Faculty of Life Sciences and Medicine, King's College London, London, UK.
School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.
J Neurooncol. 2024 Nov;170(2):235-252. doi: 10.1007/s11060-024-04795-z. Epub 2024 Aug 29.
Brain tumors, particularly glioblastoma multiforme (GBM), present significant prognostic challenges despite multimodal therapies, including surgical resection, chemotherapy, and radiotherapy. One major obstacle is the limited drug delivery across the blood-brain barrier (BBB). Focused ultrasound (FUS) combined with systemically administered microbubbles has emerged as a non-invasive, targeted, and reversible approach to transiently open the BBB, thus enhancing drug delivery. This review examines clinical trials employing BBB opening techniques to optimise pharmacotherapy for brain tumors, evaluates current challenges, and proposes directions for further research.
A systematic literature search was conducted in PubMed and ClinicalTrials.gov up to November 2023, searching for "ultrasound" AND "brain tumor". The search yielded 1446 results. After screening by title and abstract, followed by full-text screening (n = 48), 35 studies were included in the analysis.
Our analysis includes data from 11 published studies and 24 ongoing trials. The predominant focus of these studies is on glioma, including GMB and astrocytoma. One paper investigated brain metastasis from breast cancer. Evidence indicates that FUS facilitates BBB opening and enhances drug uptake following sonication. Exploration of FUS in the pediatric population is limited, with no published studies and only three ongoing trials dedicated to this demographic.
FUS is a promising strategy to safely disrupt the BBB, enabling precise and non-invasive lesion targeting, and enhance drug delivery. However, pharmacokinetic studies are required to quantitatively assess improvements in drug uptake. Most studies are phase I clinical trials, and long-term follow-up investigating patient outcomes is essential to evaluate the clinical benefit of this treatment approach. Further studies involving diverse populations and pathologies will be beneficial.
尽管采用了包括手术切除、化疗和放疗在内的多种治疗方法，但脑肿瘤，尤其是多形性胶质母细胞瘤（GBM）仍然存在显著的预后挑战。一个主要障碍是血脑屏障（BBB）的药物递送受限。聚焦超声（FUS）联合全身给予微泡已成为一种非侵入性、靶向和可逆的方法来短暂打开 BBB，从而增强药物递送。本综述检查了使用 BBB 开放技术优化脑肿瘤药物治疗的临床试验，评估了当前的挑战，并提出了进一步研究的方向。
在 PubMed 和 ClinicalTrials.gov 上进行了系统的文献检索，截至 2023 年 11 月，检索词为“ultrasound”和“brain tumor”。搜索结果为 1446 项。经过标题和摘要筛选，然后进行全文筛选（n=48），最终有 35 项研究纳入分析。
我们的分析包括 11 项已发表研究和 24 项正在进行的试验的数据。这些研究的主要重点是胶质瘤，包括 GBM 和星形细胞瘤。有一篇论文研究了乳腺癌脑转移。证据表明，FUS 有助于 BBB 开放，并在超声处理后增强药物摄取。FUS 在儿科人群中的探索有限，没有发表的研究，只有三项正在进行的试验专门针对这一人群。
FUS 是一种有前途的策略，可以安全地破坏 BBB，实现精确和非侵入性的病变靶向，并增强药物递送。然而，需要进行药代动力学研究来定量评估药物摄取的改善。大多数研究是 I 期临床试验，需要进行长期随访以调查患者结局，以评估这种治疗方法的临床获益。涉及不同人群和病变的进一步研究将是有益的。
