Biomarker-bakeoff voor vroege detectie van pancreascarcinoom: geblindeerde fase 2-validatiestudie

PURPOSE: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded Early Detection Research Network-defined phase 2 biomarker bakeoff study of blood-based biomarker panels. The aims were to evaluate panel performance, compare the panels' performance with that of cancer antigen 19-9 (CA19-9) alone, and to evaluate the performance of new combinations of the individual biomarkers. EXPERIMENTAL DESIGN: Ten biomarkers representing eight biomarker panels and CA19-9 were evaluated using plasma, serum and germline DNA from 140 stage I-IV PDAC cases and 140 controls from three tertiary care institutions, with controls frequency-matched to cases on age and sex. LASSO regression was employed to explore new biomarker combinations. The primary metric was area under the receiver operating characteristic curve (AUC). RESULTS: The study population was 51% female, median age 67.3 (minimum: 45.0, maximum: 90.0) years. Biomarker panel AUCs ranged from 89.9 to 96.3; the AUC for serum CA19-9 alone was 91.7 (95% confidence interval: 87.8, 95.6). Two panels had significantly higher AUCs than serum CA19-9 alone, the CA19-9/FUT2/3 panel (AUC=96.3, p=0.002), and the tissue factor pathway inhibitor/tenascin C (TFPI/TNC-FNIII-C) panel (AUC=95, p=0.01). Exploratory models to recombine biomarkers retained all but two biomarkers [optimism-corrected AUC=96.4 (94.0, 98.9)]. CONCLUSIONS: The CA19-9/FUT2/3 panel was the best performing panel in this biomarker bakeoff. Its evaluation in larger studies is warranted. Biomarker bakeoffs are an effective strategy for comparing the performance of promising biomarkers for pancreatic cancer early detection, and the PCDC is well poised to conduct such studies. Recommendations for performing such studies are provided.