Fig. 4

DNA methylation-based therapy monitoring of ALK-positive NSCLC patients. A Longitudinal cell-free biomarker kinetics of three representative patients. 5-mC scores, t-MAD scores, and EML4-ALK fusion abundances are illustrated from top to bottom. White dots mark data points below the markers respective limit of detection. Therapy regimens are given by the shaded color backgrounds and radiologic disease assessments are highlighted above individual graphs. B 5-mC score comparison in cases (n = 13) with available plasma samples at therapy line start and at disease progression from the same line. Shaded area illustrates the limit of detection. C Representative cases of detectable early molecular progression. Longitudinal profiles show 5-mC score kinetics from therapy line start to disease progression with resultant treatment switch or patient death. Time points of first molecular indication of PD are highlighted, and percent 5-mC score increase from therapy line nadir is illustrated. ALK, anaplastic lymphoma kinase; EML4, echinoderm microtubule-associated protein-like 4; PD, progressive disease; SD, stable disease