Purpose To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9–8.9], p < 0.001) and IL-8 (HR, 2.4 [1.2–4.7], p = 0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22–7.3], p = 0.017) and IL-8 (HR, 2.19 [1.02–4.7], p = 0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p = 0.007; IL-8, 50.0% vs. 17.4%, p = 0.011). Conclusion IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection.

Background To confirm the prognostic value of previously published baseline interleukin 6 (IL6) and IL8 cutoff values in survival and liver dysfunction in patients with advanced HCC undergoing 90Y radioembolization. Methods A total of 83 patients (77 male) represented a subset of HCC patients undergoing 90Y radioembolization combined with sorafenib as part of the prospective multicenter phase II trial SORAMIC. IL6 and IL8 levels were determined in serum samples collected at baseline. In this post hoc analysis, we sought to confirm the prognostic value of baseline cutoff values of 6.53 pg/mL and 60.8 pg/mL for IL6 and IL8, respectively, in overall survival (OS) or liver dysfunction (grade 2 bilirubin increase) after treatment. Results Median OS was 12.0 months. While low baseline albumin and high bilirubin values were associated with high IL6, liver cirrhosis, alcoholic liver disease, and portal vein infiltration were associated with high IL8. In univariate analysis, high baseline IL6 and IL8 were associated with significantly shorter overall survival (7.8 vs. 19.0 months for IL6 and 8.4 vs. 16.0 months for IL8). In addition to IL values, liver cirrhosis, Child–Pugh grade, baseline albumin (< 36 g/dL), and total bilirubin (≥ 17 µmol/L), and higher mALBI grade (2b &3) values were associated with OS. At multivariate analysis, high baseline IL6 was the only independent prognostic factor for OS (HR 2.35 [1.35–4.1], p = 0.002). Risk factors for liver dysfunction were high baseline IL6, albumin, and total bilirubin, and mALBI grade as found in univariate analysis. High baseline IL6 (HR 2.67 [1.21–5.94], p = 0.016) and total bilirubin ≥ 17 µmol/L (HR 3.73 [1.72–8.06], p < 0.001) were independently associated with liver dysfunction. Conclusion In advanced HCC patients receiving 90Y radioembolization combined with sorafenib, baseline IL6 values proved to be prognostic, confirming previous findings in patients undergoing 90Yradioembolization. IL6 might be useful for patient selection or stratification in future trials.

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IntroductionPrediction of response to treatment in patients with advanced hepatocellular carcinoma (HCC) may assist in the selection of personalized management.ObjectiveThis exploratory analysis of the palliative arm of the SORAMIC trial (ClinicalTrials.gov NCT01126645) evaluated the prognostic potential of basal and dynamic changes in systemic levels of interleukin 6 (IL-6), interleukin 8 (IL-8), systemic vascular endothelial growth factor (VEGF), and lipopolysaccharide (LPS).MethodsWe evaluated the correlations between overall survival (OS) and concentrations of IL-6, IL-8, VEGF, and LPS at follow-up approximately 7-9 weeks after treatment initialization (FU) compared to baseline (BL) in 90 patients treated either with 90Yttrium (90Y) microspheres combined with sorafenib (n = 44) or with sorafenib (n = 46) alone.ResultsChanges in IL-6 concentration during treatment showed correlations with the outcome. An increase in IL-6 concentration of less than 16.8 pg/mL over baseline readings was associated with better survival [median OS 16.3 months compared with 8.9 months (p = 0.0354)]. Correlations with survival were not observed for VEGF or LPS concentrations at baseline, at FU, or changes between these time points.ConclusionsChanges in IL 6 serum levels at 7-9 weeks after treatment initialization but not in IL 8, VEGF, or LPS add important information on the outcome of advanced HCC patients treated palliatively within the SORAMIC trial.