Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab

BackgroundSintilimab, a programmed cell death protein-1 (PD-1) inhibitor, has shown efficacy in non-small cell lung cancer (NSCLC), though response heterogeneity persists. Previous studies suggest that the Lung Immune Prognostic Index (LIPI) may predict prognosis and immune-related adverse events (i...

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Main Authors: Jian Xu, Tingting Peng, Kaikai Fan, Yuxiao Dou, Lingti Kong, Ran Sang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1569689/full
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author Jian Xu
Tingting Peng
Kaikai Fan
Yuxiao Dou
Lingti Kong
Ran Sang
author_facet Jian Xu
Tingting Peng
Kaikai Fan
Yuxiao Dou
Lingti Kong
Ran Sang
author_sort Jian Xu
collection DOAJ
description BackgroundSintilimab, a programmed cell death protein-1 (PD-1) inhibitor, has shown efficacy in non-small cell lung cancer (NSCLC), though response heterogeneity persists. Previous studies suggest that the Lung Immune Prognostic Index (LIPI) may predict prognosis and immune-related adverse events (irAEs) in immunotherapy. This study aimed to develop and validate LIPI-based nomograms for predicting overall survival (OS) and irAEs in NSCLC patients treated with sintilimab.MethodsMulticenter data stratified 356 patients into training, internal validation, and external validation cohorts. Propensity score matching (PSM) balanced baseline characteristics. Multivariable Cox regression identified OS and irAEs predictors, and nomograms were constructed using significant variables. Model performance was evaluated via concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Kaplan-Meier analysis assessed risk stratification.ResultsIndependent prognostic factors for OS include clinical stage, treatment lines, LIPI scores and albumin level. Among them, stage IV (hazard ratio [HR]=1.725, 95% confidence interval [CI] 1.529-1.902), treatment line ≥2 (HR=1.302, 95%CI: 1.125-1.569), LIPI intermediate (HR=1.736, 95%CI: 1.586-1.925), LIPI poor (HR=1.568, 95% CI: 1.361-1.637) and albumin level≥35 (HR=1.802, 95%CI: 1.698-2.023) were risk factors for OS. The OS prediction model demonstrated excellent discrimination across all cohorts, with time-dependent AUCs maintaining 0.770-0.850 for 1–2 year predictions. Consistent calibration was observed (C-index: training=0.778, internal validation=0.793, external validation=0.790). For irAEs prediction, significant predictors included age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), and LIPI scores. Similarly, the irAEs model showed robust performance (AUCs 0.754-0.835 for 1–2 year predictions; C-index: training=0.805, internal validation=0.825, external validation=0.775). Both nomograms significantly outperformed single-variable predictions in Kaplan-Meier analyses. DCA confirmed superior net clinical benefit.ConclusionLIPI-based nomograms effectively predicted OS and irAEs in sintilimab-treated NSCLC patients, offering valuable tools for personalized treatment and clinical decision-making.
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spelling doaj-art-e1031d892b3d4deead78de242861a7022025-08-20T03:52:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15696891569689Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimabJian Xu0Tingting Peng1Kaikai Fan2Yuxiao Dou3Lingti Kong4Ran Sang5Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Spinal Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Pharmacy, Suzhou Municipal Hospital, Suzhou, ChinaDepartment of Pharmacy, Hefei Eighth People’s Hospital, Hefei, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, ChinaBackgroundSintilimab, a programmed cell death protein-1 (PD-1) inhibitor, has shown efficacy in non-small cell lung cancer (NSCLC), though response heterogeneity persists. Previous studies suggest that the Lung Immune Prognostic Index (LIPI) may predict prognosis and immune-related adverse events (irAEs) in immunotherapy. This study aimed to develop and validate LIPI-based nomograms for predicting overall survival (OS) and irAEs in NSCLC patients treated with sintilimab.MethodsMulticenter data stratified 356 patients into training, internal validation, and external validation cohorts. Propensity score matching (PSM) balanced baseline characteristics. Multivariable Cox regression identified OS and irAEs predictors, and nomograms were constructed using significant variables. Model performance was evaluated via concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Kaplan-Meier analysis assessed risk stratification.ResultsIndependent prognostic factors for OS include clinical stage, treatment lines, LIPI scores and albumin level. Among them, stage IV (hazard ratio [HR]=1.725, 95% confidence interval [CI] 1.529-1.902), treatment line ≥2 (HR=1.302, 95%CI: 1.125-1.569), LIPI intermediate (HR=1.736, 95%CI: 1.586-1.925), LIPI poor (HR=1.568, 95% CI: 1.361-1.637) and albumin level≥35 (HR=1.802, 95%CI: 1.698-2.023) were risk factors for OS. The OS prediction model demonstrated excellent discrimination across all cohorts, with time-dependent AUCs maintaining 0.770-0.850 for 1–2 year predictions. Consistent calibration was observed (C-index: training=0.778, internal validation=0.793, external validation=0.790). For irAEs prediction, significant predictors included age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), and LIPI scores. Similarly, the irAEs model showed robust performance (AUCs 0.754-0.835 for 1–2 year predictions; C-index: training=0.805, internal validation=0.825, external validation=0.775). Both nomograms significantly outperformed single-variable predictions in Kaplan-Meier analyses. DCA confirmed superior net clinical benefit.ConclusionLIPI-based nomograms effectively predicted OS and irAEs in sintilimab-treated NSCLC patients, offering valuable tools for personalized treatment and clinical decision-making.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1569689/fullnomogramsnon-small cell lung cancerimmunotherapyinflammation markerspredictingsintilimab
spellingShingle Jian Xu
Tingting Peng
Kaikai Fan
Yuxiao Dou
Lingti Kong
Ran Sang
Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab
Frontiers in Immunology
nomograms
non-small cell lung cancer
immunotherapy
inflammation markers
predicting
sintilimab
title Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab
title_full Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab
title_fullStr Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab
title_full_unstemmed Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab
title_short Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab
title_sort development of a lung immune prognostic index based nomogram model for predicting overall survival and immune related adverse events in non small cell lung cancer patients treated with sintilimab
topic nomograms
non-small cell lung cancer
immunotherapy
inflammation markers
predicting
sintilimab
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1569689/full
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