Longitudinal changes in ctDNA levels during treatment evaluation. (A) Fold change in ctDNA genome equivalents (hGEs) is shown at multiple treatment-evaluation time points, including baseline, C1D8, C1D15, C2D1, C2D15, interim, and EOT. Solid lines represent patients achieving CMR on PET-CT, whereas dashed lines represent non-CMR patients. PET-CT responses are color coded: CMR (green), PMR (yellow), SD (orange) and PD (red). (B) Correlation between PET-CT TMTV and ctDNA levels (hGEs per milliliter) at baseline (grey) and EOT (green) time points (Pearson correlation coefficient, ρ = 0.90; P < .0001). (C) Comparison of PET-CT TMTV and ctDNA VAF at baseline and interim time points. Significant reductions in both TMTV (Δ = 445 cm3; median of differences) and VAF (Δ = 9%; Psigned rank test < .001). These reductions correspond to a 96.78% and 99.86% decrease, respectively, or a 31- vs 691-fold reduction. Zero values are not shown due to log scaling. Significant associations are indicated by an asterisk. PD, progressive disease; SD, stable disease.
