Putra · The Indian journal of medical research 2026 · systematic review of non-randomized clinical trials · n=12 studies (841 patients)

Focused ultrasound-induced blood-brain barrier modulation for drug delivery in recurrent glioblastoma: A systematic review.

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Level 3 - non-randomized controlled study

Systematic review of non-randomized clinical trials and early-phase studies with historical controls

PubMed 42397830 · doi:10.25259/IJMR_2529_2025 · record verified 2026-08-26

What was done

A systematic review following PRISMA guidelines and registered in PROSPERO (CRD420251010548) searched six databases (PubMed, ScienceDirect, Scopus, Cochrane Library, ClinicalTrials.gov, and Wiley Online Library) for studies published between 2015 and 2024. The study evaluated the clinical efficacy and safety of focused ultrasound-mediated blood-brain barrier modulation for drug delivery in recurrent glioblastoma. Risk of bias was assessed using ROBINS-I.

What was found

Twelve clinical trials including 841 patients evaluated platforms such as SonoCloud-1, SonoCloud-9, ExAblate Neuro, and NaviFUS (1-10 sonication sessions of 2.5-22 minutes). Blood-brain barrier opening occurred in 68-100% of procedures. Median overall survival ranged from 9.95 to 18 months, and median progression-free survival ranged from 2.2 to 3.5 months, with 6-month progression-free survival rates of 42-52% in studies comparing against historical chemotherapy-only controls. Adverse events were predominantly mild and transient (>85% Grade 1), with no treatment-related mortality.

Why it matters

This review synthesizes clinical evidence demonstrating that noninvasive focused ultrasound can reliably and safely open the blood-brain barrier in recurrent glioblastoma to facilitate drug delivery.

Limits

The included trials were non-randomized and largely relied on historical controls rather than direct concurrent comparison arms. Heterogeneity was present across ultrasound platforms, sonication parameters, and co-administered therapeutic agents, and the abstract does not report pooled statistical meta-analyses or direct intracerebral drug concentration measurements.

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