Lobar Yttrium-90 Radioembolization with BSA-Based Dosimetry for Unresectable Hepatocellular Carcinoma: Baseline Vascularity Predicts Responders to the Combination with Targeted Therapy or Immune Checkpoint Inhibition

Willie M Lüdemann,1 Johannes Kahn,2 Paul Herzler,3 Federico Collettini,1 Lynn J Savic,1 Raphael Mohr,4 Uli Fehrenbach,1 Timo Alexander Auer,1 Bernhard Gebauer,1 Holger Amthauer,3 Gero Wieners5 1Department of Diagnostic and Interventional Radiology, Charité Universitätsmedizin, Berlin, Germany; 2Department of Diagnostic and Interventional Radiology, Health and Medical University Potsdam, Potsdam, Germany; 3Department of Nuclear Medicine, Charité Universitätsmedizin, Berlin, Germany; 4Department of Hepatology and Gastroenterology, Charité Universitätsmedizin, Berlin, Germany; 5Department of Radiology, Medical University Lausitz-Carl Thiem, Cottbus, GermanyCorrespondence: Willie M Lüdemann, Email [email protected]: This retrospective study investigates the benefit of combining lobar radioembolization (TARE), performed using a body surface area (BSA) dose prescription model, with targeted therapy (TT) in hepatocellular carcinoma (HCC), and aims to identify predictors of response through contrast-enhanced MRI tumour volumetry.Methods: Ninety-two HCC patients who underwent TARE at our center between 10/2008 and 01/2022 and a baseline MRI within 60 days prior to TARE as well as follow-up MRI were included. Pre- and post-treatment target lesion volumes were measured as total-tumour-volume (TTV) and enhancing-tumour-volume (ETV). Kaplan-Meier analysis, Log rank tests, and Cox regression were used to assess the impact of clinical and imaging variables on time to target lesion progression and overall survival.Results: The mean patient age was 65 (SD 10) years; 67 patients had liver cirrhosis. Median overall survival (mOS) was 13 months (95% CI 11– 16). A baseline ETV/TTV ratio > 50% was associated with a median ETV reduction of 41% versus a 61% increase in those with low vascularity (p< 0.001), and a longer time to target lesion progression (28 vs 3 months, p=0.002). Of 45 patients receiving TT, 21 were treated within 2 months before TARE. In this subgroup with pre-interventional TT, high vascularity correlated with significantly improved mOS (> 17 vs 6 months, p=0.027), while no survival difference was observed in other cohorts.Conclusion: High baseline vascularization may help identify patients who benefit from conventional lobar TARE and a narrowly timed combination with TT in terms of mOS, suggesting synergistic effects in patients not eligible for resection or ablation.Plain Language Summary: QUESTION: In unresectable hepatocellular carcinoma (HCC), does baseline vascularity identify patients who benefit from combining conventional lobar radioembolization with targeted therapy?PERTINENT FINDINGS: In this retrospective single-center study of 92 HCC patients, those with baseline tumor arterial vascularity > 50% demonstrated significantly better MR-morphologic response and improved median overall survival when targeted therapy was administered within two months before radioembolization.IMPLICATIONS FOR PATIENT CARE: Elevated baseline vascularity may identify unresectable HCC patients who benefit from combined radioembolization and targeted therapy, suggesting synergistic effects in patients not eligible for resection or ablation. Keywords: carcinoma, hepatocellular, survival analysis, radioembolization, targeted therapy, sorafenib