title: Elevated inflammatory parameters and inflammation scores are associated with poor prognosis in patients undergoing pulmonary metastasectomy for colorectal cancer.
abstract: OBJECTIVE
  Pulmonary metastasectomy (PM) has evolved to become a standard treatment for colorectal cancer lung metastases. However, biomarkers to estimate the prognosis after PM are currently missing. We therefore investigated the prognostic impact of inflammatory-related biomarkers and scores in patients undergoing curative PM for colorectal cancer.
  
  
  METHODS
  We analysed prospectively collected datasets of 52 patients treated in our institution between April 2009 and June 2014. Fibrinogen (cut-off 325 mg/dl), C-reactive protein (CRP, cut-off 0.5 mg/dl), the modified Glasgow prognostic score (mGPS) and the neutrophil-to-lymphocyte ratio (NLR) at the time of PM were tested for their prognostic power, and correlated to time to recurrence (TTR), time to lung-specific recurrence (TTLR) and overall survival (OS).
  
  
  RESULTS
  Median OS after PM of all patients (n = 52, 21 females, 31 males, mean age ± standard deviation: 62.65 ± 11.41 years) was 36 months [95% confidence interval (CI) 24.7-47.3 months, number of events: n = 20/38.5%]. In univariable survival analyses, high fibrinogen [hazard ratio (HR) 5.51, 95% CI 1.21-25.17], elevated CRP (HR 2.81, 95% CI 1.08-7.28), mGPS >0 (HR 2.81, 95% CI 1.08-7.28) and an NLR of 4 or higher (HR 3.05, 95% CI 1.02-9.13) was associated with poor OS. Median TTR was 15 months for all patients (number of events: n = 35/67.3%). Fibrinogen (HR 3.79, 95% CI 1.32-10.94) and NLR (HR 2.99, 95% CI 1.20-7.46) but not CRP (P = 0.102) and mGPS (P = 0.102) were found to indicate TTR. With regard to TTLR (number of events: n = 26/50%), only NLR predicted early lung recurrence (HR 3.02, 95% CI 1.06-8.564). After multivariable analyses, fibrinogen was the only significant OS predictor. However, all investigated inflammatory biomarkers and scores were prognostic for TTR in multivariable analyses. Finally, we divided the study population into an inflammatory phenotype (one or more inflammatory marker/score-elevated) and a non-inflammatory phenotype group. The inflammatory phenotype was prognostic in uni- and multivariable analyses for all three outcome parameters (OS, TTR and TTLR).
  
  
  CONCLUSIONS
  Inflammatory markers provided promising prognostic information in this cohort of curative PM patients after colorectal cancer. Further validation is needed to verify the prognostic role of these markers and establish them in clinical routine.
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Bahil
authors.initials: B
authors.lastname: Ghanim
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schweiger
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Jedamzik
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Olaf
authors.initials: O
authors.lastname: Glueck
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Glogner
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: György
authors.initials: G
authors.lastname: Lang
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria konrad.hoetzenecker@meduniwien.ac.at.
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D059146:Metastasectomy / Q000379:methods*; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D002097:C-Reactive Protein
keywords: Biomarker; C-reactive protein; Fibrinogen; Modified Glasgow prognostic score; Neutrophil-to-lymphocyte ratio; Prognostic; Pulmonary metastasectomy