Nature Medicine

, volume 31 , issue 1 , pages 70-76

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma

James R M Black ^{1, 2}

Gabor Bartha ³

Charles W Abbott ³

Sean Michael Boyle ³

Takahiro Karasaki ^{1, 2, 4, 5}

Ruijiang Li ³

Rui Chen ³

Jason Harris ³

Selvaraju Veeriah ¹

Martina Colopi ¹

Maise Al Bakir ^{1, 2}

Wing Kin Liu ¹

John Lyle ³

Fabio C.P. Navarro ³

Josette Northcott ³

Rachel Marty Pyke ³

Mark S. Hill ^{1, 2}

Kerstin Thol ^{1, 6}

Ariana Huebner ^{1, 2, 6}

Chris Bailey ^{1, 2}

Emma Colliver ^{1, 2}

Carlos Martínez-Ruiz ^{1, 6}

Kristiana Grigoriadis ^{1, 2, 6}

Piotr Pawlik ^{1, 6}

David A. Moore ^{1, 2, 7}

Daniele Marinelli ^{1, 6, 8}

Oliver G Shutkever ¹

Cian Murphy ^{1, 2}

Monica Sivakumar ¹

Jason F. Lester ⁹

Amrita Bajaj ^{1, 6}

Apostolos Nakas ^{1, 4, 10}

Azmina Sodha-Ramdeen ^{1, 2}

Mohamad Tufail ³

Molly Scotland ^{1, 2, 10}

Hide authors affiliations Show authors affiliations: 10 affiliations

Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK |

Cancer Evolution and Genome Instability Laboratory., The Francis Crick Institute, London, UK |

Personalis Inc., Fremont, USA |

⁴

Cancer Metastasis Laboratory, University College London Cancer Institute, London, UK |

⁵

Department of Thoracic Surgery, Respiratory Center, Toranomon Hospital, Tokyo, Japan |

⁶

Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK |

⁷

Department of Cellular Pathology, University College London Hospitals, London, UK |

⁸

Department of Experimental Medicine, Sapienza University, Rome, Italy |

⁹

Cancer Research UK & UCL Cancer Trials Centre, London, UK |

¹⁰

Department of Oncology, University College London Hospitals, London, UK |

Publication type: Journal Article

Publication date: 2025-01-13

Springer Nature

Nature Medicine

scimago Q1

wos Q1

SJR: 18.333

CiteScore: 82.4

Impact factor: 50.0

ISSN: 10788956, 1546170X, 17447933

DOI: 10.1038/s41591-024-03216-y

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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.

Found

1 citation

Gallina Filippo

73 publications, 305 citations, 11 reviews

h-index: 10

Regina Elena National Cancer Institute

Istituti di Ricovero e Cura a Carattere Scientifico

McGill University Health Centre

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Black J. R. M. et al. Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma // Nature Medicine. 2025. Vol. 31. No. 1. pp. 70-76.

GOST all authors (up to 50) Copy

Black J. R. M. et al. Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma // Nature Medicine. 2025. Vol. 31. No. 1. pp. 70-76.

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BibTex (up to 50 authors) Copy

@article{2025_Black,

author = {James R M Black and Gabor Bartha and Charles W Abbott and Sean Michael Boyle and Takahiro Karasaki and Ruijiang Li and Rui Chen and Jason Harris and Selvaraju Veeriah and Martina Colopi and Maise Al Bakir and Wing Kin Liu and John Lyle and Fabio C.P. Navarro and Josette Northcott and Rachel Marty Pyke and Mark S. Hill and Kerstin Thol and Ariana Huebner and Chris Bailey and Emma Colliver and Carlos Martínez-Ruiz and Kristiana Grigoriadis and Piotr Pawlik and David A. Moore and Daniele Marinelli and Oliver G Shutkever and Cian Murphy and Monica Sivakumar and Jason F. Lester and Amrita Bajaj and Apostolos Nakas and Azmina Sodha-Ramdeen and Mohamad Tufail and Molly Scotland and others},

title = {Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma},

journal = {Nature Medicine},

year = {2025},

volume = {31},

publisher = {Springer Nature},

month = {jan},

url = {https://www.nature.com/articles/s41591-024-03216-y},

number = {1},

pages = {70--76},

doi = {10.1038/s41591-024-03216-y}

}

MLA

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MLA Copy

Black, James R. M., et al. “Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.” Nature Medicine, vol. 31, no. 1, Jan. 2025, pp. 70-76. https://www.nature.com/articles/s41591-024-03216-y.

Publisher

Springer Nature

Journal

Nature Medicine

scimago Q1

wos Q1

SJR

18.333

CiteScore

82.4

Impact factor

50.0

ISSN

10788956 (Print)

1546170X (Electronic)

17447933 (Electronic)

Profiles

Charles O Swanton