SURG-98. Clinical outcomes, operational metrics, and translational insights derived from trials of MR-guided, transcranial, microbubble-enhanced focused ultrasound for brain tumors: a 2010-2025 evidence analysis

Abstract INTRODUCTION Multi-factorial, complex challenges exist in developing actionable diagnostics and effective therapies for brain malignancies. Approaches that leverage biological underpinnings are increasingly recognized as necessary. Several consensus efforts and professional guidelines have recommended that future neuro-oncology efforts to develop disease management strategies should: (i) integrate longitudinal molecular profiling of tumor, and (ii) recognize/target upfront blood-brain-barrier (BBB)-related hindrance(s) to drug distribution and efficacy. Given both factors remaining to be well-resolved, breakthrough paradigms are needed. Microbubble-enhanced transcranial focused ultrasound (MR-guided MB-FUS) is an emerging, directed-energy approach, unlocking new neuro-oncology paradigms for optimized diagnosis and treatment. METHODS A comprehensive search (last update: 04/2025) for all completed and ongoing trials of MR-guided MB-FUS for brain tumors was conducted across published and grey literature. Trial-related operational metrics and clinical outcomes were extracted and synthesized, and translational readiness of MB-FUS applications was graded. Results were summarized through descriptive statistics. RESULTS A total of 19 trials of MR-guided MB-FUS for brain tumors were identified: 6 complete (across 2010-2025) and 13 ongoing/in-follow-up, with ongoing/planned involvement of over 20 North American institutions. The trials pertained to multi-modal applications of MRgFUS, including immunomodulation, radiosensitization, sonodynamic therapy, and BBB opening. All completed MRgFUS trials so far had investigated BBB opening as primary application (NCT02343991/BBB001, NCT03322813/BT004, NCT03714243/BT006, BT008NA: NCT03616860/BT008C plus NCT03551249/BT008, NCT04998864/BT008E, and NCT03712293/BT008K), demonstrating safety and clinical feasibility of BBBO for enhanced CNS delivery and efficacy of systemic therapies across a range of drug sizes, as well as sono-liquid biomarker profiling (SLB). Amongst ongoing trials, N=12/13 pertained to primary brain tumors, while the only ongoing trial for brain metastases was on combining immune checkpoint inhibitors with MRgFUS (NCT05317858/BT012). N=5/13 ongoing trials were evaluating sono-dynamic therapy. CONCLUSIONS Integrating MB-FUS into standard-of-care could potentially target the major gaps in effective management of brain malignancies. Efforts to advance MB-FUS will be aided by ongoing device evolution, support from professional societies, and multi-institutional collaboration through dedicated research consortia (like ReFOCUSED).