Intra-arterial chemotherapy for malignant gliomas: a critical analysis

Abstract

Intra-arterial (IA) chemotherapy for malignant gliomas including glioblastoma multiforme was initiated decades ago, with many preclinical and clinical studies having been performed since then. Although novel endovascular devices and techniques such as microcatheter or balloon assistance have been introduced into clinical practice, the question remains whether IA therapy is safe and superior to other drug delivery modalities such as intravenous (IV) or oral treatment regimens. This review focuses on IA delivery and surveys the available literature to assess the advantages and disadvantages of IA chemotherapy for treatment of malignant gliomas. In addition, we introduce our hypothesis of using IA delivery to selectively target cancer stem cells residing in the perivascular stem cell niche.

Figure 1

Sketch of our hypothesis on selective intra-arterial niche disruption (SIAND) and delivery A) Initially the BBB is closed and tumor stem-like cells located in the perivascular niche release VEGF and express VEGFR-2 receptors. B) The microcatheter is placed in the tumor supplying vessel and mannitol followed by bevacizumab is infused through the microcatheter. This opens the BBB and bevacizumab is able to enter into the perivascular niche to bind soluble VEGF. C) After IA treatment the BBB recloses and bevacizumab is trapped in the perivascular niche. VEGF signaling from tumor cells is blocked and VEGF signaling is diminished.

Figure 2

Sagittal (A) and coronal (E) post-gadolinium T1W images show a large left fronto-temporal located glioblastoma multiforme (arrow) in a 72-year-old man. On the un-subtracted DSA (B, F) the microcatheter tip (arrow) with regard to the craniotomy site (asterisk) indicates the point of chemotherapy injection. Contrast infusion into the distal branch of the left middle cerebral artery (C, G) as well as left anterior cerebral artery (D, H) supplying the GBM demonstrates the distribution of IA mannitol and temozolomide infusion in sagittal (C, D) and coronal (G, H) planes.