Introduction Despite years of research and continued attempts at improving surgical outcomes and chemotherapeutic regimens, glioblastoma multiforme (GBM) remains a devastating diagnosis with a dismal overall survival of approximately 15 months.¹ Given this, the need to continue innovating within the field remains. One such innovation is the use of super-selective intra-arterial delivery to better target tumors while minimizing the off-target effects. Here we discuss the current state of intra-arterial delivery of chemotherapeutic agents and novel cellular therapies and future directions within the field.

Discussion Current use of super-selective intra-arterial therapies in the treatment of GBM are focused on clinical trials. These trials are focused on one of two treatments: 1) intra-arterial chemotherapy with opening of the blood-brain barrier or 2) novel cell-based therapies. The combination of super-selective intra-arterial bevacizumab with mannitol to disrupt the blood-brain barrier is currently being studied in relapsed GMB and anaplastic astrocytoma (AA) (NCT01269853). An early report has shown radiographic benefit based on RANO criteria in a patient with prior bevacizumab failure.² Additional ongoing trials are assessing cetuximab with reirradiation for relapsed/refractor GBM, AA, and anaplastic oligoastrocytoma (AOA) (NCT02800486) and the combination of bevacizumab with temozolomide and radiation in newly diagnosed GBM (NCT05271240). Combining super-selective intra-arterial delivery with novel treatment agents is another area of significant advancement. As cell-based therapies advance, their delivery will become a pivotal factor in their success. Novel imaging techniques have been developed for the current trial utilizing super-selective intra-arterial delivery of mesenchymal stem cells loaded with an oncolytic virus (NCT03896568).³ This trial developed a method to fuse MRI and cone-beam imaging performed in the angiography suite, helping better guide infusion of the therapeutic agent. This targeted approach is designed to mitigate the off-target adverse effects of treatment. Utilization of therapies that combine immune modulation and direct oncolysis will necessitate this super-selective approach to balance antitumor effects with an overactive antiviral/inflammatory response.⁴ The question remains: where do we go from here? Challenges remain both procedurally and with the therapies themselves. Angiographically, GBMs rarely show the tumor blush seen in hypervascularized tumors. This makes the selection of feeding vessels significantly more difficult, requiring the neurointerventionalist to refer to additional imaging modalities and mentally correlate imaging to select the optimal vessel(s) for delivery. And while novel techniques have evolved to help target tumors, optimizing infusion protocols, better defining feeder vessels, and becoming increasingly more selective through smaller microcatheters all remain necessary in the future.

Conclusions Super-selective intra-arterial delivery of both chemotherapeutic and novel cell-based therapies remains at the forefront of current GBM research, bringing together the fields of neurointervention, neurosurgical oncology, and medical neuro-oncology. This work shows significant promise in its aim to provide new pathways to better treat these patients. Further advancement of microcatheters and therapies alike will continue to grow this burgeoning sub-focus within neurointervention.

References

1. Thakkar JP, et al. DOI: 10.1158/1055-9965.EPI-14-0275

2. Faltings L, et al. DOI: 10.1016/j.wneu.2019.07.137

3. Chen SR, et al. DOI: 10.1136/neurintsurg-2021-018190

4. Ene CI, et al. DOI: 10.3171/2020.11.FOCUS20853

Disclosures S. Capone: None. B. Patel: None.