Dataset Information

Implementing DPYD*2A Genotyping in Clinical Practice: The Quebec, Canada, Experience.

ABSTRACT:

Background

Fluoropyrimidines are used in chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. DPYD*2A polymorphism is one of the most studied variants. The study objective was to document the impact of implementing this test in routine clinical practice.

Methods

We retrospectively performed chart reviews of all patients who tested positive for a heterozygous or homozygous DPYD*2A mutation in samples obtained from patients throughout the province of Quebec, Canada.

Results

During a period of 17 months, 2,617 patients were tested: 25 patients tested positive. All were White. Twenty-four of the 25 patients were heterozygous (0.92%), and one was homozygous (0.038%). Data were available for 20 patients: 15 were tested upfront, whereas five were identified after severe toxicities. Of the five patients confirmed after toxicities, all had grade 4 cytopenias, 80% grade ≥3 mucositis, 20% grade 3 rash, and 20% grade 3 diarrhea. Eight patients identified with DPYD*2A mutation prior to treatment received fluoropyrimidine-based chemotherapy at reduced initial doses. The average fluoropyrimidine dose intensity during chemotherapy was 50%. No grade ≥3 toxicities were observed. DPYD*2A test results were available in an average of 6 days, causing no significant delays in treatment initiation.

Conclusion

Upfront genotyping before fluoropyrimidine-based treatment is feasible in clinical practice and can prevent severe toxicities and hospitalizations without delaying treatment initiation. The administration of chemotherapy at reduced doses appears to be safe in patients heterozygous for DPYD*2A.

Implications for practice

Fluoropyrimidines are part of chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. This retrospective analysis demonstrates that upfront genotyping of DPYD before fluoropyrimidine-based treatment is feasible in clinical practice and can prevent severe toxicities and hospitalizations without delaying treatment initiation. This approach was reported previously, but insufficient data concerning its application in real practice are available. This is likely the first reported experience of systematic DPYD genotyping all over Canada and North America as well.

SUBMITTER: Jolivet C

PROVIDER: S-EPMC8018309 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:With the emergence of antimicrobial resistance (AMR), many countries are implementing restrictive regulations to reduce antimicrobial use (AMU) in animal production. Although these measures are effective at the national level, their implementation may generate challenges for producers and veterinarians. The objective of this study was to explore the barriers and facilitators of implementing a new regulation restricting the use of antimicrobials of very high importance for human health in the dairy production sector in the province of Québec, Canada. Individual interviews were conducted with fifteen veterinarians and twenty-seven dairy producers. Thematic analysis was performed based on the COM-B model of behavior change (capability-opportunity-motivation-behavior). Our results indicated that the lack of availability of alternative treatments, the long delays related to diagnostic tests and the fear of economic consequences were major barriers to the implementation of the regulation. A small number of producers also perceived that the regulation negatively impacted the health and wellbeing of their animals. Additionally, participants acknowledged the importance of early education and training to better understand the purpose of the regulation and increase its acceptability. Lastly, most participants reported that they had not only reduced their use of antimicrobials of very high importance for human health following the regulation, but they had also increased preventive practices on their farm. This study reveals that the implementation of restrictive regulations to reduce AMU in animal production can lead to multiple challenges in practice. Our results highlight the need for better communication and training of producers and veterinarians before and during the implementation of similar regulations in the future and underline the importance of measuring the direct and indirect impacts of those regulations on productivity and on animal health and wellbeing.

Project description:BackgroundEvery week, radiotherapy centers face the complex task of scheduling hundreds of treatment sessions amongst the available linear accelerators. With the increase in cancer patient numbers, manually creating a feasible and efficient schedule has shown to be a difficult, time-consuming task. Although operations research models have been increasingly reported upon to optimize patient care logistics, there is almost no scientific evidence of implementation in practice.MethodsA mathematical operations research model was adapted to generate radiotherapy treatment schedules in two Dutch centers. The model was iteratively adjusted to fulfill the technical and medical constraints of each center until a valid model was attained. Patient data was collected for the planning horizon of one week, and the feasibility of the obtained schedules was verified by the staff of each center. The resulting optimized solutions are compared with the ones manually developed in practice.ResultsThe weekly schedule was improved in both centers by decreasing the average standard deviation between sessions' starting times from 103.0 to 50.4 minutes (51%) in one center, and the number of gaps in the schedule from 18 to 5 (72%) in the other. The number of patients requiring linac switching between sessions has also decreased from 71 to 0 patients in one center, and from 43 to 2 in the other. The automated process required 5 minutes and 1.5 hours of computation time to find an optimal weekly patient schedule, respectively, as opposed to approximately 1.5 days when performed manually for both centers.ConclusionsThe practical application of a theoretical operations research model for radiotherapy treatment scheduling has provided radiotherapy planners a feasible, high-quality schedule in an automated way. Iterative model adaptations performed in small steps, early engagement of stakeholders, and constant communication proved to facilitate the implementation of operations research models into clinical practice.