Breathlessness predicts survival in patients with malignant pleural effusions: Meta-analysis of individual patient data from five randomized controlled trials

Background: Patients with malignant pleural effusions (MPEs) experience breathlessness and poor survival. Breathlessness is associated with poor survival in other conditions. Research Question: Is breathlessness, measured using a visual analog scale for dyspnea (VASD), associated with survival in patients with MPE? Study Design and Methods: Individual patient data from five randomized controlled trials of 553 patients undergoing interventions for MPE were analyzed. VASD was recorded at baseline and daily after intervention. Patients were followed up until death or end of trial. Univariate and multivariable Cox regression were used to identify factors associated with survival. Results: Baseline VASD was significantly associated with worse survival, with a hazard ratio of 1.10 (95% CI, 1.06-1.15) for a 10-mm increase in VASD. On multivariable regression, it remained a significant predictor of survival. Mean 7-day VASD and mean total VASD were also predictors of survival (mean 7-day VASD: hazard ratio [HR], 1.26 [95% CI, 1.19-1.34]; total VASD: HR, 1.25 [95% CI, 1.15-1.37]). Other predictors of survival were serum C-reactive protein level and tumor type. Previous treatment with chemotherapy, performance status, pleural fluid lactate dehydrogenase, serum albumin, hemoglobin, serum neutrophil:lymphocyte ratio, and size of effusion were associated with survival on univariate but not multivariable analysis. Interpretation: Breathlessness, measured using VASD at baseline and postprocedure, is a predictor of survival in patients with MPE.