Strategies for Improved Intra-arterial Treatments Targeting Brain Tumors: a Systematic Review

Abstract

Conventional treatments for brain tumors relying on surgery, radiation, and systemic chemotherapy are often associated with high recurrence and poor prognosis. In recent decades, intra-arterial administration of anti-cancer drugs has been considered a suitable alternative drug delivery route to intravenous and oral administration. Intra-arterial administration is believed to offer increasing drug responses by primary and metastatic brain tumors, and to be associated with better median overall survival. By directly injecting therapeutic agents into carotid or vertebral artery, intra-arterial administration rapidly increases intra-tumoral drug concentration but lowers systemic exposure. However, unexpected vascular or neural toxicity has questioned the therapeutic safety of intra-arterial drug administration and limits its widespread clinical application. Therefore, improving targeting and accuracy of intra-arterial administration has become a major research focus. This systematic review categorizes strategies for optimizing intra-arterial administration into five categories: (1) transient blood-brain barrier (BBB)/blood-tumor barrier (BTB) disruption, (2) regional cerebral hypoperfusion for peritumoral hemodynamic changes, (3) superselective endovascular intervention, (4) high-resolution imaging techniques, and (5) others such as cell and gene therapy. We summarize and discuss both preclinical and clinical research, focusing on advantages and disadvantages of different treatment strategies for a variety of cerebral tumor types.

Keywords: blood–brain barrier; brain tumor; chemotherapy; imaging; intra-arterial; nanoparticles; superselective cerebral infusion; targeted therapy.

Figure 1

Methodological approach. (A) PRISMA flow diagram. (B) Pie chart of the total number of publications between 1981 and 2020. (C) Temporal trend graph of the numbers of publications for different strategies. Since 1981, the numbers of articles on BBB/BTB disruption published in consecutive decades are 16, 42, 22, and 14, respectively. The numbers of articles on SIACI published in consecutive decades are 12, 9, 4, and 14, respectively. The numbers of articles on imaging published in consecutive decades are 8, 9, 2, and 14, respectively. The numbers of articles on TCH published in consecutive decades are 4, 8, 2, and 10, respectively. The numbers of articles on other strategies published in consecutive decades are 15, 16, 12, and 3, respectively.

Figure 2

Schematic diagram of strategies for improving intra-arterial administration.