Ding Haolun, Yuan Min, Yang Yaning, Xu Xu Steven
Department of Statistics and Finance, School of Management, University of Science and Technology of China, Hefei, Anhui, China.
Department of Health Data Science, Anhui Medical University, Hefei, Anhui, China.
NPJ Precis Oncol. 2025 Jan 8;9(1):5. doi: 10.1038/s41698-024-00797-2.
Tumor genomic profiling is often limited to one or two timepoints due to the invasiveness of tissue biopsies, but longitudinal profiling may provide deeper clinical insights. Using ctDNA data from IMpower150 study, we examined genetic changes in metastatic non-squamous NSCLC post-first-line immunotherapy. Mutations were most frequently detected in TP53, KRAS, SPTA1, FAT3, and LRP1B at baseline and during treatment. Mutation levels rose prior to radiographic progression in most progressing patients, with specific mutations (SPTA1, STK11, KEAP1, SMARCA4, TBX3, CDH2, and MLL3) significantly enriched in those with progression or nondurable response. However, ctDNA's role in detecting hyperprogression and pseudoprogression remains uncertain. STK11, SMARCA4, KRAS, SLT2, and KEAP1 mutations showed the strongest correlation with poorer overall survival, while SMARCA4, STK11, SPTA1, TBX3, and KEAP1 mutations correlated with shorter progression-free survival. Overall, longitudinal liquid biopsy profiling provided valuable insights into lung cancer biology post-immunotherapy, potentially guiding personalized therapies and future drug development.
由于组织活检具有侵入性，肿瘤基因组分析通常仅限于一两个时间点，但纵向分析可能会提供更深入的临床见解。利用IMpower150研究中的循环肿瘤DNA（ctDNA）数据，我们研究了转移性非小细胞肺癌一线免疫治疗后的基因变化。在基线和治疗期间，最常检测到的突变发生在TP53、KRAS、SPTA1、FAT3和LRP1B基因。在大多数病情进展的患者中，突变水平在影像学进展之前升高，特定突变（SPTA1、STK11、KEAP1、SMARCA4、TBX3、CDH2和MLL3）在病情进展或无持久反应的患者中显著富集。然而，ctDNA在检测快速进展和假性进展中的作用仍不确定。STK11、SMARCA4、KRAS、SLT2和KEAP1突变与较差的总生存期显示出最强的相关性，而SMARCA4、STK11、SPTA1、TBX3和KEAP1突变与较短的无进展生存期相关。总体而言，纵向液体活检分析为免疫治疗后的肺癌生物学提供了有价值的见解，可能指导个性化治疗和未来药物开发。
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