晚期非小细胞肺癌的EGFR基因状态的临床研究
本文选题:晚期非小细胞肺癌 + EGFR基因突变 ; 参考:《广西中医药大学》2017年硕士论文
【摘要】:第一部分 EGFR基因突变与晚期非小细胞肺癌患者临床病理特征的相关性研究目的:EGFR基因突变与晚期非小细胞肺癌(NSCLC)患者临床病理特征的相关性。方法:选用2014年1月-2015年12月在广西壮族自治区人民医院收治的经病理学诊断为NSCLC且临床分期(IIIB/IV期)325例患者作为研究对象,收集病理学组织,采用ARMS法检测EGFR基因突变,分析EGFR基因突变与晚期NSCLC患者临床及病理特征的相关性。结果:325例晚期NSCLC中,EGFR基因总突变率37.5%(122/325)。其中18、19、20、21外显子分别占总突变的0.8%(1/122)、46.7%(57/122)、5.8%(8/122)、41.9%(52/122)。19、21外显子两者占总突变的88.6%。其男性206例,突变型56例,突变率27%(56/206),女性119例,突变型66例,突变率55.4%(66/119),女性的突变率明显高于男性(P=0.000);非腺癌61例,基因突变型9例,突变率14.8%(9/61),腺癌264例,基因突变型113例,突变率42.8%(113/264),腺癌突变率明显非腺癌(P=0.000);无吸烟214例,突变型97例,突变率45.3%(97/214),吸烟111例,突变型25例,突变率22.5%(25/111);中低分化110例,突变型22例,突变率20%(22/110),高分化215例,突变型110例,突变率46.5%(110/215),高分化突变率明显高于中低分化(P=0.000);两组差异均有统计学意义(P0.05)。结论:晚期NSCLC的EGFR基因突变主要发生在18、19、20、21外显子,其最常见19号外显子,其次21号外显子(L858R),19、21外显子两者占总突变的88.6%。EGFR基因突变最常见于女性、不吸烟、腺癌、分化程度较高的NSCLC患者。患者的性别、吸烟史、病理类型、肿瘤分化程度是预测EGFR基因突变的独立因素。第二部分 晚期非小细胞肺癌EGFR基因不同状态预后以及影响因素目的:分析我院晚期非小细胞肺癌不同治疗模式中位无疾病病进展(mPFS)及中位总生存期(mOS)、客观缓解率(ORR)、疾病控制率(DCR)、靶向药物及化疗药物不良反应;分析我院晚期非小细胞肺癌EGFR基因不同状态治疗模式总生存期(mOS)及无病进展生存期(mPFS)的独立预后因素。方法:本研究为回顾性队列研究,收集2014年1月到2015年12月广西壮族自治区人民医院行EGFR基因检测的经治122例为晚期NSCLC患者的住院病案资料和电话随访;用SPSS21.0软件分析中位PFS、中位OS、客观缓解率(objective response rate,ORR)、疾病进展率(disease control rate,DCR)及不良反应,行单因素、多因素生存分析。结果:1.122例行EGFR基因检测IIIB/IV期NSCLC患者中位OS 12.2个月和中位PFS 6.6个月。2.EGFR基因突变组和EGFR基因野生组中位PFS分为8.76个和5.1个月,EGFR基因突变组和EGFR基因野生组中位OS分别为14.2个月和10.9个月,EGFR突变型的客观缓解率47.4%,疾病控制率81.3%;EGFR野生型的客观缓解率31.5%,疾病控制率61.9%;EGFR-TKI药物的不良反应:皮疹和腹泻;化疗药物的不良反应:骨髓抑制和消化道反应。3.Kaplan-Meier单因素分析:ECOG评分、EGFR基因不同状态治疗方式存在生存时间的差异。4.COX回归多因素分析,影响晚期非小细胞肺癌独立预后因素有:ECOG评分、EGFR基因不同状态治疗方式。结论:1.122例行EGFR基因检测IIIB/IV期NSCLC患者中位OS 12.2个月和中位PFS 6.6个月。2.EGFR突变型比EGFR野生型预后好。3.影响晚期非小细胞肺癌独立预后因素:ECOG评分、EGFR基因不同状态治疗。
[Abstract]:Part 1 Correlation of the EGFR gene mutation with the clinicopathological features of patients with advanced non-small cell lung cancer. Objective: the correlation between the EGFR gene mutation and the clinicopathological features of patients with advanced non-small cell lung cancer (NSCLC). Methods: the pathological diagnosis of NSCL in the people's Hospital in the Guangxi Zhuang Autonomous Region, January 2014, in December, was NSCL C and clinical stage (IIIB/IV phase) 325 patients were used as the research object, collecting pathological tissue, using ARMS method to detect the mutation of EGFR gene, and analyzing the correlation between the EGFR gene mutation and the clinical and pathological features of the late NSCLC patients. Results: the total mutation rate of EGFR gene was 37.5% (122/325) in the 325 cases of late NSCLC. Among them, the 18,19,20,21 exons accounted for the total process, respectively. 0.8% (1/122), 46.7% (57/122), 5.8% (8/122), 41.9% (52/122).19,21 exons accounted for 206 cases of total mutation of 88.6%., mutation type 56 cases, mutation rate 27% (56/206), female 119 cases, mutation 66 cases, 55.4% (66/119) mutation rate, women's mutation rate was significantly higher than that of male (P=0.000); non adenocarcinoma 61 cases, gene mutation 9 cases, 14.8% mutation rate 14.8% (9) /61) adenocarcinoma 264 cases, mutation type 113 cases, mutation rate 42.8% (113/264), adenocarcinoma mutation rate is obviously non adenocarcinoma (P=0.000); no smoking 214 cases, mutation type 97 cases, mutation rate 45.3% (97/214), smoking 111 cases, mutation 25 cases, mutation rate 22.5% (25/111); middle and low differentiation 110 cases, mutation rate 20% (22/110), high differentiation 215 cases, mutant 215 cases, abrupt mutation type 110 cases, abrupt The mutation rate was 46.5% (110/215), and the high differentiation mutation rate was significantly higher than that of the middle and low differentiation (P=0.000). The difference between the two groups was statistically significant (P0.05). Conclusion: the EGFR gene mutation of late NSCLC mainly occurred in exon 19, the most common exon 19, and the second exon 21 exon (L858R), and the 88.6%.EGFR gene mutation of the exon 19,21 of 19,21. Most common in women, non smoking, adenocarcinoma, and highly differentiated NSCLC patients. The sex, smoking history, pathological type, and tumor differentiation are independent factors for predicting EGFR gene mutation. Second the prognosis of different state of EGFR gene in late non small cell lung cancer and the influence factors are to analyze the difference of non small cell lung cancer in our hospital. The progression of disease free disease (mPFS) and median total survival (mOS), objective remission rate (ORR), disease control rate (DCR), targeted drugs and adverse reactions to chemotherapeutic drugs, and the independent prognostic factors of the total survival period (mOS) and the progression free survival (mPFS) of the EGFR gene therapy mode in advanced non-small cell lung cancer in our hospital. In this study, a retrospective cohort study was conducted to collect data and telephone follow-up data of 122 patients with advanced NSCLC from January 2014 to December 2015 in the people's Hospital of the Guangxi Zhuang Autonomous Region, the Guangxi Zhuang Autonomous Region people's hospital. The SPSS21.0 software was used to analyze the median PFS, OS, the objective remission rate (objective response rate, ORR), and the rate of disease progression (diseas). E control rate, DCR) and adverse reactions, single factor and multifactor survival analysis. Results: 1.122 cases of EGFR gene detection in IIIB/IV phase NSCLC patients were divided into 8.76 and 5.1 months, 8.76 and 5.1 months in the middle PFS 6.6 month.2.EGFR gene mutation group and the EGFR gene wild group. For 14.2 months and 10.9 months, the objective remission rate of the EGFR mutant was 47.4%, the disease control rate was 81.3%, the objective remission rate of the EGFR wild type was 31.5%, the disease control rate was 61.9%; the adverse reaction of the EGFR-TKI drug: rash and diarrhea; the adverse reaction of the chemotherapeutic drugs: the single factor analysis of the myelosuppression and the dehydrated pathway.3.Kaplan-Meier: the ECOG score, the EGFR base The independent prognostic factors of advanced non-small cell lung cancer were.4.COX regression and multiple factor analysis because of the difference in the survival time of different states of treatment. The independent prognostic factors of advanced non-small cell lung cancer were: ECOG score and different state of EGFR gene therapy. Conclusion: 1.122 cases of EGFR gene detection in IIIB/IV stage NSCLC patients with OS 12.2 months and median PFS 6.6 months.2.EGFR process variant are compared to EGFR. The prognosis of the wild type is good..3. affects the independent prognostic factors of advanced non-small cell lung cancer: ECOG score and EGFR gene treatment.
【学位授予单位】:广西中医药大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R734.2
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