CEA和CYFRA21-1在EGFR-TKI治疗肺腺癌疗效及预后判定中的作用

发布时间：2018-01-19 00:10

  本文关键词： 非小细胞肺癌 CEA CYFRA21-1 EGFR-TKI　出处：《大连医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:使用EGFR-TKI治疗伴EGFR突变的晚期NSCLC患者的评价标准存在争议,因EGFR-TKI作用机制与传统的化疗药物之间的差异,单纯的RECIST评价手段科学性不足,急需新的评价标准和方法,但是限于某些功能性诊断价格昂贵,常用的经济的评估手段间的联合应用是否能起到好的评估效果。本课题通过研究CEA和CYFRA21-1变化率与EGFR-TKI治疗伴EGFR突变的晚期肺腺癌患者的疗效及生存预测意义,分析CEA和CYFRA21-1变化率在疗效判定中的差异,以期为EGFR-TKI靶向治疗的疗效评价及预后提供经济有效的手段。方法:1、收集自2011年1月至2015年1月大连医科大学附属第一医院收治的接受EGFR-TKI治疗的IV期肺癌患者90例,均经病理证实为肺腺癌,伴有EGFR19外显子突变55例,21外显子突变35例。男性患者27例(30%),女性患者63例(70%),年龄在37-79岁,中位年龄61.7岁。归纳患者基本临床信息,包括年龄,性别,吸烟史,其他转移部位,全身治疗情况,疗效评价,无进展生存期等。所有患者均有完整的治疗前及4周后的血清CEA和CYFRA21-1的检测结果,和相关影像学检查结果。2、采用spss20.0软件对数据进行统计分析。采用ROC曲线确立最佳截断点,采用秩和检验分析CEA变化率和CYFRA21-1变化率与EGFR-TKI疗效的关系,采用Kaplan-Meier·法分析无进展生存时间并绘制生存曲线,采用卡方检验分析CEA和CYFRA21-1变化率在疗效判定中的差异,本文所有检验均为双侧检验,以P＜0.05为差异有统计学意义。结果:1、筛选基线CEA水平均升高,CYFRA21-1水平可正常或升高的病例76例进行分析,CEA变化率与RECIST评价疗效的ROC曲线面积为0.643(95%CI为0.519-0.767),最佳截断点时CEA下降变化率为22.88%,最佳截断点时灵敏度是 0.719,特异度是 0.535。(P=0.035)分析CEA变化率在截断点上下与近期疗效关系,CEA变化率22.88%的有效率为52.3%,CEA变化率≤22.88%的有效率为28.1%,得出P=0.023,说明CEA变化率22.88%时,EGFR-TKI治疗的疗效更好。根据CEA变化率与RECIST评价疗效的ROC曲线确立最佳截断点,依据截断点处的CEA变化率,将76例患者分成CEA变化率22.88%组和CEA变化率≤22.88%组,比较两组的PFS,CEA降低22.88%组的中位PFS为9.5月,CEA降低≤22.88%组中位PFS为7.0月。(P=0.000)2、筛选基线CYFRA21-1水平均升高,CEA水平可正常或升高的病例69例进行分析,CYFRA21-1变化率与RECIST评价疗效的ROC曲线面积为0.677(95%CI为0.554-0.799),最佳截断点时CYFRA21-1下降变化率为28.64%,最佳截断点时灵敏度是0.788,特异度是0.595。(P=0.009)分析CYFRA21-1变化率在截断点上下与近期疗效关系,CYFRA21-1变化率28.64%的有效率为51.3%,CYFRA21-1变化率≤28.64%的有效率为23.3%,得出P=0.026,说明CYFRA21-1变化率28.64%时,EGFR-TKI治疗的疗效更好。根据CYFRA21-1变化率与RECIST评价疗效的ROC曲线确立最佳截断点,依据截断点处的CYFRA21-1变化率,将69例患者分成CYFRA21-1变化率28.64%组和CYFRA21-1变化率≤28.64%组,比较两组的PFS,CYFRA21-1降低28.64%组的中位PFS为9.0月,CYFRA21-1降低≤28.64%组中位PFS为7.0月。(P=0.009)3、选取基线CEA和CYFRA21-1水平均升高的病例55例,根据上述分析得出的截断点,筛选其中CEA和CYFRA21-1变化率均大于截断点的病例29例,将CEA22.88%和CYFRA21-128.64%分别作为两种评价疗效方法来分析疗效的差异,用卡方检验结果P0.05,考虑CEA变化率与CYFRA21-1变化率对疗效判定的差异没有统计学意义。结论:CEA下降变化率和CYFRA21-1下降变化率可作为预测晚期肺腺癌患者使用EGFR-TKI靶向药物治疗的疗效及预后的指标。
[Abstract]:Objective: to use the EGFR-TKI treatment with EGFR mutations in patients with advanced NSCLC evaluation standard is controversial, because of the difference between chemotherapy and traditional EGFR-TKI mechanism, lack of scientific evaluation means RECIST simple, need new evaluation standards and methods, but limited to the diagnosis of certain functional expensive, whether the combined application of common economy the evaluation means can play a good evaluating effect. Through the research of CEA and the change rate of CYFRA21-1 and EGFR-TKI in the treatment of patients with advanced lung adenocarcinoma patients with EGFR mutation efficacy and survival prediction significance, analysis of difference between CEA and CYFRA21-1 in the rate of change in the outcome, in order to provide economic and effective method for EGFR-TKI target to evaluate the therapeutic effect and prognosis. Methods: 1, stage IV lung cancer treated with EGFR-TKI collected from January 2011 to January 2015 from the First Affiliated Hospital of Dalian Medical University 90 patients were pathologically confirmed lung cancer, with EGFR19 mutation in exon 55, exon 21 in 35 cases. 27 cases of male patients (30%), 63 cases of female patients (70%), at the age of 37-79 years old, the median age was 61.7 years. Patients with basic clinical information including induction. Age, sex, smoking history, other sites of metastasis, evaluation of curative effect of systemic treatment, and progression free survival. Results all patients had complete before and after 4 weeks of serum CEA and CYFRA21-1, and the imaging results of.2, the data were analyzed by spss20.0 statistical software using ROC. To establish the optimal cut-off point of curve, the relationship between rank sum test was used to analyze the change rate of CEA and CYFRA21-1 rate of change and effect of EGFR-TKI, using the Kaplan-Meier method analysis of progression free survival time and survival curves were analyzed by CEA and CYFRA21-1. The rate of change in the outcome in the chi square test the difference Different, all the tests in this paper were two-sided, with P < 0.05 the difference was statistically significant. Results: 1. Screening of baseline CEA levels were increased, CYFRA21-1 levels may be normal or elevated in 76 cases were analyzed, the ROC curve area of CEA and the change rate of RECIST is 0.643 to evaluate the efficacy of (95%CI 0.519-0.767), the best when the cut-off point of CEA decline rate is 22.88%, the optimal cut-off point when the sensitivity is 0.719, specificity is 0.535. (P=0.035) CEA analysis of the rate of change of the relation between the effect and in the cut-off point on the change rate of 22.88% CEA, the efficiency is 52.3%, the change rate of CEA is less than or equal to 22.88% efficiency is 28.1%, indicating that P=0.023. The CEA change rate of 22.88%, better curative effect for the treatment of EGFR-TKI. According to the ROC curve of CEA and the change rate of RECIST to evaluate the efficacy of establishing the optimal cut-off point, according to the CEA change of truncated points rate, 76 patients were divided into 22.88% groups and the change rate of CEA CEA variance ratio The 22.88% group, compared with two groups of PFS, CEA decreased in PFS 22.88% group was 9.5 months, CEA decreased less than 22.88% group the median PFS was 7 months. 2 (P=0.000), screening baseline level of CYFRA21-1 increased, CEA levels may be normal or elevated in 69 cases were analyzed, ROC curve area change rate of CYFRA21-1 to evaluate the efficacy of 0.677 and RECIST (95%CI 0.554-0.799), the optimal cut-off point of CYFRA21-1 decline rate is 28.64%, the optimal cut-off point when the sensitivity is 0.788, specificity is 0.595. (P=0.009) CYFRA21-1 analysis of the rate of change of the relation between the effect and in the cut-off point on CYFRA21-1, the change rate of 28.64% the rate was 51.3%, CYFRA21-1 the change rate of less than 28.64% of the rate was 23.3%, that P=0.026 CYFRA21-1, the change rate of 28.64%, better curative effect for the treatment of EGFR-TKI. According to the ROC curve of CYFRA21-1 and the change rate of RECIST to evaluate the efficacy of establishing the optimal cut-off point, on the basis of truncation point C The change rate of YFRA21-1, 69 cases were divided into 28.64% groups and the change rate of CYFRA21-1 CYFRA21-1 variance ratio of 28.64%, compared with two groups of PFS, CYFRA21-1 decreased in PFS 28.64% group was 9 months, CYFRA21-1 decreased less than 28.64% group the median PFS was 7 months. (P=0.009) 3, CEA and CYFRA21-1 levels were selected baseline the increase of 55 cases, according to the above analysis of the cut-off point, the change rate of CEA and CYFRA21-1 screening were greater than the cut-off point of 29 cases, CEA22.88% and CYFRA21-128.64% respectively as two evaluation methods to analyze the effect of differences, using the chi square test results of P0.05, CEA and CYFRA21-1 consider the change rate of the rate of change was not statistically significant differences in efficacy. Conclusion: the decrease of CEA rate and CYFRA21-1 rate decreased as the EGFR-TKI target prediction in patients with advanced lung adenocarcinoma curative effect and prognosis to drug treatment index.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
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本文编号：1441771