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. 2023 Oct 9;41(10):1763-1773.e4.
doi: 10.1016/j.ccell.2023.09.007.

Dynamic circulating tumor DNA during chemoradiotherapy predicts clinical outcomes for locally advanced non-small cell lung cancer patients

Yi Pan  1 , Jia-Tao Zhang  1 , Xuan Gao  2 , Zhi-Yong Chen  1 , Bingfa Yan  2 , Pei-Xin Tan  1 , Xiao-Rong Yang  1 , Wei Gao  2 , Yuhua Gong  2 , Zihan Tian  2 , Si-Yang Maggie Liu  3 , Hui Lin  1 , Hao Sun  1 , Jie Huang  1 , Si-Yang Liu  1 , Hong-Hong Yan  1 , Song Dong  1 , Chong-Rui Xu  1 , Hua-Jun Chen  1 , Zhen Wang  1 , Pansong Li  2 , Yanfang Guan  2 , Bin-Chao Wang  1 , Jin-Ji Yang  1 , Hai-Yan Tu  1 , Xue-Ning Yang  1 , Wen-Zhao Zhong  1 , Xuefeng Xia  2 , Xin Yi  4 , Qing Zhou  5 , Yi-Long Wu  6
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Dynamic circulating tumor DNA during chemoradiotherapy predicts clinical outcomes for locally advanced non-small cell lung cancer patients

Yi Pan et al. Cancer Cell. .
Free article

Abstract

The value of circulating tumor DNA (ctDNA) during chemoradiotherapy (CRT) remains unclear but is critical for detecting molecular residual disease (MRD). In this prospective study, we sequenced 761 blood samples from 139 patients with locally advanced non-small cell lung cancer treated with definitive radiation therapy (RT). ctDNA concentrations showed a significantly declining trend as CRT progressed at on-RT and after-RT time points versus baseline. Thirty-eight (27.3%) patients with early undetectable ctDNA at both on-RT (RT reached 40 Gy) and after-RT time points, indicating early response to CRT, had better survival outcomes for both with or without consolidation immune checkpoint inhibitors. Longitudinal undetectable MRD was found in 20.1% patients. The 2-year cancer-specific progression-free survival of these patients was 88.4%, corresponding to a potentially cured population. Further analysis revealed that pretreatment ctDNA variants serve as an essential MRD informed source. These data provide clinical insights for ctDNA-MRD detection.

Keywords: circulating tumor DNA; definitive radiotherapy; molecular residual disease; non-small cell lung cancer.

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Conflict of interest statement

Declaration of interests Q.Z. declares honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi outside the submitted work. W.Z.Z. declares honoraria from AstraZeneca, BMS, MSD, Roche, and Innovent outside the submitted work. Y.L.W. declares advisory services for AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda; speaker fees from AstraZeneca, Beigene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi; and grants from AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, and Roche outside the submitted work.

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