血清肿瘤标志物与一线EGFR-TKIs治疗晚期EGFR突变型肺腺癌患者疗效相关性分析

发布时间：2018-03-07 20:36

本文选题：外周血肿瘤标志物　切入点：肺肿瘤　出处：《中国肺癌杂志》2017年09期 　论文类型：期刊论文

【摘要】：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%,P0.001),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,P0.001),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。
[Abstract]:Background & objective epidermal growth factor receptor tyrosine kinase inhibitor EGFR-TK Isa can significantly improve survival in patients with EGFR mutant lung adenocarcinoma, thus changing the treatment mode of advanced lung cancer. But not all EGFR sensitive mutants could benefit from EGFR-TKIs therapy. This study was intended to predict and guide the targeted therapy in patients with mutant lung adenocarcinoma by detection of peripheral blood tumor markers. Methods 2009. From June to June 2014, the clinical data of patients with EGFR mutant IIIb stage IV lung adenocarcinoma treated with EGFR-TKIs in a department of thoracic neoplasms at Peking University Cancer Hospital were analyzed. Results the objective effective rate of the overall population was 52.8%, and the disease control rate was 89.3.The patients with elevated baseline carcinoembryonic antigen antigen (CEA) had a better effect on EGFR-TKIs (61.3vs35.9DCR95.2d vs 95.74.4p 0.001). Months later, the effective rate of CEA, cytokeratin 19 fragments (CYFRA21-1) and decreased CA125 levels were 61.5 vs 25g, 58.5 vs 37.54,61.8 vs 2020 P0.027.Survival analysis, The progression-free survival time of patients with normal baseline CEA level was significantly shorter (median PFS 5.9 months vs 9.8-month P0. 027), while baseline CYFRA21-1 CA125 level increased significantly (median PFS 9.0 months vs11.4 0. 029 9 months vs 11.5 months P0. 023). Multivariate analysis showed that the baseline level of CYFRA21-1 + CA125 increased significantly (P 0. 029 9. 0 months vs 11. 5 months, P 0. 023). The Eastern Cooperative Oncology Group Ecog score was 0-1, and the baseline CYFRA21-1 level was normal. The total survival time of patients with positive CEA decreased after January was longer. The total survival time was associated with the increase of CYFRA21-1 + CA125 (median OS was 25.1 months vs 52.5 months P0.003 / 22.7 vs55.0 / month, respectively), while the total survival in multivariate analysis was related to the decrease of CEA. Conclusion the treatment is related to the total survival of P0. 0460.Conclusion in the multivariate analysis, the total survival is related to the decrease of CEA in patients with P0. 0460.Conclusion in the multivariate analysis, the total survival time is related to the decrease of CEA. The pre-high level of CEA and the decrease of CEA after treatment can predict the effect of first-line EGFR-TKIs in patients with advanced lung adenocarcinoma. High levels of CYFRA21-1 and CA125 predicted a shorter survival period before treatment.
【作者单位】：北京大学肿瘤医院暨北京市肿瘤防治研究所胸部肿瘤内一科恶性肿瘤发病机制及转化研究教育部重点实验室;西山煤电职工总医院肿瘤科;承德市承钢医院肿瘤科(二内科);
【基金】：国家自然科学基金青年科学基金(No.81401914) 北京市医院管理局青年人才培养“青苗”计划(No.QMS 20161112) 吴阶平医学基金会临床科研专项资助基金(No.320.6750.1361)资助~~
【分类号】：R734.2

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