title: Cytokeratin 19 fragment predicts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor in non-small-cell lung cancer harboring EGFR mutation.
abstract: 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.
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Minatojima-Minamimachi, Chuo-Ku, Kobe, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Akito
authors.initials: A
authors.lastname: Hata
authors.forename: Reiko
authors.initials: R
authors.lastname: Kaji
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: Takehiro
authors.initials: T
authors.lastname: Otoshi
authors.forename: Daichi
authors.initials: D
authors.lastname: Fujimoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawamura
authors.forename: Koji
authors.initials: K
authors.lastname: Tamai
authors.forename: Jumpei
authors.initials: J
authors.lastname: Takeshita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kazuya
authors.initials: K
authors.lastname: Monden
authors.forename: Kazuma
authors.initials: K
authors.lastname: Nagata
authors.forename: Kyoko
authors.initials: K
authors.lastname: Otsuka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Tachikawa
authors.forename: Kojiro
authors.initials: K
authors.lastname: Otsuka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tomii
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism*; D008163:Luminescent Measurements; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C102012:antigen CYFRA21.1; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib