Prognostic impact of hepatic steatosis evaluated by CT on immunotherapy for gastric cancer; associations with sarcopenia, systemic inflammation, and hormones

Introduction: Immune checkpoint inhibitors (ICIs) are expected to improve the prognosis of gastric cancer (GC). On the other hand, hepatic steatosis has been reported to be associated with cancer cachexia, and expected to be a cancer biomarker. The purpose of this study is to evaluate prognostic impact of hepatic steatosis in ICIs therapy for GC.Methods: Unresectable or recurrent GC treated with ICIs were investigated. Using unenhanced CT, liver to spleen CT attenuation ratio (LSR) was calculated as a parameter of hepatic steatosis. LSR was compared with the presence of sarcopenia, inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). These parameters were also compared with disease specific survival (DSS) and progression free survival (PFS). Associations of LSR with insulin-like growth factor 1 (IGF-1) and growth hormone were also evaluated.Results: A total of seventy patients were investigated. LSR of sarcopenia patients was significantly lower than that of non-sarcopenia ones (P=0.02). LSR showed significant negative correlations with NLR, PLR, and MLR (P=0.003, 0.03, 0.01, respectively). Lower LSR was significantly associated with higher level of serum IGF-1 (P=0.03). In univariate analysis, LSR was significantly correlated with DSS and PFS (both P<0.0001), and multivariate analysis demonstrated that LSR was the independent prognostic factor for both DSS and PFS (both P=0.01). ROC analysis demonstrated that LSR>1.263 was a good predictive marker for favorable DSS (>5.3 months) with AUC of 0.80.Conclusion: Hepatic steatosis can be a promising prognostic biomarker for ICIs therapy of GC, associated with sarcopenia and the elevation of inflammatory markers. Out data suggested that GC with steatohepatitis might be less responsive to ICIs therapy.

Automated summary

This study aimed to evaluate the prognostic impact of hepatic steatosis in ICIs therapy for gastric cancer. The results showed that hepatic steatosis was associated with prognostic indicators, particularly with sarcopenia and the elevation of inflammatory markers.