Endocrine Abstracts

JOINT813

Introduction: Anaplastic thyroid cancer (ATC) is rare, but the most aggressive type of thyroid cancer (TC), with disease-specific mortality approaching 100%. A new therapeutic option that improves overall survival is molecularly targeted therapy. To date, the tumor tissue analysis using next generation sequencing (NGS) is a gold standard for mutational profiling. The circulating tumor DNA (ctDNA) is a component of liquid biopsy, with a potential to expedite the diagnosis in a minimally invasive way. This study aims to evaluate the feasibility of NGS ctDNA analysis for the identification of molecular alterations in ATC.

Methods: A prospective, single-center study was conducted from 2023 to 2024. Treatment-naïve patients with a diagnosis of ATC were included in the study. 10 ml blood samples for ctDNA analysis were collected from patients after histological diagnosis. Tissue and ctDNA samples were analyzed using NGS with the Oncomine Precision Assay, which detects molecular alterations in 50 genes. The minimum concentration of free DNA required for the assays was 0.33 ng/µL. The results were correlated with clinical data.

Results: Ten patients (mean age: 71, 6 females) with stage IVB (n = 4) and IVC (n = 6) ATC were enrolled in the study. In 5 patients, mutations were detected both in tissue and ctDNA. The mutation-based concordance between tissue and ctDNA was 71%, with 100% concordance of negative Results The most common mutations detected in ctDNA were BRAF^V600E (20%) and TP53 (20%), followed by PIK3CA (10%) and PTEN (10%) mutations. One patient with BRAF^V600Emutation in tumor tissue, had a unique TP53 mutation in ctDNA with no evidence of other malignancy, suggesting heterogeneity of the tumor. Based on the results, dabrafenib plus trametinib treatment was introduced in three patients. Mean turnaround time was 17.75 days (range 2-33), depending on the urgency of the referral for a blood test.

Conclusion: The high concordance of detected alterations highlights the potential of liquid biopsy as an effective initial screening tool for molecular alterations in ATC. Our study shows that the detection of any alterations in ctDNA should lead to further diagnostic evaluation by tissue analysis, due to complete concordance in patients with negative Results Using ctDNA may improve and expedite the diagnostic process, contributing to more precise cancer treatment, especially in cases of inoperable tumors or lesions that are difficult to biopsy. Due to the rarity of ATC, larger multicenter studies are necessary to validate and further explore the utility of ctDNA in clinical practice.