Driver mutations and malignant pleural effusion in non-small cell lung cancer.

Abstract

Background: Malignant pleural effusion (MPE) complicates approximately 50% of non-small cell lung cancer (NSCLC) cases, signaling advanced disease and poor patient outcomes. While molecular alterations such as ALK, ROS1, and T790M mutations, as well as PD-L1 expression, are critical in NSCLC progression, their relationship with MPE development remains inadequately characterized.

Methods: This retrospective cohort study examined 130 NSCLC patients (52 with MPE, 78 without MPE). Clinical characteristics and comprehensive molecular profiles were analyzed using next-generation sequencing. Statistical comparisons were performed, and a Least Absolute Shrinkage and Selection Operator (LASSO) regularized logistic regression model identified independent predictors of MPE. Model performance was evaluated using receiver operating characteristic (ROC) analysis.

Results: PD-L1 expression demonstrated a significant association with MPE development (Odds ratio = 2.78, p < 0.01), nearly tripling the likelihood of effusion. The presence of ALK, ROS1, and T790M mutations (combined OR = 2.41, p < 0.05) also showed predictive value for MPE formation. Several clinical factors independently correlated with MPE, including advanced age, heavy smoking history (> 50 pack-years), and right inferior lobe tumor location (all p < 0.05). The predictive model demonstrated robust performance with an area under the curve of 0.80.

Conclusions: These findings establish important associations between specific driver mutations and PD-L1 expression in relation to MPE development in NSCLC patients. Identifying these genetic and clinical predictors may enhance risk stratification approaches and guide personalized treatment strategies, especially for those with advanced disease. Further prospective validation studies are needed to confirm these associations and explore their therapeutic implications.