Cytokeratin 19 Fragment Predicts the Efficacy of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor in Non-Small-Cell Lung Cancer Harboring EGFR Mutation
Cytokeratin 19 Fragment Predicts the Efficacy of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor in Non-Small-Cell Lung Cancer Harboring EGFR Mutation
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DOI：
10.1097/jto.0b013e31828c3929
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发表时间：
2013-07-01
影响因子：
20.4
通讯作者：
Katakami, Nobuyuki
中科院分区：
文献类型：
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作者：
Tanaka, Kosuke;Hata, Akito;Katakami, Nobuyuki
背景：EGFR基因突变与接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗的非小细胞肺癌(NSCLC)患者的良好反应独立相关，与性别和吸烟史无关。与腺癌患者相比，携带EGFR突变的鳞癌患者对EGFR-TKIs的反应明显更差。我们假设血清细胞角蛋白19片段(Cyfra 21-1)与EGFR-TKIs治疗EGFR突变的非小细胞肺癌患者的疗效相关。方法：我们回顾了1992至2011年间接受吉非替尼或厄洛替尼治疗的160例EGFR突变的非小细胞肺癌患者。结果：在接受EGFR-TKI治疗的160例患者中，77例CyfRA 21-1水平(2 ng/ml)高的患者的无进展生存期(PFS)明显短于CyfRA 21-1水平正常的83例患者(中位数PFS为7.5月比13.3个月；P<；0.001)。CEA升高组(5 ng/ml)和CEA正常组(中位数PFS，8.6月和11.2月；P=0.242)之间的PFS差异无统计学意义。多变量分析显示，高水平的CYFRA21-1与PFS独立相关(风险比，1.27；p=0.002)。Cyfra 21-1高表达组和正常表达组的总生存期差异无统计学意义(中位生存期分别为24.8月和39.1个月；p=0.104)。结论：高表达Cyfra 21-1的患者PFS明显缩短。在EGFR突变的非小细胞肺癌患者中，Cyfra 21-1不是预测预后的指标，而是EGFR-TKI治疗的预测标志。
Background: EGFR gene mutation is independently associated with a favorable response in non-small-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor -tyrosine kinase inhibitors (EGFR-TKIs), regardless of sex or smoking history. Squamous cell carcinoma patients harboring EGFR mutations show a significantly worse response to EGFR-TKIs compared with adenocarcinoma patients. We hypothesized that the serum cytokeratin 19 fragment (CYFRA 21-1) is associated with the efficacy of EGFR-TKIs in EGFR-mutated NSCLC patients.Methods:We retrospectively screened 160 NSCLC patients harboring EGFR mutations, who had received either gefitinib, or erlotinib between 1992 and 2011. Patients were screened for clinical characteristics, the efficacy of EGFR-TKI, and tumor markers (carcinoembryonic antigen [CEA]/CYFRA 21-1) at the initial diagnosis.Results:Of 160 eligible patients treated with EGFR-TKIs, 77 patients with high CYFRA 21-1 level (>2 ng/ml) showed significantly shorter progression-free survival (PFS) than the 83 patients with normal CYFRA 21-1 level (median PFS, 7.5 versus 13.3 months; p < 0.001). No significant difference in PFS was observed between the high-CEA group (>5 ng/ml) and the normal-CEA group (median PFS, 8.6 versus 11.2 months; p = 0.242). A multivariate analysis revealed that high CYFRA 21-1 level is independently associated with PFS (hazard ratio, 1.27; p = 0.002). No significant difference in overall survival was observed between the high- and the normal-CYFRA 21-1 groups (median overall survival, 24.8 versus 39.1 months; p = 0.104).Conclusions:Patients with a high CYFRA 21-1 level have significantly shorter PFS. CYFRA 21-1 is not a prognostic but a predictive marker of EGFR-TKI treatment in EGFR-mutated NSCLC patients.