title: Presence of pleural effusion is associated with a poor prognosis in patients with epidermal growth factor receptor-mutated lung cancer receiving tyrosine kinase inhibitors as first-line treatment.
abstract: OBJECTIVE
  This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs).
  
  
  METHODS
  Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively.
  
  
  RESULTS
  A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively].
  
  
  CONCLUSIONS
  The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients.
authors.affiliation: Departments of Hematology and Oncology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Tso-Fu
authors.initials: TF
authors.lastname: Wang
authors.affiliation: Departments of Hematology and Oncology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Sung-Chao
authors.initials: SC
authors.lastname: Chu
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Jen-Jyh
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Gee-Gwo
authors.initials: GG
authors.lastname: Yang
authors.affiliation: Departments of Hematology and Oncology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|Division of Clinical Pathology, Department of Laboratory Medicine, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.
authors.forename: Wei-Han
authors.initials: WH
authors.lastname: Huang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: En-Ting
authors.initials: ET
authors.lastname: Chang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.
authors.forename: Tissot
authors.initials: T
authors.lastname: Low
authors.affiliation: Departments of Hematology and Oncology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Departments of Hematology and Oncology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Ruey-Ho
authors.initials: RH
authors.lastname: Kao
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.|College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Chih-Bin
authors.initials: CB
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000209:etiology* / Q000473:pathology; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: pleural effusion; prognosis; tyrosine kinase inhibitor