title: Criteria to interpret cancer biomarker increments crossing the recommended cut-off compared in a simulation model focusing on false positive signals and tumour detection time.
abstract: BACKGROUND
  Several criteria have been proposed to interpret increments in serological cancer biomarker concentrations starting from low baseline concentrations crossing the cut-off. None of the criteria have been compared for their ability to signal tumour growth when ≤2% false positive results are accepted.
  
  
  METHODS
  The cancer biomarker Tissue Polypeptide Antigen was used as an example. Seven criteria to interpret increments in concentrations were investigated by computer simulations. Firstly, for each criterion, we identified a baseline concentration stratified for three levels of biological variation providing ≤2% false positive signals of tumour growth during one year of monitoring. Secondly, combining the steady state concentrations with rates of marker increase during tumour growth allowed calculation of the lengths of tumour detection times for each criterion.
  
  
  RESULTS
  The number of false positive marker signals depended on the baseline concentration, the magnitude of biological variation, and the magnitude of the required increment defined in the criterion. The lengths of the tumour detection times also depended on the rates of marker increase.
  
  
  CONCLUSIONS
  The results suggest that different types of criteria should be used within different intervals of below cut-off level concentrations if the rate of false positive signals of marker increments should be kept ≤2%.
authors: Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Denmark. Electronic address: Flemming.Lund@regionh.dk.
authors: Flemming
authors: F
authors: Lund
authors: Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Denmark; Norwegian Quality Improvement of Primary Care Laboratories (NOKLUS), Section for General Practice, University of Bergen, Bergen, Norway. Electronic address: Per.Petersen@isf.uib.no.
authors: Per Hyltoft
authors: PH
authors: Petersen
authors: Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Denmark. Electronic address: Merete.Frejstrup.Pedersen@regionh.dk.
authors: Merete Frejstrup
authors: MF
authors: Pedersen
authors: Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Denmark. Electronic address: Suher.Othman.Abu.Hassan@regionh.dk.
authors: Suher Othman
authors: SO
authors: Abu Hassan
authors: Department of Clinical Biochemistry, North Zealand Hospital, University of Copenhagen, Denmark. Electronic address: Georg.Soeletormos@regionh.dk.
authors: György
authors: G
authors: Sölétormos
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis*; D003198:Computer Simulation; D018450:Disease Progression; D005189:False Positive Reactions; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012016:Reference Values; D019396:Tissue Polypeptide Antigen / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D019396:Tissue Polypeptide Antigen
keywords: Baseline concentration; Biological variation; False positive results; Monitoring; True positive results; Tumour detection time