 Tracking early lung cancer metastatic dissemination in TRACERx using ctDNAChristopher Abbosh (),
Alexander M. Frankell,
Thomas Harrison,
Judit Kisistok,
Aaron Garnett,
Laura Johnson,
Selvaraju Veeriah,
Mike Moreau,
Adrian Chesh,
Tafadzwa L. Chaunzwa,
Jakob Weiss,
Morgan R. Schroeder,
Sophia Ward,
Kristiana Grigoriadis,
Aamir Shahpurwalla,
Kevin Litchfield,
Clare Puttick,
Dhruva Biswas,
Takahiro Karasaki,
James R. M. Black,
Carlos Martínez-Ruiz,
Maise Al Bakir,
Oriol Pich,
Thomas B. K. Watkins,
Emilia L. Lim,
Ariana Huebner,
David A. Moore,
Nadia Godin-Heymann,
Anne L’Hernault,
Hannah Bye,
Aaron Odell,
Paula Kalavakur,
Fabio Gomes,
Akshay J. Patel,
Elizabeth Manzano,
Crispin T. Hiley,
Nicolas Carey,
Joan Riley,
Daniel E. Cook,
Darren Hodgson,
Daniel Stetson,
J. Carl Barrett,
Roderik M. Kortlever,
Gerard I. Evan,
Allan Hackshaw,
Robert D. Daber,
Jacqui A. Shaw,
Hugo J. W. L. Aerts,
Abel Licon,
Josh Stahl,
Mariam Jamal-Hanjani,
Nicolai J. Birkbak,
Nicholas McGranahan () and
Charles Swanton ()
Nature, 2023, vol. 616, issue 7957, 553-562 Abstract: Abstract Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy. Date: 2023 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:616:y:2023:i:7957:d:10.1038_s41586-023-05776-4 Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-023-05776-4 Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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