NSCLC患者新辅助抗PD-1/PD-L1单抗联合化疗期间ctDNA变化轨迹及对pCR的预测研究-东南大学学报医学版

NSCLC患者新辅助抗PD-1/PD-L1单抗联合化疗期间ctDNA变化轨迹及对pCR的预测研究

单位：成都市第七人民医院/成都医学院附属肿瘤医院胸外科, 四川成都 610213

关键词：非小细胞肺癌新辅助治疗抗PD-1/PD-L1单抗化疗循环肿瘤脱氧核糖核酸病理完全缓解

分类号：R734.2

出版年·卷·期（页码）：2026·45·第二期（229-235）

摘要：

目的:探讨非小细胞肺癌(NSCLC)患者新辅助抗程序性死亡受体1(PD-1)/程序性死亡配体1(PD-L1)单抗联合化疗期间循环肿瘤脱氧核糖核酸(ctDNA)变化轨迹及对病理完全缓解(pCR)的预测价值。方法:选取2020年4月至2024年4月我院收治的拟行新辅助抗PD-1/PD-L1单抗联合化疗的NSCLC患者289例作为研究对象,于治疗前及治疗1个、2个周期后检测ctDNA变化。采用潜类别轨迹模型(LCTM)分析ctDNA变化轨迹,根据获取最优模型分为3组,比较3组治疗前及治疗1个、2个周期后ctDNA变化情况、临床资料,分析ctDNA变化轨迹对pCR情况的影响和预测价值。结果:经LCTM分析获取3个潜在类别,即T1组(低水平-快速降低)、T2组(中高水平-快速降低)、T3组(高水平-缓慢降低),T3组治疗前及治疗1个、2个周期后ctDNA＞T2组＞T1组;3组临床分期、肿瘤大小、淋巴结转移情况、pCR率比较,差异有统计学意义(P＜0.05);校正临床分期、肿瘤大小、淋巴结转移后,与T1组比较,T2、T3组获得非pCR的风险分别增加2.536倍、5.795倍(P＜0.05);治疗期间ctDNA呈低水平-快速降低变化轨迹和中高水平-快速降低变化轨迹预测pCR情况的敏感度为98.55%,特异度为74.09%。结论:NSCLC患者新辅助抗PD-1/PD-L1单抗联合化疗期间ctDNA呈降低趋势,且ctDNA变化轨迹与pCR有关,检测ctDNA变化轨迹可用于辅助评估患者pCR。

Objective: To explore the trajectory of changes in circulating tumor deoxyribonucleic acid(ctDNA) during neoadjuvant anti-programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1) monoclonal antibody combined with chemotherapy in patients with non-small cell lung cancer(NSCLC), and its predictive value for pathological complete response(pCR). Methods: 289 patients with NSCLC who were admitted to our hospital and planned to undergo neoadjuvant anti-PD-1/PD-L1 monoclonal antibody combined with chemotherapy from April 2020 to April 2024 were selected as the study subjects. Changes in circulating tumor DNA(ctDNA) were detected before treatment, after one cycle of treatment, and after two cycles of treatment. The latent class trajectory model(LCTM) was used to analyze the trajectory of ctDNA changes. Based on the optimal model obtained, the patients were divided into three groups. The changes in ctDNA and clinical data were compared before treatment, after one cycle of treatment, and after two cycles of treatment among the three groups, and the impact and predictive value of ctDNA change trajectory on pCR status were analyzed. Results: Three potential categories were obtained by LCTM analysis, namely T1 group(low level-rapid reduction), T2 group(medium-high level-rapid reduction), T3 group(high level-slow reduction). ctDNA levels in the T3 group were greater than those in the T2 group, which were greater than those in the T1 group, before treatment and after 1 and 2 cycles of treatment; there were significant differences in clinical stage, tumor size, lymph node metastasis and pCR rate among the three groups(P<0.05). After adjusting for clinical stage, tumor size and lymph node metastasis, the risk of non-pCR in T2 and T3 groups increased by 2.536 times and 5.795 times, respectively, compared with T1 group(P<0.05). The sensitivity and specificity of ctDNA low level-rapid decrease change trajectory and medium-high level-rapid decrease change trajectory in predicting pCR during treatment were 98.55% and 74.09%, respectively. Conclusion: During neoadjuvant anti-PD-1/PD-L1 monoclonal antibody combined chemotherapy in patients with NSCLC, ctDNA shows a decreasing trend, and the trajectory of ctDNA changes is associated with pCR. Detection of ctDNA trajectory can be used to assist in evaluating pCR in patients.

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