Zhao Man, Duan Xiaoling, Han Xin, Wang Jinfeng, Han Guangjie, Mi Lili, Shi Jianfei, Li Ning, Yin Xiaolei, Hou Jiaojiao, Yin Fei
Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Front Oncol. 2022 Apr 8;12:854096. doi: 10.3389/fonc.2022.854096. eCollection 2022.
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.
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.
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.
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.
包括免疫检查点抑制剂（ICIs）和酪氨酸激酶抑制剂（TKIs）在内的全身治疗方法对肝细胞癌（HCC）传统治疗方法的应用提出了挑战。确定哪些患者能从联合治疗中获益最大至关重要。本研究旨在探讨肌肉减少症和全身炎症反应指数（SIRI）与接受ICIs和TKIs治疗的HCC患者的治疗反应及疗效之间的关联，并研究肌肉减少症与炎症或免疫状态之间的相关性。
我们回顾了160例接受TKIs和ICIs治疗的HCC患者。在轴向计算机断层扫描上测量患者的腰大肌大小，并根据患者身高的平方进行标准化。该值称为腰大肌指数（PMI）。根据PMI确定肌肉减少症，并评估其与患者临床病理特征、炎症指标、外周血T细胞亚群和生存率的关系。
肌肉减少症和全身炎症反应指数（SIRI）是总生存期和无进展生存期的独立预测因素。PMI高且SIRI低的患者的中位总生存期和无进展生存期（分别为36.0个月和9.6个月）明显优于PMI低或SIRI高的患者（分别为20.8个月和6.0个月）以及SIRI高且PMI低的患者（分别为18.6个月和3.0个月）。门静脉癌栓（P = 0.003）、东部肿瘤协作组体能状态评分为1（P = 0.048）、碱性磷酸酶高（P = 0.037）、中性粒细胞与淋巴细胞比值（NLR）高（P = 0.012）、淋巴细胞与单核细胞比值（LMR）低（P = 0.031）、血小板与淋巴细胞比值（PLR）高（P = 0.022）和SIRI高（P = 0.012）与肌肉减少症发生率增加密切相关。PMI与SIRI（r = -0.175，P = 0.003）、NLR（r = -0.169，P = 0.036）和PLR（r = -0.328，P = 0.000）呈负相关，与LMR呈显著正相关（r = 0.232，P = 0.004）。高PMI组的CD3 +和CD4 + T细胞计数明显高于低PMI组。
肌肉减少症和高SIRI与接受ICIs和TKIs治疗的HCC患者生存率降低有关。肌肉减少症可能影响炎症状态和免疫微环境。
