探讨EGFR野生型进展期NSCLC患者预后因素及TKI治疗意义

发布时间：2018-04-24 04:31

本文选题：EGFR野生型 + 非小细胞肺癌　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:探讨影响EGFR野生型进展期NSCLC患者预后的相关因素及TKI治疗在其中的相关问题。方法:收集2015年1月至2016年12月在河北医科大学第四医院诊治的EGFR野生型进展期非小细胞肺癌患者的临床资料,共90例患者符合入组标准。分析影响生存的预后因素;按照既往一线含铂双药化疗失败后患者二线治疗选择的方法分为化疗组和TKI组,并根据TKI用于EGFR野生型患者的时间分一线TKI组和二线TKI组,观察两组的PFS、OS、DCR、ORR、不良反应有无统计学意义。结果:1 90例患者入组预后分析,结果针对患者预后因素,包括:年龄、性别、PS评分、吸烟指数、病理类型、分期、是否合并慢性病、凝血功能情况、远处转移情况、有无原发灶手术、有无联合局部治疗、有无联合血管靶向药、及血清CEA、SCC、NSE、CY-211水平进行单因素分析,发现患者的PS评分、分期、有无手术、凝血功能、有无远处转移,及血清NSE及CY-211水平与预后相关(P0.05),进一步多因素COX回归分析,结果显示,PS评分低、存在较多的远处转移,以及血清CY-211高于正常上限为EGFR野生型进展期NSCLC患者的OS独立不良预后因素,分别使其死亡风险增加2.589倍、1.986倍、3.546(1/0.282)倍(P=0.041,P=0.006,P=0.007)。2二线治疗中化疗与TKI的对比既往一线含铂双药化疗失败后的患者,根据其二线治疗方案的选择分为化疗组和TKI组,化疗组20例患者,TKI组10例患者,其中TKI治疗者多为高龄、体力状况差的。两组OS、ORR无明显差异(P0.05);化疗组中位PFS相比TKI组有近2.6个月的延长,P值有统计学意义(P=0.004);化疗组DCR亦优于TKI组(P=0.019)。两组不良反应无统计学意义(P0.05)。3 TKI在一线与二线治疗中的对比一线TKI治疗组入组14例患者,二线TKI组入组10例患者,一线TKI治疗组的中位OS为6个月,中位PFS为2个月;二线治疗组的中位OS为31个月,中位PFS3个月;P值分别为0.008、0.009;在两组DCR、ORR及不良反应方面均无统计学差异(P0.05)。两组病人选择TKI治疗的主要原因即患者高龄、PS评分较差,或因主观因素。4 EGFR基因检测方法的选择在90例患者中,有34例(37.8%)患者行血液ctDNA的基因检测;45例(50.0%)行组织检测;2例(2.2%)胸水ctDNA检测;8例(8.9%)组织和血液的双标检测;1例(1.1%)胸水和血液的双标检测。90.0%仅进行过1次基因检测;8.9%患者进行过2次检测,1.1%患者进行过3次检测。90例患者中,8例(8.9%)行多基因检测,余82例(91.1%)行EGFR基因常见突变形式的检测。5 EGFR基因合并其他基因变异的情况90例患者中有40例(44.4%)患者行ALK基因检测,2例(2.2%)患者合并ALK融合突变;2例行肺癌10基因检测的患者中,EGFR基因及其他基因均为野生型。6例行全基因检测的患者,在EGFR基因野生型的基础上,1例合并EML4-ALK基因融合,1例合并EGFR A767_V769dup和PI3KCA基因H1047R突变,1例合并有HER-2基因突变,1例合并有RET、HDAC4、FLT4、NOTGH1、BTK突变,1例未合并其他基因变异。总体EGFR基因野生型的患者进一步行基因检测者占44.4%,其中10%有针对性靶向治疗机会。结论:1对于EGFR野生型进展期NSCLC患者,PS评分低、存在较多的远处转移,以及血清CY-211高于正常上限为独立不良预后因素。2 EGFR野生型NSCLC患者,化疗组与TKI组对比,有PFS、DCR的优势,未显示出生存获益。3对于年龄大、PS评分差的患者易更早的选择TKI治疗。
[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.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

【参考文献】