Lyskjaer, I, Davies, C, Strobl, A-C, Hindley, J, James, S, Lalam, RK, Cross, W, Hide, G, Rankin, KS, Jeys, L, Tirabosco, R, Stevenson, J, Consortium, GER, O'Donnell, P, Cool, P ORCID: https://orcid.org/0000-0002-4985-3085 and Flanagan, AM (2021) Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations. Molecular Oncology.

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Abstract

Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi-institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre-operatively in 31/83 (37%) and in 12/31 (39%) patients post-operatively. We found that detection of ctDNA was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT), which are neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients and therefore introduction of this blood test into clinical practice as a complementary assay to current standard-of-care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS.

Item Type: Article
Additional Information: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1002/1878-0261.13102 This article is protected by copyright. All rights reserved. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Subjects: R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 30 Sep 2021 12:05
Last Modified: 30 Sep 2021 12:05
URI: https://eprints.keele.ac.uk/id/eprint/10072

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