An Early Increase in IL-10 and TNF-α Levels Following Atezolizumab Plus Bevacizumab Treatment Predicts Survival in Advanced Hepatocellular Carcinoma Patients: A Prospective Cohort Study
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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(20), 3543; https://doi.org/10.3390/cancers16203543
Submission received: 19 September 2024
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Revised: 7 October 2024
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Accepted: 18 October 2024
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Published: 21 October 2024
(This article belongs to the Special Issue New Trends in Hepatocellular Carcinoma: Artificial Intelligence, Robotics and Innovative Treatments)
Simple Summary
Due to a shortage of reliable biomarkers for predicting outcomes in hepatocellular carcinoma (HCC) following treatment with atezolizumab plus bevacizumab (Ate/Bev), we assessed the impact of early changes in cytokine levels on the clinical outcomes of advanced HCC patients. We prospectively enrolled 32 patients, analyzing changes in IL-2, IL-6, IL-10, IL-12, IL-17, IFN-γ, and TNF-α levels from blood samples collected before the first and second Ate/Bev treatments. Patients with increased IL-10, IL-17, and TNF-α levels demonstrated significantly better survival and marginally improved progression-free survival compared to those with decreased cytokine levels. Additionally, a positive correlation was found between changes in IL-10 and TNF-α levels. Multivariable analysis confirmed that increases in these cytokines are significant predictors of improved survival (p = 0.005). Early increases in IL-10 and TNF-α levels post-Ate/Bev treatment may thus serve as effective biomarkers for clinical outcomes in advanced HCC patients.
Abstract
Background/Objectives: Reliable biomarkers for predicting outcomes in hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev) are still lacking. Cytokines, which play a crucial role in immune regulation and HCC progression, have potential as predictive markers, but data supporting their use are limited. This study aimed to evaluate the impact of early changes in cytokine levels on the clinical outcomes of advanced HCC patients. Methods: We prospectively enrolled 32 advanced HCC patients, collecting blood samples before the first and second Ate/Bev treatments. These samples were analyzed for IL-2, IL-6, IL-10, IL-12, IL-17, IFN-γ, and TNF-α levels to assess changes post-treatment. The primary outcome was overall survival, with a secondary focus on progression-free survival (PFS) at 6 months. Results: The mean age of the participants was 64.2 years, with the majority being male (93.8%). Patients showing increased IL-10, IL-17, and TNF-α levels had significantly better survival (p < 0.05) and marginally improved PFS compared to those with decreased cytokine levels. Interestingly, a positive correlation was noted between changes in IL-10 and TNF-α levels (p = 0.009). Furthermore, a multivariable analysis revealed that increased levels of IL-10 and TNF-α were significant predictors of enhanced survival (hazard ratio, 0.07; 95% confidence interval, 0.01–0.46; p = 0.005). Conclusions: An early increases in IL-10 and TNF-α after Ate/Bev treatment may serve as effective biomarkers for clinical outcomes in advanced HCC patients.
