Fig. 5

The performance of somatic mutation and timMRD score in prognostication. A-B Graphical summary of the medical history and the dynamic monitoring of ctDNA mutation and cfDNA methylation profile for Patients MEDAL-059 (A) and MEDAL-109 (B). Top images show the radiological imaging at different time points and the treatment timeline for each patient. Bottom plot summarizes the dynamics of the ctDNA mutations, MethylMean, and timMRD scores at different perioperative and postoperative time points. The colored shading corresponds to the treatment modalities received by the patient at the specified time point. C-D Diagnostic performance of timMRD score and tumor-informed ctDNA mutation positive rate in identifying relapsed patients. C. Area under the receiver operating characteristic (AUROC) curve illustrating the performance of timMRD score and tumor-informed ctDNA mutation positive rate over time before radiological confirmation of disease relapse. D Receiver operating characteristic (ROC) curves plotting the specificity and sensitivity for timMRD score and tumor-informed ctDNA mutation positive rate revealing the area under the curve (AUC) at 120 days before relapse. E–F Kaplan Meier analysis of disease-free survival (DFS, expressed in days) of timMRD scores (E) and ctDNA mutation status (F) evaluated using the last postoperative follow-up sample 120 days before relapse. The patients were classified according to their timMRD scores for the last follow-up sample. The DFS of each patient was computed from the date of surgery until radiological confirmation of disease relapse. Tick marks indicate patients who were disease-free at data cut-off date. The risk table below the KM plot summarizes the number of patients included per time point. KM survival analysis was performed with log-rank statistics to compare the survival between the two subgroups. Hazard ratio (HR) and corresponding 95% confidence intervals (CI) were computed using univariable Cox proportional-hazards regression model. G Dynamic postoperative analysis of timMRD scores and mutation detection in 30 relapsed patients evaluable for tumor-informed somatic mutation status reveals the lead time before radiological confirmation of relapse for each molecular assay. The data was arranged in descending order of DFS and grouped according to ctDNA status at baseline, wherein the top 15 patients were ctDNA-positive at baseline and the bottom 15 patients were ctDNA-negative at baseline. The first data points correspond to results from Plasma B. Colored dots represent the molecular assay that detected the molecular residual disease. BothPos denotes positive status for both timMRD-score (high) and ctDNA mutation; MRDPos denotes timMRD-score high status; MutPos denotes positive tumor-informed ctDNA mutation status. Time of disease relapse is marked with ×