Valor clínico de la combinación de pruebas moleculares e inmunitarias en sangre para reducir de forma segura los...

Low-dose Computed Tomography (LDCT) screening saves lives but is limited by high false-positive rates, necessitating non-invasive risk stratification. The prospective BioMILD trial was the first to validate the combination of a plasma microRNA test (MSC) with LDCT to personalize screening intervals. The present study integrates a novel Immune Signature Classifier (ISC), based on peripheral blood mononuclear cell (PBMC) profiling, to complement MSC, maximize information from a single blood draw, and further optimize the management of suspicious lung nodules.

Plasma and PBMC samples were prospectively collected from 304 heavy smokers enrolled in the BioMILD trial who presented with LDCT-detected suspicious nodules and a 7.5-year median follow-up. MSC and ISC tests were determined by RT-qPCR. Grafting of Patient-Derived Xenograft (PDX) models, derived from the same patients, was employed as indicator of tumor aggressiveness.

ISC was associated with age (p=0.0323) and Lung-RADS (p=0.0008), and was significantly higher in patients with cancers diagnosed within 2 years (p=0.0006). Higher ISC values also correlated with successful PDX engraftment (p=0.0449). In terms of diagnostic performance, the combined ISC and MSC model achieved 96% sensitivity and 98% Negative Predictive Value (NPV) (95%CI: 0.93-0.99). It represented a significant enhancement over MSC alone (ΔNPV=+0.05; 95%CI: 0.01-0.08) and resulted in a 37% reduction of false positives.

Integration of immune and molecular markers significantly enhances LDCT screening accuracy. The higher NPV achieved by the combined model allows greater confidence in ruling out malignancy among LDCT-detected nodules, thereby reducing unnecessary follow-up exams and invasive procedures.