Detection of metastases using circulating tumour DNA in uveal melanoma

Aaron B. Beasley, Daniel P. de Bruyn, Leslie Calapre, Zeyad Al-Ogaili, Timothy Isaacs, Jacqueline Bentel, Anna L Reid, Roy S. Dwarkasing, Michelle R. Pereira, Adnan Khattak, Tarek Meniawy, Michael Millward, Erwin Brosens, Annelies de Klein, Fred Chen, Ermine Kilic, Elin S. Gray

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Pages (from-to)14953-14963
Number of pages11
JournalJournal of Cancer Research and Clinical Oncology
Issue number16
Early online date22 Aug 2023
Publication statusPublished - Nov 2023

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