Serial ctDNA analysis predicts clinical progression in patients with advanced urothelial carcinoma.

Adult Aged Aged, 80 and over Biomarkers, Tumor / blood Carcinoma, Transitional Cell / blood Circulating Tumor DNA / blood Disease Progression Female High-Throughput Nucleotide Sequencing / methods Humans Longitudinal Studies Male Middle Aged Mutation Precision Medicine / methods Prognosis Survival Rate Urinary Bladder Neoplasms / blood

Journal

British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635

Informations de publication

Date de publication:
02 2022
Historique:
received: 30 05 2021
accepted: 22 11 2021
revised: 28 10 2021
pubmed: 21 1 2022
medline: 23 2 2022
entrez: 20 1 2022
Statut: ppublish

Résumé

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). We performed targeted sequencing of 182 serial ctDNA samples from 53 patients with advanced UC. 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). Serial ctDNA analysis predicts disease progression and enables dynamic monitoring to guide precision medicine in patients with advanced UC.

Sections du résumé

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.

Identifiants

DOI: 10.1038/s41416-021-01648-8 PMID: 35046520 PMC: PMC8810988
pubmed: 35046520
doi: 10.1038/s41416-021-01648-8
pii: 10.1038/s41416-021-01648-8
pmc: PMC8810988
doi:

Substances chimiques

Biomarkers, Tumor 0
Circulating Tumor DNA 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

430-439

Subventions

Organisme : NCI NIH HHS
ID : T32 CA009566
Pays : United States

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Kyrillus S Shohdy (KS)

Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA.
Department of Clinical Oncology, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt.

Dario M Villamar (DM)

Department of Medicine, Weill Cornell Medicine, New York, NY, USA.

Yen Cao (Y)

Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.

Janson Trieu (J)

Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.

Kristin S Price (KS)

Guardant Health, Inc, Redwood City, CA, USA.
ORCID: 0000-0003-4300-6413

Rebecca Nagy (R)

Guardant Health, Inc, Redwood City, CA, USA.

Scott T Tagawa (ST)

Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA.
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0003-2777-8587

Ana M Molina (AM)

Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA.
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Cora N Sternberg (CN)

Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA.
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

David M Nanus (DM)

Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA.
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Juan Miguel Mosquera (JM)

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0003-4666-6476

Olivier Elemento (O)

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.
Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
ORCID: 0000-0002-8061-9617

Guru P Sonpavde (GP)

Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-1010-9611

Petros Grivas (P)

Department of Medical Oncology, University of Washington, Seattle, WA, USA.

Nicholas J Vogelzang (NJ)

Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. nicholas.vogelzang@usoncology.com.
ORCID: 0000-0002-7665-6079

Bishoy Morris Faltas (BM)

Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu.
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu.
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu.
Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA. bmf9003@med.cornell.edu.
ORCID: 0000-0002-6432-1693

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Serial ctDNA analysis predicts clinical...
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questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Carcinome transitionnel › Serial ctDNA analysis predicts clinical...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN tumoral › ADN tumoral circulant › Serial ctDNA analysis predicts clinical...
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