Change in tumor ctDNA is a prognostic biomarker in cHL treated with chemotherapy. (A) Waterfall plot of the log-fold change in ctDNA load after 2 courses of ABVD in 24 advanced stage cHL cases. On top of the graph, the interim PET/CT response scored according to the Deauville criteria and the final outcome of the patient are indicated. Histological subtype of cHL are shown above the plot. Each column is color coded according to the interim PET/CT results and the final patient outcome. Levels of ctDNA are normalized to baseline levels. The dash line tracks the −2-log threshold (CR, complete remission and cure; iPET, interim PET/CT; ND, not detectable; PD, progressive disease). (B) Box plot showing the fold change of ctDNA after 2 ABVD courses among patients who progressed vs patients who were cured. The band inside the box is the median, the bottom and top of the box are the first and third quartiles, and the ends of the whiskers represent the range. P value by Mann-Whitney U test. (C) Spider plot showing the log-fold change in ctDNA load after 2 courses of ABVD and at the end of therapy. Dots represent individual ctDNA measurements at the specified points. Each line is color coded according to the interim PET/CT results and the final patient outcome. (D) Maximally selected log-rank statistics identifies ∼2-log-fold reduction in ctDNA levels after 2 ABVD courses as the best cutoff for progression-free survival (PFS) anticipation. (E) Kaplan-Meier curve of PFS stratified according to whether a 2-log reduction in ctDNA was achieved or not after 2 ABVD courses in 24 advanced stage cHL cases. Among patients achieving more than 2-log reduction after 2 ABVD courses, the sole event registered was a death in remission. Conversely, among patients achieving less than 2-log reduction after 2 ABVD courses, all the events were progressions.