Dynamics of ctDNA in patients with NSCLC

Abstract

Background For many years, researchers have tried to find more effective ways to find out if a person has cancer, and find it at an early stage, when it is most curable. One idea that is gaining popularity is called liquid biopsy. Methods From 2016 to 2018 we studied 1050 patients with non-small-cell lung cancer (NSCLC). Before the treatment and then every 2 months after, whole blood was taken for qualitative assessment of ctDNA dynamics by RT-PCR. The aim of the study was to assess the relationship between the presence of mEGFR ctDNA in tumor tissue and blood plasma. Results The study involved 1050 patients, of which 462 cases were represented by adenocarcinoma of NSCLC. EGFR mutations were detected in 145/462 targeted agents (31.38%). The molecular genetic profile ctDNA was represented by the following mutations for women 33/59 (55.9%): ex19del - 20 (60.6%), L858R - 13 (39.4%); for men 13/19 (68.42%). No association was found in the detectability of the mutation with sex, age, localization of metastases, or stage. Among patients with stage III only the L858 mutation (3/3) was found. The T790m resistance mutation was detected in the primary plasma sample in 8/79 cases (10.1%). After 2 months of gefitinib, EGFR-mutation-positive ctDNA were detected in blood plasma in 23.3% of cases (13/56). Of the 42 patients in whom the ctDNA was detected before treatment, after 2 months of therapy it was detectedin only 6/42. Thus, the disappearance of the mutation was observed in 85.71% (36/42). Median progression-free survival for patients who retained ctDNA after 2 months was 16.25 months (Cl 95% 11.24 - 19.94), and for patients in whom the mutation disappeared after 2 months it was 21.10 (Cl 19.21 - 22.98). The results of the study showed that blood plasma analysis is an appropriate the method of EGFR mutation detection: sensitivity 59.2%, specificity 98.8%, prognostic positive result 91.3%, prognostic negative result 91.6%. Conclusions The integration and liquid biopsy might complement the gold standard tissue testing and is a promising candidate for studying NSCLC. ctDNA assay might be applied in identifying actionable genomic alterations, dynamically monitoring response and resistance to targeted agents, prescreening early-stage lung cancer, and tracking the spatiotemporal evolution of lung cancer. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.