Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2020 Apr 15;26(8):1924-1931. doi: 10.1158/1078-0432.CCR-19-0306. Epub 2019 Dec 18.
Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF) in cfDNA is associated with prognosis.
We performed a retrospective analysis of 298 patients with metastatic disease who underwent clinical comprehensive cfDNA analysis and assessed association between VAF and overall survival.
cfDNA mutations were detected in 240 patients (80.5%). Median overall survival (OS) was 11.5 months. cfDNA mutation detection and number of nonsynonymous mutations (NSM) significantly differed between tumor types, being lowest in appendiceal cancer and highest in colon cancer. Having more than one NSM detected was associated with significantly worse OS (HR = 2.3; < 0.0001). VAF was classified by quartiles, Q1 lowest, Q4 highest VAF. Higher VAF levels were associated with a significantly worse overall survival (VAF Q3 HR 2.3, = 0.0069; VAF Q4 HR = 3.8, < 0.0001) on univariate analysis. On multivariate analysis, VAF Q4, male sex, albumin level <3.5 g/dL, number of nonvisceral metastatic sites >0 and number of prior therapies >4 were independent predictors of worse OS.
Higher levels of cfDNA VAF and a higher number of NSMs were associated with worse OS in patients with metastatic disease. Further study is needed to determine optimal VAF thresholds for clinical decision making and the utility of cfDNA VAF as a prognostic marker in different tumor types.
医生需要评估患者的预后，以便为患者提供咨询并确定其是否适合参加临床试验。越来越多的情况下，会进行游离循环肿瘤 DNA（cfDNA）测序以用于临床决策。我们旨在确定 cfDNA 中的变异等位基因频率（VAF）是否与预后相关。
我们对 298 例接受过临床综合 cfDNA 分析的转移性疾病患者进行了回顾性分析，并评估了 VAF 与总生存期之间的关联。
在 240 例患者（80.5%）中检测到 cfDNA 突变。中位总生存期（OS）为 11.5 个月。cfDNA 突变检测和非同义突变（NSM）数量在肿瘤类型之间存在显著差异，阑尾癌中最低，结肠癌中最高。检测到的 NSM 数量超过一个与 OS 显著更差相关（HR=2.3；<0.0001）。VAF 按四分位数分类，Q1 最低，Q4 最高 VAF。较高的 VAF 水平与总生存期明显更差相关（VAF Q3 HR 2.3，=0.0069；VAF Q4 HR=3.8，<0.0001）。在多变量分析中，VAF Q4、男性、白蛋白水平<3.5 g/dL、非内脏转移部位>0 和治疗次数>4 是 OS 更差的独立预测因素。
在转移性疾病患者中，cfDNA VAF 水平较高和 NSM 数量较多与 OS 更差相关。需要进一步研究以确定最佳的 VAF 阈值用于临床决策以及 cfDNA VAF 作为不同肿瘤类型的预后标志物的效用。
