Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA

液体活检 医学 肿瘤科 内科学 背景(考古学) 生物标志物 肺癌 癌症 阶段(地层学) 腺癌 生物 古生物学 生物化学
作者
Christopher Abbosh,Alexander M. Frankell,Thomas Harrison,Judit Kisistók,Aaron T. Garnett,Laura Johnson,Selvaraju Veeriah,Mike Moreau,Adrian Chesh,Tafadzwa L. Chaunzwa,Jakob Weiss,Morgan R. Schroeder,Martin Hayward,Kristiana Grigoriadis,Aamir Shahpurwalla,Kevin Litchfield,Clare Puttick,Dhruva Biswas,Takahiro Karasaki,James R. 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 Roberts,Fábio 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,Gérard I. Evan,Allan Hackshaw,Robert Daber,Jacqui Shaw,Hugo J.W.L. Aerts,Abel Licon,Josh Stahl,Mariam Jamal‐Hanjani,J.F. Lester,Amrita Bajaj,Apostolos Nakas,Azmina Sodha-Ramdeen,Keng Ang,Mohamad Tufail,Mohammed Fiyaz Chowdhry,Molly Scotland,Rebecca Boyles,Sridhar Rathinam,Claire Wilson,Domenic Marrone,Sean Dulloo,Dean A. Fennell,Gurdeep Matharu,Lindsay Primrose,Ekaterini Boleti,Heather Cheyne,Mohammed S. Khalil,Shirley Richardson,Tracey Cruickshank,Gillian Price,Keith M. Kerr,Sarah Benafif,Kayleigh Gilbert,Babu Naidu,Aya Osman,Christer Lacson,Gerald Langman,Helen Shackleford,Madava Djearaman,Salma Kadiri,Gary Middleton,Angela Leek,Jack Davies Hodgkinson,Nicola Totten,Ángeles Montero,Elaine Smith,Eustace Fontaine,Felice Granato,Helen Doran,Juliette Novasio,Kendadai Rammohan,Leena Dennis Joseph,Paul N. Bishop,Rajesh Shah,Stuart Moss,Vijay Joshi,Philip Crosbie,Kate Brown,Mathew Carter,Anshuman Chaturvedi,Lynsey Priest,Pedro Oliveira,Colin R. Lindsay,Fiona Blackhall,Matthew Krebs,Yvonne Summers,Alexandra Clipson,Jonathan Tugwood,Alastair Kerr,Dominic G. Rothwell,Elaine Kilgour,Caroline Dive,Roland F. Schwarz,Tom L. Kaufmann,Gareth A. Wilson,Rachel Rosenthal,Peter Van Loo,Zoltán Szállási,Mateo Sokač,Roberto Salgado,Miklós Dióssy,Jonas Demeulemeester,Abigail Bunkum,Grant D. Stewart,Alastair Magness,Andrew Rowan,Angeliki Karamani,Antonia Toncheva,Benny Chain,Brittany Campbell,Carla Castignani,Chris Bailey,Clare E. Weeden,Claudia Lee,Corentin Richard,Cristina Naceur‐Lombardelli,David R. Pearce,Despoina Karagianni,Dina Levi,Elena Hoxha,Elizabeth Larose Cadieux,Emma Colliver,Emma Nye,Eva Grönroos,Felip Gálvez-Cancino,Foteini Athanasopoulou,Francisco Gimeno-Valiente,George Kassiotis,Georgia Stavrou,Gerasimos Mastrokalos,Hao-Ran Zhai,Helen L. Lowe,Ignacio Matos,Jacki Goldman,James L. Reading,Javier Herrero,Jayant K. Rane,Jérôme Nicod,Jie Min Lam,John A. Hartley,Karl S. Peggs,Katey S.S. Enfield,Kayalvizhi Selvaraju,Kerstin Thol,Kevin W. Ng,Kezhong Chen,Krijn K. Dijkstra,Krupa Thakkar,Leah Ensell,Mansi Shah,Marcos Vásquez,Maria Litovchenko,Mariana Werner Sunderland,Mark S. Hill,Michelle Dietzen,Michelle Leung,Mickael Escudero,Mihaela Angelova,Miljana Tanić,Monica Sivakumar,Nnennaya Kanu,Olga Chervova,Olivia Lucas,Othman Al‐Sawaf,Paulina Prymas,Philip Hobson,Piotr Pawlik,Richard Stone,Robert B. Bentham,Robert E. Hynds,Roberto Vendramin,Sadegh Saghafinia,Saioa López,Samuel Gamble,Seng Kuong Anakin Ung,Sergio A. Quezada,Sharon Vanloo,Simone Zaccaria,Sonya Hessey,Stefan Boeing,Stephan Beck,Supreet Kaur Bola,Tamara Denner,Teresa Marafioti,Thanos P. Mourikis,Victoria J. Spanswick,Vittorio Barbè,Wei-Ting Lu,William Hill,Wing Kin Liu,Yin Wu,Yutaka Naito,Zoe Ramsden,Catarina Veiga,G. Royle,Charles‐Antoine Collins‐Fekete,Francesco Fraioli,Paul Ashford,Tristan Clark,Martin Förster,Siow Ming Lee,Elaine Borg,Mary Falzon,Dionysis Papadatos-Pastos,James M. Wilson,Tanya Ahmad,Alexander James Procter,Asia Ahmed,Magali N. Taylor,Arjun Nair,David Lawrence,Davide Patrini,Neal Navani,Ricky M. Thakrar,Sam M. Janes,Emilie Martinoni Hoogenboom,Fleur Monk,James W. Holding,Junaid Choudhary,Kunal Bhakhri,Marco Scarci,Martin Hayward,Nikolaos Panagiotopoulos,Pat Gorman,Reena Khiroya,Robert Stephens,Yien Ning Sophia Wong,Steve Bandula,Abigail Sharp,Sean Smith,Nicole Gower,Harjot Kaur Dhanda,Kitty S. Chan,Camilla Pilotti,Rachel Leslie,Anca Grapa,Hanyun Zhang,Khalid AbdulJabbar,Xiaoxi Pan,Yinyin Yuan,David Chuter,Mairead MacKenzie,Serena Chee,Aiman Alzetani,Judith Cave,Lydia Scarlett,Jennifer Richards,Papawadee Ingram,Silvia Austin,Eric Lim,Paulo De Sousa,Simon Jordan,Alexandra Rice,Hilgardt Raubenheimer,Harshil Bhayani,Lyn Ambrose,Anand Devaraj,Hema Chavan,Sofina Begum,Silviu Buderi,Daniel Kaniu,Mpho Malima,Sarah Booth,Andrew G. Nicholson,Nadia Fernandes,Pratibha Shah,Chiara Proli,Madeleine Hewish,Sarah Danson,Michael Shackcloth,Lily Robinson,Peter Russell,Kevin G. Blyth,Craig Dick,John Le Quesne,Alan Kirk,Mo Asif,Rocco Bilancia,Nikos Kostoulas,Mathew Thomas,Nicolai J. Birkbak,Nicholas McGranahan,Charles Swanton
出处
期刊:Nature [Springer Nature]
卷期号:616 (7957): 553-562 被引量:126
标识
DOI:10.1038/s41586-023-05776-4
摘要

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. Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.
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