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体重指数、肥胖与肿瘤浸润淋巴细胞作为免疫治疗患者的预后生物标志物:多参数分析。

Body mass index, adiposity and tumour infiltrating lymphocytes as prognostic biomarkers in patients treated with immunotherapy: A multi-parametric analysis.

机构信息

Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Haemato-Oncology, University of Milano, Milan, Italy.

出版信息

Eur J Cancer. 2021 Mar;145:197-209. doi: 10.1016/j.ejca.2020.12.028. Epub 2021 Jan 22.

DOI:10.1016/j.ejca.2020.12.028
PMID:33493979
Abstract

BACKGROUND

We performed a multi-parametric analysis investigating the association between adiposity (as measured using body mass index [BMI] and computed tomography [CT]-based body composition), tumour infiltrating lymphocytes (TILs) and clinical outcomes in patients with advanced-stage cancer treated with immunotherapy in phase I clinical trials.

MATERIAL AND METHODS

All consecutive patients (N = 153) with metastatic solid tumours treated within immunotherapy-based phase I clinical trials between August 2014 and May 2019 at our institution were included. Baseline characteristics, BMI, TILs value and CT-assessed fat indices (total fat area [TFA], subcutaneous fat area [SFA] and visceral fat [VFA]) were collected. The primary endpoints were to evaluate the impact of these parameters on overall survival (OS) and progression-free survival (PFS). Kaplan-Meier method and Cox proportional-hazards model were used for survival analyses.

RESULTS

At both univariate and multivariate analyses, BMI was not associated with PFS neither when considered as continuous variable (HR 0.90, 95% CI 0.74-1.09, P = 0.28) nor as dichotomous variable (underweight/normal versus overweight/obese) (HR 0.79, 95% CI 0.55-1.14, P = 0.21). Interestingly, patients diagnosed with 'immunogenic' tumours and higher VFA/SFA ratio (1st and 2nd tertile versus 3rd tertile) presented an increased OS (HR 0.88, 95% CI 0.78-1.00, P = 0.047).

CONCLUSION

Our analysis showed that patients with tumours that are already known as responsive to ICIs with higher VFA/SFA ratio presented an increased OS. Further studies are needed to elucidate the effect of adiposity on the host immune response to immunotherapy.

摘要

背景

我们进行了一项多参数分析,研究了肥胖(通过体重指数[BMI]和基于计算机断层扫描的身体成分测量)、肿瘤浸润淋巴细胞(TILs)与接受 I 期临床试验免疫治疗的晚期癌症患者临床结局之间的关系。

材料与方法

本研究纳入了 2014 年 8 月至 2019 年 5 月期间在我们机构接受免疫治疗为基础的 I 期临床试验治疗的所有转移性实体瘤患者(N=153)。收集了基线特征、BMI、TIL 值和 CT 评估的脂肪指数(总脂肪面积[TFA]、皮下脂肪面积[SFA]和内脏脂肪[VFA])。主要终点是评估这些参数对总生存期(OS)和无进展生存期(PFS)的影响。Kaplan-Meier 法和 Cox 比例风险模型用于生存分析。

结果

在单因素和多因素分析中,BMI 与 PFS 均无相关性,无论是作为连续变量(HR 0.90,95%CI 0.74-1.09,P=0.28)还是作为二分变量(体重不足/正常与超重/肥胖)(HR 0.79,95%CI 0.55-1.14,P=0.21)。有趣的是,诊断为“免疫原性”肿瘤且 VFA/SFA 比值较高(第 1 和第 2 三分位数与第 3 三分位数相比)的患者 OS 延长(HR 0.88,95%CI 0.78-1.00,P=0.047)。

结论

我们的分析表明,已知对 ICIs 有反应的肿瘤患者,如果 VFA/SFA 比值较高,则 OS 延长。需要进一步研究阐明肥胖对宿主免疫应答免疫治疗的影响。

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