Background: We previously reported that a miRNA signature classifier (MSC) based on 24 plasma circulating microRNAs is a sensitive and early biomarker for lung cancer, able to increase the specificity of low dose computed tomography (LDCT) in screening trials (Boeri et al. PNAS 2011; Sozzi et al. JCO 2014). In the present study, we have investigated the capacity of plasma MSC to predict prognosis and monitor the disease status at follow-up in LDCT screening detected lung cancer patients.

Methods: Between 2000 and 2010, 3411 heavy smokers were enrolled in a screening program, with annual (2225) or biennial (1186) LDCT. During the first five years of screening, a total of 77 lung cancer patients underwent plasma MSC analysis, with three levels of risk: High, Intermediate or Low. Median follow-up of the alive patients was 4.5 years (Inter Quartile Range, IQR = 6.5). Changes of MSC risk profile at follow-up was assessed in 33 patients, with longitudinal plasma samples (n = 96) collected before and after surgical resection.

Results: Five-year survival was 78% for low- to intermediate risk MSC (median nc), and 35% for High risk MSC (median 2.9 yrs, p<0.01). The prognostic power of MSC persisted when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (5-years survival: 87% vs. 38% respectively, p<0.01). Within stage I, the 5-years survival was 100% in Low to Intermediate risk MSC and 77% in High risk MSC (p = 0.10). Reduction of MSC risk profile after surgery was observed in 73% of the 26 analyzable subjects who remained disease free, at median time of 18 months (IQR = 24). In all relapsing patients the MSC test returned to Intermediate or High risk at the time of second primary or metastatic progression.

Conclusions: Plasma MSC predicted lung cancer outcome and tumor recurrence at follow-up, showing potential efficacy in LDCT screening and lung cancer management.

Citation Format: Gabriella Sozzi, Stefano Sestini, Mattia Boeri, Carla Verri, Alfonso Marchiano', Carlotta Galeone, Nicola Sverzellati, Carlo La Vecchia, Ugo Pastorino. A plasma microRNAs test predicts prognosis and disease status at follow-up in screening-detected lung cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 932. doi:10.1158/1538-7445.AM2015-932