EP1.11-20 A Panel of Liquid Biomarkers for Early Response Capturing of NSCLC Therapies in Advanced Stages

Abstract

CT scans are the gold standard to measure treatment success of Non-Small Cell Lung Cancer (NSCLC) therapies. In recent years, liquid biopsies became an adequate diagnostic tool especially in advanced disease stages. Here, we investigated very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from patients were taken at baseline and day + 1 for the chemotherapy cohort (n = 25) and at baseline, day +7 and +14 for the targeted therapy cohort (n = 25). DNA mutational load, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved keratin 18 (M30 antigen) and soluble keratin 18 (M65 antigen) were measured using serum and plasma from patients. Baseline and first follow-up CT scan were evaluated by an experienced radiologist and correlated with biomarker data. In the majority of patients a decrease in glycodelin abundance as well as mutational load coincided with clinical response as assessed by CT scan. Consequently, an increase of these biomarkers implicated progressive disease. Among the measured miRNAs, miR-103, miR-628-3p, and let-7e showed largely similar behavior within individual patients upon treatment initiation. The abundance of these miRNAs increased in responding patients and in a subset of patients experiencing tumor progression. Similar observations were seen for the apoptosis markers while the best results were obtained with the detection of M65. Taken together, several investigated biomarkers showed high potential for an early response capturing in defined NSCLC cohorts.