Evaluating the prognostic potential of circulating cell-free DNA in advanced thyroid cancer

in Endocrine-Related Cancer
Authors:
Ayanthi Wijewardene Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Cancer Genetics Laboratory, Kolling Institute, The University of Sydney, Sydney, Australia
Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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https://orcid.org/0009-0007-7868-7446
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Roderick J Clifton-Bligh Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Cancer Genetics Laboratory, Kolling Institute, The University of Sydney, Sydney, Australia
Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Bin Wang Precision Medicine, SydPath, St Vincent’s Hospital, Sydney, Australia
St Vincent’s Clinical School, University of New South Wales, New South Wales, Australia

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Catherine Luxford Cancer Genetics Laboratory, Kolling Institute, The University of Sydney, Sydney, Australia
Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Bruce G Robinson Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Cancer Genetics Laboratory, Kolling Institute, The University of Sydney, Sydney, Australia
Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Martyn Bullock Cancer Genetics Laboratory, Kolling Institute, The University of Sydney, Sydney, Australia
Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Matti Gild Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Cancer Genetics Laboratory, Kolling Institute, The University of Sydney, Sydney, Australia
Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Correspondence should be addressed to A Wijewardene: Ayanthi.wijewardene@sydney.edu.au

This paper is part of a special collection highlighting the work of emerging leaders in the endocrine cancer field.

(M Bullock and M Gild contributed equally as senior authors)

DOI:
https://doi.org/10.1530/ERC-24-0227
Volume/Issue:
Volume 32: Issue 2
Article Type:
Research Article
Article ID:
e240227
Online Publication Date:
04 Jan 2025
Copyright:
© the author(s) 2025
Restricted access
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Liquid biopsies are a minimally invasive approach to obtain biomarkers including cell-free DNA (cfDNA) from peripheral blood. To date, there are limited and conflicting studies evaluating their role in thyroid cancer. Our study evaluated the utility of cfDNA in advanced thyroid cancers. Patients aged >18 years with metastatic medullary thyroid cancer (MTC), poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC) were enrolled in this prospective study between 2020 and 2024. As part of standard care, sequencing of germline and tumoral DNA was conducted, and patients with germline mutations were excluded from the study. Whole blood samples were collected in Streck cell-free DNA BCT tubes, and cfDNA was extracted from plasma using an EZ1&2 ccfDNA kit and EZ2 Connect. The extracted cfDNA was then sequenced across 50 key cancer-related genes using an Oncomine Precision Assay panel on an Ion Torrent Genexus integrated sequencer. Forty patients were included: 27 MTC, 2 ATC and 11 PDTC. Tumoral mutations were detected in 36 of the included patients (90%): cfDNA detected mutations in 18/36 patients (13 MTC, 1 ATC and 4 PDTC (50%)). The sensitivity of cfDNA was 86% (6/7) pre-tyrosine kinase inhibitor therapy and reduced to 54% on therapy (13/24), suggestive of the lack of tumor-derived DNA shedding with a strong on-target treatment efficacy. The median cfDNA concentration was higher in samples with a detected mutation (n = 43) than those without (n = 26), 11.91 ng/mL vs 5.81 ng/mL, respectively, while an increasing cfDNA was associated with worse progression-free survival (P < 0.01). cfDNA is a novel biomarker with potential to monitor disease progression in patients with advanced thyroid cancers.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2025
Article ID:
e240227
Received Date:
29 Aug 2024
Rev-recd:
11 Nov 2024
Accepted Date:
27 Nov 2024
Print Publication Date:
01 Feb 2025
Online Publication Date:
04 Jan 2025
Keywords:
cfDNA; ctDNA; metastatic thyroid cancer; next generation sequencing

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