Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Medicine Essen, Essen, Germany.
Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, Partner Site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany.
Clin Chem. 2020 Dec 1;66(12):1510-1520. doi: 10.1093/clinchem/hvaa223.
We assessed the usefulness of circulating tumor DNA (ctDNA) pre- or post-treatment initiation for outcome prediction and treatment monitoring in metastatic colorectal cancer (mCRC).
Droplet digital PCR was used to measure absolute mutant V-Ki-ras2 Kirsten rat sarcoma viral oncogene ((mut)KRAS) ctDNA concentrations in 214 healthy controls (plasma and sera) and in 151 tissue-based mutKRAS positive patients with mCRC from the prospective multicenter phase 3 trial AIO KRK0207. Serial mutKRAS ctDNA was analyzed prior to and 2-3 weeks after first-line chemotherapy initiation with fluoropyrimidine, oxaliplatin, and bevacizumab in patients with mCRC and correlated with clinical parameters.
mut KRAS ctDNA was detected in 74.8% (113/151) of patients at baseline and in 59.6% (90/151) at follow-up. mutKRAS ctDNA at baseline and follow-up was associated with poor overall survival (OS) (hazard ratio [HR] =1.88, 95% confidence interval [CI] 1.20-2.95; HR = 2.15, 95% CI 1.47-3.15) and progression-free survival (PFS) (HR = 2.53, 95% CI 1.44-4.46; HR = 1.90, 95% CI 1.23-2.95), respectively. mutKRAS ctDNA clearance at follow-up conferred better disease control (P = 0.0075), better OS (log-rank P = 0.0018), and PFS (log-rank P = 0.0018). Measurable positive mutKRAS ctDNA at follow-up was the strongest and most significant independent prognostic factor on OS in multivariable analysis (HR = 2.31, 95% CI 1.40-3.25).
Serial analysis of circulating mutKRAS concentrations in mCRC has prognostic value. Post treatment mutKRAS concentrations 2 weeks after treatment initiation were associated with therapeutic response in multivariable analysis and may be an early response predictor in patients receiving first-line combination chemotherapy.
NCT00973609.
我们评估了循环肿瘤 DNA（ctDNA）在转移性结直肠癌（mCRC）中的治疗前或治疗起始后对预后预测和治疗监测的作用。
使用液滴数字 PCR 检测来自前瞻性多中心 III 期 AIO KRK0207 试验的 214 例健康对照者（血浆和血清）和 151 例组织学阳性 mCRC 患者的绝对突变 V-Ki-ras2 Kirsten 大鼠肉瘤病毒癌基因（(mut)KRAS）ctDNA 浓度。在 mCRC 患者接受氟嘧啶、奥沙利铂和贝伐珠单抗一线化疗起始前和 2-3 周时，对连续的 mutKRAS ctDNA 进行分析，并与临床参数相关联。
基线时 74.8%（113/151）的患者和随访时 59.6%（90/151）的患者检测到 mut KRAS ctDNA。基线和随访时的 mutKRAS ctDNA 与总生存期（OS）（风险比[HR] =1.88，95%置信区间[CI] 1.20-2.95；HR = 2.15，95% CI 1.47-3.15）和无进展生存期（PFS）（HR = 2.53，95% CI 1.44-4.46；HR = 1.90，95% CI 1.23-2.95）不良相关。随访时 mutKRAS ctDNA 清除与更好的疾病控制（P = 0.0075）、更好的 OS（对数秩 P = 0.0018）和 PFS（对数秩 P = 0.0018）相关。随访时可测量的阳性 mutKRAS ctDNA 是多变量分析中 OS 的最强和最显著的独立预后因素（HR = 2.31，95% CI 1.40-3.25）。
mCRC 中循环 mutKRAS 浓度的连续分析具有预后价值。治疗起始后 2 周时治疗后 mutKRAS 浓度与多变量分析中的治疗反应相关，并且可能是接受一线联合化疗的患者的早期反应预测指标。
NCT00973609。
