ctDNA concentrations at diagnosis. (A) Box and whisker plot of baseline ctDNA concentrations for controls vs cHL patients in general and grouped by disease stage category. (B) ROC analysis for ctDNA concentrations at diagnosis determines the optimal ctDNA cutoff (Youden index) between cHL cases from controls (blue). Corresponding sensitivity and specificity are shown in blue. (C-F) Box and whisker plots of baseline ctDNA concentrations in cHL patients with treatment response vs failure (C), and for early-stage disease: absence vs presence of B symptoms (D), normal vs elevated ESR levels (E), and limited vs extensive nodal involvement (F). Outliers are defined as values 1.5 × IQR below the first or above the third quartile. *P < .05; **P < .01; ***P < .001. AUC, area under the curve; CR, complete remission.