老年营养风险指数在晚期NSCLC免疫治疗预后及免疫相关不良反应中的预测价值

doi:10.3760/cma.j.cn371439-20260203-00057

摘要/Abstract

摘要：

目的探讨老年营养风险指数（GNRI）在晚期非小细胞肺癌（NSCLC）患者免疫治疗预后及免疫相关不良反应（irAE）中的预测价值。方法回顾性分析2016年9月至2020年6月山西医科大学第一医院肿瘤呼吸科收治的108例接受免疫检查点抑制剂（ICI）治疗晚期 NSCLC患者的临床资料。参照既往 GNRI风险分层标准，将患者分为高 GNRI组（>92， n=59）和低 GNRI组（≤92， n=49）。绘制Kaplan-Meier生存曲线，采用log-rank检验比较高、低GNRI组间患者总生存期（OS）差异，采用Cox比例风险回归模型分析预后的影响因素，采用Spearman相关性分析GNRI与中性粒细胞与淋巴细胞比值（NLR）的相关性，绘制受试者操作特征（ROC）曲线评估GNRI对irAE的预测效能。结果高、低GNRI组接受ICI治疗晚期NSCLC患者中位OS分别为32.0、16.0个月，差异有统计学意义（χ²=10.39， P=0.001）。单因素分析显示，临床分期（HR=2.02， 95%CI为1.21~3.39， P=0.008）、GNRI（HR=2.29， 95%CI为1.36~3.83， P=0.002）、NLR（HR=1.87， 95%CI为1.05~3.33， P=0.032）、预后营养指数（PNI）（HR=1.83， 95%CI为1.10~3.06， P=0.020）均是接受ICI治疗晚期NSCLC患者OS的影响因素。多因素分析显示，临床分期（HR=1.92， 95%CI为1.12~3.31， P=0.018）、GNRI（HR=2.40， 95%CI为1.25~4.60， P=0.008）均是接受ICI治疗晚期NSCLC患者OS的独立影响因素。Spearman相关性分析显示，接受ICI治疗晚期NSCLC患者GNRI与NLR呈负相关（r=-0.44， P<0.001）。为排除极端值干扰，剔除1例极端离群点（残差>3， NLR=93.38）后进行敏感性分析， GNRI与NLR依然呈负相关（r=-0.43， P<0.001）。共59例患者发生irAE，其中Ⅰ~Ⅱ级48例， Ⅲ~Ⅴ级11例。低GNRI组接受ICI治疗晚期NSCLC患者irAE发生率为77.55%（38/49），高GNRI组为35.59%（21/59），差异有统计学意义（χ²=19.01， P<0.001）。ROC曲线分析显示， GNRI预测接受ICI治疗晚期NSCLC患者发生irAE的曲线下面积（AUC）为0.76（95%CI为0.67~0.85），最佳截断值为93.06，此时预测的敏感性为71.2%，特异性为75.5%。Kaplan-Meier生存分析显示，以93.06为界值对接受ICI治疗晚期NSCLC患者重新分组后，低GNRI组（≤93.06， n=54）患者的中位OS依然显著短于高GNRI（>93.06， n=54）患者（16.70个月比28.10个月），差异有统计学意义（χ²=5.85， P=0.016）。结论高GNRI组接受ICI治疗晚期NSCLC患者中位OS长于低GNRI组患者， GNRI是接受ICI治疗晚期NSCLC患者预后的独立影响因素，且与全身炎症状态指标NLR呈负相关。GNRI对接受ICI治疗晚期NSCLC患者irAE具有较好的预测效能。

关键词: 癌, 非小细胞肺, 免疫疗法, 预后, 药物相关性副作用和不良反应, 老年营养风险指数

Abstract:

Objective To investigate the predictive value of the geriatric nutritional risk index（GNRI）for prognosis and immune-related adverse events（irAEs）in patients with advanced non-small cell lung cancer（NSCLC）receiving immunotherapy. Methods The clinical data of 108 patients with advanced NSCLC who received immune checkpoint inhibitor（ICI）therapy at the Department of Oncology Respiratory， First Hospital of Shanxi Medical University from September 2016 to June 2020 were retrospectively analyzed. Based on the previous GNRI risk stratification criteria， the patients were divided into a high GNRI group（>92， n=59）and a low GNRI group（≤92， n=49）. Kaplan-Meier survival curves were drawn and the log-rank test were used to compare the difference in overall survival（OS）between the high and low GNRI groups. A Cox proportional hazards regression model was used to analyze the influencing factors of prognosis. Spearman correlation analysis was used to analyze the correlation between GNRI and neutrophil to lymphocyte ratio（NLR）. Receiver operator characteristic（ROC）curves were drawn to evaluate the predictive efficacy of GNRI for irAEs. Results The median OS of patients with advanced NSCLC receiving ICI therapy in the high and low GNRI groups were 32.0 and 16.0 months， respectively， with a statistically significant difference（χ²=10.39， P=0.001）. Univariate analysis showed that， clinical stage（HR=2.02， 95%CI：1.21-3.39， P=0.008）， GNRI（HR=2.29， 95%CI：1.36-3.83， P=0.002）， NLR（HR=1.87， 95%CI：1.05-3.33， P=0.032）， and prognostic nutritional index（PNI）（HR=1.83， 95%CI：1.10-3.06， P=0.020）were all influencing factors for OS in patients with advanced NSCLC receiving ICI therapy. Multivariate analysis showed that， clinical stage（HR=1.92， 95%CI：1.12-3.31， P=0.018）and GNRI（HR=2.40， 95%CI：1.25-4.60， P=0.008）were independent influencing factors for OS in patients with advanced NSCLC receiving ICI therapy. Spearman correlation analysis showed that， GNRI was negatively correlated with NLR in patients with advanced NSCLC receiving ICI therapy（r=-0.44， P<0.001）. To eliminate the interference of extreme values， sensitivity analysis was performed after excluding 1 extreme outlier（residual>3， NLR=93.38）， and GNRI still showed a negative correlation with NLR（r=-0.43， P<0.001）. A total of 59 patients experienced irAEs， among which 48 cases were grade Ⅰ-Ⅱ and 11 cases were grade Ⅲ-Ⅴ. The incidence of irAEs in patients with advanced NSCLC receiving ICI therapy was 77.55%（38/49）in the low GNRI group and 35.59%（21/59）in the high GNRI group， with a statistically significant difference（χ²=19.01， P<0.001）. ROC curve analysis showed that， the area under the curve（AUC）of GNRI for predicting irAEs in patients with advanced NSCLC receiving ICI therapy was 0.76（95%CI：0.67-0.85）. The optimal cutoff value was 93.06， at which point the predictive sensitivity was 71.2% and the specificity was 75.5%. Kaplan-Meier survival analysis showed that after regrouping the patients with advanced NSCLC receiving ICI therapy using 93.06 as the cutoff value， the median OS of patients in the low GNRI group（≤93.06， n=54）was still significantly shorter than that in the high GNRI group（>93.06， n=54）（16.70 months vs. 28.10 months）， and there was a statistically significant difference（χ²=5.85， P=0.016）. Conclusions The median OS of patients with advanced NSCLC receiving ICI therapy in the high GNRI group is longer than that in the low GNRI group. GNRI is an independent influencing factor for the prognosis of patients with advanced NSCLC receiving ICI therapy， and it is negatively correlated with the systemic inflammatory status index NLR. GNRI has a good predictive efficacy for irAEs in patients with advanced NSCLC receiving ICI therapy.

Key words: Carcinoma, non-small-cell lung, Immunotherapy, Prognosis, Drug-related side effects and adverse reactions, Geriatric nutritional risk index

李岩松, 贾军梅. 老年营养风险指数在晚期NSCLC免疫治疗预后及免疫相关不良反应中的预测价值[J]. 国际肿瘤学杂志, 2026, 53(6): 355-360.

Li Yansong, Jia Junmei. Predictive value of the geriatric nutritional risk index for prognosis in advanced NSCLC treated with immunotherapy and immune-related adverse events[J]. Journal of International Oncology, 2026, 53(6): 355-360.

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一般临床资料	低GNRI组（n=49）	高GNRI组（n=59）	U/χ²值	P 值
年龄^a（岁）	71.00 （67.00，74.00）	66.00 （59.50，71.00）	4.02	<0.001
性别^b
女	13	6	4.94	0.026
男	36	53	4.94	0.026
吸烟史^b
无	15	25	1.59	0.208
有	34	34	1.59	0.208
病理类型^b
腺癌	28	30	0.43	0.514
鳞状细胞癌	21	29	0.43	0.514
免疫治疗方案^b
单药治疗	11	9	0.50	0.478
联合治疗	38	50	0.50	0.478
临床分期^b
Ⅲ期	18	33	3.23	0.073
Ⅳ期	31	26	3.23	0.073
NLR^a	6.92 （4.34，11.27）	4.33 （3.24，6.12）	4.24	<0.001
PLR^a	197.58 （112.50，292.11）	218.47 （150.11，303.12）	0.53	0.593
SII^a	1 300.99 （755.76，2 389.42）	1 023.62 （669.86，1 526.89）	2.24	0.025
PNI^a	39.05 （34.60，41.85）	42.85 （40.98，46.70）	5.32	<0.001

因素	HR值	95%CI	P值
年龄	1.01	0.97~1.05	0.576
性别	1.24	0.61~2.52	0.549
吸烟史	1.12	0.66~1.92	0.671
病理类型	1.11	0.67~1.83	0.690
免疫治疗方案	0.57	0.31~1.07	0.079
临床分期	2.02	1.21~3.39	0.008
GNRI	2.29	1.36~3.83	0.002
NLR	1.87	1.05~3.33	0.032
PLR	0.78	0.41~1.48	0.443
SII	1.61	0.91~2.86	0.103
PNI	1.83	1.10~3.06	0.020

因素	HR值	95%CI	P值
年龄	0.99	0.96~1.03	0.732
性别	2.08	0.84~5.13	0.111
吸烟史	0.55	0.27~1.13	0.102
病理类型	1.26	0.75~2.11	0.390
免疫治疗方案	0.60	0.31~1.13	0.115
临床分期	1.92	1.12~3.31	0.018
GNRI	2.40	1.25~4.60	0.008
NLR	1.40	0.79~2.49	0.247