1. Serial ctDNA analysis predicts clinical progression in patients with advanced urothelial carcinoma.
- Author
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Shohdy KS, Villamar DM, Cao Y, Trieu J, Price KS, Nagy R, Tagawa ST, Molina AM, Sternberg CN, Nanus DM, Mosquera JM, Elemento O, Sonpavde GP, Grivas P, Vogelzang NJ, and Faltas BM
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor blood, Carcinoma, Transitional Cell blood, Carcinoma, Transitional Cell genetics, Circulating Tumor DNA blood, Disease Progression, Female, High-Throughput Nucleotide Sequencing methods, Humans, Longitudinal Studies, Male, Middle Aged, Prognosis, Survival Rate, Urinary Bladder Neoplasms blood, Urinary Bladder Neoplasms genetics, Biomarkers, Tumor genetics, Carcinoma, Transitional Cell pathology, Circulating Tumor DNA genetics, Mutation, Precision Medicine methods, Urinary Bladder Neoplasms pathology
- Abstract
Background: Targeted sequencing of circulating tumour DNA (ctDNA) is a promising tool to monitor dynamic changes in the variant allele frequencies (VAF) of genomic alterations and predict clinical outcomes in patients with advanced urothelial carcinoma (UC)., Methods: We performed targeted sequencing of 182 serial ctDNA samples from 53 patients with advanced UC., Results: Serial ctDNA-derived metrics predicted the clinical outcomes in patients with advanced UC. Combining serial ctDNA aggregate VAF (aVAF) values with clinical factors, including age, sex, and liver metastasis, improved the performance of prognostic models. An increase of the ctDNA aVAF by ≥1 in serial ctDNA samples predicted disease progression within 6 months in 90% of patients. The majority of patients with aVAFs ≤0.7 in three consecutive ctDNA samples achieved durable clinical responses (≥6 months)., Conclusions: Serial ctDNA analysis predicts disease progression and enables dynamic monitoring to guide precision medicine in patients with advanced UC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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