Abstract
PurposeTo evaluate the safety, feasibility, and preliminary efficacy of yttrium-90 (90Y) radioembolization (RE) as a minimally invasive treatment in a canine model with presumed spontaneous brain cancers.MaterialsThree healthy research dogs (R1–R3) and five patient dogs with spontaneous intra-axial brain masses (P1–P5) underwent cerebral artery RE with 90Y glass microspheres (TheraSphere). 90Y-RE was performed on research dogs from the unilateral internal carotid artery (ICA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) while animals with brain masses were treated from the ICA. Post-treatment 90Y PET/CT was performed along with serial neurological exams by a veterinary neurologist. One month after treatment, research dogs were euthanized and the brains were extracted and sent for microdosimetric and histopathologic analyses. Patient dogs received post-treatment MRI at 1-, 3-, and 6-month intervals with long-term veterinary follow-up.ResultsThe average absorbed dose to treated tissue in R1–R3 was 14.0, 30.9, and 73.2 Gy, respectively, with maximum doses exceeding 1000 Gy. One month after treatment, research dog pathologic analysis revealed no evidence of cortical atrophy and rare foci consistent with chronic infarcts, e.g., < 2-mm diameter. Absorbed doses to masses in P1–P5 were 45.5, 57.6, 58.1, 45.4, and 64.1 Gy while the dose to uninvolved brain tissue was 15.4, 27.6, 19.2, 16.7, and 33.3 G, respectively. Among both research and patient animals, 6 developed acute neurologic deficits following treatment. However, in all surviving dogs, the deficits were transient resolving between 7 and 33 days post-therapy. At 1 month post-therapy, patient animals showed a 24–94% reduction in mass volume with partial response in P1, P3, and P4 at 6 months post-treatment. While P2 initially showed a response, by 5 months, the mass had advanced beyond pre-treatment size, and the dog was euthanized.ConclusionThis proof of concept demonstrates the technical feasibility and safety of 90Y-RE in dogs, while preliminary, initial data on the efficacy of 90Y-RE as a potential treatment for brain cancer is encouraging.
Highlights
Glioblastoma multiforme (GBM) is the most common and aggressive cancer of the central nervous system, with an age-adjusted incidence rate of 3.2 per 100,000 individuals [1] and a median survival time of 15 months [2]
Research dog pathologic analysis revealed no evidence of cortical atrophy and rare foci consistent with chronic infarcts, e.g., < 2-mm diameter
Because of the tight tortuosity of the Treatment efficiencies and delivery rates Owing to the small lumen of the Excelsior SL-10 microcatheter (0.021”, 1.7 Fr), the 20-mass vol 2.76 (mL)/min minimum infusion rate recommended for the TheraSphere delivery system could not be achieved
Summary
Glioblastoma multiforme (GBM) is the most common and aggressive cancer of the central nervous system, with an age-adjusted incidence rate of 3.2 per 100,000 individuals [1] and a median survival time of 15 months [2]. Standard of care radiation therapy as a part of new-onset GBM treatment using external beam radiation therapy (EBRT) is typically prescribed with fractionated doses over 6 weeks for a total dose of 60 Gy to the tumor, a threshold at which survival benefits are maximal and neurotoxicity is minimal [8, 9]. RE minimizes non-target radiation with an average tissue penetration of 4.1 mm [14] as opposed to 3–4 cm in typical I-125 brachytherapy or EBRT where the entire cortex may be exposed to substantial doses of radiation [15,16,17]. The potential of RE to treat GBM will depend on the balance of embolic-related ischemic effects and the inherent ability to deliver high doses of radiation to hypervascular tumors while limiting normal tissue exposure
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