenocarcinoma (PDAC) informs eligibility for precision therapies. However, institutional disparities in the implementation of comprehensive genomic profiling (CGP) are not well characterized. Notably, more than half of cancer patients in the United States receive care in community oncology settings. Methods: A total of 9,273 PDAC samples from the AACR Project GENIE (v18.0) were analyzed to compare academic medical centers and community practices. Actionable mutations assessed included homologous recombination deficiency (HRD) genes (BRCA1, BRCA2, PALB2, ATM), oncogenic drivers (KRAS, BRAF), and fusion targets (NTRK1/2/3). Statistical significance was determined using Chi-square and Fisher exact tests. Results: The academic centers accounted for 88.1% of the samples (8,167/9,273) compared to 11.9% (1,106/9,273) from the community practices. The community panels had a smaller median size (82 vs 328 genes, p < 0.001), however, 93% of the community samples were from one network using comprehensive panels (613 genes), resulting in an average of 543 genes per patient compared to 690 genes per patient in the academic setting. Despite this slight difference in testing comprehensiveness, mutation detection varied significantly across all categories (all p < 0.001) (Table). Based on academic detection rates, a significant proportion of community patients may have missed eligibility for targeted therapy: HRD 107 (91% of expected) including 61 BRCA1/2 (92%), BRAF 23 (92%), and NTRK 40 (98%). An additional 831 patients with KRAS-mutations (87%) were undetected, missing clinical trial access for emerging KRAS inhibitors. Conclusions: Community PDAC patients face considerable inequities in actionable mutation detection, with 7- to 13-fold lower detection rates for common alterations, and up to 41-fold for rare fusions, despite only 1.3-fold difference in average genes tested per patient. These disparities likely stem from variations in gene panel content, testing algorithms, or variant interpretation rather than sequencing capacity alone. Standardized CGP with quality assurance across all practice settings and academic-community partnerships is urgently needed to ensure equitable access to precision oncology. Actionable mutation detection rates. Category Genes Community n (%) Academic n (%) Fold Diff HRD (Individual) BRCA1/2 5 (0.45) 487 (5.96) 13x PALB2 1 (0.09) 105 (1.29) 14x ATM 6 (0.54) 399 (4.89) 9x HRD Combined All 4 genes* 11 (0.99) 875 (10.71) 11x Oncogenic Drivers KRAS 128 (11.57) 7084 (86.74) 7.5x BRAF 2 (0.18) 183 (2.24) 12x Fusion Targets NTRK1/2/3 1 (0.09) 301 (3.69) 41x *BRCA1+BRCA2+PALB2+ATM. All comparisons p<0.001.