Detection of Cancers Three Years Prior to Diagnosis Using Plasma Cell-Free DNA.

Details

• Alternative Title:
  Cancer Discovery, 2025, v. 15, no. 9: Detection of Cancers Three Years Prior to Diagnosis Using Plasma Cell-Free DNA.
• Journal Article:
  Cancer Discovery
• Personal Author:
  Wang, Yuxuan ; Joshu, Corinne E. ; Curtis, Samuel D. ; Douville, Christopher ; Burk, Vernon A. ; Ru, Meng ; Popoli, Maria ; Ptak, Janine ; Dobbyn, Lisa ; Silliman, Natalie ; Coresh, Josef ; Boerwinkle, Eric ; Prizment, Anna ; Bettegowda, Chetan ; Kinzler, Kenneth W. ; Papadopoulos, Nickolas ; Platz, Elizabeth A. ; Vogelstein, Bert
• Description:
  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.
  
  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.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Neoplasms
  • Male
  • Early Detection of Cancer
  • Female
  • Middle Aged
  • Aged
  • Circulating Tumor DNA
  • Cell-Free Nucleic Acids
  • Biomarkers, Tumor
  More +
• Source:
  Cancer Discovery, 2025, v. 15, no. 9
• DOI:
  https://doi.org/10.1158/2159-8290.CD-25-0375
• ISSN:
  2159-8274 ; 2159-8290
• Pubmed ID:
  40402478
• Pubmed Central ID:
  PMC12354160
• Document Type:
  Text
• Funding:
  Commonwealth Fund (CF)/ ; 75N92022D00002/HL/NHLBI NIH HHSUnited States/ ; P30 CA006973/CA/NCI NIH HHSUnited States/ ; Maryland Department of Health (DHMH)/ ; Virginia and D.K. Ludwig Fund for Cancer Research (D.K. Ludwig Fund)/ ; R21 NS113016/NS/NINDS NIH HHSUnited States/ ; 75N92022D00004/HL/NHLBI NIH HHSUnited States/ ; RA37CA230400/National Institutes of Health (NIH)/ ; MD/Conquer Cancer Foundation (CCF)/ ; 75N92022D00003/HL/NHLBI NIH HHSUnited States/ ; Career Award for Medical Scientists/Burroughs Wellcome Fund (BWF)/ ; 75N92022D0000/U.S. Department of Health and Human Services (HHS)/ ; Endowed Young Investigator Award/Conquer Cancer Foundation (CCF)/ ; Cooperative Agreement NU58DP007114/Centers for Disease Control and Prevention (CDC)/ ; T32 GM135083/GM/NIGMS NIH HHSUnited States/ ; U01CA230691/National Institutes of Health (NIH)/ ; HHMI/Howard Hughes Medical InstituteUnited States/ ; Ovarian Cancer SPORE DRP 80057309/National Institutes of Health (NIH)/ ; U01 CA230691/CA/NCI NIH HHSUnited States/ ; V scholar award/V Foundation for Cancer Research (VFCR)/ ; 75N92022D00005/HL/NHLBI NIH HHSUnited States/ ; 75N92022D0000/National Heart, Lung, and Blood Institute (NHLBI)/ ; Fred J. Ansfield/Conquer Cancer Foundation (CCF)/ ; 75N92022D0000/National Institutes of Health (NIH)/ ; Maryland Cigarette Restitution Fund/ ; UE5 NS065729/NS/NINDS NIH HHSUnited States/ ; U01 CA164975/CA/NCI NIH HHSUnited States/ ; 75N92022D00001/HL/NHLBI NIH HHSUnited States/ ; R37 CA230400/CA/NCI NIH HHSUnited States/ ; R21NS113016/National Institutes of Health (NIH)/
• Genre:
  Journal Article
• Pages in Document:
  1794-1802 (18 pdf pages)
• Volume:
  15
• Issue:
  9
• Download URL:
  https://stacks.cdc.gov/view/cdc/261398/cdc_261398_DS1.pdf
• File Type:
  [PDF - 490.12 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:35c09d3aec6eebde309832cb09e44ace35a871822c8446857b835b6f16e4bed7351bf605753cc609ea7bf3eaac218b51cda94a47898047712c6c49679515d627