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@ARTICLE{CortsIbez:287029,
      author       = {F. O. Cortés-Ibáñez$^*$ and T. Johnson$^*$ and M.
                      Mascalchi$^*$ and V. Katzke$^*$ and S. Delorme$^*$ and R.
                      Kaaks$^*$},
      title        = {{S}erum-based biomarkers associated with lung cancer risk
                      and cause-specific mortality in the {G}erman randomized
                      {L}ung {C}ancer {S}creening {I}ntervention ({LUSI}) trial.},
      journal      = {Translational Lung Cancer Research},
      volume       = {12},
      number       = {12},
      issn         = {2218-6751},
      address      = {[Erscheinungsort nicht ermittelbar]},
      publisher    = {[Verlag nicht ermittelbar]},
      reportid     = {DKFZ-2024-00136},
      pages        = {2460 - 2475},
      year         = {2023},
      note         = {#EA:C020#LA:C020#},
      abstract     = {Lung cancer (LC) screening can be optimized using
                      individuals' estimated risks of having a detectable lung
                      tumor, as well as of mortality risk by competing causes, to
                      guide decisions on screening eligibility, ideal screening
                      intervals and stopping ages. Besides age, sex and smoking
                      history, blood-based biomarkers may be used to improve the
                      assessment of LC risk and risk of mortality by competing
                      causes.In the German randomized Lung Screening Intervention
                      Trial (LUSI), we measured growth/differentiation factor-15
                      (GDF-15), interleukin-6 (IL-6), C-reactive protein (CRP) and
                      N-terminal pro-brain natriuretic protein (NT-proBNP), in
                      blood serum samples collected at start of the trial.
                      Participants in the computed tomography (CT)-screening arm
                      also had a pulmonary function test. Regression models were
                      used to examine these markers as predictors for impaired
                      lung function, LC risk and mortality due to LC or other
                      causes, independently of age, sex and smoking history.Our
                      models showed increases in LC risk among participants with
                      elevated serum levels of GDF-15 [odds ratio (OR)Q4-Q1 =2.47,
                      $95\%$ confidence interval (CI): 1.49-4.26], IL-6 [ORQ4-Q1
                      =2.36 (1.43-4.00)] and CRP [ORQ4-Q1 =1.81 (1.08-2.75)].
                      Likewise, proportional hazards models showed increased risks
                      for LC-related mortality, hazard ratio (HR)Q4-Q1 of 4.63
                      $(95\%$ CI: 2.13-10.07) for GDF-15, 3.56 (1.72-7.37) for
                      IL-6 and 2.34 (1.24-4.39) for CRP. All four markers were
                      associated with increased risk of mortality by causes other
                      than LC, with strongest associations for GDF-15 [HRQ4-Q1
                      =3.04 (2.09-4.43)] and IL-6 [HRQ4-Q1 =2.98 (2.08-4.28)].
                      Significant associations were also observed between IL-6,
                      CRP, GDF-15 and impaired pulmonary function [chronic
                      obstructive pulmonary disease (COPD), preserved ratio
                      impaired spirometry (PRISm)]. Multi-marker models identified
                      GDF-15 and IL-6 as joint risk predictors for risk of LC
                      diagnosis, without further discrimination by CRP or
                      NT-proBNP. A model based on age, sex, smoking-related
                      variables, GFD-15 and IL-6 provided moderately strong
                      discrimination for prediction of LC diagnoses within 9 years
                      after blood sampling [area under the curve (AUC) $=74.3\%$
                      $(57.3-90.2\%)],$ compared to $67.0\%$ $(49.3-84.8\%)$ for a
                      model without biomarkers. For mortality by competing causes,
                      a model including biomarkers resulted in an AUC of $76.2\%$
                      $(66.6-85.3\%)],$ compared to $70.0\%$ $(60.9-77.9\%)$ a
                      model including age, sex and smoking variables.Serum GDF-15
                      and IL-6 may be useful indicators for estimating risks for
                      LC and competing mortality among long-term smokers
                      participating in LC screening, to optimize LC screening
                      strategies.},
      keywords     = {Serum biomarkers (Other) / lung cancer screening (LC
                      screening) (Other) / lung function impairment (spirometry)
                      (Other) / mortality (Other) / risk modeling (Other)},
      cin          = {C020 / C050},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331 / I:(DE-He78)C050-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38205209},
      pmc          = {pmc:PMC10775005},
      doi          = {10.21037/tlcr-23-548},
      url          = {https://inrepo02.dkfz.de/record/287029},
}