Molecular responses in ctDNA during therapy. (A) Line graph showing the dynamic changes in the ctDNA concentration (y-axis) incorporated with temporal MRD test results in the patients with midstaging plasma samples available. Colors of the lines represent different clinical courses. Numbers for the patients with relapse samples available indicate months from diagnosis. (B) Waterfall plot of quantified molecular responses (log10-transformed fold-change in ctDNA concentration, y-axis) after 3 cycles of therapy. Patients (columns, x-axis) arranged according to responses and MRD test results. Bar colors represent midstaging responses according to CT-scan. (C) Crosstabulation of midstaging MRD and CT-scan results. (D) Kaplan-Meier survival estimate for failure-free survival (FFS) according to MRD test results at midstaging. (E) Waterfall plot of the quantified molecular responses between midstaging and endstaging plasma samples (log10-transformed fold-change in ctDNA concentration, y-axis) in evaluable patients (x-axis, n = 53). Patients with MRD^end- shown with an arbitrary negative value for fold-change. Patients deemed MRD-negative at midstaging and MRD-positive at endstaging are not included. Bar colors represent end-of-therapy responses according to PET-CT. (F) Kaplan-Meier survival estimate for FFS according to end-of-treatment MRD test result. (G,H) Dot plots representing end-of-treatment MRD test results and ctDNA concentration (y-axis) per patient according to (G) end-of-therapy response evaluation results from PET-CT (Deauville score [D-S]) and (H) whether a PET-avid lesion was tissue biopsied after therapy. Numbers of patients are shown in parenthesis, and black dots with red borders indicate patients who experienced lymphoma progression during follow-up. (G) Crosstabulation below the plot shows the number of patients according to D-S and MRD test results. (H) Round shape of dots denotes biopsies negative for viable lymphoma (9 of 10), and the triangle denotes the only patient with tissue biopsy deemed positive for lymphoma. Tissue-biopsied cases who relapsed during follow-up are annotated for their end-of-therapy PET-CT responses. MRD, minimal residual disease; CR/CRu, complete response (unconfirmed); PR, partial response; PD, progressive disease.