Intra-Arterial Super-Selective Delivery of Yttrium-90 for the Treatment of Recurrent Glioblastoma: In Silico Proof of Concept with Feasibility and Safety Analysis.

Abstract

Background: Intra-arterial cerebral infusion (IACI) of radiotherapeutics is a promising treatment for glioblastoma (GBM) recurrence. We investigated the in silico feasibility and safety of Yttrium-90-Poly(vinyl alcohol)-Microbubble (⁹⁰Y-PVA-MB) IACI in patients with recurrent GBM and compared the results with those of external beam radiation therapy (EBRT). Methods: Contrast-enhanced T1-weighted magnetic resonance imaging (T1W-MRI) was used to delineate the tumor volumes and CT scans were used to automatically segment the organs at risk in nine patients with recurrent GBM. Volumetric Modulated Arc Therapy (VMAT) treatment plans were generated using a clinical treatment planning system. Assuming the relative intensity of each voxel from the MR-T1W as a valid surrogate for the post-IACI ⁹⁰Y-PVA-MB distribution, a specific ⁹⁰Y dose voxel kernel was obtained through Monte Carlo (MC) simulations and convolved with the MRI, resulting in a ⁹⁰Y-PVA-MB-based dose distribution that was then compared with the VMAT plans. Results: The physical dose distribution obtained from the simulation of 1GBq of ⁹⁰Y-PVA-MBs was rescaled to ensure that 95% of the prescribed dose was delivered to 95% or 99% of the target (i.e., A95% and A99%, respectively). The calculated activities were A95% = 269.2 [63.6-2334.1] MBq and A99% = 370.6 [93.8-3315.2] MBq, while the mean doses to the target were 58.2 [58.0-60.0] Gy for VMAT, and 123.1 [106.9-153.9] Gy and 170.1 [145.9-223.8] Gy for A95% and A99%, respectively. Additionally, non-target brain tissue was spared in the ⁹⁰Y-PVA-MB treatment compared to the VMAT approach, with a median [range] of mean doses of 12.5 [12.0-23.0] Gy for VMAT, and 0.6 [0.2-1.0] Gy and 0.9 [0.3-1.5] Gy for the ⁹⁰Y treatments assuming A95% and A99%, respectively. Conclusions: ⁹⁰Y-PVA-MB IACI using MR-T1W appears to be feasible and safe, as it enables the delivery of higher doses to tumors and lower doses to non-target volumes compared to the VMAT approach.