Circulating Tumor DNA as a Biomarker for Disease Surveillance in Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) is a highly lethal malignancy in which early detection of progression could allow timely treatment modifications and potentially improve outcomes. Novel circulating tumor DNA (ctDNA) assays allow the detection of molecular residual disease. We aimed to investigate the utility of ctDNA as a biomarker in ATC.

Retrospective cohort study of patients with ATC and at least one ctDNA drawn before systemic therapy start (referred to as baseline) between February 2021 and August 2024. ctDNA was correlated with concomitant imaging and/or pathologic results. Patients with ≥1 additional ctDNA on systemic therapy were included in a secondary analysis to evaluate the detection of ctDNA as a molecular evidence of disease recurrence/progression. These patients were divided into two subgroups: recurrence detection after curative-intent therapy (group 1) or treatment response monitoring if known residual disease (group 2).

Forty-five patients met the inclusion criteria. At baseline, ctDNA result correlated with disease status in 93% of patients (75% true positives, 18% true negatives, 7% false negatives [FNs], 0% false positive). Thirty-one patients had ≥1 follow-up ctDNA on systemic therapy, with a total of 130 evaluable results. In group 1(n = 60), ctDNA had 77% sensitivity, 100% specificity, 92% negative predictive value (NPV), and 100% positive predictive value (PPV). In group 2 (n = 70), ctDNA had 78% sensitivity, 100% specificity, 84% NPV, and 100% PPV. Potential reasons for FN ctDNA included low tumor burden, lung-only/brain-only metastatic disease, and heterogeneous molecular profiles in ATC.

ctDNA is a promising tumor biomarker for disease monitoring in ATC, with a high specificity and PPV. It should be considered in addition to standard-of-care surveillance methods to better inform treatment decision making.