Part 1 of 2 Background Measurable Residual Disease (MRD) monitoring – for purposes of this blog – will be the act of looking for somatic variants in a liquid biopsy sample by analyzing circulating cell-free DNA (ccfDNA). This is done to monitor the disappearance of a metastatic solid tumor during treatment and to follow any future reemergence of that cancer. Analyzing ccfDNA assumes that circulating tumor DNA (ctDNA) will be present, and the median ctDNA frequency in patient samples across cancers seems to be around 0.5 to 1 %. Thus, the median variant allele frequencies (VAFs) of the somatic variants will start around this range, and the goal of MRD monitoring is to be able to detect them at much lower VAFs. This can be challenging and if we are going to design an assay for MRD monitoring, then we need to be aware of them and overcome them.