SCI

14 October 2024

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

 (Cancer Cell, IF: 48.8)

  • Xu J, Wan R, Cai Y, et al: Circulating tumor DNA-based stratification strategy for chemotherapy plus PD-1 inhibitor in advanced non-small-cell lung cancer. Cancer Cell 42:1598-1613.e4, 2024

Abstract 摘要

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.

化疗加 PD-1抑制剂治疗晚期非小细胞肺癌(NSCLC)的分层策略是迫切需要的。在3期 CHOICE-01研究的不同时间点，我们对来自460名患者的前瞻性收集的循环肿瘤 DNA (ctDNA)标本进行了基于高通量面板的深度二代测序和低通量全基因组测序。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，我们建立了一个综合的基于 ctDNA 的分层策略，基于血液的基因组免疫亚型(bGIS)方案，以区分从 PD-1抑制剂加入到一线化疗中获益的患者。此外，我们还展示了动态监测 ctDNA 的潜在应用。总的来说，我们提出了一种基于 ctDNA 分层策略的潜在治疗算法，阐明了晚期非小细胞肺癌患者免疫化疗的个体化管理。


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