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背景与目的表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)在EGFR突变型肺腺癌人群中能显著提高生存,从而改变了晚期肺癌的治疗模式,但并不是所有EGFR敏感突变者均能从EGFR-TKIs治疗中获益。本研究欲通过外周血肿瘤标志物的检测对突变型肺腺癌患者的靶向治疗进行预测及指导。方法回顾性分析2009年6月-2014年6月于北京大学肿瘤医院胸部肿瘤内一科一线接受EGFR-TKIs治疗的EGFR突变型IIIb期-IV期肺腺癌患者的临床资料,分析其基线肿瘤标志物与EGFR-TKIs疗效及生存的关系。结果总体人群客观有效率(objective response rate,ORR)52.8%,疾病控制率(disease control rate,DCR)89.3%。基线癌胚抗原(carcino-embryonic antigen,CEA)水平升高者对EGFR-TKIs疗效更佳(ORR 61.3%vs35.9%,DCR 95.2%vs 74.4%,P<0.001),治疗1个月后CEA、细胞角蛋白19片段(cytokeratin 19 fragments,CYFRA21-1)以及CA125水平下降者有效率更高(ORR分别是61.5%vs 25%,P=0.002;58.5%vs 37.5%,P=0.004;61.8%vs 20%,P=0.027)。生存分析中,基线CEA水平正常者较高水平者无进展生存期(progression-free survival,PFS)明显缩短(中位PFS 5.9个月vs 9.8个月,P=0.027),而基线CYFRA21-1、CA125水平升高者PFS明显缩短(中位PFS 9.0个月vs11.4个月,P=0.029;9.0个月vs 11.5个月,P=0.023)。多因素分析显示,美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)评分0-1分、基线CYFRA21-1正常水平、治疗1月后CEA下降阳性患者PFS更长。总生存期(overall survival,OS)与CYFRA21-1、CA125升高有关(中位OS分别为25.1个月vs 52.5个月,P=0.003;22.7个月vs55.0个月,P<0.001),而多因素分析中总生存与CEA下降有关(P=0.046)。结论治疗前高水平CEA以及治疗后CEA下降可以预测晚期肺腺癌患者一线接受EGFR-TKIs的疗效,而治疗前高水平CYFRA21-1以及CA125则预示着生存期缩短。
BACKGROUND & OBJECTIVE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve the survival of patients with EGFR mutant lung adenocarcinoma, thereby changing the treatment model of advanced lung cancer, However, not all EGFR-sensitive mutants benefit from EGFR-TKIs treatment. This study aims to predict and guide the targeted therapy of patients with mutant lung adenocarcinoma by detecting the peripheral blood tumor markers. Methods The clinical data of patients with EGFR mutant stage IIIb-IV lung adenocarcinoma receiving EGFR-TKIs in the first-line department of Peking University Cancer Hospital from June 2009 to June 2014 were retrospectively analyzed. The changes of the baseline tumor The Relationship between EGFR-TKIs Efficacy and Survival. Results The overall objective response rate (ORR) of 52.8% and the disease control rate (DCR) 89.3%. Patients with elevated levels of carcinoembryonic antigen (CEA) had a better response to EGFR-TKIs (ORR 61.3% vs 35.9%, DCR 95.2% vs 74.4%, P <0.001), and CEA , Cytokeratin 19 fragments (CYFRA21-1), and decreased CA125 levels (OR = 61.5% vs 25%, P = 0.002; 58.5% vs 37.5%, P = 0.004; vs 20%, P = 0.027). Survival analysis showed a significantly shorter progression-free survival (PFS) at baseline (median PFS 5.9 months vs 9.8 months, P = 0.027), while baseline CYFRA21-1, PFS was significantly shorter in patients with elevated CA125 levels (median PFS 9.0 months vs 11.4 months, P = 0.029; 9.0 months vs 11.5 months, P = 0.023). Multivariate analysis showed that the Eastern Cooperative Oncology Group (ECOG) scored 0-1 points and had a normal baseline level of CYFRA21-1. PFS was longer in patients with positive CEA decline after 1 month of treatment. Overall survival (OS) was associated with an increase in CYFRA21-1 and CA125 (median OS was 25.1 months vs. 52.5 months, P = 0.003; 22.7 months vs. 55.0 months, P <0.001) Overall survival in multivariate analysis was associated with decreased CEA (P = 0.046). Conclusion The high level of CEA before treatment and the decrease of CEA after treatment may predict the first-line response to EGFR-TKIs in patients with advanced lung adenocarcinoma. However, the high level of CYFRA21-1 and CA125 before treatment may indicate the shortened survival.