Abstract

BackgroundTo 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.MethodsA 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.ResultsMedian 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.ConclusionIn 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.

Highlights

  • 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 Hepatocellular carcinoma (HCC) undergoing 90Y radioembolization

  • In advanced HCC patients receiving 90Y radioembolization combined with sorafenib, baseline IL6 values proved to be prognostic, confirming previous findings in patients undergoing 90Yradioembolization

  • Baseline characteristics Out of 424 patients included in the palliative arm of the SORAMIC trial, 216 patients were randomized to RE and sorafenib treatment

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Summary

Introduction

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. 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. Chronic inflammation causes epithelial cell death, but the high regenerative capacity of the liver compensates for this damage by inducing cell proliferation. During this process, the accumulation of reactive oxygen species and DNA mutations cause hepatocarcinogenesis. Previous authors have found increased interleukin 6 levels in patients with chronic liver disease [4]

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