Authors: Nitesh Vijay Patel, MD; Lukas Faltings, BA; Tamika Wong, MPH; Sherese Fralin, NP; Ashley Ray, NP; Mona Li, BA; Rafael Ortiz, MD; David Langer, MD; John Boockvar, MD (Bloomfield, NJ)

Introduction Glioblastoma multiforme (GBM) has a 2-year survival of 26.5%. The perivascular cancer stem cell (CSC) niche is of high-interest and pre-clinical evidence suggests bevacizumab depletes this niche. We explore intra-arterial (IA) bevacizumab in patients with newly diagnosed GBM. Methods An open-label, single-arm, non-randomized trial enrolled patients with newly diagnosed GBM. Lesions had an endovascularly accessible arterial supply and location limiting significant resection. Mannitol (20%, 12.5 mL) opened the BBB and IA bevacizumab was delivered (15 mg/kg; 1 mL/s). On Day 0, patients underwent either biopsy or subtotal resection. At approximately day 30, a single dose of IA bevacizumab was given followed by standard radiation and oral temozolomide (TMZ) for 42 days. At day 72, a 1 month rest period was started; at approximately day 100, maintenance oral TMZ was started (150-200 mg/m 2 ; 5 days on / 23 days off x 6-12 months). At days 120 and 210, repeat IA bevacizumab was delivered. Overall survival (OS) and progression free survival (PFS) were computed and adverse events (AE) were recorded. Results Fourteen patients were analyzed. Average age was 57 + 13 with equal males/females. Eleven completed all three IA treatments; the remaining 3 completed 2 of 3 treatments but further treatment was stopped due to progression or AE. Median OS was 38.2 months (92.3% survival at 1 year; 51.3% at 3 years). Median PFS was 29.5 months (62.2% PFS at 1 year; 31.2% at 3 years). Adverse events included seizures (2), deep venous thrombosis (3), pulmonary embolus (1), and intracranial hemorrhage (1); all managed non-operatively with full recovery to baseline. Conclusions Delivery of IA bevacizumab is safe and may be particularly effective for the CSC niche. Our findings suggest IA bevacizumab may be a useful adjunct as OS and PFS are significantly longer in this cohort relative to comparable series in the literature.