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Implementing DPYD genotyping to predict chemotherapy toxicity in Australia: a feasibility study
Cassandra White1,2, Christine Paul1,2, Esther Liet3
1College of Health, Medicine and Wellbeing, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Background:
Implementing pharmacogenomic-guided management in cancer patients equitably and effectively in a large population presents challenges. DPYD genotyping determines clinically significant variants of patients at increased risk of developing grade3-5 fluoropyrimidine (FP) toxicity. FP chemotherapies are prescribed for ~16,000 Australians with a 10%-40% grade3-4 toxicity incidence and 1% mortality. Variant carriers can have FP dosing adjusted to improve treatment tolerance without compromising anticancer effect. This strategy has not been formally adopted within Australia, despite widespread international standardisation.
Aim:
This pilot study determined genotyping turnaround-times (TAT) for 4 DPYD variants (c.1905+1G>A, c.1679T>G, c.2846A>T and c.1236G>A/Haplotype B3) in Australian patients. Secondary objectives were identification of FP toxicities of DPYD variant carriers, and analysis of healthcare stakeholder perspectives, including enablers/barriers to implementation.
Methods:
Genotyping was determined by Real-Time Polymerase Chain Reaction. Qualitative data were determined through semi-structured questionnaire.
Results:
104 patients recruited over 24 months had a mean TAT of 7.2 days, 5.2 business days (range 1-30). Grade3-4 toxicity occurred in 9/16 DPYD variant carriers, including 2 ICU admissions and 1 death. Themes from 30 questionnaire respondents suggest that clinical environment and resources were fundamental barriers, and motivation to improve patient care was the predominant enabler of change.
Conclusion:
DPYD genotyping is feasible for improving precision-oncology for patients requiring FP chemotherapies. A TAT of 7 days is acceptable by both stakeholder respondents and national oncology clinician groups. This pilot study, although small, informs a large national project evaluating prospective DPYD genotyping and its impact on FP tolerability, patient safety and cost-effectiveness in Australia.
Insights
DPYD genotyping is feasible for Australian cancer patients, with a 7-day turnaround time. This precision oncology approach can reduce fluoropyrimidine toxicity and improve patient safety.
Area of Science:
- Pharmacogenomics
- Oncology
- Clinical Chemistry
Background:
- Implementing pharmacogenomic-guided cancer treatment presents challenges in equitable and effective large-scale application.
- DPYD genotyping identifies patients at risk of severe fluoropyrimidine (FP) toxicity, a common chemotherapy regimen in Australia.
- Current Australian practice has not formally adopted DPYD variant screening despite international standardization.
Purpose of the Study:
- To determine the genotyping turnaround time (TAT) for four key DPYD variants in Australian patients.
- To identify fluoropyrimidine toxicities in DPYD variant carriers.
- To analyze healthcare stakeholder perspectives on implementing DPYD genotyping, including barriers and enablers.
Main Methods:
- Real-Time Polymerase Chain Reaction (PCR) was used for DPYD variant genotyping.
- Qualitative data on stakeholder perspectives were collected through semi-structured questionnaires.
Main Results:
- A mean TAT of 7.2 days (5.2 business days) was achieved for 104 patients over 24 months.
- 9 out of 16 DPYD variant carriers experienced grade 3-4 toxicity, including ICU admissions and one death.
- Key barriers to implementation included clinical environment and resources, while motivation to improve patient care was a primary enabler.
Conclusions:
- DPYD genotyping is a feasible strategy for enhancing precision oncology in patients receiving FP chemotherapies.
- A 7-day TAT is considered acceptable by stakeholders and national oncology groups.
- This pilot study provides crucial data for a national project assessing the impact of DPYD genotyping on FP tolerability, patient safety, and cost-effectiveness in Australia.
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