本文關(guān)鍵詞： 非小細(xì)胞肺癌 CEA CYFRA21-1 EGFR-TKI　出處：《大連醫(yī)科大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：目的:使用EGFR-TKI治療伴EGFR突變的晚期NSCLC患者的評(píng)價(jià)標(biāo)準(zhǔn)存在爭(zhēng)議,因EGFR-TKI作用機(jī)制與傳統(tǒng)的化療藥物之間的差異,單純的RECIST評(píng)價(jià)手段科學(xué)性不足,急需新的評(píng)價(jià)標(biāo)準(zhǔn)和方法,但是限于某些功能性診斷價(jià)格昂貴,常用的經(jīng)濟(jì)的評(píng)估手段間的聯(lián)合應(yīng)用是否能起到好的評(píng)估效果。本課題通過(guò)研究CEA和CYFRA21-1變化率與EGFR-TKI治療伴EGFR突變的晚期肺腺癌患者的療效及生存預(yù)測(cè)意義,分析CEA和CYFRA21-1變化率在療效判定中的差異,以期為EGFR-TKI靶向治療的療效評(píng)價(jià)及預(yù)后提供經(jīng)濟(jì)有效的手段。方法:1、收集自2011年1月至2015年1月大連醫(yī)科大學(xué)附屬第一醫(yī)院收治的接受EGFR-TKI治療的IV期肺癌患者90例,均經(jīng)病理證實(shí)為肺腺癌,伴有EGFR19外顯子突變55例,21外顯子突變35例。男性患者27例(30%),女性患者63例(70%),年齡在37-79歲,中位年齡61.7歲。歸納患者基本臨床信息,包括年齡,性別,吸煙史,其他轉(zhuǎn)移部位,全身治療情況,療效評(píng)價(jià),無(wú)進(jìn)展生存期等。所有患者均有完整的治療前及4周后的血清CEA和CYFRA21-1的檢測(cè)結(jié)果,和相關(guān)影像學(xué)檢查結(jié)果。2、采用spss20.0軟件對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析。采用ROC曲線確立最佳截?cái)帱c(diǎn),采用秩和檢驗(yàn)分析CEA變化率和CYFRA21-1變化率與EGFR-TKI療效的關(guān)系,采用Kaplan-Meier·法分析無(wú)進(jìn)展生存時(shí)間并繪制生存曲線,采用卡方檢驗(yàn)分析CEA和CYFRA21-1變化率在療效判定中的差異,本文所有檢驗(yàn)均為雙側(cè)檢驗(yàn),以P＜0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、篩選基線CEA水平均升高,CYFRA21-1水平可正�；蛏叩牟±�76例進(jìn)行分析,CEA變化率與RECIST評(píng)價(jià)療效的ROC曲線面積為0.643(95%CI為0.519-0.767),最佳截?cái)帱c(diǎn)時(shí)CEA下降變化率為22.88%,最佳截?cái)帱c(diǎn)時(shí)靈敏度是 0.719,特異度是 0.535。(P=0.035)分析CEA變化率在截?cái)帱c(diǎn)上下與近期療效關(guān)系,CEA變化率22.88%的有效率為52.3%,CEA變化率≤22.88%的有效率為28.1%,得出P=0.023,說(shuō)明CEA變化率22.88%時(shí),EGFR-TKI治療的療效更好。根據(jù)CEA變化率與RECIST評(píng)價(jià)療效的ROC曲線確立最佳截?cái)帱c(diǎn),依據(jù)截?cái)帱c(diǎn)處的CEA變化率,將76例患者分成CEA變化率22.88%組和CEA變化率≤22.88%組,比較兩組的PFS,CEA降低22.88%組的中位PFS為9.5月,CEA降低≤22.88%組中位PFS為7.0月。(P=0.000)2、篩選基線CYFRA21-1水平均升高,CEA水平可正�；蛏叩牟±�69例進(jìn)行分析,CYFRA21-1變化率與RECIST評(píng)價(jià)療效的ROC曲線面積為0.677(95%CI為0.554-0.799),最佳截?cái)帱c(diǎn)時(shí)CYFRA21-1下降變化率為28.64%,最佳截?cái)帱c(diǎn)時(shí)靈敏度是0.788,特異度是0.595。(P=0.009)分析CYFRA21-1變化率在截?cái)帱c(diǎn)上下與近期療效關(guān)系,CYFRA21-1變化率28.64%的有效率為51.3%,CYFRA21-1變化率≤28.64%的有效率為23.3%,得出P=0.026,說(shuō)明CYFRA21-1變化率28.64%時(shí),EGFR-TKI治療的療效更好。根據(jù)CYFRA21-1變化率與RECIST評(píng)價(jià)療效的ROC曲線確立最佳截?cái)帱c(diǎn),依據(jù)截?cái)帱c(diǎn)處的CYFRA21-1變化率,將69例患者分成CYFRA21-1變化率28.64%組和CYFRA21-1變化率≤28.64%組,比較兩組的PFS,CYFRA21-1降低28.64%組的中位PFS為9.0月,CYFRA21-1降低≤28.64%組中位PFS為7.0月。(P=0.009)3、選取基線CEA和CYFRA21-1水平均升高的病例55例,根據(jù)上述分析得出的截?cái)帱c(diǎn),篩選其中CEA和CYFRA21-1變化率均大于截?cái)帱c(diǎn)的病例29例,將CEA22.88%和CYFRA21-128.64%分別作為兩種評(píng)價(jià)療效方法來(lái)分析療效的差異,用卡方檢驗(yàn)結(jié)果P0.05,考慮CEA變化率與CYFRA21-1變化率對(duì)療效判定的差異沒(méi)有統(tǒng)計(jì)學(xué)意義。結(jié)論:CEA下降變化率和CYFRA21-1下降變化率可作為預(yù)測(cè)晚期肺腺癌患者使用EGFR-TKI靶向藥物治療的療效及預(yù)后的指標(biāo)。
[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.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R734.2
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本文編號(hào)：1441771