title: Serum Neuron-Specific Enolase Levels Predict the Efficacy of First-Line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Patients With Non-Small Cell Lung Cancer Harboring EGFR Mutations.
abstract: Our study aimed to determine the predictive and prognostic values of the serum neuron-specific enolase (NSE) level in patients who had non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and who had been treated with EGFR-tyrosine kinase inhibitors (TKIs).
  
  
  
  We retrospectively analyzed 151 patients who had NSCLC harboring EGFR mutations and had received either gefitinib or erlotinib as first-line treatment between 2005 and 2014. The serum NSE level was measured before initiation of EGFR-TKI treatment.
  
  
  
  Of the 151 patients, 92 (60.9%) had elevated NSE levels (> 16.3 ng/mL). Patients with elevated NSE levels showed significantly shorter progression-free survival (PFS) after EGFR-TKI treatment than those with normal NSE levels (median PFS, 10.5 months vs. 15.4 months; P = .034). Multivariate analysis demonstrated that elevated NSE levels (hazard ratio [HR], 1.656; P = .017), CNS metastasis at diagnosis (HR, 1.567; P = .037), and male gender (HR, 1.840; P = .005) were independent predictive factors for short PFS. A significant difference in overall survival (OS) was observed between patient groups with elevated and normal NSE levels (median OS, 17.0 months vs. 29.1 months; P < .001), and serum NSE level remained an independent prognostic factor for OS in multivariate analysis (HR, 2.671; P < .001).
  
  
  
  Patients with elevated serum NSE levels have significantly shorter PFS and OS. The NSE level is both a predictive marker of EGFR-TKI treatment and a prognostic marker in EGFR-mutant NSCLC patients.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Koung Jin
authors.initials: KJ
authors.lastname: Suh
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. Electronic address: bhumsuk@snu.ac.kr.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D054316:Biomarkers, Pharmacological; D047428:Protein Kinase Inhibitors; D010751:Phosphopyruvate Hydratase
keywords: NSE; Predictive value; Prognosis; Progression-free survival; Tumor heterogeneity