Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients

Abstract Aim To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs. Methods We used propensity score matching (PSM) to ma...

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Main Authors: Apostolos Tsiachristas, Grant Vallance, Rositsa Koleva-Kolarova, Harriet Taylor, Luke Solomons, Giovanni Rizzo, Catherine Chaytor, Junel Miah, Sarah Wordsworth, A. Bassim Hassan
Format: Article
Language:English
Published: BMC 2022-04-01
Series:BMC Cancer
Online Access:https://doi.org/10.1186/s12885-022-09576-3
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author Apostolos Tsiachristas
Grant Vallance
Rositsa Koleva-Kolarova
Harriet Taylor
Luke Solomons
Giovanni Rizzo
Catherine Chaytor
Junel Miah
Sarah Wordsworth
A. Bassim Hassan
author_facet Apostolos Tsiachristas
Grant Vallance
Rositsa Koleva-Kolarova
Harriet Taylor
Luke Solomons
Giovanni Rizzo
Catherine Chaytor
Junel Miah
Sarah Wordsworth
A. Bassim Hassan
author_sort Apostolos Tsiachristas
collection DOAJ
description Abstract Aim To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs. Methods We used propensity score matching (PSM) to match 466 patients tested with ToxNav® with 1556 patients from a historical cohort, and performed regression analysis to estimate the impact of ToxNav®on toxicity, depression, and hospital costs. Results ToxNav® appeared to reduce the likelihood of experiencing moderate (OR: 0.59; 95%CI: 0.45–0.77) and severe anaemia (OR: 0.55; 95%CI: 0.33–0.90), and experience of pain for more than 4 days a week (OR: 0.50; 95%CI: 0.30–0.83), while it increased the likelihood of mild neutropenia (OR: 1.73; 95%CI: 1.27–2.35). It also reduced the cost of chemotherapy by 12% (95%CI: 3–31) or £9765, the cost of non-elective hospitalisation by 23% (95%CI: 8–36) or £2331, and the cost of critical care by 21% (95%CI: 2–36) or £1219 per patient. For the DPYD variant associated with critical risk of toxicity (rs3918290), the improved non-elective hospital costs were > £20,000, whereas variants associated with hand-foot syndrome toxicity had no detectable cost improvement. Conclusion Upfront testing of DPYD variants appears to reduce the toxicity burden of Capecitabine and 5-FU in cancer patients and can lead to substantial hospital cost savings, only if the dose management of the drugs in response to variants detected is standardised and regulated.
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spelling doaj.art-58f8ffe3049c47f5a849a3e126d1d17d2022-12-22T03:03:49ZengBMCBMC Cancer1471-24072022-04-0122111110.1186/s12885-022-09576-3Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patientsApostolos Tsiachristas0Grant Vallance1Rositsa Koleva-Kolarova2Harriet Taylor3Luke Solomons4Giovanni Rizzo5Catherine Chaytor6Junel Miah7Sarah Wordsworth8A. Bassim Hassan9Nuffield Department of Population Health, University of OxfordOxford University Hospitals NHS TrustNuffield Department of Population Health, University of OxfordOxford University Hospitals NHS TrustOxford University Hospitals NHS TrustOxford University Hospitals NHS TrustOxford University Hospitals NHS TrustOxford University Hospitals NHS TrustNuffield Department of Population Health, University of OxfordOxford University Hospitals NHS TrustAbstract Aim To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs. Methods We used propensity score matching (PSM) to match 466 patients tested with ToxNav® with 1556 patients from a historical cohort, and performed regression analysis to estimate the impact of ToxNav®on toxicity, depression, and hospital costs. Results ToxNav® appeared to reduce the likelihood of experiencing moderate (OR: 0.59; 95%CI: 0.45–0.77) and severe anaemia (OR: 0.55; 95%CI: 0.33–0.90), and experience of pain for more than 4 days a week (OR: 0.50; 95%CI: 0.30–0.83), while it increased the likelihood of mild neutropenia (OR: 1.73; 95%CI: 1.27–2.35). It also reduced the cost of chemotherapy by 12% (95%CI: 3–31) or £9765, the cost of non-elective hospitalisation by 23% (95%CI: 8–36) or £2331, and the cost of critical care by 21% (95%CI: 2–36) or £1219 per patient. For the DPYD variant associated with critical risk of toxicity (rs3918290), the improved non-elective hospital costs were > £20,000, whereas variants associated with hand-foot syndrome toxicity had no detectable cost improvement. Conclusion Upfront testing of DPYD variants appears to reduce the toxicity burden of Capecitabine and 5-FU in cancer patients and can lead to substantial hospital cost savings, only if the dose management of the drugs in response to variants detected is standardised and regulated.https://doi.org/10.1186/s12885-022-09576-3
spellingShingle Apostolos Tsiachristas
Grant Vallance
Rositsa Koleva-Kolarova
Harriet Taylor
Luke Solomons
Giovanni Rizzo
Catherine Chaytor
Junel Miah
Sarah Wordsworth
A. Bassim Hassan
Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
BMC Cancer
title Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
title_full Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
title_fullStr Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
title_full_unstemmed Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
title_short Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
title_sort can upfront dpyd extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy a propensity score matched analysis of 2022 uk patients
url https://doi.org/10.1186/s12885-022-09576-3
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