Abstract
Circulating tumour DNA (ctDNA) has been increasingly incorporated into the treatment of cancer patients. ctDNA is generally accepted as a powerful diagnostic tool, whereas the utility of ctDNA to monitor disease activity needs to be fully validated. Central to this challenge is the question of whether changes in longitudinal ctDNA measurements reflect disease activity or merely biological variation. Thus, the aim of this study was to explore the intra‐individual biological variation of ctDNA in lung cancer patients. We identified tumour‐specific mutations using next‐generation sequencing. Day‐to‐day and hour‐to‐hour variations in plasma concentrations of the mutant allele and wild‐type cell‐free DNA (cfDNA) were determined using digital PCR. The levels of the mutant alleles varied by as much as 53% from day to day and 27% from hour to hour. cfDNA varied up to 19% from day to day and up to 56% from hour to hour, as determined using digital PCR. Variations were independent of the concentration. Both mutant allele concentrations and wild‐type cfDNA concentrations showed considerable intra‐individual variation in lung cancer patients with nonprogressive disease. This pronounced biological variation of the circulating DNA should be investigated further to determine whether ctDNA can be used for monitoring cancer activity.
Highlights
Tumour DNA genotyping is becoming the standard practice in the treatment of cancer (Hench, Hench and Tolnay, 2018)
Circulating tumour DNA is currently implemented as a diagnostic tool, but ctDNA holds tremendous potential as a biomarker for monitoring cancer evolution and disease activity (Murtaza et al, 2015; Murtaza et al, 2013; Oellerich et al, 2017)
An increase in the concentration of ctDNA during ongoing treatment precedes disease progression (Demuth et al, 2018; Provencio et al, 2017; Xiong et al, 2017). These findings offer new hope for monitoring disease activity using ctDNA and emphasise how ctDNA may be a valuable tool in the treatment– decision pathway in the near future
Summary
Tumour DNA genotyping is becoming the standard practice in the treatment of cancer (Hench, Hench and Tolnay, 2018). By targeting specific gene alterations, cancer therapy is moving towards a more personalised approach (Oellerich et al, 2017). Since it can be challenging in some cases to obtain the tissue suitable for genetic analysis (Fenizia et al, 2015), circulating tumour DNA (ctDNA) has been studied intensively as a way to gain genetic information in a less invasive way (Oxnard et al, 2014). Circulating tumour DNA is currently implemented as a diagnostic tool, but ctDNA holds tremendous potential as a biomarker for monitoring cancer evolution and disease activity (Murtaza et al, 2015; Murtaza et al, 2013; Oellerich et al, 2017).
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