title: Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma.
abstract: BACKGROUND
  To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients.
  
  
  METHODS
  A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees.
  
  
  RESULTS
  In total, 176 MPM patients (mean age: 63.5 years ± 10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (≥ 390 mg dl(-1)) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (≤ 627 mg dl(-1)) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months) when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl(-1)) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS).
  
  
  CONCLUSIONS
  Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.
authors.affiliation: 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Ghanim
authors.affiliation: 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: M A
authors.initials: MA
authors.lastname: Hoda
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Klikovits
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: M-P
authors.initials: MP
authors.lastname: Winter
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Alimohammadi
authors.affiliation: Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Grusch
authors.affiliation: 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] National Koranyi Institute of Pulmonology, Budapest 1121, Hungary [3] Department of Thoracic Surgery, National Institute of Oncology, Budapest, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Dome
authors.affiliation: Department of Pulmonology, LKH Hochegg, 2803 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Arns
authors.affiliation: Department of Pulmonology, LKH Hochegg, 2803 Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Schenk
authors.affiliation: University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center, Zagreb 10000, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Jakopovic
authors.affiliation: University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center, Zagreb 10000, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Samarzija
authors.affiliation: University of Zagreb, School of Medicine, Institute of Pathology, Zagreb 10000, Croatia.
authors.forename: L
authors.initials: L
authors.lastname: Brcic
authors.affiliation: Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Filipits
authors.affiliation: 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] Department of Biological Physics, Eötvös University, Budapest 1117, Hungary.
authors.forename: V
authors.initials: V
authors.lastname: Laszlo
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.affiliation: 1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna 1090, Vienna, Austria [2] Institute of Cancer Research, Department of Internal Medicine I, Medical University of Vienna 1090, Vienna, Austria [3] MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest 1091, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Hegedus
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D003131:Combined Modality Therapy; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000601:surgery*; D008297:Male; D008654:Mesothelioma / Q000097:blood* / Q000188:drug therapy / Q000601:surgery*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D005340:Fibrinogen