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

• Published in: Cancer cell Vol. 41; no. 10; pp. 1763 - 1773.e4
• Main Authors: Pan, Yi, Zhang, Jia-Tao, Gao, Xuan, Chen, Zhi-Yong, Yan, Bingfa, Tan, Pei-Xin, Yang, Xiao-Rong, Gao, Wei, Gong, Yuhua, Tian, Zihan, Liu, Si-Yang Maggie, Lin, Hui, Sun, Hao, Huang, Jie, Liu, Si-Yang, Yan, Hong-Hong, Dong, Song, Xu, Chong-Rui, Chen, Hua-Jun, Wang, Zhen, Li, Pansong, Guan, Yanfang, Wang, Bin-Chao, Yang, Jin-Ji, Tu, Hai-Yan, Yang, Xue-Ning, Zhong, Wen-Zhao, Xia, Xuefeng, Yi, Xin, Zhou, Qing, Wu, Yi-Long
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 09.10.2023
• Subjects: circulating tumor DNA; definitive radiotherapy; molecular residual disease; non-small cell lung cancer; non-small cell lung cancer; molecular residual disease; definitive radiotherapy; circulating tumor DNA
• ISSN: 1535-6108; 1878-3686; 1878-3686
• DOI: 10.1016/j.ccell.2023.09.007

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. [Display omitted] •Early undetectable MRD during CRT predicts better outcome•Longitudinal undetectable MRD defines potentially cured population•Blood-informed MRD detection strategy is essential for locally advanced NSCLC Pan et al. describe the dynamic circulating tumor DNA changes during chemoradiation for patients with localized advanced NSCLC and identify the positive prognostic and predictive value of early undetectable ctDNA.