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Introduction: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T)., Methods: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤3.7 μg/L and ≤0.9 μg/L, respectively. The Kaplan-Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups., Results: Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036)., Conclusion: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients., Competing Interests: Shadi Chamseddine and Michael LaPelusa are co-first authors for this study. Dr Dan Duda reports grants from BMS, Bayer, Exelixis, Surface Oncology; personal fees from Innocoll, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Chamseddine et al.)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide and is associated with significant health care costs and burden. Management of HCC is guided based on the Barcelona Clinic Liver Cancer (BCLC) system and includes liver transplantation, surgical resection, and liver-directed and systemic therapies. In recent years, there have been significant advancements in understanding the immunogenicity of HCC and this has led to approval of different targeted agents as well as immunotherapy for advanced HCC. Tremelimumab is a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blocking antibody and has recently been approved in combination with durvalumab (a programmed death-ligand 1 [PDL1] inhibitor) as first-line therapy for advanced (Barcelona Clinic Liver Cancer Stage C) HCC. In this article, we review the different available systemic therapies for advanced HCC with special focus on the clinical utility of tremelimumab for the treatment of unresectable HCC., Competing Interests: Dr David Victor 3rd is part of the speaker bureau for Gilead and Intercept, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Ahmed et al.)

Purpose: The most common cause of death in advanced/metastatic hepatocellular carcinoma (HCC) is liver failure due to tumor progression. While retrospective studies and meta-analyses of systemic therapy combined with liver-directed therapy have been performed, prospective studies of safety/efficacy of antiangiogenesis followed by intra-arterial therapies are lacking. We tested our hypothesis that sorafenib followed by yttrium 90 glass microspheres ( 90 Y GMs) is safe and that survival outcomes may improve by controlling hepatic tumors., Methods: We enrolled 38 Child-Pugh A patients with advanced/metastatic HCC. In sum, 34 received sorafenib, followed after 4 weeks by 90 Y GMs. Analysis of safety and survival outcomes was performed to assess adverse events, median progression-free survival, and overall survival., Results: A total of 34 patients were evaluable: 14 (41.2%) with chronic hepatitis, nine (26.5%) with vascular invasion, and eleven (32.4%) with extrahepatic diseases. Safety analysis revealed that the combination therapy was well tolerated. Grade III-IV adverse events comprised fatigue (n=3), diarrhea (n=2), nausea (n=1), vomiting (n=2), hypertension (n=4), thrombocytopenia (n=1), hyperbilirubinemia (n=1), proteinuria (n=1), hyponatremia (n=1), and elevated alanine or aspartate aminotransferase (n=5). Median progression-free and overall survival were 10.4 months (95% CI 5.8-14.4) and 13.2 months (95% CI 7.9-18.9), respectively. Twelve patients (35.3%) achieved partial responses and 16 (47.0%) stable disease. Median duration of sorafenib was 20 (3-90) weeks, and average dose was 622 (466-800) mg daily. Dosimetry showed similar mean doses between planned and delivered calculations to normal liver and tumor:normal liver uptake ratio, with no significant correlation with adverse events at 3 and 6 months post- 90 Y treatment., Conclusion: This is the first prospective study to evaluate sorafenib followed by 90 Y in patients with advanced HCC. The study validated our hypothesis of safety with encouraging efficacy signals of the sequencing treatment, and provides proof of concept for future combination modalities for patients with advanced or metastatic HCC., Clinical Trial Registration Number: NCT01900002., Competing Interests: SCK has received research grants from Boston Scientific and ABK Biomedical and served as a consultant for Sirtex Medical, Boston Scientific, ABK Biomedical, and Terumo Medical. JK reports personal fees from Johnson and Johnson, Boston Scientific and grants from LungLife AI outside the submitted work. AM reports grants and personal fees from BTG, Sirtex Medical, and ABK Biomedical outside the submitted work. The authors declare no other potential conflicts of interest., (© 2021 Kaseb et al.)