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INTRODUCTION: In this study (PRECISE), we assess the clinical utility of a germline DNA sequencing-based test (ToxNav) for mutations in DPYD and ENOSF1 genes to alter clinician-prescribed fluoropyrimidine doses and the use of a digital application (PROMinet) to record patient-reported chemotherapy toxicity. MATERIALS AND METHODS: Adult patients with a histological diagnosis of colorectal cancer (CRC) who consented to fluoropyrimidine-based chemotherapy were recruited prospectively and given a digital application to monitor and record associated toxicities. Patient samples were analyzed for 18 germline coding variants in DPYD and 1 ENOSF1 variant. RESULTS: Genetic testing was performed for 60 patients and identified one patient at increased risk of fluoropyrimidine-based toxicities. Uptake of genetic testing was high and results were available on average 17 days from initial clinical encounter. Patient-reported chemotherapy toxicity identified differences in 5-fluorouracil vs capecitabine regime profiles and identified profiles associated with subsequent need for chemotherapy dose reduction and hospital admission. DISCUSSION: The PRECISE clinical trial demonstrated that a germline DNA sequencing-based test can provide clinically relevant information to alter clinicians' fluoropyrimidine prescription. The study also obtained high volume, high granularity patient-reported toxicity data that might allow the improvement and personalization of chemotherapy management.

Original publication




Conference paper

Publication Date





6305 - 6314


Colorectal cancer, DPYD, ENOSF1, chemotherapy, fluoropyrimidine, genetic testing, germline, toxicity, toxicity monitoring, Aged, Alleles, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Colorectal Neoplasms, Female, Gene Frequency, Genetic Testing, Germ-Line Mutation, Humans, Hydro-Lyases, Male, Microsatellite Repeats, Middle Aged, Mobile Applications