乳酸脱氢酶与晚期非小细胞肺癌患者免疫治疗效果的关系

Relationship between lactate dehydrogenase lactate dehydrogenase and immunotherapy effect in patients with advanced non-small cell lung cancer

目的 探讨乳酸脱氢酶(LDH)等血液参数和生化指标对初次接受免疫检查点抑制剂(ICIs)治疗的晚期非小细胞肺癌(NSCLC)患者疗效及其预后的预测价值。方法 回顾性分析2019-03-01-2021-10-30在山东省肿瘤医院首次接受ICIs治疗的136例晚期NSCLC患者临床资料。收集患者初次接受ICIs治疗前的临床基本特征,采用Kaplan-Meier法绘制生存率曲线,log-rank检验比较组间生存率。单因素和多因素Cox回归分析各临床特征及血液生化参数与无进展生存期(PFS)和总生存期(OS)的关系。结果 136例患者中疾病稳定39例,因疾病进展死亡84例,失访13例。患者的中位随访时间为39.01个月(95%CI:38.19~39.83),中位PFS(mPFS)为7.14个月(95%CI:6.06~8.22),中位OS(mOS)为19.24个月(95%CI:14.54~23.94)。Kaplan-Meier生存分析结果显示,与无肝转移组相比,肝转移组PFS和OS均更短[mPFS:(8.26 vs 3.87)个月,P=0.001;mOS:(21.75 vs 11.54)个月,P=0.011];与低LDH组(<209.5 U/L)相比,高LDH组(≥209.5 U/L)PFS和OS均更短[mPFS:(8.33 vs 5.88)个月,P=0.002;mOS:(32.89 vs 15.01)个月,P=0.001];与高白蛋白(ALB)组(≥42.95 g/L)相比,低ALB组(<42.95 g/L)OS更差[mOS:(23.37 vs 12.89)个月,P=0.007]。单因素Cox回归结果示,LDH、既往放疗史、LDH/白蛋白比值(LAR)、肝转移和抗血管药物治疗是患者PFS的影响因素,均P<0.05;多因素分析表明,LDH与肝转移是影响PFS的独立预后因素(LDH:HR=1.748,95%CI:1.181~2.587,P=0.005;肝转移:HR=1.885,95%CI:1.235~2.877,P=0.003)。单因素Cox回归结果示,肝转移、绝对单核细胞计数(AMC)、LDH、ALB、中性粒细胞/淋巴细胞比值(NLR)、LAR、单核细胞/淋巴细胞比值(MLR)及全身炎症反应指数(SIRI)是患者OS的影响因素,均P<0.05。多因素分析表明,LDH、肝转移和ALB是影响患者OS的独立预后因素(LDH:HR=2.087,95%CI:1.298~3.354,P=0.002;肝转移:HR=1.909,95%CI:1.164~3.130,P=0.010;ALB:HR=0.514,95%CI:0.331~0.801,P=0.003)。结论 基线LDH可作为一种无创且易获取的生物标志物预测晚期NSCLC患者免疫治疗的疗效及预后。

Objective To explore the effect and prognosis of blood and biochemical parameters such as lactate dehydrogen-ase(LDH)in patients with advanced non-small cell lung cancer(NSCLC)who received immune checkpoint inhibitors(ICIS)for the first time.Methods This study retrospectively included 136 patients with advanced NSCLC who received ICIs treatment for the first time in Shandong Cancer Hospital from March 2019 to October 2021,and there were 108 male patients and 27 female patients.The basic clinical characteristics of patients before the first ICIs treatment were collected,and the survival rate curves were drawn by Kaplan-Meier method,and the survival rate curves between groups were compared by Log-rank test.Univariate and multivariate Cox regression were used to analyze the relationship between clinical features,blood biochemical parameters and progression-free survival(PFS)and overall survival(OS).Results Among 136 patients with advanced NSCLC,39 cases were stable,84 cases died due to disease progression,and 13 cases were lost to follow-up.The median follow-up time was 39.01 months(95%CI:38.19-39.83),the median PFS was 7.14 months(95%CI:6.06-8.22)and the median OS was 19.24 months(95%CI:14.54-23.94).Kaplan-Meier survival analysis showed that the PFS and OS of patients with liver metastasis were shorter than those without liver metastasis[mPFS:(8.26 us 3.87)months,P=0.001;mOS:(21.75 us 11.54)months,P=0.011].Compared with patients in low LDH group(<209.5 U/L,),patients in high LDH group(≥209.5 U/L)had shorter PFS and OS[mPFS:(8.33 us 5.88)months,P=0.002;mOS:(32.89 us 15.01)months,P=0.001].Compared with patients in high albumin(ALB)group(≥42.95 g/L),patients in low ALB group(<42.95 g/L)had worse OS[mOS:(23.37 us 12.89)months,P=0.007].Univariate Cox regression showed that LDH,previous radiotherapy,LAR,liver metastasis and anti-vascular drugs treatment were possible factors to predict PFS,all P<0.05.Multivariate analysis showed that LDH and liver metastasis were still independent factors of PFS(LDH:HR=1.748,95%CI:1.181-2.587,P=0.005;liver metastasis:HR=1.885,95%CI:1.235-2.877,P=0.003).Univariate Cox regression showed that liver metastasis,absolute monocyte count(AMC),LDH,albumin(ALB),neutrophil/lymphocyte ratio(NLR),LAR,monocyte/lymphocyte ratio(MLR)and systemic inflammatory response index(SIRI)were possible factors to influence patients OS,all P<0.05.Multivariate analysis showed that LDH,liver metastasis and ALB were independent prognostic factors in predicting OS(LDH:HR=2.087;95%CI:1.298-3.354,P=0.002;liver metastasis:HR=1.909;95%CI:1.164-3.130,P=0.010;ALB:HR=0.514;95%CI:0.331-0.801,P=0.003).Conclusion Baseline LDH may serve as a noninvasive and easily available biomarker to predict the efficacy and prognosis of ICIs treatment in patients with advanced NSCLC.