Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Abstract

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.

Next-generation sequencing impact on cancer care: applications, challenges, and future directions

“…VAF are important measures of genetic variation that are used in a broad range of tumor assessments, including its’ purity and ploidy, and it can be measured from both genomic (DNA) and transcriptomic (RNA) sequencing data as the encoded and expressed allele frequencies, respectively ( Slowinski et al, 2020 ). VAF can be assessed using either tissue samples or ctDNA isolated from liquid biopsy, and it may distinguish driver from passenger mutations and the potential germline status of genomic alterations ( Galant et al, 2024 ). Thus, by calculating this genomic biomarker, VAF may represent a surrogate for mutation clonality and can act as a tool to evaluate the genomic heterogeneity of tumors ( Boscolo Bielo et al, 2023 ), which is why lately, an extensive amount of research has focused on using VAF in ctDNA analyses in several types of tumors.…”