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