Surveillance of cfDNA Hot Spot Mutations in NSCLC Patients during Disease Progression.

Non-small cell cancer (NSCLC) has been identified with a great variation of mutations that can be surveyed during disease progression. The aim of the study was to identify and monitor lung cancer-specific mutations incidence in cell-free DNA as well as overall plasma cell-free DNA load by means of targeted next-generation sequencing. Sequencing libraries were prepared from cell-free DNA (cfDNA) isolated from 72 plasma samples of 41 patients using the Oncomine Lung cfDNA panel covering hot spot regions of 11 genes. Sequencing was performed with the Ion Torrent™ Ion S5™ system. Four genes were detected with highest mutation incidence: (43.9% of all cases), followed by (36.6%), (31.7%), and (29.3%). Seven patients had co-occurring + (6/41, 14.6%) or + (7/41, 17.1%) mutations. Moreover, the mutational status of as well an overall cell-free DNA load were confirmed to be predictors of poor progression-free survival (HR = 2.5 [0.8-7.7]; = 0.029 and HR = 2.3 [0.9-5.5]; = 0.029, respectively) in NSCLC patients. In addition, mutation status significantly predicts shorter overall survival (HR = 3.4 [1.2-9.7]; < 0.001). We demonstrated that mutation incidence as well as a cell-free DNA load can be used as biomarkers for NSCLC monitoring and can help to detect the disease progression prior to radiological confirmation of the status.