title: Cut-off-independent tumour marker evaluation using ROC approximation.
abstract: BACKGROUND
  The analysis of tumour markers is based on the evaluation of data in relation to defined cut-off values. Changes in the method of determination or reference study group have led to different results. Cut-off-independent diagnostic evaluation of laboratory parameters can avoid laboratory-based and method-derived systematic errors. The decision guarantee (DG) is an appropriate parameter that can be determined using a defined reference population and its respective receiver operating characteristic (ROC) curve. The influence of ROC differences on the determination of DG is examined.
  
  
  METHODS
  A group of 281 consecutive patients with newly diagnosed, histologically confirmed lung cancer and a control group of 231 patients were examined. Histological classification of the tumour cases defined in 59 small-cell carcinoma, 102 squamous cell carcinomas, 66 adenocarcinomas and 54 large-cell carcinomas or mixed bronchial carcinomas without classification. The control group without tumours consisted of 23 healthy subjects, 125 patients with silicosis or asbestosis, 27 with chronic obstructive pulmonary diseases (COPD) and 56 suffering from inflammatory lung diseases.
  
  
  RESULTS
  Cytokeratin-19 fragments (CYFRA 21-1) was the most sensitive marker with a sensitivity of 57.3% and a specificity of 94.9%. Sensitivity and specificity influence each other. Related to the ROC curve, the method described here ensured the diagnosis of lung cancer on the basis of the data collected in comparison with a reference population. Thus, it was possible to determine with statistical certainty whether the evaluation of the sample data would lead to a diagnosis of lung cancer.
  
  
  CONCLUSIONS
  The DG provides the basis for a laboratory-and method-independent support for a diagnosis including fairer information about the reference population in the data analysis.
authors.affiliation: Medizin und Service GmbH, Zwickauer Str. 227, D-09116 Chemnitz, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Bitterlich
authors.forename: Joachim
authors.initials: J
authors.lastname: Schneider
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood; D014408:Biomarkers, Tumor / Q000032:analysis*; D002272:Carcinoembryonic Antigen / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053539:Keratin-19; D007633:Keratins / Q000097:blood; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood; D012372:ROC Curve; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; C102012:antigen CYFRA21.1; D007633:Keratins; D010751:Phosphopyruvate Hydratase