{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:01:42Z","timestamp":1790596902640,"version":"4.1.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Fluoropyrimidines are widely used in the treatment of solid tumors but may cause severe toxicity in patients with reduced dihydropyrimidine dehydrogenase activity caused by specific DPYD variants. Although pretreatment DPYD genotyping is guideline supported, implementation remains inconsistent when testing, interpretation, and result reporting are not integrated into routine care pathways. This study evaluated the implementation of an in-house DPYD genotyping program embedded in prechemotherapy workflows at a multisite cancer center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A prospective observational cohort study was performed from May 2024 through July 2025 at a multisite community-academic cancer center. Peripheral blood specimens underwent in-house DPYD genotyping for c.1905\u2009+\u20091G\u2009&amp;gt;\u2009A, c.1679T\u2009&amp;gt;\u2009G, c.1236G\u2009&amp;gt;\u2009A as a proxy for c.1129-5923C\u2009&amp;gt;\u2009G, c.2846A\u2009&amp;gt;\u2009T, and c.557A\u2009&amp;gt;\u2009G using TaqMan allelic discrimination. Raw instrument output was processed through an internally developed automated pipeline that supported genotype calling, quality control review, phenotype and activity assignment, and generation of a note with this information for release into the electronic health record after medical director review. Of 617 genotyped patients, 505 who received systemic fluoropyrimidine-based therapy were included in the primary analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 505 included patients, pretreatment testing was performed in 439 (86.9%), although only 197 of 439 (44.9%) had results available before cycle 1 chemotherapy. Twenty-two (4.4%) patients were heterozygous for a DPYD variant: c.1236G\u2009&amp;gt;\u2009A in 11, c.2846A\u2009&amp;gt;\u2009T in 5, c.1905\u2009+\u20091G\u2009&amp;gt;\u2009A in 4, and c.557A\u2009&amp;gt;\u2009G in 2. In the pretreatment cohort, 10 of 21 (47.6%) patients heterozygous for a DPYD variant underwent dose reduction at cycle 1, and 9 of these reductions were documented as genotype guided. Severe treatment-related adverse events requiring urgent evaluation or hospitalization occurred in 5 of 505 (1.0%) patients, including 1 patient heterozygous for a c.1236G\u2009&amp;gt;\u2009A variant whose result returned after treatment initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In-house DPYD genotyping with integrated clinical reporting was feasible in routine practice and identified actionable variants in a clinically meaningful proportion of patients. The principal implementation limitation was not assay turnaround time itself but rather failure to return results before the first treatment decision in pretreatment-ordered cases. These findings support the value of laboratory-led pharmacogenomic programs that combine rapid testing, structured interpretation, and direct electronic reporting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajcp\/aqag104","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:51:55Z","timestamp":1788616315000},"source":"Crossref","is-referenced-by-count":0,"title":["Implementation and early outcomes of an in-house\n                    <i>DPYD<\/i>\n                    genotyping program for fluoropyrimidine safety"],"prefix":"10.1093","volume":"166","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5123-0602","authenticated-orcid":false,"given":"Harpreet","family":"Virk","sequence":"first","affiliation":[{"name":"Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine , Cleveland, OH,","place":["United 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