Bin Qiu; Wei Guo; Fan Zhang; Fang Lv; Ying Ji; Yue Peng; Xiaoxi Chen; Hua Bao; Yang Xu; Yang Shao; Fengwei Tan; Qi Xue; Shugeng Gao; Jie He · 2021 · Nature Communications
Paper
Accurately evaluating minimal residual disease (MRD) could facilitate early intervention and personalized adjuvant therapies. Here, using ultradeep targeted next-generation sequencing (NGS), we evaluate the clinical utility of circulating tumor DNA (ctDNA) for dynamic recurrence risk and adjuvant chemotherapy (ACT) benefit prediction in resected non-small cell lung cancer (NSCLC). Both postsurgical and post-ACT ctDNA positivity are significantly associated with worse recurrence-free survival. In stage II-III patients, the postsurgical ctDNA positive group benefit from ACT, while ctDNA negative patients have a low risk of relapse regardless of whether or not ACT is administered. During disease surveillance, ctDNA positivity precedes radiological recurrence by a median of 88 days. Using joint modeling of longitudinal ctDNA analysis and time-to-recurrence, we accurately predict patients' postsurgical 12-month and 15-month recurrence status. Our findings reveal longitudinal ctDNA analysis as a promising tool to detect MRD in NSCLC, and we show pioneering work of using postsurgical ctDNA status to guide ACT and applying joint modeling to dynamically predict recurrence risk, although the results need to be further confirmed in future studies.
Analysis
This study demonstrates that longitudinal ctDNA analysis using ultradeep NGS can dynamically predict recurrence risk and identify patients who benefit from adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC), with ctDNA positivity preceding radiological recurrence.
Discovery
Hyukjung Kwon; Sun Hye Shin; Hyun Ho Kim; Na Young Min; Yugyeong Lim; T. Joo; Kyoung Joo Lee; Minseon Jeong; Hyojung Kim; Seon-young Yun; Yoon-Hee Kim; Dabin Park; Joungsu Joo; Jin‐Sik Bae; Sunghoon Lee; Byeong‐Ho Jeong; Kyungjong Lee; Hayemin Lee; Hong Kwan Kim; Kyongchol Kim; Sang‐Won Um; Changhyeok An; Min Seob Lee
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; Sophia Ward; 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 Kalavakur; 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 Bishop; Rajesh Shah; Stuart Moss; Vijay Joshi; Philip Crosbie
Siobhan Connal; James M. Cameron; Alexandra Sala; Paul M. Brennan; David Scott Palmer; Joshua D. Palmer; Haley K. Perlow; Matthew J. Baker
Giovanna Maria Stanfoca Casagrande; Marcela de Oliveira Silva; Rui Manuel Reis; Letícia Ferro Leal
Saife N. Lone; Sabah Nisar; Tariq Masoodi; Mayank Singh; Arshi Rizwan; Sheema Hashem; Wael El‐Rifai; Davide Bedognetti; Surinder K. Batra; Mohammad Haris; Ajaz A. Bhat; Muzafar A. Macha
David L. Crosby; Sangeeta N. Bhatia; Kevin M. Brindle; Lisa M. Coussens; Caroline Dive; Mark Emberton; Sadik C. Esener; Rebecca C. Fitzgerald; Sanjiv S. Gambhir; Peter Kühn; Timothy R. Rebbeck; Shankar Balasubramanian
Source record