Circulating Tumor DNA

For patients with BRAF wild-type stage III and IV melanoma, there is an urgent clinical need to identify prognostic biomarkers and biomarkers predictive of treatment response. Circulating tumour DNA (ctDNA) is emerging as a blood-based biomarker and has shown promising results for many cancers, including melanoma. The purpose of this study was to identify targetable, tumour-derived mutations in patient blood that may lead to treatment alternatives and improved outcomes for BRAF-negative melanoma patients. Using a CAPP-seq pan-cancer gene panel, ctDNA from 150 plasma samples (n=106 patients) were assessed, including serial blood collections for a subset of patients (n=16). Circulating tumour DNA (ctDNA) variants were detected in 85% of patients, all in targetable pathways such as VEGFR, EGFR, PI3K/AKT, Bcl2/mTOR, ALK/MET, CDK4/6. Stage IV patients with low ctDNA concentrations, <10ng/ml, had significantly better disease-specific survival and progression free survival. Patients with both high concentration of ctDNA and any detectable ctDNA variants had the worst prognosis. Additionally, these results indicated that longitudinal changes in ctDNA correlated with treatment response and disease progression determined by radiology. This study confirms that ctDNA has potential to be used as a non-invasive liquid biopsy to identify recurrent disease and detect targetable variants in patients with late-stage melanoma.