2026 Southeastern Residency Conference

Background: 
Fluoropyrimidines (5-fluorouracil and capecitabine) and irinotecan are chemotherapy agents commonly used to treat upper and lower gastrointestinal malignancies, and various other solid tumors. These medications have important pharmacogenomic (PGx) considerations involving the dihydropyrimidine dehydrogenase (DPYD) and uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) genes. Variants in these genes can impair drug metabolism and increase the risk of severe hematologic and gastrointestinal toxicity. Between 2024 and 2025, revisions to medication labeling and National Comprehensive Cancer Network (NCCN) guidelines-initiated support for preemptive DPYD testing. While PGx testing is available within the Salisbury VA Health Care System (SVAHCS), the extent to which it is utilized in oncology practice remains unclear.  This quality improvement project evaluated the utilization of multi-gene PGx testing among Veterans receiving fluoropyrimidine- or irinotecan-based chemotherapy within the SVAHCS. 

Methods: 
This IRB-exempt, retrospective, quality improvement project evaluated Veterans initiating fluoropyrimidine (5-fluorouracil or capecitabine) or irinotecan-based chemotherapy across three oncology sites within the SVAHCS between November 1, 2024, and November 30, 2025. Eligible patients were identified using Computerized Patient Record System (CPRS) chemotherapy orders. Patients receiving oncology care exclusively outside the VA system or receiving topical fluorouracil were excluded. A retrospective chart review was performed. REDCap database software was utilized to collect patient demographics, cancer type, chemotherapy regimen, and relevant PGx testing information. For patients who underwent testing, PGx phenotypes, PGx-guided therapy modifications, and testing turnaround times were evaluated. Reasons for omission of PGx testing were also recorded when available. 
 
Results: 
A total of 70 Veterans receiving fluoropyrimidine- or irinotecan-based chemotherapy were identified. 40 Veterans were included in the analysis. The mean patient age was 66.35 years, and the cohort was predominantly male (95%). The most common malignancies were colon cancer (52.5%) and pancreatic cancer (22.5%). PGx testing was ordered in 25 patients (62.5%). Documented rationale for not obtaining PGx testing included: prior tolerance of therapy, prior PGx results on file, needing to rapidly initiate chemotherapy, and awaiting eligibility for an investigational treatment. Of the 15 patients for whom PGx testing was not obtained there was no documented reason for the lack of testing in 7 patients (46.7%). Among patients with PGx results, DPYD phenotypes were normal in 96% (n=24), and intermediate in 4% (n=1). UGT1A1 phenotypes were normal in 72% (n=18), intermediate in 16% (n=4), and poor in 12% (n=3). PGx-guided irinotecan dose reductions were documented in all patients that were poor UGT1A1 metabolizers and receiving irinotecan (n=2). Median turnaround time from PGx order to vendor report was 12 days (IQR: 9-13), and the median time from vendor report to CPRS result posting was 6 days (IQR: 3-9).  
 
Conclusions: 
Multi-gene (PGx) testing for DPYD and UGT1A1 genes increased following updated guidance in October 2025, however, it was not consistently utilized during the review period.  Over one-third of the review population did not undergo testing, with most lacking documented rationale for omission. The lack of definitive guidance before updates to the VA clinical oncology pathways may have contributed to the limited use of PGx testing among these Veterans.  Among those tested, actionable UGT1A1 results led to irinotecan starting dose reductions, demonstrating potential clinical impact. Standardized, preemptive testing workflows represent an opportunity to improve uptake and optimize the safety of chemotherapy within the Veteran population.