Circulating tumor DNA-based stratification strategy for chemotherapy plus PD-1 inhibitor in advanced non-small-cell lung cancer

IF 48.8 1区 医学 Q1 CELL BIOLOGY Cancer Cell Pub Date : 2024-09-09 DOI:10.1016/j.ccell.2024.08.013
Jiachen Xu, Rui Wan, Yiran Cai, Shangli Cai, Lin Wu, Baolan Li, Jianchun Duan, Ying Cheng, Xiaoling Li, Xicheng Wang, Liang Han, Xiaohong Wu, Yun Fan, Yan Yu, Dongqing Lv, Jianhua Shi, Jianjin Huang, Shaozhang Zhou, Baohui Han, Guogui Sun, Jie Wang
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Abstract

Stratification strategies for chemotherapy plus PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) are critically demanded. We performed high-throughput panel-based deep next-generation sequencing and low-pass whole genome sequencing on prospectively collected circulating tumor DNA (ctDNA) specimens from 460 patients in the phase 3 CHOICE-01 study at different time points. We identified predictive markers for chemotherapy plus PD-1 inhibitor, including ctDNA status and genomic features such as blood-based tumor mutational burden, intratumor heterogeneity, and chromosomal instability. Furthermore, we established an integrated ctDNA-based stratification strategy, blood-based genomic immune subtypes (bGIS) scheme, to distinguish patients who benefit from the addition of PD-1 inhibitor to first-line chemotherapy. Moreover, we demonstrated potential applications for the dynamic monitoring of ctDNA. Overall, we proposed a potential therapeutic algorithm based on the ctDNA-based stratification strategy, shedding light on the individualized management of immune-chemotherapies for patients with advanced NSCLC.

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基于循环肿瘤 DNA 的晚期非小细胞肺癌化疗加 PD-1 抑制剂分层策略
晚期非小细胞肺癌(NSCLC)化疗加 PD-1 抑制剂的分层策略需求量很大。我们对 CHOICE-01 3 期研究中 460 例患者在不同时间点的循环肿瘤 DNA(ctDNA)标本进行了基于高通量面板的深度新一代测序和低通滤波全基因组测序。我们确定了化疗加 PD-1 抑制剂的预测标志物,包括 ctDNA 状态和基因组特征,如基于血液的肿瘤突变负荷、肿瘤内异质性和染色体不稳定性。此外,我们还建立了一种基于ctDNA的综合分层策略--基于血液的基因组免疫亚型(bGIS)方案,以区分哪些患者可从一线化疗加用PD-1抑制剂中获益。此外,我们还展示了ctDNA动态监测的潜在应用。总之,我们提出了一种基于ctDNA分层策略的潜在治疗算法,为晚期NSCLC患者的免疫化疗个体化管理提供了启示。
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来源期刊
Cancer Cell
Cancer Cell 医学-肿瘤学
CiteScore
55.20
自引率
1.20%
发文量
179
审稿时长
4-8 weeks
期刊介绍: Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.
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