Endocrine Abstracts

Thyroid cancer is the most common endocrine malignancy accounting for 1% of new cancer cases each year. Even after treatment, one in five patients develop recurrence eventually. Therefore, close follow up is crucial after treatment. Current tumour biomarkers are not perfect, and there is a need for a more sensitive and specific way of detecting early recurrence. Liquid biopsies have emerged as a novel marker in tumour surveillance and monitoring response to treatment. In particular, Circulating cell-free Tumour DNA (ctDNA) have been investigated. Here, we review the available evidence regarding the use of ctDNA as a liquid biopsy in the diagnosis and monitoring of thyroid cancer response to treatment.

Methodology: Online database search of PubMed (Medline) was performed using keywords; Circulating Tum* DNA, ctDNA, cfDNA, liquid biopsy, thyroid cancer, thyroid neoplasm*, thyroid carcinoma, papillary, medullary, follicular, anaplastic. Reference lists were reviewed for relevant literature. Modified PRISMA model was adopted for article extraction. Due to significant heterogeneity in trial population characteristics, methodology and outcomes, meta-analysis was not feasible.

Results: After filtering our search to human only trials, some articles were excluded after title reading and screening the text. 11 relevant articles were identified from the online database. 8 more articles were identified from reference lists of relevant reviews raising the total number of articles to 19. Trials included a total of 1163 patients. Of the different tumour types, papillary thyroid cancer (PTC) was the most common type in 71% of patients followed by medullary (MTC) then anaplastic thyroid cancer (ATC) in 14.4% and 10.3% of patients respectively. BRAF^V600E was the most commonly sought after ctDNA variant amongst others which included RET and TP53. Tissue mutant DNA detection was performed using digital droplet PCR (ddPCR) and real-time PCR (qPCR) in most trials. Few trials used targeted Next Generation Sequencing technique limited to previously reported mutational hotspot. Concordance rate of tissue-to-peripheral blood mutant DNA detection rate varied from 0% to 86% in trials of diagnosis and surveillance for disease recurrence. The main pitfall was that seeking mutations commonly reported in the literature in both tissue and blood risks missing ctDNA containing less common/unique mutations thereby reducing ctDNA analysis sensitivity.

Conclusion: cT-DNA offers a novel and minimally invasive tool for surveillance and monitoring of thyroid cancer. Research utilizing wider or individualised gene mutation panels is warranted to improve test sensitivity.