Figure 3 from Paxalisib with Trastuzumab for HER2-Positive Metastatic Breast Cancer with Active Brain Metastases: A Phase II Trial with Integrated Plasma and CSF ctDNA Analyses

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Abstract
TF dynamics, clonal evolution, and phylogenetic analyses from plasma and CSF and plasma ctDNA. A, Median TF estimated by ULP-WGS in paired plasma and CSF samples at baseline and cycle 2 day 1 (C2D1). TF was consistently higher in CSF than plasma at both timepoints (n = 10 samples/5 patients). B, Longitudinal CSF TF dynamics in individual patients relative to changes in CNS target lesions assessed by RANO-BM criteria (n = 10 samples/5 patients). Patients with declining CSF TF exhibited reductions in CNS tumor burden, whereas increasing TF was associated with lesion growth or nonevaluable disease. The asterisk (*) identifies the patient who derived clinical benefit. C, Clonal evolution in CSF ctDNA from patient #5, showing changes in cancer cell fraction (|ΔCCF| >0.20) between timepoints. D, Phylogenetic reconstruction for patient #4 based on WES of plasma and CSF ctDNA, illustrating shared truncal mutations and CSF subclones present at low clonality in plasma. CB, clinical benefit.