Kyrillus S Shohdy1,2, Dario M Villamar3, Yen Cao4, Janson Trieu4, Kristin S Price5, Rebecca Nagy5, Scott T Tagawa1,6,7, Ana M Molina1,6,7, Cora N Sternberg1,6,7, David M Nanus1,6,7, Juan Miguel Mosquera6,7,8, Olivier Elemento6,9, Guru P Sonpavde10, Petros Grivas11, Nicholas J Vogelzang12, Bishoy Morris Faltas13,14,15,16. 1. Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA. 2. Department of Clinical Oncology, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt. 3. Department of Medicine, Weill Cornell Medicine, New York, NY, USA. 4. Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. 5. Guardant Health, Inc, Redwood City, CA, USA. 6. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. 7. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. 8. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. 9. Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. 10. Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 11. Department of Medical Oncology, University of Washington, Seattle, WA, USA. 12. Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. nicholas.vogelzang@usoncology.com. 13. Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu. 14. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu. 15. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu. 16. Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu.
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.
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.
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