EP1591 - ECE_2886 - Assessment of BRAF V600E-mutated circulating tumour DNA in papillary thyroid microcarcinoma

Abstract

Papillary thyroid microcarcinoma (PTMC) is a tumour ≤1 cm with a generally favourable prognosis. Management options include surgery, percutaneous ablation or active surveillance, based on clinical risk and patient preference. To date, the role of molecular assessment in the risk stratification and clinical decision-making of PTMC is limited due to insufficient evidence. Although the BRAF V600E mutation is detected in up to 70% of PTMC, previous studies have reported conflicting results on this mutation as a risk factor. Detection of BRAF V600E-mutated circulating tumour DNA (ctDNA), reflecting the release of mutated DNA from tumour cells and potentially indicating more aggressive tumour biology, may therefore be investigated as a potential marker of disease risk. The aim of this study was to investigate the clinical utility of detection of BRAF V600E-mutated ctDNA in plasma as a minimally invasive adjunct to the primary diagnosis of PTMC. This prospective, single-center study was conducted between 2021 and 2024. Patients with focal thyroid lesions who were scheduled for total thyroidectomy were enrolled. Blood samples of 10 mL were collected during the perioperative period and subsequently centrifuged. The plasma was frozen and biobanked. Plasma samples from patients with confirmed BRAF V600E-positive PTMC were tested for the presence of circulating nucleic acids. Positive samples were further tested for the BRAF V600E mutation using digital droplet PCR (ddPCR). The reference test was the detection of the BRAF V600E mutation in tumour tissue using real-time PCR. Patients diagnosed with other malignant tumours were excluded from the final analysis. The obtained results were correlated with clinical data. 19 plasma samples from patients with BRAF V600E-positive PTMC were included in the final analysis. All patients had stage I PTMC. Median time from blood sampling to surgery was 26 days (IQR: 9-35). The median size of a tumour was 7 mm (IQR: 5-8.5). No plasma samples were positive for BRAF V600E-mutated ctDNA. The assessment of circulating tumour DNA does not seem to be a suitable test to supplement the diagnosis of PTMC, presumably due to low release of free DNA into circulation.