Abstract 2753: Mutational profiles from targeted NGS combine with miRNA-based liquid biopsy to predict survival in LDCT screening-detected lung cancers
Authors: Boeri Mattia , Verri Carla , Borzi Cristina , Holscher Todd , Dugo Matteo , Devecchi Andrea , Romeo Elisa , Sestini Stefano , Suatoni Paola , Pastorino Ugo , Sozzi Gabriella 
Published: July 2017

Abstract
In order to increase cost-effectiveness of low-dose computed tomography (LDCT) lung cancer screening programs, a change in the management of screening-detected lung tumors should be considered. The higher percentage and the better 5-year overall survival of early stage tumors in LDCT screening series than in clinical practice argue in favor of screening programs. On the other hand, the overall limited reduction of mortality observed in screening trials with an observational control arm suggests that some of the screening-detected early stage tumors might be over-diagnosed. In our Institution we are trying to address this issue by the development of complementary biomarkers able to improve detection of aggressive disease. Targeted next-generation sequencing was performed in 94 LDCT screening-detected lung tumors resected from subjects participating in 3 screening trials enrolling 9,248 volunteers. Mutation profile was associated with subjects’ clinicopathologic features and with the risk profile of a plasma microRNA signature classifier (MSC). Using data available through The Cancer Genome Atlas database (TCGA), we compared the mutations of a selected set of non-small cell lung cancer (NSCLC) cases detected in standard clinical practice to LDCT screening-detected NSCLC cases. The 5-year overall survival (OS) of screening patients with and without mutations in the tumors was 64% and 100%, respectively (p=0.019). By combining the mutational status with the MSC, patients were stratified into 3 groups with 5-year OS ranging from 41% to 96% (p&lt;0.0001) and the prognostic value was significant even when controlling for stage (p=0.017). The comparison with TCGA data revealed a higher number of non-mutated NSCLC among screening patients (21% vs. 13%), despite the similar spectrum and frequency of mutations. In addition, the difference in 5-year OS between subjects with and without mutations was exclusively detected in screening patients. The mutation profile of screening-detected tumors, while similar to that of clinically detected tumors, was a strong predictor of OS. The combination of tumor mutational status and a circulating miRNA-based risk classifier predicts tumor aggressiveness and clinical outcome and may find rapid application in LDCT screening programs.
Citation Format: Mattia Boeri, Carla Verri, Cristina Borzi, Todd Holscher, Matteo Dugo, Andrea Devecchi, Elisa Romeo, Stefano Sestini, Paola Suatoni, Ugo Pastorino, Gabriella Sozzi. Mutational profiles from targeted NGS combine with miRNA-based liquid biopsy to predict survival in LDCT screening-detected lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2753. doi:10.1158/1538-7445.AM2017-2753