ArticleJournal of thoracic disease2026
Predictive value of combined inflammatory and coagulation markers for immune-related pneumonitis in non-small cell lung cancer patients on immunotherapy: a retrospective cohort study.
Article in Journal of thoracic disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Immune checkpoint inhibitors (ICIs) have improved survival for patients with non-small cell lung cancer (NSCLC). However, immune-related pneumonitis (irPneumonitis) remains a major challenge, and predictive biomarkers are scarce. This study evaluated a panel of peripheral blood biomarkers. Methods: This retrospective cohort study included NSCLC patients who received ICI therapy. Baseline clinical and laboratory data were collected to calculate a spectrum of inflammatory and coagulation markers. The primary endpoints were the incidence of irPneumonitis (any grade and Grade ≥3) and overall survival (OS). Receiver operating characteristic (ROC) curve analysis was used to evaluate predictive performance. Multivariable logistic regression was used to identify risk factors. Additionally, time-dependent Cox regression models were employed to assess the prognostic value of biomarkers on OS, adjusting for the onset of severe irPneumonitis. Results: The incidence of any-grade and severe (Grade ≥3) irPneumonitis was 14.2% and 3.4%, respectively. ROC analysis demonstrated strong predictive ability for both the systemic immune-inflammation index (SII) [area under the curve (AUC) =0.892] and D-dimer (AUC =0.863). After multivariable adjustment, high SII [adjusted odds ratio (aOR) =4.88, 95% confidence interval (CI): 2.58-9.21, P<0.001] and high D-dimer (aOR =3.92, 95% CI: 2.05-7.49, P<0.001) were independent predictors for any-grade irPneumonitis. These associations were even stronger for severe irPneumonitis (SII aOR =6.12; D-dimer aOR =5.33; both P<0.001). In time-dependent survival analysis, both high SII [adjusted hazard ratio (aHR) =1.72, P=0.001] and high D-dimer (aHR =1.58, P=0.005) remained robust, independent predictors of poorer OS, even after adjusting for the occurrence of severe irPneumonitis. Conclusions: Pretreatment SII and D-dimer are potent, independent biomarkers for predicting irPneumonitis risk and survival outcomes in NSCLC patients treated with ICIs. These readily available markers, reflecting a pro-thromboinflammatory state, hold significant promise for improving risk stratification and guiding personalized monitoring strategies in clinical practice.
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