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

SIMPLE SUMMARY: High-grade glioma (HGG) is a burdening oncological pathology for which maximum safe resection followed by combined chemoradiation therapy is still the gold standard. Despite these treatments the overall survival is less than 2 years. Alternative strategies are currently being investigated, including Focused Ultrasound (FUS). Given its non-invasiveness and promising pre-clinical results for tumor ablation, brain-blood barrier (BBB) opening and drug delivery, FUS is poised to achieve a therapeutic role in HGG treatment. This systematic review aims to identify the different modalities of how FUS can be used, how it impacts on survival in the clinic, based on the existing evidence. FUS-mediated tumor ablation still needs further investigation due to its controversial effects and complications. FUS-mediated BBB opening is showing positive results with low complication rate, as such potentially a gamechanger in future oncological treatments. Ongoing trials will clarify FUS impact on HGG patients. 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.