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Clinical Trial
. 2022 Feb;148(2):475-485.
doi: 10.1007/s00432-021-03627-1. Epub 2021 Apr 14.

Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

Osman Öcal  1 , Kerstin Schütte  2 , Juozas Kupčinskas  3 , Egidijus Morkunas  3 , Gabija Jurkeviciute  3 , Enrico N de Toni  4 , Najib Ben Khaled  4 , Thomas Berg  5 , Peter Malfertheiner  4 , Heinz Josef Klümpen  6 , Christian Sengel  7 , Bristi Basu  8 , Juan W Valle  9 , Julia Benckert  10 , Antonio Gasbarrini  11 , Daniel Palmer  12 , Ricarda Seidensticker  1 , Moritz Wildgruber  1 , Bruno Sangro  13 , Maciej Pech  14 , Jens Ricke  1 , Max Seidensticker  15
Affiliations
Clinical Trial

Baseline Interleukin-6 and -8 predict response and survival in patients with advanced hepatocellular carcinoma treated with sorafenib monotherapy: an exploratory post hoc analysis of the SORAMIC trial

Osman Öcal et al. J Cancer Res Clin Oncol. 2022 Feb.

Abstract

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.

Keywords: Hepatocellular carcinoma; Interleukin; Response; Sorafenib.

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Conflict of interest statement

Maciej Pech: Grants: Sirtex, Bayer; Personal fees: Sirtex. Peter Malfertheiner: Grants: Bayer, Sirtex. Jens Ricke: Grants: Sirtex, Bayer; Personal fees: Sirtex, Bayer. Max Seidensticker: Personal fees: Bayer, Sirtex.

Figures

Fig. 1
Fig. 1
Consort diagram
Fig. 2
Fig. 2
The receiver-operating characteristics (ROC) curve showing the sensitivity and specificity of various cut-off values of baseline: a interleukin (IL)-6 and b IL-8 levels to analyze the overall survival
Fig. 3
Fig. 3
Kaplan–Meier curve showing overall survival of patients grouped by baseline IL-6 values according to cut-off of 8.58 pg/mL
Fig. 4
Fig. 4
Kaplan–Meier curve showing overall survival of patients grouped by baseline IL-8 values according to cut-off of 59.7 pg/mL
Fig. 5
Fig. 5
Kaplan–Meier curve showing overall survival of patients according to interleukin score
See this image and copyright information in PMC

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