本文選題：EGFR野生型 + 非小細(xì)胞肺癌��； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:探討影響EGFR野生型進(jìn)展期NSCLC患者預(yù)后的相關(guān)因素及TKI治療在其中的相關(guān)問題。方法:收集2015年1月至2016年12月在河北醫(yī)科大學(xué)第四醫(yī)院診治的EGFR野生型進(jìn)展期非小細(xì)胞肺癌患者的臨床資料,共90例患者符合入組標(biāo)準(zhǔn)。分析影響生存的預(yù)后因素;按照既往一線含鉑雙藥化療失敗后患者二線治療選擇的方法分為化療組和TKI組,并根據(jù)TKI用于EGFR野生型患者的時(shí)間分一線TKI組和二線TKI組,觀察兩組的PFS、OS、DCR、ORR、不良反應(yīng)有無統(tǒng)計(jì)學(xué)意義。結(jié)果:1 90例患者入組預(yù)后分析,結(jié)果針對(duì)患者預(yù)后因素,包括:年齡、性別、PS評(píng)分、吸煙指數(shù)、病理類型、分期、是否合并慢性病、凝血功能情況、遠(yuǎn)處轉(zhuǎn)移情況、有無原發(fā)灶手術(shù)、有無聯(lián)合局部治療、有無聯(lián)合血管靶向藥、及血清CEA、SCC、NSE、CY-211水平進(jìn)行單因素分析,發(fā)現(xiàn)患者的PS評(píng)分、分期、有無手術(shù)、凝血功能、有無遠(yuǎn)處轉(zhuǎn)移,及血清NSE及CY-211水平與預(yù)后相關(guān)(P0.05),進(jìn)一步多因素COX回歸分析,結(jié)果顯示,PS評(píng)分低、存在較多的遠(yuǎn)處轉(zhuǎn)移,以及血清CY-211高于正常上限為EGFR野生型進(jìn)展期NSCLC患者的OS獨(dú)立不良預(yù)后因素,分別使其死亡風(fēng)險(xiǎn)增加2.589倍、1.986倍、3.546(1/0.282)倍(P=0.041,P=0.006,P=0.007)。2二線治療中化療與TKI的對(duì)比既往一線含鉑雙藥化療失敗后的患者,根據(jù)其二線治療方案的選擇分為化療組和TKI組,化療組20例患者,TKI組10例患者,其中TKI治療者多為高齡、體力狀況差的。兩組OS、ORR無明顯差異(P0.05);化療組中位PFS相比TKI組有近2.6個(gè)月的延長(zhǎng),P值有統(tǒng)計(jì)學(xué)意義(P=0.004);化療組DCR亦優(yōu)于TKI組(P=0.019)。兩組不良反應(yīng)無統(tǒng)計(jì)學(xué)意義(P0.05)。3 TKI在一線與二線治療中的對(duì)比一線TKI治療組入組14例患者,二線TKI組入組10例患者,一線TKI治療組的中位OS為6個(gè)月,中位PFS為2個(gè)月;二線治療組的中位OS為31個(gè)月,中位PFS3個(gè)月;P值分別為0.008、0.009;在兩組DCR、ORR及不良反應(yīng)方面均無統(tǒng)計(jì)學(xué)差異(P0.05)。兩組病人選擇TKI治療的主要原因即患者高齡、PS評(píng)分較差,或因主觀因素。4 EGFR基因檢測(cè)方法的選擇在90例患者中,有34例(37.8%)患者行血液ctDNA的基因檢測(cè);45例(50.0%)行組織檢測(cè);2例(2.2%)胸水ctDNA檢測(cè);8例(8.9%)組織和血液的雙標(biāo)檢測(cè);1例(1.1%)胸水和血液的雙標(biāo)檢測(cè)。90.0%僅進(jìn)行過1次基因檢測(cè);8.9%患者進(jìn)行過2次檢測(cè),1.1%患者進(jìn)行過3次檢測(cè)。90例患者中,8例(8.9%)行多基因檢測(cè),余82例(91.1%)行EGFR基因常見突變形式的檢測(cè)。5 EGFR基因合并其他基因變異的情況90例患者中有40例(44.4%)患者行ALK基因檢測(cè),2例(2.2%)患者合并ALK融合突變;2例行肺癌10基因檢測(cè)的患者中,EGFR基因及其他基因均為野生型。6例行全基因檢測(cè)的患者,在EGFR基因野生型的基礎(chǔ)上,1例合并EML4-ALK基因融合,1例合并EGFR A767_V769dup和PI3KCA基因H1047R突變,1例合并有HER-2基因突變,1例合并有RET、HDAC4、FLT4、NOTGH1、BTK突變,1例未合并其他基因變異�？傮wEGFR基因野生型的患者進(jìn)一步行基因檢測(cè)者占44.4%,其中10%有針對(duì)性靶向治療機(jī)會(huì)。結(jié)論:1對(duì)于EGFR野生型進(jìn)展期NSCLC患者,PS評(píng)分低、存在較多的遠(yuǎn)處轉(zhuǎn)移,以及血清CY-211高于正常上限為獨(dú)立不良預(yù)后因素。2 EGFR野生型NSCLC患者,化療組與TKI組對(duì)比,有PFS、DCR的優(yōu)勢(shì),未顯示出生存獲益。3對(duì)于年齡大、PS評(píng)分差的患者易更早的選擇TKI治療。
[Abstract]:Objective: To explore the related factors affecting the prognosis of EGFR wild type NSCLC patients and the related problems in TKI treatment. Methods: to collect the clinical data of the patients with advanced non small cell lung cancer in the fourth hospital of Hebei Medical University from January 2015 to December 2016, and 90 patients were in conformity with the standard of entry group. The prognosis factors of survival were divided into chemotherapy group and group TKI according to the second line of platinum double drug chemotherapy failure. According to the time of TKI used in EGFR wild type patients, the group of TKI and second line TKI were divided into two groups of PFS, OS, DCR, ORR, and no statistical significance. Results: the prognosis of the 190 patients was in the group prognosis. The results were based on a single factor analysis of patients' prognostic factors, including age, sex, PS score, smoking index, pathological type, staging, chronic disease, coagulation function, distant metastasis, or without primary surgery, combined local treatment, or not combined blood vessel targeting drugs, and serum CEA, SCC, NSE, and CY-211 levels. The PS score, staging, operation, coagulation function, distant metastasis, and serum NSE and CY-211 levels were associated with the prognosis (P0.05). Further multivariate COX regression analysis showed that the PS score was low, more distant metastasis was present, and the serum CY-211 was higher than the normal limit for OS independent preconditioning for NSCLC patients with EGFR wild-type progression. After factors, the risk of death was increased by 2.589 times, 1.986 times, 3.546 (1/0.282) times (P=0.041, P=0.006, P=0.007) in the second line of.2 second line treatment. The patients were divided into chemotherapy group and TKI group, 20 patients in chemotherapy group and 10 patients in TKI group, among which, TKI was treated by TKI. There was no significant difference between the two groups of OS and ORR (P0.05). The median PFS in the chemotherapy group was longer than that in the TKI group, and the P value was statistically significant (P=0.004), and the DCR in the chemotherapy group was also superior to the TKI group (P=0.019). The two groups had no statistical significance (P0.05). In the group of 14 patients and 10 patients in the second line TKI group, the median OS of the first line TKI treatment group was 6 months and the median PFS was 2 months; the middle OS of the second line treatment group was 31 months, the median PFS3 month and the P value were 0.008,0.009, and the two groups of DCR, ORR and adverse reactions were no difference (P0.05). The two group selected the main cause of TKI treatment. That is, the elderly, poor PS score, or the choice of the subjective factor.4 EGFR gene detection method in 90 patients, 34 cases (37.8%) of the blood ctDNA gene detection, 45 cases (50%), 2 (2.2%) chest water ctDNA detection; 8 (8.9%) tissue and blood double standard detection; 1 cases (1.1%) chest water and blood double standard detection.90.0% only 1 tests were carried out in 1 times; 8.9% patients were tested for 2 times, 1.1% were detected in 3 times, 8 (8.9%) were detected by multiple genes, and 82 cases (91.1%) had common mutations in the EGFR gene. The.5 EGFR gene was combined with other genetic variations, and 90 patients with 90 patients were detected by ALK gene, 2 (2.2%). The ALK fusion mutation was combined. In 2 patients with lung cancer 10 gene detection, the EGFR gene and other genes were all wild type.6 routine full gene detection patients. On the basis of the EGFR gene wild-type, 1 cases combined with EML4-ALK gene fusion, 1 cases with EGFR A767_V769dup and PI3KCA based H1047R mutation, 1 cases with HER-2 gene mutation, 1 case combined with gene mutation. There were RET, HDAC4, FLT4, NOTGH1, BTK mutations in 1 cases without other genetic variations. The overall EGFR gene wild-type patients had a further gene detection rate of 44.4%, of which 10% had targeted targeted therapy opportunities. Conclusion: 1 for NSCLC patients in the EGFR wild type NSCLC patients, the PS score is low, there are more distant metastasis, and the serum CY-211 is higher than normal. The upper limit was.2 EGFR wild type NSCLC patients with independent prognostic factors. Compared with the TKI group, the chemotherapy group had the advantage of PFS, DCR, and did not show the survival benefit.3 for the older, and the patients with poor PS score were easy to choose the TKI treatment earlier.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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