目的 探讨外周血循环肿瘤DNA预测晚期非小细胞肺癌（NSCLC）免疫治疗疗效及预后的价值。 方法 对2021年1-12月收治于河北北方学院附属第一医院呼吸与危重症医学科住院的78例晚期驱动基因阴性使用替雷利珠单抗治疗的NSCLC患者进行前瞻性研究，免疫治疗2周期后按照实体瘤疗效评价标准（RECIST1.1）评价疗效，包括完全缓解（CR）、部分缓解（PR）、疾病稳定及疾病进展，将CR和PR患者定义为观察组（n = 48），其他患者被定义为对照组（n = 30），测定两组患者治疗前后外周血中ctDNA水平，采用ROC曲线分析外周血ctDNA水平对于免疫治疗后达客观缓解的预测价值。对所有患者进行随访，统计其无进展生存期，采用单因素及多因素回归分析免疫治疗后患者预后的影响因素，采用Spearman相关系数对ctDNA水平与PFS进行相关性分析，采用 Kalplan-Meier 生存曲线进行生存分析。 结果 观察组治疗前后外周血ctDNA水平分别为（4.47 ± 1.21）、（2.65 ± 1.14）ng/μL（t = 7.559，P < 0.001），对照组治疗前后外周血ctDNA水平为（4.54 ± 1.15）、（4.29 ± 1.57）ng/μL（t = 0.699，P = 0.487），两组患者在治疗前外周血ctDNA水平差异无统计学意义（t = -0.25，P = 0.801），观察组治疗后外周血ctDNA水平较对照组下降（t = -5.35，P < 0.001）。ROC曲线分析外周血ctDNA水平预测免疫治疗后达客观缓解的曲线下面积为0.819，预测的敏感性度81.3%，特异度为80%，外周血ctDNA水平与患者无进展生存期（PFS）呈负相关（r = -0.784，P < 0.001），采用单因素Cox回归对入组患者的临床病理特征及ctDNA水平进行分析，结果显示肿瘤最大径> 5 cm（HR = 0.501，95%CI：0.282 ~ 0.890）、肿瘤Ⅳ期（HR = 0.392，95%CI：0.227 ~ 0.677）、治疗方式（HR = 15.473，95%CI：6.731 ~ 35.567）及ctDNA水平（HR = 4.567，95%CI：3.182 ~ 6.555）均为晚期NSCLC患者免疫治疗后PFS的影响因素，再将有统计学差异的上述指标进行多因素分析，结果显示：治疗方式（HR = 2.981，95%CI：1.019 ~ 8.722）及外周血ctDNA水平（HR = 3.918，95%CI：2.619 ~ 5.861）是晚期NSCLC患者PFS的独立影响因素，采用Kalplan-Meier生存曲线进行分析，结果显示观察组的中位PFS为8.4个月，对照组的中位PFS为5.4个月，差异有统计学意义（χ ² = 46.828，P = 0.000）。 结论 免疫联合化疗可增强杀伤肿瘤细胞的能力，外周血ctDNA水平可评估免疫治疗的疗效及预后，可用于指导晚期NSCLC患者的免疫治疗。

Objective To explore the value of peripheral blood circulating DNA in predicting the efficacy and prognosis of immunotherapy for advanced non-small cell lung cancer. Method A retrospective study was conducted on 78 NSCLC patients who were admitted to the Respiratory and Critical Care Medicine Department of the First Affiliated Hospital of Hebei North University and were treated with tirelizumab for advanced driver gene negativity from January 2021 to December 2021. After 2 cycles of immunotherapy， the efficacy was evaluated according to the Solid Tumor Efficacy Evaluation Criteria （RECIST 1.1）， including complete remission， partial remission， disease stability， and disease progression. CR and PR patients were defined as the experimental group （n = 48） Other patients were defined as the control group （n = 30）， and the ctDNA levels in peripheral blood were measured before and after treatment in both groups. ROC curves were used to analyze the predictive value of peripheral blood ctDNA levels for achieving objective remission after immunotherapy.All patients were followed up and their progression free survival were calcutated.Using univariate and multivariate regression analysis identified the factors affecting the prognosis of patients after immunotherapy. Using Spearman correlation coefficient analyzed the correlation between ctDNA levels and PFS. Kalplan Meier survival curve were used for survival analysis. Result The peripheral blood ctDNA levels before and after treatment in the experimental group were （4.47 ± 1.21）ng/μL and （2.65 ± 1.14） ng/μL， respectively （t = 7.559，P < 0.001）， while those in the control group were （4.54 ± 1.15）ng/mL and （4.29 ± 1.57） ng/μL， respectively （t = 0.699，P = 0.487）. There was no statistically significant difference in peripheral blood ctDNA levels between the two groups before treatment （t = -0.25，P = 0.801）. The peripheral blood ctDNA levels in the experimental group decreased compared to the control group after treatment （t = -5.35，P < 0.001）. The ROC curve analysis showed that the area under the curve for predicting objective remission after immunotherapy based on peripheral blood ctDNA levels was 0.819， with a sensitivity of 81.3% and specificity of 80%. Peripheral blood ctDNA levels were negatively correlated with progression free survival （r = -0.784，P = 0.000）. Single factor COX regression was used to analyze the clinical and pathological characteristics and ctDNA levels of enrolled patients， and the results showed that the maximum tumor diameter was greater than 5 cm （HR = 0.501， 95% CI： 6.731 ~ 35.567） Tumor stage IV （HR = 0.392，95% CI： 0.227 ~ 0.677）， treatment approach （HR = 15.473，95% CI： 6.731 ~ 35.567）， and ctDNA levels （HR = 4.657，95% CI： 3.182 ~ 6.555） are all influencing factors for PFS in advanced NSCLC patients after immunotherapy. Multiple factor analysis was conducted on the appeal indicators with statistical differences， and the results showed that treatment approach （HR = 2.981，95% CI：1.019 ~ 8.722） and peripheral blood ctDNA levels （HR = 3.918，95% CI： 2.619 ~ 5.861） It is an independent influencing factor of PFS in advanced NSCLC patients. The Kalplan Meier survival curve was used for analysis， and the results showed that the median PFS of the treatment effective group was 8.4 months， while the median PFS of the control group was 5.4 months. （χ ² = 49.277， P = 0.000）. Conclusion Immunotherapy combined with chemotherapy can enhance the ability to kill tumor cells， and peripheral blood ctDNA levels can evaluate the efficacy and prognosis of immunotherapy， which can be used to guide immunotherapy in advanced NSCLC patients.