Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC

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 () and Jie He
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Bin Qiu: Chinese Academy of Medical Sciences and Peking Union Medical College
Wei Guo: Chinese Academy of Medical Sciences and Peking Union Medical College
Fan Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Fang Lv: Chinese Academy of Medical Sciences and Peking Union Medical College
Ying Ji: Chinese Academy of Medical Sciences and Peking Union Medical College
Yue Peng: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaoxi Chen: Nanjing Geneseeq Technology Inc
Hua Bao: Nanjing Geneseeq Technology Inc
Yang Xu: Nanjing Geneseeq Technology Inc
Yang Shao: Nanjing Geneseeq Technology Inc
Fengwei Tan: Chinese Academy of Medical Sciences and Peking Union Medical College
Qi Xue: Chinese Academy of Medical Sciences and Peking Union Medical College
Shugeng Gao: Chinese Academy of Medical Sciences and Peking Union Medical College
Jie He: Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-27022-z

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