动态循环肿瘤 DNA 在放化疗期间可预测局部晚期非小细胞肺癌患者的临床结局。
Dynamic circulating tumor DNA during chemoradiotherapy predicts clinical outcomes for locally advanced non-small cell lung cancer patients.
机构信息
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Geneplus-Beijing Institute, Beijing, China.
出版信息
Cancer Cell. 2023 Oct 9;41(10):1763-1773.e4. 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.
循环肿瘤 DNA（ctDNA）在放化疗（CRT）期间的价值尚不清楚，但对于检测分子残留疾病（MRD）至关重要。在这项前瞻性研究中，我们对 139 名接受根治性放疗（RT）治疗的局部晚期非小细胞肺癌患者的 761 份血样进行了测序。ctDNA 浓度在 CRT 进展时（在-RT 和 post-RT 时间点）与基线相比呈现出显著下降趋势。38 名患者在 on-RT（RT 达到 40 Gy）和 post-RT 时间点的早期 ctDNA 均不可检测，这表明对 CRT 的早期反应，无论是否进行巩固免疫检查点抑制剂治疗，都有更好的生存结果。20.1%的患者发现了纵向不可检测的 MRD。这些患者的 2 年癌症特异性无进展生存率为 88.4%，对应于潜在治愈人群。进一步分析显示，预处理 ctDNA 变体是一个重要的 MRD 信息来源。这些数据为 ctDNA-MRD 检测提供了临床见解。
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