Circulating microRNA signature and lung cancer outcome in low-dose computed tomography (LDCT) screening.

1529 Background: The efficacy of low-dose computed tomography (LDCT) screening is currently being tested in prospective randomized trials worldwide. Some of these trials are also investigating the value of non-invasive biomarkers, to improve the cost-benefit ratio of LDCT by individual risk assessment. In the present study, we have analyzed the capacity of a miRNA signature classifier (MSC) based on 24 previously refined microRNAs circulating in plasma to predict the outcome of lung cancer patients within the LDCT screening program. 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 111 consecutive subjects developed lung cancer. The actuarial five-year survival according to clinical and pathological characteristics was calculated for all patients, and for the subset of 76 patients suitable for plasma MSC analysis, according to three different risk groups (High, Intermediate or Low). Median follow-up of the alive patients was 4.5 years (Inter Quartile Range = 6.5). Results: Five-year survival was 55% in overall (median 7.9 yrs), 63% for LDCT-detected cases (median nc), 90% for pStage I (median nc), 9% for pStage II-IV (median 1.5 yrs, p<0.001), 68% for cancers detected in the initial two years of screening (median nc), and 38% for years 3 to 5 (median 3.0 yrs, p<0.004). None of the 13 interval cancers survived 4 years (median 0.8 yrs, p<0.001). In the subset suitable for plasma MSC analysis , survival was 76% for low- to intermediate risk MSC (median nc), and 35% for High risk MSC (median 2.9 yrs, p=0.002). The prognostic power of MSC persisted when the analysis was restricted to LDCT-detected cases after exclusion of interval cancers (85 vs. 38% respectively, p<0.001). No cancer deaths were observed in the subset of 28 patients with pStage I and low- to intermediate risk MSC. Conclusions: Patients developing interval lung cancer or with a Stage higher than I had a very poor outcome, despite LDCT monitoring. Plasma MSC predicted lung cancer outcome effectively, and might improve the individual risk assessment and performance of LDCT screening in the near future. Clinical trial information: INT 05-53.