Abstract
Survival prediction in patients with esophageal cancer is receiving a lot of attention from sarcopenia, myosteatosis, and systemic immune-inflammatory index (SII). The aim of this study was to investigate the survival prediction value of these parameters in esophageal cancer patients treated with immune checkpoint inhibitors (ICIs). Retrospective analysis of 178 patients with esophageal cancer who received immunotherapy and CT imaging. X-tile plots were utilized to determine optimal survival thresholds for skeletal muscle density (SMD), skeletal muscle index (SMI), and SII. The relationship between these parameters and patients’ overall survival (OS) and progression-free survival (PFS) was explored by Cox regression modeling and survival curve analysis. For OS, the Fine-Gray test was used to analyze competing risks. In addition, correlation and interaction analyses were performed on these indicators. Sarcopenia (mOS 10.3 months vs. 23.6 months; P < 0.001), and myosteatosis (mOS 13.0 months vs. 23.4 months; P = 0.008), high SII (14.4 months vs. 40.7 months; P = 0.002) were associated with poor OS. Multifactorial regression showed that sarcopenia (HR: 2.15; 95%CI: 1.19 ~ 3.88; P = 0.012), myosteatosis (HR: 2.34; 95%CI: 1.31 ~ 4.18; P = 0.004), and high SII (HR: 1.91; 95%CI: 1.15 ~ 3.18; P = 0.013) were the independent risk factors for OS in patients with esophageal cancer, but not for PFS. No significant association was found between sarcopenia, myosteatosis, or a high SII and non-cancer mortality in the competing risk model. In addition, there was a low positive correlation (r = 0.219, P = 0.004) and interaction (p = 0.008) between sarcopenia and myosteatosis. The SMI-SMD-SII score was established, and OS was significantly shorter in patients with score ≥ 2 than in patients with score = 0 and 1 (p < 0.001). This study found that sarcopenia, myosteatosis, and SII correlate significantly with survival in patients with advanced esophageal cancer receiving immunotherapy. However, the OS-PFS discrepancy may be confounded by subsequent therapies and does not directly reflect initial efficacy. Prospective studies are needed to validate these findings and inform personalized treatment.
Data availability
The data supporting the findings of this study are available upon request from the corresponding author. The data are not publicly available because of privacy or ethical restrictions.
References
Williams, G. R. et al. Skeletal muscle measures and physical function in older adults with cancer: Sarcopenia or myopenia? Oncotarget 8, 33658–33665 (2017).
Cruz-Jentoft, A. J. et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 48, 16–31 (2019).
Morgan, E. et al. The global landscape of esophageal squamous cell carcinoma and esophageal adenocarcinoma incidence and mortality in 2020 and projections to 2040: new estimates from GLOBOCAN 2020. Gastroenterology 163, 649–658e2 (2022).
Han, B. et al. Cancer incidence and mortality in China, 2022. J. Natl. Cancer Cent. 4, 47–53 (2024).
Jogiat, U. M. et al. Sarcopenia reduces overall survival in unresectable oesophageal cancer: a systematic review and meta-analysis. J. Cachexia Sarcopenia Muscle. 13, 2630–2636 (2022).
Xiao, X. et al. Impact of skeletal muscle loss and sarcopenia on outcomes of locally advanced esophageal cancer during neoadjuvant chemoradiation. Ann. Surg. Oncol. 31, 3819–3829 (2024).
Deng, G. M. et al. Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor. World J. Gastroenterol. 30, 863–880 (2024).
Kim, N. et al. Incorporating sarcopenia and inflammation with radiation therapy in patients with hepatocellular carcinoma treated with nivolumab. Cancer Immunol. Immunother. 70, 1593–1603 (2021).
Shinohara, S. et al. Impact of sarcopenia on surgical outcomes in Non-small cell lung cancer. Ann. Surg. Oncol. 27, 2427–2435 (2020).
Lee, C. M. & Kang, J. Prognostic impact of myosteatosis in patients with colorectal cancer: A systematic review and meta-analysis. J. Cachexia Sarcopenia Muscle. 11, 1270–1282 (2020).
Lee, J. et al. Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer. J. Cachexia Sarcopenia Muscle. 10, 814–826 (2019).
Arayne, A. A., Gartrell, R., Qiao, J., Baird, P. N. & Yeung, J. M. Comparison of CT derived body composition at the thoracic T4 and T12 with lumbar L3 vertebral levels and their utility in patients with rectal cancer. BMC Cancer. 23, 56 (2023).
Dabiri, S. et al. Muscle segmentation in axial computed tomography (CT) images at the lumbar (L3) and thoracic (T4) levels for body composition analysis. Comput. Med. Imaging Graph Off J. Comput. Med. Imaging Soc. 75, 47–55 (2019).
Miao, S. et al. Deep learning radiomics under multimodality explore association between muscle/fat and metastasis and survival in breast cancer patients. Brief. Bioinform. 23, bbac432 (2022).
Go, S. et al. Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J. Cachexia Sarcopenia Muscle. 7, 567–576 (2016).
Xia, H. et al. Prognostic value of skeletal muscle measured by CT at the T4 level in advanced EGFR-positive non-small cell lung cancer patients treated with ecotinib]. Zhonghua Yi Xue Za Zhi. 104, 1590–1600 (2024).
Yang, M. et al. The consistency of skeletal muscle mass measured by CT at L1 and L3 levels and the correlation of skeletal muscle density at L1 level with prognosis in Dialysis patients]. Zhonghua Yi Xue Za Zhi. 103, 2850–2858 (2023).
Tan, L. et al. Diagnosing sarcopenia and myosteatosis based on chest computed tomography images in healthy Chinese adults. Insights Imaging. 12, 163 (2021).
Van den Broeck, J. et al. The correlation of muscle quantity and quality between all vertebra levels and level L3, measured with CT: an exploratory study. Front. Nutr. 10, 1148809 (2023).
van Heusden, H. C. et al. Feasibility of assessment of skeletal muscle mass on a single cross-sectional image at the level of the fourth thoracic vertebra. Eur J. Radiol 142, 109879 (2021).
Jogiat, U. M. et al. Thoracic muscle mass predicts survival among patients with locally advanced esophageal cancer. Clin. Nutr. 49, 90–97 (2025).
Cortellini, A. et al. Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study. Sci. Rep. 10, 1456 (2020).
Wu, Y. H., Hwang, A. C., Liu, L. K., Peng, L. N. & Chen, L. K. Sex differences of sarcopenia in Asian populations: the implications in diagnosis and management. J. Clin. Gerontol. Geriatr. 7, 37–43 (2016).
Stretch, C. et al. Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas. PLoS ONE. 13, e0196235 (2018).
Youn, S. et al. Myosteatosis is prognostic in metastatic melanoma treated with nivolumab. Clin. Nutr. ESPEN. 42, 348–353 (2021).
Tranoulis, A. et al. Prevalence of computed tomography-based sarcopenia and the prognostic value of skeletal muscle index and muscle Attenuation amongst women with epithelial ovarian malignancy: A systematic review and meta-analysis. Eur. J. Surg. Oncol. J. Eur. Soc. Surg. Oncol. Br. Assoc. Surg. Oncol. 48, 1441–1454 (2022).
Kim, Y. Y. et al. Prognostic significance of sarcopenia in microsatellite-stable gastric cancer patients treated with programmed death-1 inhibitors. Gastric Cancer. 24, 457–466 (2021).
Robert, C. A decade of immune-checkpoint inhibitors in cancer therapy. Nat. Commun. 11, 3801 (2020).
Quinn, L. S. Interleukin-15: A muscle-derived cytokine regulating fat-to-lean body composition1,2. J. Anim. Sci. 86, E75–E83 (2008).
Wu, J. et al. Skeletal muscle antagonizes antiviral CD8 + T cell exhaustion. Sci. Adv. 6, eaba3458 (2020).
Li, C. et al. Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review. J. Cachexia Sarcopenia Muscle. 13, 781–794 (2022).
Waickman, A. T. & Powell, J. D. mTOR, metabolism, and the regulation of T-cell differentiation and function. Immunol. Rev. 249, 43–58 (2012).
Onur, İ. D. et al. Impact of sarcopenia on paclitaxel-induced peripheral neuropathy in early-stage breast cancer: a prospective observational study (the neuro-sarc study). Support Care Cancer. 33, 1061 (2025).
Haik, L. et al. The impact of sarcopenia on the efficacy and safety of immune checkpoint inhibitors in patients with solid tumours. Acta Oncol. 60, 1597–1603 (2021).
Hu, B. et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin. Cancer Res. 20, 6212–6222 (2014).
Jomrich, G. et al. High systemic immune-inflammation index is an adverse prognostic factor for patients with gastroesophageal adenocarcinoma. Ann. Surg. 273, 532–541 (2021).
Passardi, A. et al. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer. Oncotarget 7, 33210–33219 (2016).
Pinedo, H., Verheul, H., D’Amato, R. & Folkman, J. Involvement of platelets in tumour angiogenesis? Lancet 352, 1775–1777 (1998).
Palumbo, J. S. et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell–mediated elimination of tumor cells. Blood 105, 178–185 (2005).
Elgueta, R. et al. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol. Rev. 229, 152–172 (2009).
Chapman, L. M. et al. Platelets present antigen in the context of MHC class I. J. Immunol. 189, 916–923 (2012).
Teijeira, Á. et al. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity 52, 856–871e8 (2020).
Müller, I., Munder, M., Kropf, P. & Hänsch, G. M. Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms? Trends Immunol. 30, 522–530 (2009).
Ostrand-Rosenberg, S., Beury, D. W., Parker, K. H. & Horn, L. A. Survival of the fittest: how myeloid-derived suppressor cells survive in the inhospitable tumor microenvironment. Cancer Immunol. Immunother. 69, 215–221 (2020).
Ferrone, C. & Dranoff, G. Dual roles for immunity in Gastrointestinal cancers. J. Clin. Oncol. 28, 4045–4051 (2010).
Cederholm, T. et al. Diagnostic criteria for malnutrition – an ESPEN consensus statement. Clin. Nutr. 34, 335–340 (2015).
Dolan, R. D. et al. The relationship between computed tomography-derived body composition, systemic inflammatory response, and survival in patients undergoing surgery for colorectal cancer. J. Cachexia Sarcopenia Muscle. 10, 111–122 (2019).
Kroenke, C. H. et al. Muscle radiodensity and mortality in patients with colorectal cancer. Cancer 124, 3008–3015 (2018).
Gruberg, L. et al. The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with diabetes mellitus. J. Am. Coll. Cardiol. 39, 1930–1936 (2002).
Romero-Corral, A. et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 368, 666–678 (2006).
Hainer, V. Aldhoon-Hainerová, I. Obesity paradox does exist. Diabetes Care. 36, S276–S281 (2013).
Armandi, A., Rosso, C., Caviglia, G. P., Ribaldone, D. G. & Bugianesi, E. The impact of dysmetabolic sarcopenia among insulin sensitive tissues: A narrative review. Front. Endocrinol. 12, 716533 (2021).
Li, S. et al. Correlation between sarcopenia and esophageal cancer: a narrative review. World J. Surg. Oncol. 22, 27 (2024).
Funding
This study was supported by the Open Subject Fund of Key Laboratory of Radiobiology in Fujian Province Universities (2023FSSW-01).
Author information
Authors and Affiliations
Contributions
Yanjing Zeng, Jinmei Chen, Liuyu Li performed the research and assisted in data collection. Xinpeng Wang, Ying Ye, Tingjie Xiong collected the clinical data. Yanjing Zeng, Jinmei Chen, Liuyu Li analysed the data and wrote the paper. Wenmin Ying and Zhichao Fu designed the study and revised the manuscript. All authors contributed to the article and approved the submitted version.
Corresponding authors
Ethics declarations
Ethics approval and consent to participate
All studies were approved by the relevant ethical review board, Due to the retrospective nature of the study, ethical review board waived the need of obtaining informed consent.
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Zeng, Y., Chen, J., Li, L. et al. Sarcopenia, myosteatosis and systemic immunoinflammatory index in the prediction of survival in patients undergoing immunotherapy for esophageal cancer. Sci Rep (2026). https://doi.org/10.1038/s41598-025-34513-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-025-34513-2
