Implementing DPYD testing prior to treatment with fluoropyrimidines at Lahey Clinic.

Abstract

45 Background: Fluoropyrimidines are foundational therapies for the treatment of many cancers. Carriers of pathogenic DPYD variants face a 5–8 fold increased risk of grade ≥3 toxicity. In 2025, the FDA added a boxed warning to the capecitabine label recommending DPYD testing prior to treatment initiation. Despite this, preemptive DPYD testing remains inconsistently implemented across U.S. institutions. Lahey Clinic lacked a systematic pretreatment DPYD testing program, representing a gap in patient safety. Methods: This project utilizes the IHI Model for Improvement, employing Plan-Do-Study-Act (PDSA) cycles. The primary aim is to increase DPYD testing rates to over 90% for eligible patients. In PDSA #1, team members proactively identified 10 consecutive patients scheduled for fluoropyrimidine therapy and notified the patient's primary oncologist via a standardized electronic message to approve the DPYD test order. A SmartPhrase was created to facilitate documentation and the prior authorization (PA) process. In PDSA #2, the next 50 cases were tracked for baseline measures for the system including turnaround time, rates of intermediate metabolizer variants, as well as addressing workflow barriers. Results: Between January and June 2026, 60 patients were identified as candidates for DPYD testing. In PDSA #1, 9 out of 10 pts (90%) had DPYD testing completed; 1 was denied by insurance. In PDSA #2, 43 out of 50 pts (86%) completed DPYD testing. The average turnaround time was 8 days. The proportion of intermediate metabolizers was 4 out of 60 pts (6.6%). Key barriers to testing completion included urgent treatment initiation, insurance delays, and patient availability for lab draws. Conclusions: The initial PDSA cycle demonstrated the feasibility of a systematic DPYD testing workflow, with 90% of eligible patients completing testing. In PDSA #2, the completion rate was not sustained due to several factors. The 6.6% intermediate metabolizer variant rate reinforces the clinical relevance of universal pretreatment testing and pursuing the goal of high rates of testing. Next steps include resolving identified barriers with targeted provider education for prompt ordering, collaborating with laboratory services for shortening turnaround time, and considering mobile phlebotomy for patients unable to return for testing.