乳酸脱氢酶对晚期食管鳞状细胞癌免疫治疗的预后价值研究

Prognostic Value of Lactate Dehydrogenase in Advanced Esophageal Squamous Cell Carcinoma Patients with Immunotherapy

背景仅有少量晚期食管鳞状细胞癌(ESCC)患者可从免疫治疗中获益,总体疗效不令人满意。因此,选择有效的预后观察指标十分重要。目的探讨乳酸脱氢酶(LDH)预测晚期ESCC患者免疫治疗的预后价值。方法选取2016年10月至2019年10月在河南省肿瘤医院经病理及影像学检查确诊为晚期ESCC患者为研究对象。从医院电子病历系统中回顾性收集患者基线资料,并收集患者免疫治疗第8周LDH水平。随访截至2021-08-31,记录随访结果。观察死亡情况、患者疾病缓解情况,并记录无进展生存期(PFS)和总生存期(OS)。采用Kaplan-Meier法绘制不同基线LDH水平患者PFS、OS生存曲线以进行生存分析,生存曲线的比较采用Log-rank检验;采用多因素Cox比例风险回归分析探究晚期ESCC患者免疫治疗PFS、OS的影响因素。结果44例患者中基线LDH低水平(基线LDH<200 U/L)者28例,基线LDH高水平(基线LDH≥200 U/L)者16例。基线LDH低水平的患者客观缓解率(ORR)高于基线LDH高水平患者(χ^(2)=8.522,P=0.013)。44例患者中病情进展(PD)8例,无PD患者36例。PD患者ΔLDH(治疗过程中LDH的变化)高于无PD患者(t=2.394,P=0.021)。截至2021-08-31,9例(20.5%)患者存活;中位PFS为6(2,11)个月;中位OS为11(7,18)个月。基线LDH低水平与基线LDH高水平患者PFS、OS比较,差异均有统计学意义(χ^(2)值分别为6.790、12.327,P值分别为0.009、<0.001)。多因素Cox比例风险回归分析结果显示,基线LDH水平是晚期ESCC患者免疫治疗后PFS的影响因素〔HR=2.686,95%CI(1.274,5.664),P=0.009〕;基线LDH水平〔HR=17.440,95%CI(2.254,134.962),P=0.001〕、血红蛋白〔HR=0.005,95%CI(<0.001,0.120),P=0.001〕、单核细胞计数〔HR=0.066,95%CI(0.008,0.525),P=0.010〕是晚期ESCC患者免疫治疗后OS的影响因素。结论基线LDH可作为晚期ESCC患者免疫治疗预后的预测指标,且基线LDH低水平者有更好的PFS及OS。

Background The overall efficacy of immunotherapy is unsatisfactory in patients with advanced esophageal squamous cell carcinoma(ESCC),since only a few cases could obtain benefits from the therapy.Therefore,it is of great importance to select effective prognostic indicators.Objective To investigate the prognostic value of lactate dehydrogenase(LDH)in advanced ESCC patients with immunotherapy.Methods This study enrolled patients diagnosed with advanced ESCC by pathological and imaging examinations in Henan Cancer Hospital from October 2016 to October 2019.Data were collected,including baseline data obtained from the electronic medical record system,LDH level at the 8th week of immunotherapy,and results〔containing death,disease remission,progression-free survival(PFS)and overall survival(OS)〕of a follow-up until August 31,2021.Log-rank test was used to compare Kaplan-Meier curves of PFS and OS by baseline LDH.Multivariate Cox regression analysis was used to analyze the potential factors associated with PFS and OS.Results Of the 44 cases enrolled,a higher objective response rate was found in those with lower baseline LDH(n=28,baseline LDH<200 U/L)instead of those with higher baseline LDH(n=16,baseline LDH≥200 U/L)(χ^(2)=8.522,P=0.013).Eight patients with disease progression(PD)had higherΔLDH than 36 patients without PD(t=2.394,P=0.021).At the end of follow-up,9 patients(20.5%)survived,with a median PFS of 6(2,11)months,and a median OS of 11(7,18)months.PFS was significantly different in those with higher and lower baseline LDH levels(χ^(2)=6.790,P=0.009).OS was also significantly different in those with higher and lower baseline LDH levels(χ^(2)=12.327,P<0.001).The baseline LDH〔HR=2.686,95%CI(1.274,5.664),P=0.009〕was associated with the PFS after immuotherapy.And the multivariate analyses showed that baseline LDH〔HR=17.440,95%CI(2.254,134.962),P=0.001〕,hemoglobin〔HR=0.005,95%CI(<0.001,0.120),P=0.001〕,monocyte count〔HR=0.066,95%CI(0.008,0.525),P=0.010〕were associated with the OS after immunotherapy(P<0.05).Conclusion Baseline LDH may be used as a prognostic marker after immunotherapy in patients with advanced ESCC,and a lower baseline LDH may be associated with longer PFS and OS.