@article{discovery10205077, year = {2025}, month = {January}, publisher = {NATURE PORTFOLIO}, journal = {Nature Medicine}, pages = {70--76}, volume = {31}, title = {Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma}, note = {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/.}, author = {Black, James RM and Bartha, Gabor and Abbott, Charles W and Boyle, Sean M and Karasaki, Takahiro and Li, Bailiang and Chen, Rui and Harris, Jason and Veeriah, Selvaraju and Colopi, Martina and Al Bakir, Maise and Liu, Wing Kin and Lyle, John and Navarro, Fabio CP and Northcott, Josette and Pyke, Rachel Marty and Hill, Mark S and Thol, Kerstin and Huebner, Ariana and Bailey, Chris and Colliver, Emma C and Martinez-Ruiz, Carlos and Grigoriadis, Kristiana and Pawlik, Piotr and Moore, David A and Marinelli, Daniele and Shutkever, Oliver G and Murphy, Cian and Sivakumar, Monica and Shaw, Jacqui A and Hackshaw, Allan and McGranahan, Nicholas and Jamal-Hanjani, Mariam and Frankell, Alexander M and Chen, Richard O and Swanton, Charles}, url = {https://doi.org/10.1038/s41591-024-03216-y}, issn = {1078-8956}, abstract = {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 {\ensuremath{<}}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.} }