血清LDH在EGFR-TKI治疗晚期非小细胞肺癌中的应用价值

Application value of serum LDH in advanced non-small cell lung cancer patients treated with EGFR-TKI

目的探讨血清乳酸脱氢酶(LDH)在表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKI)治疗晚期非小细胞肺癌(NSCLC)中的价值.方法回顾性分析2011年7月至2015年7月在广东省珠海市人民医院经病理确诊、基因检测为EGFR敏感突变的190例晚期NSCLC患者的资料,包括治疗前LDH水平、一般病理资料、肿瘤分期、用药情况等.根据治疗前的LDH水平,将患者分为LDH正常组(LDH≤252 U/L)和LDH升高组(LDH >252 U/L),其中LDH正常组78例,LDH升高组112例.对患者定期进行影像学评价,记录患者的无进展生存期(PFS)和总生存期(OS).采用Kaplan-Meier法绘制生存曲线,log-rank检验比较不同LDH水平间的生存差异,Cox回归分析患者预后因素.结果 LDH正常组和LDH升高组患者的客观缓解率分别为76.9%(60/78)、71.4%(80/112),疾病控制率分别为89.7%(70/78)、85.7%(96/112),差异均无统计学意义(χ^2=0.716,P=0.398;χ^2=0.676,P=0.411).LDH正常组和LDH升高组患者的中位PFS分别为11.5个月、9.7个月(χ^2 =5.92,P=0.015),中位OS分别为31.0个月、26.1个月(χ^2=4.79,P=0.029),治疗前LDH升高患者的PFS和OS均较正常者缩短.Cox多因素回归分析显示,肿瘤分期(HR=1.652,95% CI为1.386 ~2.259,P=0.018)、PS评分(HR=2.248,95% CI为1.507 ~3.846,P<0.001)、癌胚抗原(CEA)水平(HR=1.250,95% CI为1.066 ~1.703,P=0.037)、治疗前LDH水平(HR=1.771,95% CI为1.324~1.947,P=0.015)是晚期NSCLC患者的独立预后因素.结论治疗前LDH水平不影响EGFR-TKI治疗晚期NSCLC的客观缓解率和疾病控制率,但影响患者的PFS和OS,是影响生存的预后因素.

Objective To investigate the value of serum lactate dehydrogenase (LDH) in advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI).Methods Pretreatment LDH level,pathological characteristic,tumor staging and treatment situation of 190 advanced NSCLC patients with EGFR sensitive mutation confirmed by pathology were retrospectively collected in Zhuhai People's Hospital of Guangdong Provice from July 2011 to July 2015.All the patients were divided into LDH normal group (LDH ≤252 U/L,n =78) and elevated group (LDH > 252 U/L,n =112) according to pretreatment LDH level.Inaging evaluations of the patients were performed regularly,and the progression-free survival (PFS) and overall survival (OS) were recorded.The survival curves were plotted by Kaplan-Meier method and survival difference between patients with different LDH level was compared by logrank test.Cox regression analysis was used to analyze prognostic factors for mortality.Results The objective response rate of the LDH normal group was 76.9%(60/78),and the elevated group was 71.4%(80/112),with no statistically significant difference (χ^2 =0.716,P =0.398).The disease control rate of the LDH normal group was 89.7%(70/78),and the elevated group was 85.7%(96/112),with no statistically significant difference (χ^2 =0.676,P =0.411).The median PFS of the LDH normal group was 11.5 months,and the elevated group was 9.7 months (χ^2 =5.92,P =0.015).The median OS was 31.0 months in the LDH normal group,and 26.1 months in the elevated LDH group (χ^2 =4.79,P =0.029).Both PFS and OS of patients with elevated LDH were shorter than those of patients with normal LDH.Cox multivariate regression analysis showed that tumor staging (HR =1.652,95% CI:1.386-2.259,P =0.018),PS score (HR =2.248,95% CI:1.507-3.846,P < 0.001),carcino-embryonic antigen (CEA) level (HR =1.250,95% CI:1.066-1.703,P =0.037) and LDH level (HR =1.771,95 % CI:1.324-1.947,P =0.015) were independent prognostic factors in patients with advanced NSCLC.Conclusion Pretreatment serum LDH can not affect the objective response rate and disease control rate of EGFR-TKI in the treatment of advanced NSCLC,but can affect the PFS and OS of patients.Pretreatment serum LDH is an independent prognostic factor.