Multimodal lung cancer screening using the ITALUNG biomarker panel and low dose computed tomography. Results of the ITALUNG biomarker study

Abstract

Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71 and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%.

MicroRNA Biomarker hsa-miR-195-5p for Detecting the Risk of Lung Cancer

“…In addition to these models comprised of classical phenotypes, some researchers discovered biomarkers to improve the prediction accuracy of the models [33]. The ITALUNG biomarker panel (IBP) combined with low-dose computed tomography achieved good performance for the identification of lung cancers at baseline screening, with a sensitivity of 90.0% and specificity of 89.0% [34]. A study suggested that a panel of four biomarkers composed of prolactin, CRP, NY-ESO-1, and HGF to screen for lung cancer.…”

Challenges and research opportunities for lung cancer screening in China

“…As discussed earlier, integrating molecular studies into LDCT screening programs provides a unique opportunity to resolve some of these problems. This modality has already been adopted in some recent large programs [ 22 – 24 ]. For example, a biomarker panel composed of plasma DNA and genomic analyses in the ITALUNG biomarker study was as sensitive as LDCT (90%) and increased screening specificity from 71% (LDCT alone) to 89% via a multimodal approach [ 22 ].…”

“…This modality has already been adopted in some recent large programs [ 22 – 24 ]. For example, a biomarker panel composed of plasma DNA and genomic analyses in the ITALUNG biomarker study was as sensitive as LDCT (90%) and increased screening specificity from 71% (LDCT alone) to 89% via a multimodal approach [ 22 ]. Another diagnostic test consisting of seven autoantibodies is currently under a randomized controlled trial among 12,000 Scotsmen, aiming to examine whether pre-screening with this test would be helpful to identify high-risk candidates, thereby increasing the overall effectiveness of LDCT screening [ 23 ].…”

Lungenkrebsfrüherkennung – eine Bestandsaufnahme

“…Es fand sich eine hohe Übereinstimmung eines positiven Biomarker-Befunds mit der Karzinomdiagnose. Der positive Vorhersagewert (PPV) stieg von 4,3 % für die LDCT-Diagnostik allein auf 10,6 % bei der Kombination von LDCT und Biomarker-Panel [23]. Dies sind erste Hinweise, dass zukünftig eine Kombination von blutbasierter Diagnostik mit einem LDCT-Screening eine gezieltere Selektion von Risikopersonen ermöglichen könnte.…”