1147 Effects of Sonodynamic Therapy on Clonogenic Properties of Glioblastoma Cells

INTRODUCTION: Sonodynamic therapy (SDT) is a novel treatment modality in glioblastoma (GBM) that relies on combining non-ablative sonication of tumor tissue via focused ultrasound with administration of 5-amino-levulinic acid (5ALA), to induce tumor cell kill. A multi-institutional Phase 1/2 clinical trial evaluating the safety and preliminary efficacy of SDT in recurrent GBM is currently underway (NCT05370508). In preclinical studies, SDT has been shown to cause oxidative stress and induce apoptosis in glioma cells leading to inhibition of tumor growth and increased survival in rodent glioma models. However, it remains unclear whether this paradigm has functional anti-tumor effects at the cellular level in clinical GBM patients. METHODS: A subject with recurrent multifocal GBM, who was already enrolled in the Phase 1 trial, underwent planned resection of a progressing focus of disease one day after SDT. Within the focus, SDT was applied to half of the tumor territory. After informed consent, resected tumor was used to establish regional patient-derived cultures from treated and untreated tissue. RESULTS: Cells from SDT-treated and untreated tumor territories were subjected to tumorsphere formation assays, which assess clonogenic potential, a property that has been ascribed to stem-like GBM cells. Cells from treated regions of the tumor formed fewer spheres compared to untreated regions, suggesting SDT-induced impairment in clonogenic ability. CONCLUSIONS: Our data constitute the first proof-of-concept analysis of in-human functional effects of SDT on GBM clonogenicity and tumor growth. We are currently pursuing additional functional characterization, as well as in-depth analysis of molecular biomarkers in SDT-treated and untreated tumor regions.