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肥胖对免疫检查点抑制剂治疗疗效影响的多维度分析。

A multidimensional analysis of the impact of obesity on immune checkpoint inhibitor therapy efficacy.

作者信息

Xu Wenjing, Yang Yifan, Yu Yue, Wu Lu, Ma Dong, Li Rongrong, Yang Lu, Sun Hengwen

机构信息

Department of Radiotherapy, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.

Department of Interventional Radiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), 106 Zhongshan Second Rd, Guangzhou, 510080, Guangdong, China.

出版信息

Cancer Cell Int. 2024 Oct 29;24(1):358. doi: 10.1186/s12935-024-03532-w.

DOI:10.1186/s12935-024-03532-w
PMID:39472922
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11523605/
Abstract

BACKGROUND

Obesity is a well-known risk factor for developing malignant tumors and promoting tumor cell growth and spread. However, recent studies have shown that obese cancer patients, who typically have a worse prognosis than nonobese cancer patients, show a significant improvement in survival after receiving immune checkpoint inhibitor (ICI) therapy. This phenomenon is known as the "obesity paradox". However, this phenomenon is influenced by tumor type and sex. Therefore, this study aimed to explore the impact of obesity on immunotherapy efficacy from multiple perspectives, aiming to verify this paradox and provide new scientific evidence on the effect of obesity on ICI efficacy.

METHODS

This retrospective study evaluated the data of patients who received ICI therapy between June 2019 and August 2023. Automatic segmentation of skeletal muscle, subcutaneous fat, and visceral fat was performed using Slice-O-Matic software, and the corresponding skeletal muscle index (SMI), subcutaneous fat index (SFI) and visceral fat index (VFI) were calculated. The neutrophil-to-lymphocyte ratio (NLR) was determined by dividing the neutrophil count by the lymphocyte count. Univariate and multivariate Cox regression analyses were used to evaluate the correlation between body mass index (BMI), body composition parameters, and the NLR with overall survival (OS) and progression-free survival (PFS) in obese patients receiving ICI therapy.

RESULTS

We analyzed 219 patients with a median age of 60 years (IQR 53-69 years; 155 men and 64 women). Obese patients, particularly those with visceral fat accumulation, exhibited extended OS after ICI therapy (log-rank P = 0.027). Cox multivariate analysis revealed that the NLR (HR = 1.036; 95% CI: 0.996 to 1.078; P = 0.002) was independently associated with OS. Patients with a high NLR had worse OS than those with a low NLR.

CONCLUSIONS

This study corroborates the veracity of the "obesity paradox" under specific conditions and identifies NLR as an independent prognostic factor, with elevated NLR indicative of a poor prognosis.

摘要

背景

肥胖是已知的发生恶性肿瘤以及促进肿瘤细胞生长和扩散的风险因素。然而,最近的研究表明,肥胖癌症患者通常比非肥胖癌症患者预后更差,但在接受免疫检查点抑制剂(ICI)治疗后生存率有显著提高。这种现象被称为“肥胖悖论”。然而,这一现象受肿瘤类型和性别的影响。因此,本研究旨在从多个角度探讨肥胖对免疫治疗疗效的影响,旨在验证这一悖论,并为肥胖对ICI疗效的影响提供新的科学证据。

方法

这项回顾性研究评估了2019年6月至2023年8月期间接受ICI治疗的患者数据。使用Slice - O - Matic软件对骨骼肌、皮下脂肪和内脏脂肪进行自动分割,并计算相应的骨骼肌指数(SMI)、皮下脂肪指数(SFI)和内脏脂肪指数(VFI)。中性粒细胞与淋巴细胞比值(NLR)通过中性粒细胞计数除以淋巴细胞计数来确定。单因素和多因素Cox回归分析用于评估体重指数(BMI)、身体成分参数和NLR与接受ICI治疗的肥胖患者的总生存期(OS)和无进展生存期(PFS)之间的相关性。

结果

我们分析了219例患者,中位年龄为60岁(四分位间距53 - 69岁;男性155例,女性64例)。肥胖患者,尤其是那些有内脏脂肪堆积的患者,在ICI治疗后表现出更长的总生存期(对数秩检验P = 0.027)。Cox多因素分析显示,NLR(HR = 1.036;95%置信区间:0.996至1.078;P = 0.002)与总生存期独立相关。NLR高的患者总生存期比NLR低的患者更差。

结论

本研究证实了特定条件下“肥胖悖论”的真实性,并将NLR确定为一个独立的预后因素,NLR升高表明预后不良。

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