Frontiers in immunology · 2026
A comprehensive prognostic model for older patients with advanced non-small cell lung cancer receiving immunotherapy: a multicenter real-world study.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Song Xinyu, Lv Juncai, Qi Yiming, Zheng Hongying, Ren Ziyuan, Wang Peilin, Sun Haiwang, Shen Hongbo
Аннотация
OBJECTIVE: Older patients (aged ≥ 75 years) with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy represent a growing but understudied population, yet few tools incorporate multidimensional host factors that influence prognosis. We therefore developed and externally validated a real-world prognostic model using bedside-available clinical variables, and compared its performance against conventional indices.
METHODS: This multicenter retrospective study included patients aged ≥ 75 years with advanced NSCLC receiving first-line immunotherapy. Cox regression analyses were performed to identify potential survival-associated host variables. A composite model, based on clinically relevant candidate variables identified through univariate screening, was developed using endpoint-specific L2-penalized Cox regression and internally validated with 1,000 bootstrap resamples. The final model was externally validated in two independent cohorts. Model performance was assessed using Harrell's C-index, inverse probability of censoring-weighted (IPCW) cumulative/dynamic area under the curve (AUC), calibration, decision curve analysis, and Kaplan-Meier survival analysis with log-rank tests. The model was formally compared with conventional indices using paired bootstrap analyses.
RESULTS: A total of 241 patients were included, with 115 in the development cohort and 126 in the pooled external validation cohort. We developed the CALI (Comorbidity-Advanced Lung Cancer Inflammation Index) model integrating comorbidity burden (hypertension, diabetes, chronic obstructive pulmonary disease), recent weight loss, and inflammatory-nutritional status represented by ALI. In the development cohort, 1- and 2-year AUCs were 0.587 and 0.712 for overall survival (OS), 0.584 and 0.708 for progression-free survival (PFS), with significant stratification for OS (P = 0.013) and PFS (P = 0.021). In the pooled validation cohort, 1- and 2-year AUCs were 0.561 and 0.806 for OS, 0.553 and 0.793 for PFS, also significant stratification for OS (P = 0.006) and PFS (P = 0.008). In paired comparisons, CALI showed modest but significant OS improvements over conventional indices, whereas PFS gains were less consistent.
CONCLUSION: CALI provided modest prognostic discrimination and risk stratification in older patients with advanced NSCLC receiving immunotherapy, with stronger and more consistent performance for OS than for PFS. The model offers a simple, bedside-applicable tool using routinely available clinical variables, and can be easily accessed via our online calculator (https://jccclv.github.io/CALI-calculator) for individualized risk stratification.
METHODS: This multicenter retrospective study included patients aged ≥ 75 years with advanced NSCLC receiving first-line immunotherapy. Cox regression analyses were performed to identify potential survival-associated host variables. A composite model, based on clinically relevant candidate variables identified through univariate screening, was developed using endpoint-specific L2-penalized Cox regression and internally validated with 1,000 bootstrap resamples. The final model was externally validated in two independent cohorts. Model performance was assessed using Harrell's C-index, inverse probability of censoring-weighted (IPCW) cumulative/dynamic area under the curve (AUC), calibration, decision curve analysis, and Kaplan-Meier survival analysis with log-rank tests. The model was formally compared with conventional indices using paired bootstrap analyses.
RESULTS: A total of 241 patients were included, with 115 in the development cohort and 126 in the pooled external validation cohort. We developed the CALI (Comorbidity-Advanced Lung Cancer Inflammation Index) model integrating comorbidity burden (hypertension, diabetes, chronic obstructive pulmonary disease), recent weight loss, and inflammatory-nutritional status represented by ALI. In the development cohort, 1- and 2-year AUCs were 0.587 and 0.712 for overall survival (OS), 0.584 and 0.708 for progression-free survival (PFS), with significant stratification for OS (P = 0.013) and PFS (P = 0.021). In the pooled validation cohort, 1- and 2-year AUCs were 0.561 and 0.806 for OS, 0.553 and 0.793 for PFS, also significant stratification for OS (P = 0.006) and PFS (P = 0.008). In paired comparisons, CALI showed modest but significant OS improvements over conventional indices, whereas PFS gains were less consistent.
CONCLUSION: CALI provided modest prognostic discrimination and risk stratification in older patients with advanced NSCLC receiving immunotherapy, with stronger and more consistent performance for OS than for PFS. The model offers a simple, bedside-applicable tool using routinely available clinical variables, and can be easily accessed via our online calculator (https://jccclv.github.io/CALI-calculator) for individualized risk stratification.