eprintid: 10205077 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/20/50/77 datestamp: 2025-02-21 13:15:29 lastmod: 2025-02-21 13:15:29 status_changed: 2025-02-21 13:15:29 type: article metadata_visibility: show sword_depositor: 699 creators_name: Black, James RM creators_name: Bartha, Gabor creators_name: Abbott, Charles W creators_name: Boyle, Sean M creators_name: Karasaki, Takahiro creators_name: Li, Bailiang creators_name: Chen, Rui creators_name: Harris, Jason creators_name: Veeriah, Selvaraju creators_name: Colopi, Martina creators_name: Al Bakir, Maise creators_name: Liu, Wing Kin creators_name: Lyle, John creators_name: Navarro, Fabio CP creators_name: Northcott, Josette creators_name: Pyke, Rachel Marty creators_name: Hill, Mark S creators_name: Thol, Kerstin creators_name: Huebner, Ariana creators_name: Bailey, Chris creators_name: Colliver, Emma C creators_name: Martinez-Ruiz, Carlos creators_name: Grigoriadis, Kristiana creators_name: Pawlik, Piotr creators_name: Moore, David A creators_name: Marinelli, Daniele creators_name: Shutkever, Oliver G creators_name: Murphy, Cian creators_name: Sivakumar, Monica creators_name: Shaw, Jacqui A creators_name: Hackshaw, Allan creators_name: McGranahan, Nicholas creators_name: Jamal-Hanjani, Mariam creators_name: Frankell, Alexander M creators_name: Chen, Richard O creators_name: Swanton, Charles title: Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D19 divisions: H01 divisions: G99 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/. 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 <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. date: 2025-01 date_type: published publisher: NATURE PORTFOLIO official_url: https://doi.org/10.1038/s41591-024-03216-y oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2352912 doi: 10.1038/s41591-024-03216-y medium: Print-Electronic pii: 10.1038/s41591-024-03216-y lyricists_name: Hackshaw, Allan lyricists_name: Swanton, Robert lyricists_name: McGranahan, Nicholas lyricists_name: Jamal-Hanjani, Mariam lyricists_name: Veeriah, Selvaraju lyricists_name: Black, James lyricists_name: Moore, David lyricists_id: AHACK11 lyricists_id: CSWAN79 lyricists_id: NLMCG29 lyricists_id: MJAMA72 lyricists_id: RVEER62 lyricists_id: JBLAC10 lyricists_id: DMOOR09 actors_name: Hackshaw, Allan actors_id: AHACK11 actors_role: owner funding_acknowledgements: UCL/12/0279 [University College London]; C11496/A17786 [Cancer Research UK (CRUK)]; C444/A15953 [Cancer Research UK (CRUK)]; [CRUK Lung Cancer Centre of Excellence]; C7893/A26233 [CRUK City of London Centre Award]; 202060447 [Japan Society for the Promotion of Science (JSPS)]; [Rosetrees Trust]; [NIHR University College London Hospitals Biomedical Research Centre]; 211179/Z/18/Z [Royal Society]; [NIHR BRC at University College London Hospitals]; [CRUK University College London Experimental Cancer Medicine Centre]; CC2041 [Francis Crick Institute from Cancer Research UK]; C11496/A17786 [Cancer Research UK]; C416/A21999 [Cancer Research UK]; C11496/A30025 [Cancer Research UK Lung Cancer Centre of Excellence]; [Butterfield Trust]; [Stoneygate Trust]; ID16584 [NovoNordisk Foundation]; RP/EA/180007 [Royal Society Professorship Enhancement Award]; RF\ERE\231118 [Royal Society Professorship Enhancement Award]; [National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre]; [Cancer Research UK-University College London Centre]; [Experimental Cancer Medicine Centre]; BCRF-22-157 [Breast Cancer Research Foundation (US)]; EDDPMA-Nov21/100034 [Cancer Research UK Early Detection an Diagnosis Primer Award]; 21-029-ASP [Mark Foundation for Cancer Research Aspire Award]; 23-034-ASP [Mark Foundation for Cancer Research ASPIRE Phase II award]; 835297 [ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union's Horizon 2020 research and innovation program]; [UCL Experimental Cancer Medicine Centre]; [NIHR]; [UKI NETs]; 211179/Z/18/Z [Wellcome Trust]; CC2041 [Wellcome Trust]; CC2041 [UK Medical Research Council] full_text_status: public publication: Nature Medicine volume: 31 pagerange: 70-76 pages: 24 event_location: United States issn: 1078-8956 citation: Black, James RM; Bartha, Gabor; Abbott, Charles W; Boyle, Sean M; Karasaki, Takahiro; Li, Bailiang; Chen, Rui; ... Swanton, Charles; + view all <#> Black, James RM; Bartha, Gabor; Abbott, Charles W; Boyle, Sean M; Karasaki, Takahiro; Li, Bailiang; Chen, Rui; Harris, Jason; Veeriah, Selvaraju; Colopi, Martina; Al Bakir, Maise; Liu, Wing Kin; Lyle, John; Navarro, Fabio CP; Northcott, Josette; Pyke, Rachel Marty; Hill, Mark S; Thol, Kerstin; Huebner, Ariana; Bailey, Chris; Colliver, Emma C; Martinez-Ruiz, Carlos; Grigoriadis, Kristiana; Pawlik, Piotr; Moore, David A; Marinelli, Daniele; Shutkever, Oliver G; Murphy, Cian; Sivakumar, Monica; Shaw, Jacqui A; Hackshaw, Allan; McGranahan, Nicholas; Jamal-Hanjani, Mariam; Frankell, Alexander M; Chen, Richard O; Swanton, Charles; - view fewer <#> (2025) Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma. Nature Medicine , 31 pp. 70-76. 10.1038/s41591-024-03216-y <https://doi.org/10.1038/s41591-024-03216-y>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10205077/1/Ultrasensitive%20ctDNA%20detection%20for%20preoperative%20disease%20stratification%20in%20early-stage%20lung%20adenocarcinoma.pdf