Dataset Information

From Focused Ultrasound Tumor Ablation to Brain Blood Barrier Opening for High Grade Glioma: A Systematic Review.

ABSTRACT:

Background

Focused Ultrasound (FUS) is gaining a therapeutic role in neuro-oncology considering its novelty and non-invasiveness. Multiple pre-clinical studies show the efficacy of FUS mediated ablation and Blood-Brain Barrier (BBB) opening in high-grade glioma (HGG), but there is still poor evidence in humans, mainly aimed towards assessing FUS safety.

Methods

With this systematic review our aim is, firstly, to summarize how FUS is proposed for human HGG treatment. Secondly, we focus on future perspectives and new therapeutic options. Using PRISMA 2020 guidelines, we reviewed case series and trials with description of patient characteristics, pre- and post-operative treatments and FUS outcomes. We considered nine case series (five about tumor ablation and four about BBB opening) with FUS-treated HGG patients between 1991 and 2021.

Results

Sixty-eight patients were considered in total, mostly males (67.6%), with a mean age of 50.5 ± 15.3 years old. Major complication rates were found in the tumor ablation group (26.1%). FUS has been rarely applied for direct tumoral ablation in human HGG patients with controversial results, but at the best of current studies, FUS-mediated BBB opening is showing good results with very low complication rates, paving the way for a new reliable technique to improve local chemotherapy delivery and antitumoral immune response.

Conclusions

FUS can become a complementary technique to surgical resection and standard radiochemotherapy in recurrent HGG. Ongoing trials could provide in the near future more data on FUS-mediated BBB opening impact on progression-free survival, overall survival and potential drug-delivery capacities.

SUBMITTER: Paun L

PROVIDER: S-EPMC8615744 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Focused ultrasound (FUS) in combination with systemically injected microbubbles can be used to non-invasively open the blood-brain barrier (BBB) in targeted regions for a variety of therapeutic applications. Over the past two decades, preclinical research into the safety and efficacy of FUS-induced BBB opening has proven this technique to be transient and efficacious, propelling FUS-induced BBB opening into several clinical trials in recent years. However, as clinical trials further progress, the neuroinflammatory response to FUS-induced BBB opening needs to be better understood. In this study, we provide further insight into the relationship of microbubble cavitation and the resulting innate immune response to FUS-induced BBB opening. By keeping ultrasound parameters fixed (i.e. frequency, pressure, pulse length, etc.), three groups of mice were sonicated using a real-time cavitation controller until a target cavitation dose was reached (1 x 107 V2•s, 5 x 107 V2•s, 1 x 108 V2•s). The change in relative gene expression of the mouse inflammatory cytokines and receptors were evaluated at three different time-points (6 h, 24 h, and 72 h) after FUS. At both 6 and 24 h time-points, significant changes in relative gene expression of inflammatory cytokines and receptors were observed across all cavitation groups. However, the degree of changes in relative expression levels and the number of genes with significant changes in expression varied across the cavitation groups. Groups with a higher cavitation dose exhibited both greater changes in relative expression levels and greater number of significant changes. By 72 h post-opening, the gene expression levels returned to baseline in all cavitation dose groups, signifying a transient inflammatory response to FUS-induced BBB opening at the targeted cavitation dose levels. Furthermore, the real-time cavitation controller was able to produce consistent and significantly different BBB permeability enhancement volumes across the three different cavitation dose groups. These results indicate that cavitation monitoring and controlling during FUS-induced BBB opening can be used to potentially modulate or limit the degree of neuroinflammation, further emphasizing the importance of implementing cavitation controllers as FUS-induced BBB opening is translated into the clinic.