晚期非小细胞肺癌D-二聚体、纤维蛋白原水平与化疗效果关系的研究

发布时间：2018-07-26 21:01

【摘要】：目的本文通过测定晚期非小细胞肺癌患者化疗前及化疗过程中体内血浆D-二聚体及纤维蛋白原水平,研究二者的异常升高和变化与一线化疗的治疗效果和无进展生存期的关系,探讨两个指标在判断肿瘤进展和预测化疗效果中的意义。材料及方法回顾性分析2013年7月至2014年6月期间于山东大学附属省立医院呼吸内科就诊且组织病理学或细胞学确诊为晚期(ⅢB期及Ⅳ期)非小细胞肺癌(NSCLC)的患者55例,收集其临床资料,包括第一次化疗、第二次化疗与第三次化疗前患者的血浆D-二聚体、纤维蛋白原(fibrinogen, FIB)水平,肿瘤的病理类型、分期及无进展生存期(progression-free survival,PFS),同时收集30例门诊健康体检者的相关指标(血浆D-二聚体D、纤维蛋白原F)作对照,使用SPSS17.0进行统计学分析,研究晚期NSCLC患者化疗前血浆D-二聚体与纤维蛋白原水平的升高及化疗过程中二者水平的变化与肺癌的进展和治疗效果是否存在相关性。结果1.化疗前晚期NSCLC患者D-二聚体和FIB的升高表现与年龄、性别、肿瘤的分期和病理类型均不相关,各P值均大于0.05(P=0.311,P=0.448,P=0.232,P=0.670)。2.化疗前晚期NSCLC患者血浆D-二聚体和FIB的中位数分别为0.97mg/L和4.35g/L,对照组的中位数分别为0.485mg/L和3.85g/L,对照组显著低于NSCLC组,且差异有统计学意义(p=0.000,p=0.004)。3.化疗两周期后有效(PR+SD)的晚期NSCLC患者,其化疗前血浆D-二聚体和FIB的中位数分别为0.69mg/L和2.75g/L,无效(PD)的患者中位数分别为1.75mg/L和4.63g/L。有效组水平显著低于无效组,其差异有统计学意义(P=0.000,P=0.001)。4.晚期NSCLC患者PFS的中位数是5.6个月(95%置信区间为5.2-7.5个月),化疗前血浆D-二聚体和FIB阳性的患者,其PFS显著短于阴性的患者,且差异有统计学意义(P=0.002,P=0.001)。在COX回归的单变量和多变量分析中,D-二聚体的和FIB的阳性均与PFS显著相关(P=0.001,P=0.000),并且是PFS的独立预测因素。5.将化疗有效的晚期NSCLC患者三次化疗前的血浆D-二聚体水平D1、D2、D3进行对比,结果显示D1、D2、D3中位数分别为0.69mg/L、0.58 mg/L、0.51 mg/L,数值虽逐渐降低,但差异无统计学意义(D1与D2比较P=0.153,D2与D3比较P=0.228)。将有效组化疗前后FIB水平F1、F2、F3进行对比,中位数分别为3.25g/L、2.91 g/L、2.53 g/L,虽然化疗后水平较化疗前下降,但差异同样无统计学意义(F1与F2比较P=0.124,F2与F3比较P=0.219)。结论1.晚期NSCLC患者血浆化疗前D-二聚体及FIB水平高于健康人,对于排除其他引起凝血障碍的疾病、同时具有可疑肺部症状的患者,二个指标的异常升高可提示肺癌的诊断；2.对于初诊的晚期NSCLC患者,一线化疗前血浆D-二聚体和FIB水平低者,其化疗效果比高者好,一线化疗前二者水平为阴性者,其无进展生存期比阳性者长,因此监测化疗前血浆D-二聚体和纤维蛋白原的水平可以预测患者化疗效果。3.初诊时发现血浆D-二聚体和FIB水平异常升高,应警惕患者出现化疗效果不佳和PFS较短的情况,治疗过程中可适当缩短影像学检查间隔时间,有利于密切监测肿瘤进展情况,及时调整治疗方案,延长无进展生存期。
[Abstract]:Objective to investigate the relationship between the abnormal elevation and change of the two patients with D- two polymer and fibrinogen in patients with advanced non-small cell lung cancer before and after chemotherapy, and to explore the significance of the two indicators in predicting the progress of the tumor and predicting the effect of chemotherapy. Materials and Methods Retrospective analysis of 55 patients with advanced (stage III B and stage IV) non small cell lung cancer (NSCLC) in the Department of respiratory medicine, affiliated Provincial Hospital of Shandong University, from July 2013 to June 2014, and collected its clinical data, including the first chemotherapy, second chemotherapy and third pre chemotherapy patients. The plasma D- two polymer, fibrinogen (fibrinogen, FIB) level, tumor pathological type, staging and progression free survival (progression-free survival, PFS) were used to collect the related indexes (plasma D- two D, fibrinogen F) in 30 cases of outpatient clinic as control, and to use SPSS17.0 for statistical analysis, and to study late NSCLC. The increase of plasma D- two polymer and fibrinogen level before chemotherapy and the changes of two levels in the course of chemotherapy are related to the progress of lung cancer and the effect of treatment. Results 1. the elevation of D- two polymer and FIB in patients with advanced pre chemotherapy was not related to age, sex, tumor staging and pathological type, and all P values were all large. The median of plasma D- two polymer and FIB in advanced NSCLC patients before.2. chemotherapy in 0.05 (P=0.311, P=0.448, P=0.232, P=0.670).2. were 0.97mg/L and 4.35g/L respectively. The median of the control group was 0.485mg/L and 3.85g/L, and the control group was significantly lower than those in the control group, and the difference was statistically significant. In NSCLC patients, the median of plasma D- two polymer and FIB before chemotherapy was 0.69mg/L and 2.75g/L respectively. The median of invalid (PD) patients were significantly lower than that of the effective group of 1.75mg/L and 4.63g/L., respectively. The difference was statistically significant (P=0.000, P=0.001), the median of the late NSCLC patients was 5.6 months (95% confidence interval). In patients with D- two polymer and FIB positive before chemotherapy, the PFS was significantly shorter than that of the negative patients, and the difference was statistically significant (P=0.002, P=0.001). In the single variable and multivariable analysis of COX regression, the positive of D- two polymer and FIB were significantly correlated with PFS (P= 0.001, P=0.000), and was an independent predictor of PFS. The plasma D- two polymer level D1, D2, D3 before three time chemotherapy were compared. The results showed that the median of D1, D2 and D3 were 0.69mg/L, 0.58 mg/L, and 0.51 mg/L, but the difference was not statistically significant. The median number was 3.25g/L, 2.91 g/L, 2.53 g/L, although the level after chemotherapy was lower than that before chemotherapy, but the difference was not statistically significant (F1 compared with F2 P=0.124, F2 and F3 P=0.219). Conclusion the D- two polymer and FIB level before chemotherapy in 1. advanced NSCLC patients were higher than those of the healthy people, and were at the same time to exclude other disorders causing coagulation disorders. In patients with suspected pulmonary symptoms, abnormal elevation of two indicators could indicate the diagnosis of lung cancer; 2. for patients with early diagnosis of advanced NSCLC, the plasma D- two polymer and low levels of FIB before chemotherapy were better than those with high levels of chemotherapy, and the level of two before the first line chemotherapy was negative, and the non progressive survival period was longer than that of the positive ones, so the monitoring of pre chemotherapy blood was therefore monitored. The level of plasma D- two polymer and fibrinogen can predict the abnormal increase of plasma D- two polymer and FIB level during the first diagnosis of patients with chemotherapy, and should be vigilant to patients with poor chemotherapy effect and short PFS. The interval of imaging examination can be shortened properly during the treatment process, and it is beneficial to monitor the progress of the tumor closely and adjust it in time. The whole treatment regimen extended the progression free survival.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R734.2

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