Endocrine Abstracts

Introduction: Current imaging modalities for anaplastic thyroid cancer (ATC) have limited efficacy in evaluating remission and predicting recurrence due to residual disease. Circulating tumour DNA (ctDNA), isolated from liquid biopsies, could complement these methods and enhance diagnostic follow-up and disease monitoring. However, clinical follow-up studies using ctDNA in ATC remain scarce.

Case report : An eighty-one-year-old woman with a history of HER2⁺ breast cancer (BC), in remission since 2021, presented in July 2022 with a 9 cm exophytic stage IVb ATC. Due to the patient’s frail status, a 24-hour cytology-based BRAF p.V600E diagnosis was performed, and she was immediately put on Dabrafenib plus Trametinib (DT) therapy. A remarkable DT response was observed with tumour shrinkage to 6 cm (first month) and further to 3.4 cm (fourth month), with disappearance of the exophytic component. In the fifth month the patient underwent total thyroidectomy (TT), which was uneventful. Still under DT, a PET-CT scan performed 12 months later showed a new liver metastatic lesion, subsequently biopsied and diagnosed as a BRAF- negative BC metastasis. Six months later, the metastatic disease progressed with pronounced BC markers expression, without evidence of ATC recurrence. To investigate the utility of ctDNA concentration and ctDNA BRAF⁺ (ct BRAF⁺) analysis by droplet digital PCR (ddPCR), blood samples were collected between the diagnosis (baseline/pre-DT) and the end of follow-up and matched with PET-CT. Baseline ctDNA concentration decreased throughout follow-up (179 to 97 ng/mL), paralleling the tumour volume’s reduction. Following TT, ctDNA stabilized at approximately 58.2 ng/mL, but increased one month prior to the emergence of BC liver metastasis (129 ng/mL). By the end of the follow-up period (at 18 months), the patient’s ctDNA increased to 788 ng/ml. In this case, ctDNA levels varied along with ATC/BC disease burden. Baseline ctBRA F⁺ was detected with a VAF of 4.3%. By the 3^rd month and until the end of follow-up, ctBRAF ⁺ was no longer detected (0% VAF), despite the BC liver metastasis. The ddPCR- ctBRAF ⁺ assay sensitivity and specificity were 76.9% [95% CI 49-97%] and 91.6% [95% CI 64-99%], respectively. Notably, ctBRAF ⁺ aligned with pre-treatment BRAF diagnosis and ATC DT clinical response.

Conclusions: This case report suggests that ctDNA/ ctBRAF⁺ may be useful as monitoring biomarkers for ATC, offering a promising method for assessing therapeutic response through minimally invasive and readily available methods. However, further studies are needed to validate the clinical utility of liquid biopsy in additional ATC cases, with longer follow-up periods.