免疫检查点抑制剂（ICIs）在非小细胞肺癌（NSCLC）中的使用具有临床获益的高度异质性。我们前瞻性地招募了 113 名接受 ICI 治疗的晚期 NSCLC 患者，并在 ICI 开始时 (T1​​)、3 周后 (T2) 和放射学评估时 (T3) 进行了液体活检。分子变量与结果终点相关：cfDNA 定量、其动态变化 (ΔT2-T1)、NGS 基线检测到的最高频率基因的变异等位基因频率 (VAF) (maxVAF) 及其动态变化 (ΔT2- T1）。在多变量分析中，PD-L1 阴性、T1 cfDNA、cfDNA 增加 (ΔT2-T1) 和 T2 VAF 与较短的无进展生存期 (PFS) 显着相关； PD-L1 阴性、鳞状组织学、T1 cfDNA、cfDNA (ΔT2-T1) 增加和 T2 maxVAF 影响总生存期 (OS)。在一线治疗的高 PD-L1 表达患者中，T2 maxVAF 升高和 cfDNA 增加 (ΔT2-T1) 与较差的 PFS 相关； T2 maxVAF 和 cfDNA 增加 (ΔT2-T1) 越高，OS 越差。派生的集成模型用于构建列线图并对不同的风险组进行分类。© 2024。作者。

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2-T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2-T1). At multivariate analysis, PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2-T1), and T2 VAF were significantly associated with shorter progression-free survival (PFS); PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2-T1) increase, and T2 maxVAF affected overall survival (OS). Among high PD-L1 expressing patients treated in first-line, elevated T2 maxVAF and cfDNA increase (∆T2-T1) correlated with worse PFS; higher T2 maxVAF and cfDNA increase (∆T2-T1) with worse OS. Derived integrated models were used to build nomograms and categorize different risk groups.© 2024. The Author(s).