新辅助免疫联合化疗在局部晚期非小细胞肺癌的真实世界单中心数据分析

Real-world data analysis of neoadjuvant immunochemotherapy in locally advanced NSCLC in a single center

目的评估新辅助免疫治疗联合化疗对接受根治性切除手术的局部晚期NSCLC患者的疗效, 及程序性死亡受体配体1(PD-L1)表达水平、外周血细胞计数预测病理缓解的价值。方法本研究为观察性研究。采用非随机抽样的方法的方法收集2019年10月至2021年12月首都医科大学附属北京胸科医院行新辅助免疫联合化疗后接受根治性切除手术的局部晚期NSCLC患者51例。新辅助治疗方案为免疫检查点抑制剂(程序性死亡受体1抑制剂), 化疗为含铂双药。以21 d为1个治疗周期, 每2个周期进行影像学评估。疗效评价包括完全缓解、部分缓解、病情稳定、病情进展。病理评价指标为主要病理缓解(MPR)和完全病理缓解(pCR)。分析患者的临床和病理特征, 评价新辅助治疗的效果。通过二元logistic回归模型评估影响MPR和pCR的临床因素。结果 51例患者中完全缓解0例, 部分缓解占66.7%(34/51), 病情稳定占33.3%(17/51);MPR占54.9%(28/51), pCR占41.2%(21/61)。经影像学评估达到部分缓解的患者中, MPR占73.5%(25/34), pCR占52.9%(18/34);经影像学评估为病情稳定的患者中, MPR占17.6%(3/17), 且均为pCR。术前活检标本PD-L1阳性表达率为74.5%(38/51), 其中高表达率为51.0%(26/51)。PD-L1高表达患者与PD-L1阴性/低表达患者在性别、吸烟状态、临床分期、病理类型、pCR方面均无统计学差异(均P>0.05);PD-L1高表达的患者中MPR占69.2%(18/26), PD-L1阴性/低表达的患者中MPR占40.0%(10/25), 差异有统计学意义(χ^(2)=4.40, P<0.05)。二元logistic回归结果显示, PD-L1高表达是预测MPR的独立因素(OR=3.375, 95%CI:1.063~10.711, P=0.039), 更低的NLR是预测pCR的独立因素(OR=0.166, 95%CI:0.044~0.634, P=0.009)。结论新辅助免疫联合化疗对接受根治性切除手术的局部晚期NSCLC患者治疗有效, PD-L1高表达可以预测MPR, 更低的NLR可以预测pCR。

Objective To evaluate the efficacy of neoadjuvant immunotherapy combined with chemotherapy in patients with locally advanced non-small cell lung cancer(NSCLC)who were treated with radical resection,and to assess the predictive value of programmed death ligand 1(PD-L1)expression and peripheral complete blood count in predicting the pathological remission.Methods This was a cross-sectional study involving 51 patients with locally advanced NSCLC treated with radical resection after neoadjuvant immunotherapy from October 2019 to December 2019 by non-random sampling in the Affiliated Beijing Chest Hospital of Capital Medical University.The neoadjuvant regimen consisted of an immune checkpoint inhibitor(PD-1 inhibitor)and platinum-contained chemotherapy,with 21 days as a treatment cycle.Every two cycles,the therapeutic efficacy of complete response,partial response,stable disease,and disease progression was evaluated by imaging evaluations.The pathological evaluation indexes were major pathological response(MPR)and complete pathological response(pCR).The clinical and pathological characteristics of the patients were analyzed and the effect of neoadjuvant therapy was evaluated.The correlation between pathological remission with PD-L1 level,platelet-to-lymphocyte ratio(PLR),neutrophil lymphocyte count ratio(NLR)and clinicopathologic features was explored by the binary logistic regression analysis.Results Among the 51 patients,none of them had complete response,66.7%(34/51)had partial response,and 33.3%(17/51)had stable disease.MPR and pCR accounted for 54.9%(28/51)and 41.2%(21/61),respectively,which accounted for 73.5%(25/34)and 52.9%(18/34)in patients who achieved partial response by imaging assessment,respectively.MPR and pCR accounted for 17.6%(3/17)and 100%(17/17)in patients with stable disease after imaging assessment,respectively.The positive expression rate of PD-L1 in preoperative biopsy specimens was 74.5%(38/51),and the high-expression rate was 51.0%(26/51).There were no significantdifferences in gender,smoking status,clinical stage,pathological type and pCR between patients with high PD-L1 expression and negative/low expression(all P values>0.05).The rate of MPR was significantly higher in patients with high PD-L1 expression than those with negative/low PD-L1 expression(69.2%[18/26]vs 40.0%[10/25],χ^(2)=4.40,P<0.05).The binary logistic regression showed that high expressionof PD-L1 was an independent predictor of MPR(OR=3.375,95%CI:1.063-10.711,P=0.039)and lower NLR was an independent predictor of pCR(OR=0.166,95%CI:0.044-0.634,P=0.009).Conclusions Neoadjuvant immunotherapy combined with chemotherapy is effective for the treatment of operable locally advanced NSCLC,and high PD-L1 expression and low NLR can predict pCR.