Department of Biomedical Science, Macquarie University, Sydney, New South Wales, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Clin Cancer Res. 2020 Aug 1;26(15):4064-4071. doi: 10.1158/1078-0432.CCR-19-3926. Epub 2020 Apr 22.
Brain involvement occurs in the majority of patients with metastatic melanoma. The potential of circulating tumor DNA (ctDNA) for surveillance and monitoring systemic therapy response in patients with melanoma brain metastases merits investigation.
This study examined circulating , and mutations in patients with melanoma with active brain metastases receiving PD-1 inhibitor-based therapy. Intracranial and extracranial disease volumes were measured using the sum of product of diameters, and response assessment performed using RECIST. Longitudinal plasma samples were analyzed for ctDNA over the first 12 weeks of treatment (threshold 2.5 copies/mL plasma).
Of a total of 72 patients, 13 patients had intracranial metastases only and 59 patients had concurrent intracranial and extracranial metastases. ctDNA detectability was 0% and 64%, respectively, and detectability was associated with extracranial disease volume ( < 0.01). Undetectable ctDNA on-therapy was associated with extracranial response ( < 0.01) but not intracranial response. The median overall survival in patients with undetectable ( = 34) versus detectable ( = 38) ctDNA at baseline was 39.2 versus 10.6 months [HR, 0.51; 95% confidence interval (CI), 0.28-0.94; = 0.03] and on-therapy was 39.2 versus 9.2 months (HR, 0.32; 95% CI, 0.16-0.63; < 0.01).
ctDNA remains a strong prognostic biomarker in patients with melanoma with brain metastases, especially in patients with concurrent extracranial disease. However, ctDNA was not able to detect or monitor intracranial disease activity, and we recommend against using ctDNA as a sole test during surveillance and therapeutic monitoring in patients with melanoma.
转移黑色素瘤患者多数存在脑部受累。循环肿瘤 DNA（ctDNA）在监测和评估黑色素瘤脑转移患者的系统治疗应答中的作用值得研究。
本研究检测了接受 PD-1 抑制剂治疗的脑转移黑色素瘤患者的循环和 基因突变情况。采用最长径乘积之和测量颅内和颅外疾病体积，并根据 RECIST 评估应答。在治疗的前 12 周内，对纵向血浆样本进行 ctDNA 分析（血浆阈值 2.5 拷贝/ml）。
总共 72 例患者中，13 例患者仅有颅内转移，59 例患者同时存在颅内和颅外转移。ctDNA 检测率分别为 0%和 64%，检测率与颅外疾病体积相关（ < 0.01）。治疗期间 ctDNA 不可检测与颅外反应相关（ < 0.01），但与颅内反应无关。基线时 ctDNA 不可检测（ = 34）与可检测（ = 38）的患者总生存期分别为 39.2 个月与 10.6 个月[风险比（HR），0.51；95%置信区间（CI），0.28-0.94； = 0.03]，治疗期间分别为 39.2 个月与 9.2 个月（HR，0.32；95% CI，0.16-0.63； < 0.01）。
ctDNA 仍然是黑色素瘤脑转移患者的一个强有力的预后生物标志物，尤其是在同时存在颅外疾病的患者中。然而，ctDNA 不能检测或监测颅内疾病活动，我们建议不要将其作为黑色素瘤患者监测和治疗监测中的唯一检测手段。
