CIO 2021-11 A Global Evaluation of Advanced Dosimetry in Radioembolization of Hepatocellular Carcinoma: Analyses From TARGET

Purpose: The primary aims of TARGET were to determine relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and outcomes in hepatocellular carcinoma patients treated with yttrium-90 glass microspheres. Additionally, the reproducibility of TAD and NTAD between centers was evaluated.

Material and Methods: TARGET is an international, single-arm, retrospective study of 209 patients from 13 centers located in 8 countries. Patient inclusion criteria: liver-dominant disease ± portal vein thrombosis; ≤10 tumors per lobe (at least one ≥3 cm); Child-Pugh stage A or B7; BCLC stage A, B, or C; and no prior intra-arterial treatment. Multicompartment dosimetry was calculated retrospectively with Simplicit90Y™ software (Mirada). Logistic regression was used to evaluate associations between objective response (OR) and TAD and Cox regression between overall survival (OS) and TAD. Multicompartment dosimetry inter-observer reproducibility was evaluated by the reproducibility coefficient (RDC) for TAD and NTAD (8 reviewers at 8 centers for 20 patients). Volumes of interest were delineated based on CT or MRI. RDC representing the maximum ratio of the dosimetric measurement between 2 reviewers was computed using a random effects model on log transformed data.

Results: A relationship between ≥Grade 3 hyperbilirubinemia and NTAD was not found, indicating a threshold NTAD was not reached. OR, defined as complete or partial response by mRECIST, was 61.7% over all lesions. Increasing TAD was associated with higher OR (p=0.044). OR in patients with a TAD < 200 Gy was 52.7%; with a TAD of 200-300 Gy, 64.9%; and with a TAD > 300 Gy, 72.1%. Increasing TAD was associated with longer OS (p=0.009). Median OS in patients with a TAD < 200 Gy was 16.1 months (95% CI: 11.3, 19.4); with a TAD of 200-300 Gy, 25.1 months (95% CI: 14.5, 32.9); and with a TAD > 300 Gy, 36.7 months (95% CI: 20.2, 43.9). The RDC for total perfused TAD using a CT/MRI workflow was 1.84 (95% CI: 1.66, 2.56); for total perfused NTAD tissue was 1.46 (95% CI: 1.39, 2.25) demonstrating acceptable inter-observer reproducibility.

Conclusions: Real world data from 8 countries confirmed that a significant association exists between TAD and OR, as well as between TAD and OS. The advanced dosimetry methods demonstrated acceptable inter-observer reproducibility, indicating multicompartment dosimetry using Simplicit90Y produced consistent results in a variety of clinical settings.