Development and Validation of a Blood Test Informed Risk Prediction Model for Lung Cancer—The Copenhagen Lung Cancer Risk Model (CPH-Lung)
Menée au Danemark sur 689 patients fumeurs atteints d'un cancer du poumon et 1 924 témoins puis validée sur 3 195 personnes fumeuses, cette étude évalue, par rapport au modèle prédictif PLCOm2012, la sensibilité et la spécificité d'un modèle basé sur des variables épigénétiques, cliniques et sanguines (méthylation du gène AHRR, nombre de paquets-années, sevrage tabagique de deux ans ou moins, niveau d'éducation, antécédents de cancer, concentration de l'hémoglobine et des plaquettes sanguines...) pour estimer le risque à 6 ans de développer la maladie
Purpose : Lung cancer screening reduces lung cancer mortality, but identifying high-risk individuals remains difficult. We wanted to develop a blood test–based risk model (CPH-Lung) to improve risk stratification before image-based screening.
Materials and Methods : We included individuals from two prospective general population cohorts to model 6-year lung cancer risk; the Copenhagen General Population Study (CGPS) for training and the Copenhagen City Heart Study (CCHS) for validation. We analyzed clinical and biochemical variables from ever-smokers (689 cases and 1,924 controls) nested within CGPS to train a 6-year lung cancer risk model. CPH-Lung was validated in a cohort of ever-smokers age
≥
50 years in the Copenhagen City Heart Study (CCHS, 3,195 individuals) and compared with the validated PLCOm2012 model.
Results : There were 689 and 68 events of 6-year lung cancer in the CGPS and the CCHS. In the CCHS validation study, the CPH-Lung versus the PLCOm2012 yielded AUCs of 0.783 (95% CI, 0.731 to 0.835) versus 0.720 (95% CI, 0.669 to 0.770) for detection of all 6-year lung cancers (P = .0059). The discrimination was similar in the CGPS. At specificity of 77.7% (as would have been achieved using currently applied screening criteria, eg, NELSON or NLST), sensitivities were 57.6% versus 39.2% in women (P < .0001) and 61.4% versus 54.7% in men (P = .004) for CPH-Lung versus PLCOm2012. The mean age at diagnosis was 68.2 years (standard deviation [SD], 7.50) in the 120 individuals with lung cancer predicted exclusively by CPH-Lung compared with 76.5 years (SD, 8.04) in the 37 individuals predicted exclusively by PLCOm2012 (P < .0001).
Conclusion : After inclusion of blood test information, the CPH-Lung model was more sensitive in the Danish population than PLCOm2012 for prediction of 6-year lung cancer risk particularly among women and younger individuals.
Journal of Clinical Oncology , article en libre accès, 2026