EP56 Targeted single low-dose intra-arterial bevacizumab for steroid-refractory radiation necrosis of the brain

• Published in: Journal of neurointerventional surgery Vol. 13; no. Suppl 2; p. A23
• Main Authors: Dashti, SR, Kadner, RJ, Folley, BS, Sheehan, JP, Han, DY, Kryscio, RJ, Carter, MB, Shields, LBE, Plato, BM, La Rocca, RV, Spalding, AC, Yao, TL, Fraser, JF
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.08.2021
• Subjects: Edema; Monoclonal antibodies; Necrosis; Radiation; Steroids
• ISSN: 1759-8478; 1759-8486
• DOI: 10.1136/neurintsurg-2021-ESMINT.55

IntroductionPhase II, single-arm, prospective trial in patients with steroid-refractory brain radiation necrosis (RN).AimEvaluate safety and efficacy of single low-dose targeted intra-arterial (IA) bevacizumab following osmotic blood-brain barrier disruption (BBBD).MethodsFollowing BBBD, 10 adults underwent targeted 2.5 mg/kg IA bevacizumab. RN, edema, headache, steroid dependency were quantified at baseline and 12-months. Data (mean±SEM) analyzed using Wilcoxon signed-rank tests and one-way repeated measures ANOVA test of linear trend. Null hypothesis rejected for p<0.05.ResultsRN decreased by 74.4±5.2% with significant linear trend [F(1)=10.940, n=8, p=0.013, effect size=0.610]. Vasogenic edema decreased by 50.1±13.2% but linear trend did not reach significance [p=0.102]. Headache decreased by 84.4±6.5% with significant linear trend [F(1)=9.299, n=8, p=0.019, effect size=0.571]. Only 1/10 patients were steroid dependent 12-months after bevacizumab. 0/10 died or exhibited AEs attributed to bevacizumab alone. 4 AEs of short duration and moderate severity were probably related to BBBD (tonic/clonic seizures with altered mental status 2-hours post-procedure) or BBBD+bevacizumab (mono-ocular blurred vision with diplopia on day 1). 2/10 patients who experienced marked improvement at 3 months exhibited RN recurrence requiring intervention (surgery at 10-months; 4-cycles IV bevacizumab at 11-months, respectively).ConclusionsSingle low-dose targeted intra-arterial bevacizumab led to durable radiographic and clinical improvement of RN during 12-months follow-up in 8/10 patients. To our knowledge this is the first prospective report of this novel approach in adults. Randomized trials are needed comparing targeted low-dose IA bevacizumab to multi-cycle IV bevacizumab at higher doses to determine which is longer-lasting, safer, cheaper alternative in brain RN.ReferencesDashti SR, Spalding A, Kadner RJ, et al. Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain. J Neurosurg Pediatr 2015;15(1):20–25. doi:10.3171/2014.9.PEDS14198Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 2011;79(5):1487–1495. doi:10.1016/j.ijrobp.2009.12.061DisclosureNothing to disclose