2025/05/22 by Yuxuan Wang, Corinne E. Joshu, Samuel D. Curtis +15 · 2 voices · 15 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Biology #Cancer #Cancer Genomics and Diagnostics #Cell-free fetal DNA #Circulating tumor DNA #Genetic Associations and Epidemiology #Genetics #Internal medicine #Medicine #Multiple and Secondary Primary Cancers #Oncology #Pathology
paper · open access · doi:10.1158/2159-8290.cd-25-0375
published in Cancer Discovery 15(9), 1794-1802 (American Association for Cancer Research)
openalex publication_date 2025/05/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
To explore how early cancers can be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, 8 of these 52 participants scored positively with a multicancer early detection test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these eight participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six participants, the same mutations detected by the multicancer early detection test could be identified but at 8.6- to 79-fold lower mutant allele fractions. These results demonstrate that it is possible to detect ctDNA more than 3 years prior to clinical diagnosis and provide benchmark sensitivities required for this purpose. SIGNIFICANCE: Earlier detection is a promising strategy to reduce cancer mortality. For cancers of all stages, therapies are more effective with a lower disease burden. In this study, we demonstrate that ctDNA is detectable 3 years or more before cancer diagnosis and provide estimates for the sensitivity required to achieve such very early detection. See related commentary by Crisafulli et al., p. 1774.