2.5. ctDNA fraction calculation

ctDNA fraction was estimated on the basis of the allele fractions of autosomal somatic mutations, as described previously [22]. Briefly, the mutant allele fraction (MAF) and the ctDNA fraction were related, as MAF=(ctDNA*1)/([1-ctDNA]*2+ctDNA*1); therefore, ctDNA=2/([1/MAF]+1). Somatic mutations in genes with a detectable copy number amplification were omitted from ctDNA fraction estimates. ctDNA fractions were then estimated as the product of ctDNA fraction and total cfDNA yield in the corresponding sample following a normalization by plasma volume.