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Purpose: To retrospectively compare early response to yttrium-90 radioembolization (Y90) according to volumetric iodine uptake (VIU) changes, Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) and modified RECIST (mRECIST) in patients with intermediate-advanced hepatocellular carcinoma (HCC) and to explore their association with survival.Materials and Methods: Twenty-four patients treated with Y90 and evaluated with dual-energy computed tomography before and 6 weeks after treatment were included. VIU was measured on late arterial phase spectral images; 6-week VIU response was defined as: complete response (CR, absence of enhancing tumor), partial response (PR, ≥ 15% VIU reduction), progressive disease (PD, ≥ 10% VIU increase) and stable disease (criteria of CR/PR/PD not met). RECIST 1.1 and mRECIST were evaluated at 6 weeks and 6 months. Responders included CR and PR. Overall survival (OS) was evaluated by Kaplan-Meier analysis and compared by Cox regression analysis.Results: High intraobserver and interobserver agreements were observed in VIU measurements (k > 0.98). VIU identified a higher number of responders (18 patients, 75%), compared to RECIST 1.1 (12.5% at 6 weeks and 23.8% at 6 months) and mRECIST (29.2% at 6 weeks and 61.9% at 6 months). There was no significant correlation between OS and RECIST 1.1 (P = 0.45 at 6 weeks; P = 0.21 at 6 months) or mRECIST (P = 0.38 at 6 weeks; P = 0.79 at 6 months); median OS was significantly higher in VIU responders (17.2 months) compared to non-responders (7.4 months) (P = 0.0022; HR 8.85; 95% CI 1.29-88.1).Conclusion: VIU is highly reproducible; as opposite to mRECIST and RECIST 1.1, early VIU response correlates with OS after Y90 in intermediate-advanced HCC patients. [ABSTRACT FROM AUTHOR]