Safety of intra-arterial chemotherapy with or without osmotic blood-brain barrier disruption for the treatment of patients with brain tumors

Kutluay Uluc; Prakash Ambady; Matthew K McIntyre; John Philip Tabb; Cymon N Kersch; Caleb S Nerison; Amy Huddleston; Jesse J Liu; Aclan Dogan; Ryan A Priest; Rongwei Fu; Joao Prola Netto; Dominic A Siler; Leslie L Muldoon; Seymur Gahramanov; Edward A Neuwelt

doi:10.1093/noajnl/vdac104

Safety of intra-arterial chemotherapy with or without osmotic blood-brain barrier disruption for the treatment of patients with brain tumors

Neurooncol Adv. 2022 Jun 25;4(1):vdac104. doi: 10.1093/noajnl/vdac104. eCollection 2022 Jan-Dec.

Authors

Kutluay Uluc¹, Prakash Ambady¹, Matthew K McIntyre², John Philip Tabb², Cymon N Kersch¹, Caleb S Nerison³, Amy Huddleston¹, Jesse J Liu², Aclan Dogan², Ryan A Priest⁴, Rongwei Fu⁵, Joao Prola Netto⁶, Dominic A Siler², Leslie L Muldoon¹, Seymur Gahramanov⁷, Edward A Neuwelt¹

Affiliations

¹ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
² Department of Neurosurgery, Oregon Health & Science University, Portland, Oregon, USA.
³ Western University of Health Sciences COMP-NW, Lebanon, Oregon, USA.
⁴ Department of Interventional Radiology, Oregon Health & Science University, Portland, Oregon, USA.
⁵ School of Public Health, Oregon Health & Science University, Portland, Oregon, USA.
⁶ TRG Medical Imaging, Portland, Oregon, USA.
⁷ Capital Neurosurgery Specialists, Salem Health, Salem, Oregon, USA.

Abstract

Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures.

Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor.

Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients.

Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor.

Keywords: blood–brain barrier; brain tumor; intra-arterial chemotherapy; neuro-oncology.