Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma

Abstract

Purpose: To identify predictive factors of tumor response, progression-free survival (PFS), overall survival (OS), and toxicity using three-dimensional (3D) voxel-based dosimetry in patients with intermediate and advanced stage hepatocellular carcinoma (HCC) treated by yttrium-90 (⁹⁰Y) resin microspheres radioembolization (RE).

Materials and methods: From February 2012 to December 2015, 45 ⁹⁰Y resin microspheres RE procedures were performed for HCC (Barcelona Clinic Liver Cancer stage B/C; n = 15/30). Area under the dose-volume histograms (AUDVHs) were calculated from 3D voxel-based dosimetry to measure ⁹⁰Y dose deposition. Factors associated with tumor control (ie, complete/partial response or stable disease on Modified Response Evaluation Criteria in Solid Tumors) at 6 months were investigated. PFS and OS analyses were performed (Kaplan-Meier). Toxicity was assessed by occurrence of radioembolization-induced liver disease (REILD).

Results: Tumor control rate was 40.5% (17/42). Complete tumor targeting (odds ratio = 36.97; 95% confidence interval, 1.83-747; P < .001) and AUDVH_tumor (odds ratio = 1.027; 95% confidence interval, 1.002-1.071; P = .033) independently predicted tumor control. AUDVH_tumor ≥ 61 Gy predicted tumor control with 76.5% sensitivity and 75% specificity. PFS and OS in patients with incomplete tumor targeting were significantly shorter than in patients with complete tumor targeting (median PFS, 2.7 months [range, 0.8-4.6 months] vs 7.9 months [range, 2.1-39.5 months], P < .001; median OS, 4.5 months [range, 1.4-23 months] vs 19.2 months [range, 2.1-46.9 months], P < .001). Patients with incomplete tumor targeting and AUDVH_tumor < 61 Gy, incomplete tumor targeting and AUDVH_tumor > 61 Gy, complete tumor targeting and AUDVH_tumor < 61 Gy, and AUDVH_tumor > 61 Gy had median PFS of 2.7, 1.8, 6.3, and 12.1 months (P < .001). REILD (n = 4; 9.5%) was associated with higher dose delivered to normal liver (P = .04).

Conclusions: Complete tumor targeting and ⁹⁰Y dose to tumor are independent factors associated with tumor control and clinical outcomes.