基于老年营养风险指数构建老年非小细胞肺癌患者的预后模型

A Prognostic Model of Elderly Patients with Non-small Cell Lung Cancer Based on Geriatric Nutritional Risk Index

背景与目的癌症患者的营养状况与预后之间的关系已成为研究关注的热点。本研究旨在探索老年营养风险指数(geriatric nutritional risk index,GNRI)在老年非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后评估中的应用价值,构建预测老年NSCLC患者预后的列线图模型。方法回顾性分析郑州大学第一附属医院于2016年1月至2019年12月初治的、≥65岁的153例NSCLC患者的资料。使用受试者工作特征(receiver operating characteristic,ROC)曲线确定GNRI的最佳截断值,把患者分为高GNRI组和低GNRI组,通过Kaplan-Meier曲线和Log-rank检验对两组患者总生存期(overall survival,OS)进行比较。使用单因素和多因素Cox回归分析探讨老年NSCLC患者不良预后的危险因素,利用R软件构建预测老年NSCLC患者生存率的列线图模型,并验证该模型。结果高GNRI组和低GNRI组在年龄、性别、体重指数(body mass index,BMI)、组织学类型、白蛋白水平、治疗方式、中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)、预后营养指数(prognostic nutritional index,PNI)、全身免疫炎症指数(systemic immuneinflammation index,SII)和细胞角蛋白19片段(cytokeratin 19 fragment,CYFRA21-1)方面存在统计学差异(P<0.05)。Kaplan-Meier曲线显示低GNRI组的患者总生存期较短。多因素Cox回归分析显示CYFRA21-1>3.3 ng/mL是影响NSCLC患者OS的独立危险因素,GNRI>97.09是保护因素[风险比(hazard ratio,HR)=0.52,95%置信区间(confidence interval,CI):0.34-0.79,P<0.05]。Ⅳ期患者发生死亡的风险是I期患者的1.98倍(95%CI:1.02-3.86,P<0.05)。与行综合治疗的患者相比,行单一化疗的患者发生死亡的风险增加3.58倍(95%CI:2.03-6.32,P<0.05)。基于GNRI构建的列线图模型对老年NSCLC患者OS进行预测,其一致性指数(concordance index,C-index)为0.70(95%CI:0.65-0.76),预测1、2年生存率的曲线下面积(area under the curve,AUC)分别为0.93(95%CI:0.87-0.98)、0.72(95%CI:0.63-0.80),校准曲线显示该模型的预测符合度较好。结论高GNRI评分与改善老年NSCLC患者的生存率显著相关,依靠截断值可能提供恰当的营养支持时机。该研究构建的列线图可作为一种有效预测老年NSCLC患者生存率的工具,具有很强的临床实用性。

Background and objective The relationship between nutritional status and prognosis of cancer patients has emerged as a hotspot for research.The aim of this study is to explore the application value of the geriatric nutritional risk index(GNRI)in assessing the prognosis of elderly patients with non-small cell lung cancer(NSCLC),and establish a Nomogram to predict the prognosis of elderly patients with NSCLC.Methods The data of patients with NSCLC aged≥65 years who were initially treated in the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were retrospectively analyzed.To determine the optimal cut-off value for GNRI,receiver operating characteristic(ROC)curve was constructed,and the patients were divided into high and low GNRI groups.Kaplan-Meier curve and Log-rank test were used to compare overall survival(OS)of the two groups.Univariate and multivariate Cox regression was used to analyze the risk factors for poor prognosis in elderly patients with NSCLC.Nomogram predicting survival in elderly patients with NSCLC was constructed and validated by using R software.Results Statistically significant differences in age,gender,body mass index(BMI),histological type,albumin,treatment methods,neutrophil to lymphocyte ratio(NLR),prognostic nutritional index(PNI),systemic immune-inflammation index(SII)and cytokeratin 19 fragment(CYFRA21-1)were observed between the high and low GNRI groups(P<0.05).The Kaplan-Meier curve showed a shorter OS in the low-GNRI group.Multivariate Cox regression analysis showed that CYFRA21-1>3.3 ng/mL was an independent risk factor for the development of OS in patients with NSCLC,and GNRI>97.09 was a protective factor[hazard ratio(HR)=0.52,95%confidence interval(CI):0.34-0.79,P<0.05].Patients in the stage IV had a 1.98-fold increased risk of death compared with patients in the stage I(95%CI:1.02-3.86,P<0.05).The risk of death was 3.58 times higher in patients receiving chemotherapy alone compared with those receiving combination therapy(95%CI:2.03-6.32,P<0.05).A Nomogram constructed on the basis of GNRI,which predicted the OS of elderly patients with NSCLC with a concordance index(C-index)of 0.70(95%CI:0.65-0.76),and the area under the curve(AUC)for 1 and 2-year survival rates to be 0.93(95%CI:0.87-0.98)and 0.72(95%CI:0.63-0.80),respectively,and the calibration curve has a good coincidence of prediction.Conclusion High GNRI scores are significantly associated with improved survival in elderly patients with NSCLC,and reliance on cut-off values may provide the appropriate timing for nutritional support.The Nomogram constructed in this study can be used as an effective tool to predict the survival rate of elderly patients with NSCLC,which has strong clinical practicability.