TY  - JOUR
ID  - discovery10205077
N2  - 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.
SN  - 1078-8956
PB  - NATURE PORTFOLIO
UR  - https://doi.org/10.1038/s41591-024-03216-y
JF  - Nature Medicine
A1  - Black, James RM
A1  - Bartha, Gabor
A1  - Abbott, Charles W
A1  - Boyle, Sean M
A1  - Karasaki, Takahiro
A1  - Li, Bailiang
A1  - Chen, Rui
A1  - Harris, Jason
A1  - Veeriah, Selvaraju
A1  - Colopi, Martina
A1  - Al Bakir, Maise
A1  - Liu, Wing Kin
A1  - Lyle, John
A1  - Navarro, Fabio CP
A1  - Northcott, Josette
A1  - Pyke, Rachel Marty
A1  - Hill, Mark S
A1  - Thol, Kerstin
A1  - Huebner, Ariana
A1  - Bailey, Chris
A1  - Colliver, Emma C
A1  - Martinez-Ruiz, Carlos
A1  - Grigoriadis, Kristiana
A1  - Pawlik, Piotr
A1  - Moore, David A
A1  - Marinelli, Daniele
A1  - Shutkever, Oliver G
A1  - Murphy, Cian
A1  - Sivakumar, Monica
A1  - Shaw, Jacqui A
A1  - Hackshaw, Allan
A1  - McGranahan, Nicholas
A1  - Jamal-Hanjani, Mariam
A1  - Frankell, Alexander M
A1  - Chen, Richard O
A1  - Swanton, Charles
TI  - Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma
EP  - 76
SP  - 70
AV  - public
VL  - 31
Y1  - 2025/01//
N1  - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article?s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article?s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
ER  -