Implementation of DPYD genetic testing at a safety net oncology clinic.

Abstract

628 Background: DPYD gene variants are associated with severe, potentially fatal toxicity from fluoropyrimidines (5-fluorouracil and capecitabine). Approximately 4-8% of the population carries deleterious variants affecting dihydropyrimidine dehydrogenase (DPD) activity. In October 2025, the FDA issued a black box warning to the capecitabine label, recommending DPYD testing before initiation. ASCO GI 2026, further supported universal pre-treatment testing before fluoropyrimidines. This project aimed to streamline the process of DPYD testing in a safety net oncology clinic and improve provider education to reduce chemotherapy-related toxicity. Methods: A quality improvement initiative was implemented at NYC Health + Hospitals/Bellevue Cancer Center in February 2026. Interventions included: (1) development and dissemination of a DPYD testing workflow map via email and placement in provider work areas for point-of-care reference; (2) multidisciplinary educational sessions for physicians, nurse practitioners, and nurses, detailing clinical significance, ordering workflow, and dose-adjustment strategies; and (3) proposal submission for EMR-based ordering prompts to institutional leadership. DPYD test ordering data was collected and compared between the 4-month pre- and post-intervention periods. Results: During the pre-intervention period, DPYD testing at fluoropyrimidine initiation was absent, with 0% of patients (0/21) starting therapy with documented DPYD testing. Following implementation of workflow standardization and multidisciplinary education in February 2026, the proportion of patients initiating therapy with DPYD testing increased to 72.4% (21/29), demonstrating substantial improvement in guideline-concordant DPYD testing utilization. Conclusions: Implementation of a structured workflow and multidisciplinary education significantly increased DPYD testing in a safety net oncology clinic. Expansion of EMR-based clinical decision support may further improve adherence to testing recommendations and improve patient safety by reducing preventable fluoropyrimidine toxicity. Impact of quality improvement intervention on DPYD testing utilization. Time Period Patients Newly Initiated on Fluoropyrimidines Patients Initiated Without a DPYD Test DPYD Testing at Initiation (%) Intervention Status October 2025 - January 2026 21 21 0% Pre-Intervention February 2026 - May 2026 29 8 72.4% Post-Intervention