Our group has previously reported that the mTBI of ctDNA can correlate with changes in tumor burden in response to HER2-targeted therapy.15 The mTBI was calculated using the mean allele fraction of mutations in a mutation cluster with the highest cellular prevalence of ctDNA at each time point.15 In this study, we fully considered the temporal and spatial heterogeneity of tumors and the characteristics of ctDNA and constructed a new ctDNA-based mTBI algorithm that may be more universally applicable. This evidence concerns the gene ERBB2 and neoplasm.