Lung cancer (Amsterdam, Netherlands) · 2026
Immune-inflammatory predictors of early and brain recurrence in young patients with resected non-small cell lung cancer.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Brascia Debora, Mangiameli Giuseppe, Congedo Maria Teresa, Mastromarino Maria Giovanna, Catelli Chiara, Schiavon Marco, Giudici Veronica, Senatore Alessia, Bonis Alessandro, Lucchi Marco, Luzzi Luca, Magaritora Stefano, Rea Federico, Marulli Giuseppe
Аннотация
OBJECTIVES: Non-small-cell lung cancer (NSCLC) diagnosed before the age of 50 is uncommon and remains poorly characterized from a prognostic perspective. This study aimed to identify clinical, pathological, and inflammatory-immune predictors of recurrence, early recurrence, and brain metastasis after curative resection in young patients.
METHODS: This multicenter retrospective study included 224 consecutive patients aged <50 years who underwent anatomical lung resection between 2015 and 2024 at five Italian centers. Recurrence-free survival (RFS) was analyzed using Fine-Gray competing-risk regression and overall survival (OS) using Cox proportional hazards models. Early recurrence was defined as occurring within 12 months after surgery. The prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR), PD-L1 expression, and their combined phenotypes was explored. An exploratory ROC-derived NLR cut-off of 2.35 was used for stratification.
RESULTS: During follow-up, 65 patients (29.0%) experienced recurrence, with brain metastases representing the most frequent distant site (10.3% overall). Early recurrence occurred in 11.6% of patients. On multivariable analysis, higher NLR independently predicted recurrence (sHR 1.37, 95% CI 1.09-1.73), mortality (HR 1.82, 95% CI 1.27-2.61), and early recurrence (OR 3.61, 95% CI 1.07-12.21). PD-L1 expression alone was not prognostic; however, when combined with NLR, it identified inflammatory-immunologic phenotypes with different risks of brain metastasis among patients who recurred (p = 0.051).
CONCLUSIONS: Young-onset NSCLC is characterized by a high burden of early and distant recurrence, particularly involving the brain. Preoperative NLR is a robust predictor of recurrence, early relapse, and mortality. Combined NLR-PD-L1 phenotypes identify a subgroup at increased risk of neurotropic relapse.
METHODS: This multicenter retrospective study included 224 consecutive patients aged <50 years who underwent anatomical lung resection between 2015 and 2024 at five Italian centers. Recurrence-free survival (RFS) was analyzed using Fine-Gray competing-risk regression and overall survival (OS) using Cox proportional hazards models. Early recurrence was defined as occurring within 12 months after surgery. The prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR), PD-L1 expression, and their combined phenotypes was explored. An exploratory ROC-derived NLR cut-off of 2.35 was used for stratification.
RESULTS: During follow-up, 65 patients (29.0%) experienced recurrence, with brain metastases representing the most frequent distant site (10.3% overall). Early recurrence occurred in 11.6% of patients. On multivariable analysis, higher NLR independently predicted recurrence (sHR 1.37, 95% CI 1.09-1.73), mortality (HR 1.82, 95% CI 1.27-2.61), and early recurrence (OR 3.61, 95% CI 1.07-12.21). PD-L1 expression alone was not prognostic; however, when combined with NLR, it identified inflammatory-immunologic phenotypes with different risks of brain metastasis among patients who recurred (p = 0.051).
CONCLUSIONS: Young-onset NSCLC is characterized by a high burden of early and distant recurrence, particularly involving the brain. Preoperative NLR is a robust predictor of recurrence, early relapse, and mortality. Combined NLR-PD-L1 phenotypes identify a subgroup at increased risk of neurotropic relapse.