Measurement of ctDNA Tumor Fraction Identifies Informative Negative Liquid Biopsy Results and Informs Value of Tissue Confirmation.
Clin Cancer Res
; 30(11): 2452-2460, 2024 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-38526394
ABSTRACT
PURPOSE:
Liquid biopsy (LBx) for tumor profiling is increasingly used, but concerns remain regarding negative results. A lack of results may truly reflect tumor genomics, or it may be a false negative that would be clarified by tissue testing. A method of distinguishing between these scenarios could help clarify when follow-on tissue testing is valuable. EXPERIMENTALDESIGN:
Here we evaluate circulating tumor DNA (ctDNA) tumor fraction (TF), a quantification of ctDNA in LBx samples, for utility in identifying true negative results. We assessed concordance between LBx and tissue-based results, stratified by ctDNA TF, in a real-world genomic dataset of paired samples across multiple disease types. We also evaluated the frequency of tissue results identifying driver alterations in patients with lung cancer after negative LBx in a real-world clinicogenomic database.RESULTS:
The positive percent agreement and negative predictive value between liquid and tissue samples for driver alterations increased from 63% and 66% for all samples to 98% and 97% in samples with ctDNA TF ≥1%. Among 505 patients with lung cancer with no targetable driver alterations found by LBx who had subsequent tissue-based profiling, 37% had a driver, all of which had ctDNA TF <1%.CONCLUSIONS:
Patients with lung cancer with negative LBx and ctDNA TF ≥1% are unlikely to have a driver detected on confirmatory tissue testing; such informative negative results may benefit instead from prompt treatment initiation. Conversely, negative LBx with ctDNA TF <1% will commonly have a driver identified by follow-up tissue testing and should be prioritized for reflex testing.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
DNA Tumoral Circulante
Limite:
Female
/
Humans
Idioma:
En
Revista:
Clin Cancer Res
/
Clin. cancer res
/
Clinical cancer research
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article