title: Small-cell lung cancer detection in never-smokers: clinical characteristics and multigene mutation profiling using targeted next-generation sequencing.
abstract: BACKGROUND
  Once regarded as a smoker's disease, small-cell lung cancer (SCLC) has been occasionally detected in never-smokers as smoking rates decrease worldwide. We investigated the clinical and genetic characteristics of SCLC in never-smokers.
  
  
  METHODS
  Patients diagnosed with SCLC were grouped into smokers and never-smokers. The clinical outcomes of the two groups were compared. For SCLC in never-smokers, somatic mutation profiling was carried out using the AmpliSeq™ Cancer Hotspot Panel v2 and semiconductor sequencing technology. Epidermal growth factor receptor (EGFR) mutation was confirmed by PNAClamp™.
  
  
  RESULTS
  In total, 391 SCLC patients treated over a 5-year period were analyzed. Fifty patients (13%) were never-smokers. The median overall survival was 18.2 months in never-smokers and 13.1 months in smokers (P = 0.054). Never-smoking history was independently a good prognostic factor [hazard ratio = 0.645, 95% confidence interval (CI) 0.456-0.914], as were limited disease (HR = 0.372, 95% CI 0.294-0.471), and lower age (HR = 0.709, 95% CI 0.566-0.888). The objective response rates to first-line etoposide/cisplatin therapy were similar between never-smokers and smokers (75% versus 81%). Of 28 genetically evaluable never-smokers, EGFR mutations were detected in four cases (two L858R, one deletion in exon 19, and one G719A). Other mutations were in TP53 (n = 26), RB1 (n = 7), PTEN (n = 5), MET (n = 4), and SMAD4 (n = 3).
  
  
  CONCLUSIONS
  Never-smokers with SCLC are increasingly prevalent and have a better prognosis than smokers with SCLC in Korea. Our study warrants further investigation in this group.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine.
authors.forename: J-M
authors.initials: JM
authors.lastname: Sun
authors.affiliation: Division of Hematology-Oncology, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Ji
authors.affiliation: Division of Hematology-Oncology, Department of Medicine.
authors.forename: J S
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Division of Hematology-Oncology, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: K-M
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.affiliation: Division of Hematology-Oncology, Department of Medicine.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Ahn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine. Electronic address: kpark@skku.edu.
authors.forename: K
authors.initials: K
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002945:Cisplatin / Q000627:therapeutic use; D066246:ErbB Receptors / Q000235:genetics*; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D017422:Sequence Analysis, DNA; D051901:Smad4 Protein / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D016160:Retinoblastoma Protein; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D002945:Cisplatin
keywords: epidermal growth factor receptor mutation; never-smoker; next-generation sequencing; small-cell lung cancer; survival