Abstract No. LB02 A global study of advanced dosimetry in the treatment of hepatocellular carcinoma with Yttrium-90 glass microspheres: analyses from the TARGET study

Abstract

The primary objective of TARGET was to collect clinical data to generate predictive models of relationships between absorbed dose (AD), radioembolization-specific adverse events (AEs), and objective response (OR) in hepatocellular carcinoma (HCC) patients treated with yttrium-90 (90Y) glass microspheres. TARGET was an international, retrospective, single-arm study. Inclusion criteria: liver-dominant disease with or without portal vein thrombosis (PVT); ≤10 HCC 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. TARGET included 209 patients from 13 centers in 8 countries. Of those, 79.4% were male; median age was 66 years; 70.8% had unilobar disease; 89.5% and 10.5% were Child-Pugh A and B7; 33.0% had PVT; and 12.9%, 32.5%, and 54.5% were BCLC A, B, and C. Data collection included patient, disease, and treatment-specific variables; treatment-related AEs; and tumor response measurements. Multicompartment pre-/post-treatment dosimetry was retrospectively determined with Simplicit90Y™ software (Mirada). Logistic regression was used to evaluate relationships between 1) OR by mRECIST and total perfused tumor AD (TAD) and 2) AEs of ≥ Grade 3 hyperbilirubinemia without disease progression and normal tissue AD (NTAD). Multivariate Cox regression was used to evaluate associations between predictive/clinical variables and overall survival (OS). Bland-Altman (BA) analysis was used to assess agreement between pre-/post-treatment TAD and NTAD. No relationship was found between ≥ Grade 3 hyperbilirubinemia (in 4.8% of patients) and NTAD. The OR rate was 66.5%. Responders and non-responders had geometric mean TADs of 225.5 Gy and 188.3 Gy; corresponding to a 17% (95% CI: 0-30%; p=0.048) reduction. The probability of an OR was higher with increasing TAD (p=0.044). Median OS was 20.3 months (95% CI = 16.7-26.4 months). Higher TAD was associated with longer OS (HR per 100 Gy increase in TAD = 0.84, 95% CI: 0.72-0.97; p=0.016). BA analysis showed good agreement between pre- and post-treatment ADs for total perfused tumor (Bias = -0.73 Gy; 95% CI: -39.8-38.4 Gy) and normal tissue (Bias = -0.99 Gy; 95% CI: -4.7-2.7 Gy). Global real-world data confirmed a significant association between TAD and OR and between TAD and OS in HCC patients treated with (90Y) glass microspheres. With a low incidence, a relationship between ≥ Grade 3 hyperbilirubinemia and NTAD was not found.