Herbreteau Guillaume, Vallée Audrey, Knol Anne-Chantal, Théoleyre Sandrine, Quéreux Gaelle, Frénard Cécile, Varey Emilie, Hofman Paul, Khammari Amir, Dréno Brigitte, Denis Marc G
Department of Biochemistry, CHU Nantes, 44093 Nantes, France.
Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA) Inserm 1232, Centre Hospitalier Universitaire de Nantes (CHU Nantes), 44093 Nantes, France.
Cancers (Basel). 2020 Jul 11;12(7):1871. doi: 10.3390/cancers12071871.
Circulating tumour DNA (ctDNA) can be used to identify gene alterations. The purpose of this study was to determine whether the detection of ctDNA, based on the identification of and mutations before systemic treatment initiation, was associated with the prognosis of metastatic melanoma. In total, 68 or -mutated stage IV or unresectable stage III metastatic cutaneous melanoma patients were included and tested for the presence of and mutations in circulating DNA before treatment initiation, using the Cobas BRAF/NRAS Mutation Test (Roche). The expected mutation was detected in the plasma of 34/68 patients (50% sensitivity). ctDNA detection was associated with AJCC stage, along with the number and nature of metastases. ctDNA was less frequently detected in -mutated than in -mutated melanoma (36% and 66%, respectively). At initiation of first-line treatment, ctDNA detection was associated with poor prognosis in Progression Free Survival (PFS) and Overall Survival (OS) in univariate analysis (log-rank: = 0.002 and < 0.0001, respectively). In multivariate analysis, ctDNA detection was an independent factor of poor prognosis in OS, after adjustment for AJCC stage, number and nature of metastases and gender (HR = 4.384; 95% CI: (1.308; 14.699); = 0.017).
循环肿瘤DNA（ctDNA）可用于识别基因改变。本研究的目的是确定在全身治疗开始前基于检测[具体基因1]和[具体基因2]突变的ctDNA检测是否与转移性黑色素瘤的预后相关。总共纳入了68例[具体基因1]或[具体基因2]突变的IV期或不可切除的III期转移性皮肤黑色素瘤患者，并在治疗开始前使用Cobas BRAF/NRAS突变检测（罗氏公司）检测循环DNA中[具体基因1]和[具体基因2]突变的存在情况。在34/68例患者（50%的灵敏度）的血浆中检测到预期突变。ctDNA检测与美国癌症联合委员会（AJCC）分期以及转移灶的数量和性质相关。在[具体基因1]突变的黑色素瘤中ctDNA检测频率低于[具体基因2]突变的黑色素瘤（分别为36%和66%）。在一线治疗开始时，单因素分析中ctDNA检测与无进展生存期（PFS）和总生存期（OS）的不良预后相关（对数秩检验：PFS的P = 0.002，OS的P < 0.0001）。在多因素分析中，在对AJCC分期、转移灶的数量和性质以及性别进行调整后，ctDNA检测是OS不良预后的独立因素（风险比[HR] = 4.384；95%置信区间：(1.308; 14.699)；P = 0.017）。
