Voxel-based dosimetry for predicting treatment response to transarterial radioembolization in hepatocellular carcinoma: significance of intratumoral dose distribution.

PURPOSE: We applied a voxel-based personalized dosimetry method using multiple voxel S-values (VSVs) to assess the intratumoral dose distribution in hepatocellular carcinoma (HCC) patients treated with trans-arterial radioembolization (TARE) using glass microspheres. This study aimed to evaluate the predictive value of dose metrics for treatment response and local progression-free survival (L-PFS). METHODS: Ninety patients with HCC who underwent TARE between November 2015 and December 2019 were retrospectively analyzed. Post-treatment 90Y-microsphere PET/CT images were used to generate voxel-wise absorbed dose maps via convolution with CT-derived multiple VSV kernels. Tumor volumes were manually delineated on contrast-enhanced CT co-registered with dose map. Dose-volume histogram (DVH) parameters, including V-V205 (tumor volume receiving < 205 Gy) and D70, were calculated. Dose heterogeneity was assessed using the coefficient of variation (CoV) of voxel doses. The performance of dose parameters for predicting complete response (CR) and L-PFS was evaluated using logistic and Cox regression analyses. RESULTS: Among 90 patients, 57 (63.3%) achieved CR. PET average dose, D70, V-V205, and CoV significantly differed according to treatment response. ROC analysis showed good predictive performance for CR with D70 (AUC 0.908), V-V205 (0.903), PET average dose (0.876), and CoV (0.870). In multivariate logistic regression, only small V-V205 (< 22.8 mL; OR 12.50, P = 0.002) remained an independent predictor of CR. For L-PFS, multivariate Cox analysis identified V-V205 < 22.8 mL (HR 0.07, P = 0.013) and CR (HR 0.29, P = 0.034) as independent prognostic factors. CONCLUSION: Voxel-based dosimetry using multiple VSV kernels enables quantitative assessment of intratumoral dose distribution in HCC patients treated with TARE. Among voxel-level parameters, D70, V-V205, and CoV showed good performance in predicting CR, and V-V205 was the only independent predictor for both treatment response and L-PFS. These findings support the added prognostic value of voxel-based dose metrics beyond average tumor absorbed dose.