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      Sarcopenia and Systemic Inflammation Response Index Predict Response to Systemic Therapy for Hepatocellular Carcinoma and Are Associated With Immune Cells

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          Abstract

          Background

          Systemic therapies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have challenged the use of conventional therapies for hepatocellular carcinoma (HCC). It is crucial to determine which patients could benefit most from combination therapy. This study aims to examine the associations of sarcopenia and systemic inflammation response index (SIRI) with the treatment responses and efficacies in patients with HCC treated with ICIs and tyrosine kinase inhibitors TKIs, as well as investigate the correlation between sarcopenia and inflammatory or immune states.

          Methods

          We reviewed 160 patients with HCC treated with TKIs and ICIs. The patients’ psoas muscle size was measured on axial computed tomography scans and normalized for the patients’ height squared. This value was referred to as the psoas muscle index (PMI). Sarcopenia was determined from PMI and their relationships with patients’ clinicopathological characteristics, inflammation indexes, peripheral blood T-cell subsets and survival were evaluated.

          Results

          Sarcopenia and systemic inflammation response index (SIRI) were independent predictors for overall survival and progression-free survival. Patients with high PMI and low SIRI demonstrated significantly better median overall survival and progression-free survival (36.0 months and 9.6 months, respectively) than those with either low PMI or high SIRI (20.8 months and 6.0 months, respectively) and those with both high SIRI and low PMI (18.6 months and 3.0 months, respectively). Portal vein tumor thrombus (P=0.003), eastern cooperative oncology group performance status score of 1 (P=0.048), high alkaline phosphatase (P=0.037), high neutrophil-to-lymphocyte ratio (NLR) (P=0.012), low lymphocyte-to-monocyte ratio (LMR) (P=0.031), high platelet-to-lymphocyte ratio (PLR) (P=0.022) and high SIRI (P=0.012) were closely associated with an increased incidence of sarcopenia. PMI was negatively correlated with SIRI (r = -0.175, P=0.003), NLR (r = -0.169, P=0.036), and PLR (r = -0.328, P=0.000) and was significantly positively correlated with LMR (r = 0.232, P=0.004). The CD3+ and CD4+ T-cell counts of the high PMI group were significantly higher than those of the low PMI group.

          Conclusion

          Sarcopenia and high SIRI were associated with reduced survival in patients with HCC treated with ICIs and TKIs. Sarcopenia could affect inflammatory states and the immune microenvironment.

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          Most cited references37

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          Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

          Richard S Finn, Shukui Qin, Masafumi Ikeda … (2020)
          The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
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            Lisa M Coussens, Zena Werb (2002)
            Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
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              Immunity, inflammation, and cancer.

              Sergei I. Grivennikov, Florian Greten, Michael Karin (2010)
              Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. This review outlines the principal mechanisms that govern the effects of inflammation and immunity on tumor development and discusses attractive new targets for cancer therapy and prevention. 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Oncol
                Journal ID (iso-abbrev): Front Oncol
                Journal ID (publisher-id): Front. Oncol.
                Title: Frontiers in Oncology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2234-943X
                Publication date (Electronic): 08 April 2022
                Publication date Collection: 2022
                Volume: 12
                Electronic Location Identifier: 854096
                Affiliations
                [1] Department of Gastroenterology, The Fourth Hospital of Hebei Medical University , Shijiazhuang, China
                Author notes

                Edited by: Zhaohui Huang, Affiliated Hospital of Jiangnan University, China

                Reviewed by: Natally Horvat, Memorial Sloan Kettering Cancer Center, United States; Guifang Guo, Sun Yat-sen University Cancer Center (SYSUCC), China

                *Correspondence: Fei Yin, yinfei_4y@ 123456sina.com

                This article was submitted to Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers, a section of the journal Frontiers in Oncology

                Article
                DOI: 10.3389/fonc.2022.854096
                PMC ID: 9024177
                PubMed ID: 35463384
                SO-VID: 5b96200b-bd1c-4bad-a7b1-fdf1e69fbe5d
                Copyright © Copyright © 2022 Zhao, Duan, Han, Wang, Han, Mi, Shi, Li, Yin, Hou and Yin
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 13 January 2022
                Date accepted : 15 March 2022
                Page count
                Figures: 5, Tables: 5, Equations: 1, References: 37, Pages: 11, Words: 4850
                Categories
                Subject: Oncology
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hepatocellular carcinoma,sarcopenia,psoas muscle index,systemic inflammatory response index,immune cell
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hepatocellular carcinoma, sarcopenia, psoas muscle index, systemic inflammatory response index, immune cell

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