Molecular and Pharmaco-Epidemiology Unit Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, Milan, Italy.
Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
Crit Rev Oncol Hematol. 2021 Jan;157:103187. doi: 10.1016/j.critrevonc.2020.103187. Epub 2020 Nov 27.
We reviewed and meta-analysed the available evidence (until December 2019) about circulating tumour DNA (ctDNA) levels and melanoma patients survival. We included twenty-six studies (>2000 patients overall), which included mostly stage III-IV cutaneous melanoma patients and differed widely in terms of systemic therapy received and somatic mutations that were searched. Patients with detectable ctDNA before treatment had worse progression-free survival (PFS) (summary hazard ratio (SHR) 2.47, 95 % confidence intervals (CI) 1.85-3.29) and overall survival (OS) (SHR 2.98, 95 % CI 2.26-3.92), with no difference by tumour stage. ctDNA detectability during follow-up was associated with poorer PFS (SHR 4.27, 95 %CI 2.75-6.63) and OS (SHR 3.91, 95 %CI 1.97-7.78); in the latter case, the association was stronger (p = 0.01) for stage IV vs. III melanomas. Between-estimates heterogeneity was low for all pooled estimates. ctDNA is a strong prognostic biomarker for advanced-stage melanoma patients, robust across tumour (e.g. genomic profile) and patients (e.g. systemic therapy) characteristics.
我们回顾和荟萃分析了截至 2019 年 12 月关于循环肿瘤 DNA（ctDNA）水平和黑色素瘤患者生存的现有证据。我们纳入了 26 项研究（总体上超过 2000 名患者），这些研究主要包括 III 期和 IV 期皮肤黑色素瘤患者，并且在接受的系统治疗和搜索的体细胞突变方面差异很大。治疗前可检测到 ctDNA 的患者无进展生存期（PFS）（综合危险比（SHR）2.47，95%置信区间（CI）1.85-3.29）和总生存期（OS）（SHR 2.98，95%CI 2.26-3.92）更差，与肿瘤分期无关。随访期间 ctDNA 的可检测性与较差的 PFS（SHR 4.27，95%CI 2.75-6.63）和 OS（SHR 3.91，95%CI 1.97-7.78）相关；在后一种情况下，IV 期黑色素瘤与 III 期黑色素瘤的相关性更强（p=0.01）。所有汇总估计的组间异质性均较低。ctDNA 是晚期黑色素瘤患者的强有力预后生物标志物，在肿瘤（例如基因组特征）和患者（例如系统治疗）特征方面均具有稳健性。
