Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, The Republic of Korea.
Innovative Institute for Precision Medicine, Samsung Medical Center, Seoul, The Republic of Korea.
J Immunother Cancer. 2022 Aug;10(8). doi: 10.1136/jitc-2022-005226.
BACKGROUND: The obesity paradox is a topic of increasing interest in oncology and epidemiology research. Although this phenomenon has been observed in melanoma patients receiving immune checkpoint inhibitors, little is known about its mechanism. We aim to investigate the prognostic value of obesity and its association with adiposity and systemic inflammation. METHODS: This retrospective study evaluates the data of patients who received pembrolizumab or nivolumab for unresectable or metastatic melanoma between June 2015 and April 2021. The skeletal muscle index (SMI) and visceral fat index (VFI) (cm/m) were calculated by dividing the cross-sectional areas of skeletal muscle and visceral fat by height squared. The systemic immune-inflammation index (SII) was defined as the total peripheral platelet count×neutrophil/lymphocyte ratio. Cox proportional hazard regression analysis was conducted to determine the association with overall survival. RESULTS: We analyzed 266 patients with a median age of 60 years (IQR 51-69 years; 135 men and 131 women). The protective effect of obesity was independent of covariates (HR 0.60; 95% CI 0.37 to 0.99; p=0.048), but disappeared after adjusting for VFI (HR 0.76; 95% CI 0.41 to 1.40; p=0.380) or SII (HR 0.71; 95% CI 0.42 to 1.18; p=0.186). An increase of 10 cm/m in VFI was associated with longer overall survival after adjusting for covariates (HR 0.88; 95% CI 0.79 to 0.99; p=0.029). The prognostic value of VFI remained and predicted favorable overall survival after additional adjustment for SMI (HR 0.86; 95% CI 0.76 to 0.98; p=0.025), but disappeared with adjustment for SII (HR 0.92; 95% CI 0.82 to 1.03; p=0.142). An increase of 100×10/L in SII was associated with poor overall survival when adjusted for covariates (HR 1.08; 95% CI 1.05 to 1.11; p<0.001) or when additionally adjusted for VFI (HR 1.07; 95% CI 1.04 to 1.10; p<0.001). CONCLUSIONS: Visceral adiposity and systemic inflammation are significant prognostic factors in patients with unresectable or metastatic melanoma receiving immune checkpoint inhibitors. The prognostic impact of visceral adiposity is dependent on systemic inflammation status.
背景：肥胖悖论是肿瘤学和流行病学研究中日益关注的话题。尽管这种现象在接受免疫检查点抑制剂治疗的黑色素瘤患者中已经观察到，但对于其机制知之甚少。我们旨在研究肥胖的预后价值及其与肥胖和全身炎症的关系。
方法：本回顾性研究评估了 2015 年 6 月至 2021 年 4 月期间接受 pembrolizumab 或 nivolumab 治疗的不可切除或转移性黑色素瘤患者的数据。通过将骨骼肌和内脏脂肪的截面积除以身高的平方来计算骨骼肌指数（SMI）和内脏脂肪指数（VFI）（cm/m）。系统免疫炎症指数（SII）定义为外周血小板总数×中性粒细胞/淋巴细胞比值。Cox 比例风险回归分析用于确定与总生存的关联。
结果：我们分析了 266 名中位年龄为 60 岁（IQR 51-69 岁；135 名男性和 131 名女性）的患者。肥胖的保护作用独立于协变量（HR 0.60；95%CI 0.37 至 0.99；p=0.048），但在调整 VFI（HR 0.76；95%CI 0.41 至 1.40；p=0.380）或 SII（HR 0.71；95%CI 0.42 至 1.18；p=0.186）后消失。调整协变量后，VFI 增加 10 cm/m 与总生存时间延长相关（HR 0.88；95%CI 0.79 至 0.99；p=0.029）。VFI 的预后价值仍然存在，并在进一步调整 SMI 后预测总生存时间良好（HR 0.86；95%CI 0.76 至 0.98；p=0.025），但在调整 SII 后消失（HR 0.92；95%CI 0.82 至 1.03；p=0.142）。调整协变量后，SII 增加 100×10/L 与总生存不良相关（HR 1.08；95%CI 1.05 至 1.11；p<0.001），或在进一步调整 VFI 后（HR 1.07；95%CI 1.04 至 1.10；p<0.001）。
结论：内脏肥胖和全身炎症是接受免疫检查点抑制剂治疗的不可切除或转移性黑色素瘤患者的重要预后因素。内脏肥胖的预后影响取决于全身炎症状态。
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