School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
J Cancer Res Clin Oncol. 2023 Nov;149(16):14953-14963. doi: 10.1007/s00432-023-05271-3. Epub 2023 Aug 22.
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.
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.
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.
Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.
根据原发性肿瘤的遗传特征，约有 50%的葡萄膜黑色素瘤（UM）患者会发展为转移性疾病。患者需要根据预后进行 3-12 个月的每月扫描，这既昂贵又常常缺乏特异性。循环肿瘤 DNA（ctDNA）定量可作为一种检测方法，用于检测和监测患者的早期转移和治疗反应迹象。
我们使用液滴数字 PCR 在三个不同的 UM 队列中评估了 ctDNA 作为生物标志物：（A）对原发性 UM 患者进行回顾性分析，以预测转移；（B）对原发性肿瘤消退后的 UM 患者进行前瞻性分析，以早期发现转移；（C）监测转移性 UM 患者的治疗反应。
队列 A：ctDNA 水平与转移的发展无关。队列 B：ctDNA 在 25 例有影像学诊断转移的患者中检测到 17 例（68%）。在多变量分析中，ctDNA 是总生存率的最强预测因素（HR=15.8，95%CI 1.7-151.2，p=0.017）。队列 C：对接受免疫治疗的患者进行 ctDNA 监测显示，联合免疫治疗患者的 ctDNA 水平降低。
我们的概念验证研究表明，ctDNA 监测在葡萄膜黑色素瘤患者的临床管理中有作为生物标志物的潜力。
