posted on 2025-01-24, 10:47authored byJames RM Black, Gabor Bartha, Charles W Abbott, Sean M Boyle, Takahiro Karasaki, Bailiang Li, Rui Chen, Jason Harris, Selvaraju Veeriah, Martina Colopi, Maise Al Bakir, Wing Kin Liu, John Lyle, Fábio CP Navarro, Josette Northcott, Rachel Marty Pyke, Mark S Hill, Kerstin Thol, Ariana Huebner, Chris Bailey, Emma C Colliver, Carlos Martínez-Ruiz, Kristiana Grigoriadis, Piotr Pawlik, David A Moore, Daniele Marinelli, Oliver G Shutkever, Cian Murphy, Monica Sivakumar, TRACERx consortium, Jacqui A Shaw, Allan Hackshaw, Nicholas McGranahan, Mariam Jamal-Hanjani, Alexander M Frankell, Richard O Chen, Charles Swanton
Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.9% specificity. Through an analysis of 171 patients with early-stage lung cancer from the TRACERx study, we detected ctDNA pre-operatively within 81% of patients with lung adenocarcinoma (LUAD), including 53% of those with pathological TNM (pTNM) stage I disease. ctDNA predicted worse clinical outcome, and patients with LUAD with <80 ppm preoperative ctDNA levels (the 95% limit of detection of a ctDNA detection approach previously published in TRACERx) experienced reduced overall survival compared with ctDNA-negative patients with LUAD. Although prospective studies are needed to confirm the clinical utility of the assay, these data show that our approach has the potential to improve disease stratification in early-stage LUADs.
Funding
Crick (Grant ID: CC2041, Grant title: Swanton CC2041)
Crick (Grant ID: CC2008, Grant title: Van Loo CC2008)
Crick (Grant ID: CC2088, Grant title: Kassiotis CC2088)
Crick (Grant ID: CC1064, Grant title: STP Genomics)
Crick (Grant ID: CC1119, Grant title: STP Scientific Computing)
Crick (Grant ID: CC1062, Grant title: STP Flow Cytometry)
Crick (Grant ID: CC1061, Grant title: STP Experimental Histopathology)
Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics)
Novo Nordisk UK Research Foundation (Grant ID: NNF15OC0016584, Grant title: NovoNordisk Foundation 16584)
European Research Council (Grant ID: 835297 - PROTEUS, Grant title: ERC 835297 - PROTEUS)