J Thorac Oncol. 2013 Jul;8(7):892-8. doi: 10.1097/JTO.0b013e31828c3929. [5 j, C. V# W- k
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Cytokeratin 19 fragment predicts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor in non-small-cell lung cancer harboring EGFR mutation.3 m' J4 c/ c% X: _
4 T: E& V: {& |Tanaka K, Hata A, Kaji R, Fujita S, Otoshi T, Fujimoto D, Kawamura T, Tamai K, Takeshita J, Matsumoto T, Monden K, Nagata K, Otsuka K, Nakagawa A, Tachikawa R, Otsuka K, Tomii K, Katakami N.$ f" n! `# O* i; X
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Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Minatojima-Minamimachi, Chuo-Ku, Kobe, Japan.
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Abstract
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BACKGROUND:
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, Y* x+ [3 `! L2 k2 Y3 B9 }6 ^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.' T7 ~+ X/ b/ {6 U9 }0 U# F
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METHODS: & T4 `0 ]6 @3 o" M1 i+ B
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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.
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RESULTS:
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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).
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2 y1 _: R8 I. Z& y& R/ T+ L160名合格的患者接受了EGFR-TKIs的治疗,对比82位具有正常水平的CYFRA21-1的患者来说,77名拥有较高水平的血清CYFRA21-1的患者表现出了显著缩短的无进展生存期(中位PFS,13.3个月 vs 7.5个月)。而对于高CEA水平组(大于5ng/ml)和正常CEA水平组来说,PFS没有表现出显著性差异(中位PFS,8.6个月 vs 11.2个月)。多变量分析揭露出高水平的CYFRA21-1是关联PFS的独立因素。在高水平CYFRA21-1组和正常CYFRA21-1组的OS对比中,没有观察到显著性差异(中位OS,24.8个月 vs 39.1个月;p=0.104)。( H: }! d/ s1 {5 Y. ]3 @) B" ^
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CONCLUSIONS: $ D5 ?" t: s# U
3 b: d3 n/ H1 {+ A D5 J$ rPatients 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.+ ?2 r/ q1 o1 y
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