The Sphere Conundrum: Using Voxel-based Dosimetry to evaluate sphere concentration and tumor dose in Hepatocellular Carcinoma treated with Y-90 Radioembolization

Purpose To evaluate sphere concentration delivered to tumor and non-tumor tissue using voxel-based dosimetry as it relates to treatment, pathologic outcomes, and adverse events.Methods A retrospective, single-center analysis of patients (n = 57) with solitary HCC who were treated with Y90 radiation segmentectomy with Y90 glass microsphere infusion (TheraSphere; Boston Scientific, Marlborough, MA, USA) from 2020 to 2022 was performed. Post-treatment dosimetry was evaluated using Mirada DBx Build 1.2.0 Simplicit90Y dosimetry software. Voxel-based dosimetry and MIRD formula were utilized to calculate sphere concentration to tumor and non-tumor tissue. Time to progression (TTP), treatment response, pathologic response, and adverse events were studied.Results Fifty-seven patients with solitary tumors were analyzed with a median tumor diameter of 3.4cm (range 1.2-6.8cm). The median tumor absorbed dose was 692Gy (range, 256-1332Gy) with a median perfused treatment volume of 113mL (range, 33.6-442mL). Median sphere activity (SA) at time of delivery was 1428Bq (range, 412-2589Bq). Using voxel-based dosimetry and the MIRD formula, median tumor sphere concentration was 12,339 spheres/mL (range, 2,689 − 37,649 spheres/mL). Sphere concentration to tumor exhibited a weak, inverse correlation with perfused treatment volume (R2 = 0.25). However, tumor sphere concentration and non-tumor sphere concentration exhibited a direct, positive correlation (R2 = 0.72). Of the 52 tumors with post-treatment imaging, objective response was noted in 50 patients (96%) and complete response in 41 patients (79%). 98% of all treated tumors demonstrated a durable response at 2 years. The median time to progression for all patients was not reached with a 2-year progression rate of 11%. Multivariate analysis demonstrated target dose as the only statistically significant variable associated with TTP (p = 0.033). 14 patients underwent liver transplant. Median tumor necrosis was 99% (range, 80–100%).Conclusion Voxel-based dosimetry following Y90 radioembolization can be utilized to measure sphere concentration into tumor and non-tumoral tissue. Higher SA allows increased tumor absorbed dose with limited sphere/mL tumor capacity.