{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T21:40:34Z","timestamp":1777585234106,"version":"3.51.4"},"reference-count":74,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am Soc Clin Oncol Educ Book"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Recent regulatory and guideline changes have established pretreatment\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      genotyping as a critical strategy to prevent severe fluoropyrimidine toxicity. Following earlier European leadership by the European Medicines Agency, the US Food and Drug Administration added boxed warnings to capecitabine and 5-fluorouracil labels recommending genetic testing before therapy. Concurrent updates from the National Comprehensive Cancer Network and ASCO align US with European practice supporting universal testing. Fluoropyrimidines remain foundational treatments across multiple cancers but can cause life-threatening toxicity in patients with dihydropyrimidine dehydrogenase (DPD) deficiency, most commonly because of inherited\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      variants.\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      variant carriers receiving standard doses experience markedly increased risk of severe toxicity and treatment-related mortality, emphasizing the clinical importance of\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      testing and genotype-guided dosing. Evidence demonstrates that dose individualization based on guidance from the Clinical Pharmacogenetics Implementation Consortium reduces toxicity risk while maintaining treatment effectiveness and potentially reducing overall costs. Patient advocacy, particularly efforts led by Advocates for Universal DPD\/\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      Testing, has accelerated policy change, increased clinician awareness, and highlighted ethical implications of preventable harm. Despite growing adoption, implementation challenges persist, including workflow integration, clinician education, and equitable access. Integrated health systems such as the Veterans Health Administration demonstrate how centralized infrastructure and clinical decision support can facilitate uptake. Barriers are more pronounced in resource-constrained settings, where limited infrastructure, reimbursement uncertainty, and insufficient pharmacogenomic education hinder implementation. Regional initiatives illustrate education-focused, context-adapted strategies to expand testing and address population-specific variant knowledge gaps. Collectively, emerging evidence, regulatory alignment, and advocacy efforts position\n                      <jats:italic toggle=\"yes\">DPYD<\/jats:italic>\n                      genotyping as a patient-safety imperative necessary to achieve safer, more equitable fluoropyrimidine therapy worldwide.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/edbk-26-521184","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:59:07Z","timestamp":1777406347000},"source":"Crossref","is-referenced-by-count":0,"title":["Importance of and Strategies for Implementing\n                    <i>DPYD<\/i>\n                    Testing to Prevent Severe Fluoropyrimidine Chemotherapy Toxicity in Health Care Systems"],"prefix":"10.1200","volume":"46","author":[{"given":"Jeremy","family":"Kratz","sequence":"first","affiliation":[{"name":"University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI"},{"name":"Center for Human Genomics and Precision Medicine, University of Wisconsin, Madison, WI"},{"name":"William S. Middleton Memorial Veterans Hospital, Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Merritt","sequence":"additional","affiliation":[{"name":"Advocates for Universal DPD\/DPYD Testing (AUDT), Chelan, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"University of Wisconsin Hospitals and Clinics, Madison, WI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Comfort","family":"Kanji","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Abel","family":"Qui\u00f1ones","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile"},{"name":"Department of Pharmaceutical Sciences and Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile"},{"name":"Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF), Santiago, Chile"},{"name":"Center for Cancer Prevention and Control (CECAN), Santiago, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-1035","authenticated-orcid":true,"given":"Daniel L.","family":"Hertz","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_4_2_2","volume-title":"5-Fluorouracil (I.V.), Capecitabine and Tegafur Containing Products: Pre-Treatment Testing to Identify DPD-deficient Patients at Increased Risk of Severe Toxicity","author":"Agency EM","year":"2020","unstructured":"Agency EM: 5-Fluorouracil (I.V.), Capecitabine and Tegafur Containing Products: Pre-Treatment Testing to Identify DPD-deficient Patients at Increased Risk of Severe Toxicity. 2020"},{"key":"e_1_3_4_3_2","volume-title":"Prescribing Information for XELODA\u00ae (Capecitabine) Tablets","unstructured":"Prescribing Information for XELODA\u00ae (Capecitabine) Tablets. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/020896s044s045s046s047s048s049s050s051lbl.pdf"},{"key":"e_1_3_4_4_2","volume-title":"Safety Labeling Update for Capecitabine and Fluorouracil (5-FU) on Risks Associated with Dihydropyrimidine Dehydrogenase (DPD) Deficiency","author":"Administration USFD","year":"2026","unstructured":"Administration USFD: Safety Labeling Update for Capecitabine and Fluorouracil (5-FU) on Risks Associated with Dihydropyrimidine Dehydrogenase (DPD) Deficiency. 2026"},{"key":"e_1_3_4_5_2","volume-title":"Colon Cancer (Version 5.2025)","author":"National Comprehensive Cancer Network","unstructured":"National Comprehensive Cancer Network: Colon Cancer (Version 5.2025). https:\/\/www.nccn.org"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-02115"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14102119"},{"key":"e_1_3_4_8_2","volume-title":"Breast Cancer (Version 4.2022)","author":"National Comprehensive Cancer Network","unstructured":"National Comprehensive Cancer Network: Breast Cancer (Version 4.2022). https:\/\/www.nccn.org"},{"key":"e_1_3_4_9_2","volume-title":"Rectal Cancer (Version 1.2022)","author":"National Comprehensive Cancer Network","unstructured":"National Comprehensive Cancer Network: Rectal Cancer (Version 1.2022). https:\/\/www.nccn.org"},{"key":"e_1_3_4_10_2","unstructured":"National Comprehensive Cancer Network: Referenced from the NCCN Clinical Practice Guidelines in Oncology (NCCN guidelines\u00ae) for Pancreatic Adenocarcinoma V.2.2021. \u00a9 National Comprehensive Cancer Network Inc 2021. 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