PO-493 ctDNA profiles of metastatic melanoma patients under therapy

Introduction In precision oncology it is a great interest to develop novel disease and therapy monitoring technologies that are non-invasive and highly sensitive. Specifically, our project aims to establish blood-based assays that allow ‘real-time’ monitoring and quantitative detection of circulating tumour DNA (ctDNA) as a biomarker that corresponds to the tumour load in patients. ctDNA fragments are released from all parts of the tumours by apoptosis and necrosis, thus, it reflects the full spectrum of specific mutations of a systemically progressed tumour. Material and methods The usefulness of ctDNA analyses is highlighted in this study, in which we have analysed 545 plasma samples from 77 stage III and IV melanoma patients with the BRAF V600E mutation, with mutations at the Q61 codon of the NRAS gene, and mutations in the promoter region of TERT gene. Characterisation and analysis of these mutations were performed on droplet digital PCR (ddPCR) platform. The patients received either MAPK-targeted treatment or immune checkpoint blockade. Additionally, plasma samples from 96 healthy donors were analysed to test the positive and negative predictive values of our assays. Results and discussions ROC analyses showed over 90% AUC for all our assays. Our analyses revealed that increasing ctDNA levels were associated with disease progression from loco-regional (IIIB or IIIC) to systemic disease (IV) with p Conclusion In brief, our results show the potential role of ctDNA measurement as a sensitive monitoring tool for the early assessment of disease progression and therapeutic response/resistance in melanoma patients.