{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:17:42Z","timestamp":1785860262994,"version":"3.56.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Ligue Contre le Cancer comit\u00e9 d\u00e9partemental du Maine et Loire, France"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Dose-Response"],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Fluoropyrimidines (FPs) carry around 20% risk of G3-5 toxicity and 0.2-1% risk of death, due to dihydropyrimidine dehydrogenase (DPD) deficiency. Several screening approaches exist for predicting toxicity, however there is ongoing debate over which method is best. This study compares 4 screening approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method:<\/jats:title>\n                    <jats:p>\n                      472 patients treated for colorectal, head-and-neck, breast, or pancreatic cancers, who had not been tested pre-treatment for FP toxicity risk, were screened using: DPYD genotyping (G); phenotyping via plasma Uracil (U); phenotyping via plasma-dihydrouracil\/uracil ratio (UH\n                      <jats:sub>2<\/jats:sub>\n                      \/U); and a Multi-Parametric Method (MPM) using genotype, phenotype, and epigenetic data. Performance was compared, particularly the inability to detect at-risk patients (false negatives).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      False negative rates for detecting G5 toxicity risk were 51.2%, 19.5%, 9.8% and 2.4%, for G, U, UH\n                      <jats:sub>2<\/jats:sub>\n                      \/U and MPM, respectively. False negative rates for detecting G4-5 toxicity risk were 59.8%, 36.1%, 21.3% and 4.7%, respectively. MPM demonstrated significantly (p &lt; 0.001) better prediction performance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>MPM is the most effective method for limiting G4-5 toxicity. Its systematic implementation is cost-effective and significantly improves the risk-benefit ratio of FP-treatment. The use of MPM, rather than G or U testing, would avoid nearly 8,000 FP-related deaths per year globally (500 in France), and spare hundreds of thousands from G4 toxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1559325820951367","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T06:13:54Z","timestamp":1600064034000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparison of 4 Screening Methods for Detecting Fluoropyrimidine Toxicity Risk: Identification of the Most Effective, Cost-Efficient Method to Save Lives"],"prefix":"10.1177","volume":"18","author":[{"given":"Olivier","family":"Capitain","sequence":"first","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Seegers","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Metges","sequence":"additional","affiliation":[{"name":"CHU H\u00f4pital Morvan, Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Faroux","sequence":"additional","affiliation":[{"name":"CH D\u00e9partemental Vend\u00e9e La Roche sur Yon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Stampfli","sequence":"additional","affiliation":[{"name":"CH Laval, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Ferec","sequence":"additional","affiliation":[{"name":"CH Pays de Morlaix, Morlaix, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara Matysiak","family":"Budnik","sequence":"additional","affiliation":[{"name":"CHU H\u00f4tel Dieu, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Senellart","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Rossi","sequence":"additional","affiliation":[{"name":"CH Ch\u00e2teau Gontier, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nad\u00e8ge","family":"Blouin","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Dauv\u00e9","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Campone","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie de l\u2019Ouest, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"bibr1-1559325820951367","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040958"},{"key":"bibr2-1559325820951367","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.08.009"},{"key":"bibr3-1559325820951367","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2017.02.008"},{"key":"bibr4-1559325820951367","doi-asserted-by":"publisher","DOI":"10.1067\/mcn.2001.116058"},{"key":"bibr5-1559325820951367","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.4.1105"},{"key":"bibr6-1559325820951367","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03686.x"},{"key":"bibr7-1559325820951367","unstructured":"National Cancer Institute, Division of Cancer Treatment & Diagnosis. 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