Focused ultrasound-mediated enhancement of blood-brain barrier permeability for brain tumor treatment: a systematic review of clinical trials.

IF 3.2 2区 医学 Q2 CLINICAL NEUROLOGY
Honglin Zhu, Caitlin Allwin, Monica G Bassous, Antonios N Pouliopoulos
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引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Abstract Image

聚焦超声介导的用于脑肿瘤治疗的血脑屏障通透性增强:临床试验系统回顾。
目的:尽管采用了包括手术切除、化疗和放疗在内的多模式疗法,脑肿瘤,尤其是多形性胶质母细胞瘤(GBM)的预后仍面临重大挑战。其中一个主要障碍是药物通过血脑屏障(BBB)的能力有限。聚焦超声(FUS)与全身给药微气泡相结合,已成为一种非侵入性、靶向性和可逆性的方法,可瞬时打开血脑屏障,从而增强给药效果。这篇综述探讨了采用BBB开放技术优化脑肿瘤药物治疗的临床试验,评估了当前面临的挑战,并提出了进一步研究的方向:方法:在PubMed和ClinicalTrials.gov上进行了系统的文献检索,搜索 "超声 "和 "脑肿瘤",搜索时间截至2023年11月。共搜索到 1446 条结果。经过标题和摘要筛选以及全文筛选(n = 48)后,35 项研究被纳入分析:我们的分析包括来自 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 GMB 和星形细胞瘤。一篇论文调查了乳腺癌的脑转移。有证据表明,FUS 可促进 BBB 开放,并在超声处理后增强药物吸收。FUS在儿科人群中的应用还很有限,目前还没有公开发表的研究,只有三项正在进行的试验专门针对这一人群:结论:FUS 是一种很有前景的策略,可安全地破坏 BBB,实现精确、无创的病灶靶向,并增强药物输送。然而,要定量评估药物吸收的改善情况,还需要进行药代动力学研究。大多数研究都是 I 期临床试验,要评估这种治疗方法的临床疗效,就必须对患者的预后进行长期跟踪调查。进一步开展涉及不同人群和病理的研究将大有裨益。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Neuro-Oncology
Journal of Neuro-Oncology 医学-临床神经学
CiteScore
6.60
自引率
7.70%
发文量
277
审稿时长
3.3 months
期刊介绍: The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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