{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T17:26:25Z","timestamp":1789233985540,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>In April 2019, French authorities mandated dihydropyrimidine dehydrogenase (DPD) screening, specifically testing uracilemia, to mitigate the risk of toxicity associated with fluoropyrimidine\u2010based chemotherapy. However, this subject is still of debate as there is no consensus on a standardized DPD deficiency screening test. We conducted a real\u2010life retrospective study with the aim of assessing the impact of DPD screening on the occurrence of severe toxicity and exploring the potential benefits of complete genotyping using next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All adult patients consecutively treated with 5\u2010fluorouracil (5\u2010FU) or its oral prodrug at six cancer centers between March 2018 and February 2019 were considered for inclusion. Dihydropyrimidine dehydrogenase deficiency screening included gene encoding DPD (<jats:italic>DPYD)<\/jats:italic> genotyping using complete genome sequencing and DPD phenotyping (uracilemia or dihydrouracilemia\/uracilemia ratio) or both tests. Associations between each DPD screening method and (i) severe (grade\u2009\u22653) early toxicity and (ii) fluoropyrimidine dose reduction in the second chemotherapy cycle were evaluated using multivariable logistic regression analysis. Furthermore, we assessed the concordance between DPD genotype and phenotype using Cohen's kappa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 551 patients were included. Most patients were tested for DPD deficiency (86%) including <jats:italic>DPYD<\/jats:italic> genotyping only (6%), DPD phenotyping only (8%), or both (72%). Complete DPD deficiency was not detected in the study population. Severe early toxicity events were observed in 73 patients (13%), with two patients (0.30%) presenting grade 5 toxicity. Despite the numerically higher toxicity rate in untested patients, the occurrence of severe toxicity was not significantly associated with the DPD screening method (<jats:italic>p<\/jats:italic>\u2009=\u20090.69). Concordance between the DPD genotype and phenotype was weak (Cohen's kappa of 0.14).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Due to insufficient numbers, our study was not able to demonstrate any added value of <jats:italic>DPYD<\/jats:italic> genotyping using complete genome sequencing to prevent 5\u2010FU toxicity. The optimal strategy for DPD screening before fluoropyrimidine\u2010based chemotherapy requires further clinical evaluation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7066","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T07:28:26Z","timestamp":1711351706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Complete <i>DPYD<\/i> genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3199-5907","authenticated-orcid":false,"given":"C\u00f4me","family":"De\u00a0Metz","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Centre Oscar Lambret  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0302-6049","authenticated-orcid":false,"given":"Benjamin","family":"Hennart","sequence":"additional","affiliation":[{"name":"Toxicology Unit, Biology and Pathology Centre Lille University Medical Centre  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Aymes","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Centre Oscar Lambret  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Yves","family":"Cren","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Centre Oscar Lambret  Lille France"},{"name":"Department of Biostatistics Centre Oscar Lambret  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Martign\u00e8ne","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Centre Oscar Lambret  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5243-1548","authenticated-orcid":false,"given":"Nicolas","family":"Penel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Centre Oscar Lambret  Lille France"},{"name":"Univ. Lille, CHU Lille, ULR 2694 \u2010 Metrics: Evaluation des technologies de sant\u00e9 et des pratiques m\u00e9dicales  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u00ebl","family":"Barthoulot","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Centre Oscar Lambret  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2933-4066","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Carnot","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Centre Oscar Lambret  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00286-7"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.11.3537"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198916040-00002"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(97)00253-3"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1784"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.94"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2608"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30686-7"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175998"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs-2022-0135"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0962-z"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.34"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2482"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0423-8"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14102119"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213923"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100125"},{"key":"e_1_2_13_19_1","first-page":"21032","article-title":"F\u00f6rdelaktigt med genetisk analys f\u00f6re behandling med 5\u2010fluorouracil [new recommendation on pharmacogenetic screening prior to 5\u2010fluorouracil based cancer treatment \u2010 Swedish experience indicates less adverse effects and healthcare cost savings]","volume":"118","author":"Schultz A","year":"2021","journal-title":"Lakartidningen"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12762"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15536"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/17588359221148536"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.289"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1020"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.116"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.7066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T05:21:33Z","timestamp":1726723293000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.7066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/cam4.7066"],"URL":"https:\/\/doi.org\/10.1002\/cam4.7066","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e7066"}}