Despite the different possible paths of treatment, lung cancer remains one of the leading causes of death in oncological patients. New tools guiding the therapeutic process are under scientific investigation, and one of the promising indicators of the effectiveness of therapy in patients with NSCLC is variant allele frequency (VAF) analysis. VAF is a metric characterized as the measurement of the specific variant allele proportion within a genomic locus, and it can be determined using methods based on NGS or PCR. It can be assessed using not only tissue samples but also ctDNA (circulating tumor DNA) isolated from liquid biopsy. The non-invasive characteristic of liquid biopsy enables a more frequent collection of material and increases the potential of VAF analysis in monitoring therapy. Several studies have been performed on patients with NSCLC to evaluate the possibility of VAF usage. The research carried out so far demonstrates that the evaluation of VAF dynamics may be useful in monitoring tumor progression, remission, and recurrence during or after treatment. Moreover, the use of VAF analysis appears to be beneficial in making treatment decisions. However, several issues require better understanding and standardization before VAF testing can be implemented in clinical practice. In this review, we discuss the difficulties in the application of ctDNA VAF analysis in clinical routine, discussing the diagnostic and methodological challenges in VAF measurement in liquid biopsy. We highlight the possible applications of VAF-based measurements that are under consideration in clinical trials in the monitoring of personalized treatments for patients with NSCLC.
尽管存在多种可能的治疗路径，肺癌仍是肿瘤患者死亡的主要原因之一。目前科学界正在研究指导治疗过程的新工具，其中变异等位基因频率（VAF）分析是非小细胞肺癌患者疗效评估中具有前景的指标之一。VAF作为基因组位点内特定变异等位基因比例的量化指标，可通过基于二代测序或聚合酶链式反应的技术进行测定。其评估不仅可采用组织样本，亦可使用液体活检分离的循环肿瘤DNA。液体活检的无创特性使得样本采集更为便捷，从而增强了VAF分析在治疗监测中的应用潜力。多项针对非小细胞肺癌患者的研究已对VAF的应用可能性展开评估。现有研究表明，VAF动态评估有助于监测治疗期间或治疗后的肿瘤进展、缓解及复发情况。此外，VAF分析在制定治疗决策方面亦显示出应用价值。然而，在VAF检测应用于临床实践之前，仍需对若干问题建立更深入的理解与标准化规范。本综述探讨了循环肿瘤DNA VAF分析在临床常规应用中的难点，重点分析了液体活检中VAF检测面临的诊断学与方法学挑战，并着重阐述了基于VAF的检测在非小细胞肺癌个体化治疗监测临床试验中的潜在应用方向。
肿瘤(癌症)患者之家