Advances in endovascular neuro-oncology: endovascular selective intra-arterial (ESIA) infusion of targeted biologic therapy for brain tumors

Abstract

BackgroundMalignant gliomas continue to have a poor clinical outcome with available therapies. In the past few years, new targeted biologic therapies have been studied, with promising results. However, owing to problems with ineffective IV delivery of these newer agents, an alternative, more direct delivery mechanism is needed. Simultaneously, advancements in neuroendovascular technology have allowed endovascular selective intra-arterial approaches to delivery. This method has the potential to increase drug delivery and selectively target tumor vasculature.ObjectiveTo review the history of IA therapy for brain tumors, prior failures and successes, the emergence of new technologies and therapies, and the future direction of this young field.MethodsA comprehensive literature search of two databases (PubMed, Ovid Medline) was performed for several terms including ‘brain tumor’, ‘glioma’, and ‘endovascular intra-arterial’. Forty-five relevant articles were identified via a systematic review following PRISMA guidelines. Additional relevant articles were selected for further in-depth review. Emphasis was given to articles discussing selective intra-arterial intracranial delivery using microcatheters.ResultsEndovascular intra-arterial therapy with chemotherapy has had mixed results, with currently active trials using temozolomide, cetuximab, and bevacizumab. Prior attempts at IA chemotherapy with older-generation medications did not surpass the efficacy of IV administration. Advances in neuro-oncology have brought to the forefront new targeted biologic therapies.ConclusionsIn this review, we discuss the emerging field of endovascular neuro-oncology, a field that applies modern neuroendovascular techniques to the delivery of new therapeutic agents to brain tumors. The development of targeted therapies for brain tumors has been concurrent with the development of microcatheter technology, which has made superselective distal intracranial arterial access feasible and safe.

Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis

“…We identified 271 articles and 20 trials to meet our inclusion criteria. These numbers are reflected in the quoted numbers reported by recently published reviews [31,84], even though this is the first study to offer a precise number of clinical trials involving intraarterial brain tumor therapy, highlighting a previously unreported area in the field as to how many distinct trials have officially been registered and conducted since the technique was first described in 1950 [85]. The complexity of successfully translating intra-arterial drug delivery into the clinic is demonstrated by the fact that in the last 20 years, only 6 trials eligible for this review have completed recruitment [69,74,76,77,82,86], and results of just a single study are publicly available at the ClinicalTrials.gov portal as of August 2021 [69].…”

A Multifaceted Approach to Optimizing AAV Delivery to the Brain for the Treatment of Neurodegenerative Diseases

“…In the past decade, the utilization of interventional approaches for the treatment of neurologic conditions has increased dramatically (Cox et al, 2019), mostly in the setting of neurovascular diseases such as strokes, aneurysms, and vascular malformations. As result, there have been considerable advancements in neuro-interventional technologies (Srinivasan et al, 2020). Unlike IT-CM delivery, which remains in its infancy, most large academic hospitals have neuro-interventionalists already with the skill set necessary to deliver AAVs IA.…”

Intraarterial delivery of virotherapy for glioblastoma

“…25 Thus far, the therapeutic agent has been chemotherapy, including older agents such as cisplatin/vincristine, and more recently "newer" agents such as temozolomide 26 and bevacizumab. 27,28 These agents have had some limited success, but have not progressed beyond phase 2 studies (www.clinicaltrials.gov no. : NCT01811498).…”

“…The next generation of therapies for GBMs, which includes OVs, has the potential to overcome some of the mechanistic limitations of these chemotherapies as well as their dose-related side effects. ESIA therapy can theoretically be used with a variety of classes of agents, 28 including OVs 30 (Fig. 1).…”

“…30 Whereas some clinical studies of oHSV used in the resection bed of GBMs resulted in "washout," ESIA infusion with loading in MSCs and proapoptotic variant oHSV-TRAIL (tumor necrosis factor-related apoptosisinducing ligand) may overcome these shortcomings. 28 Other methods of using OVs can also be considered. Similar to conventional IA delivery, ESIA delivery can be performed with replication-selective viruses with therapeutic transgenes.…”