Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
Clinical Value of Combining Molecular and Immune Blood Tests to Safely Reduce False Positives in Low-Dose Computed Tomography Lung Cancer Screening.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zanghì Anna, Moro Massimo, Fortunato Orazio, Segale Miriam, Sabia Federica, Suatoni Paola, Ledda Roberta E, Rolli Luigi, Marchianò Alfonso, Pastorino Ugo, Sozzi Gabriella, Boeri Mattia
Аннотация
INTRODUCTION: Low-dose computed tomography (LDCT) screening saves lives but is limited by high false-positive rates, necessitating noninvasive risk stratification. The prospective Bio-Multicentric Italian Lung Detection (BioMILD) trial was the first to validate the combination of a plasma microRNA test (MSC) with LDCT to personalize screening intervals. This study integrates a novel immune signature classifier (ISC), based on peripheral blood mononuclear cell profiling, to complement MSC, maximize information from a single blood draw, and further optimize the management of suspicious lung nodules.
METHODS: Plasma and peripheral blood mononuclear cell 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 real-time quantitative polymerase chain reaction. Grafting of patient-derived xenograft models, obtained from the same patients, was used as indicator of tumor aggressiveness.
RESULTS: 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 patient-derived xenograft 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% confidence interval: 0.93-0.99). It represented a significant enhancement than MSC alone (ΔNPV = +0.05; 95% confidence interval: 0.01-0.08) and resulted in a 37% reduction of false positives.
CONCLUSION: 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 examinations and invasive procedures.
METHODS: Plasma and peripheral blood mononuclear cell 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 real-time quantitative polymerase chain reaction. Grafting of patient-derived xenograft models, obtained from the same patients, was used as indicator of tumor aggressiveness.
RESULTS: 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 patient-derived xenograft 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% confidence interval: 0.93-0.99). It represented a significant enhancement than MSC alone (ΔNPV = +0.05; 95% confidence interval: 0.01-0.08) and resulted in a 37% reduction of false positives.
CONCLUSION: 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 examinations and invasive procedures.