Detection of metastases using circulating tumour DNA in uveal melanoma

Authors

Aaron B. Beasley, Edith Cowan UniversityFollow
Daniël P. de Bruyn
Leslie Calapre, Edith Cowan UniversityFollow
Zeyad Al-Ogaili
Timothy W. Isaacs
Jacqueline Bentel
Anna L. Reid, Edith Cowan UniversityFollow
Roy S. Dwarkasing
Michelle R. Pereira, Edith Cowan University
Muhammad A. Khattak, Edith Cowan University
Tarek M. Meniawy
Michael Millward
Erwin Brosens
Annelies de Klein
Fred K. Chen
Emine Kiliҫ
Elin S. Gray, Edith Cowan UniversityFollow

Document Type

Journal Article

Publication Title

Journal of Cancer Research and Clinical Oncology

Publisher

Springer

School

Centre for Precision Health / School of Medical and Health Sciences

RAS ID

60328

Funders

Open Access funding enabled and organized by CAUL and its Member Institutions. This study was funded by a Raine Medical Research Foundation Priming Grant and an Ophthalmic Research Institute of Australia Grant to ESG and an Australian Melanoma Research Foundation Postgraduate research grant awarded to ABB.

Comments

Beasley, A. B., de Bruyn, D. P., Calapre, L., Al-Ogaili, Z., Isaacs, T. W., Bentel, J., ... & Gray, E. S. (2023). Detection of metastases using circulating tumour DNA in uveal melanoma. Journal of Cancer Research and Clinical Oncology, 149, 14953-14963. https://doi.org/10.1007/s00432-023-05271-3

Abstract

Background: Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3–12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response. Methods: We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients. Results: Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7–151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy. Conclusions: Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.

DOI

10.1007/s00432-023-05271-3

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.