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This randomized, controlled trial showed that, among patients with malignant pleural effusion, the insertion of talc into the pleural space through an indwelling catheter resulted in a higher frequency of successful pleurodesis than placebo.

Malignant pleural effusion (MPE) is a common complication of advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to be efficient in suppressing the accumulation of pleural fluid. However, whether intrapleural delivery of bevacizumab can be used to treat MPE remains unknown. The aim of the present study was to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin, an antineoplastic agent, in controlling MPE. A total of 72 NSCLC study subjects with MPE were randomly assigned to one of two groups. The first group received intrapleural bevacizumab (300 mg) with cisplatin (30 mg) therapy and the second group received intrapleural cisplatin (30 mg) therapy alone. Pleural fluid was collected from both groups prior to and following treatment. The levels of VEGF and carcinoembryonic antigen (CEA) in the pleural fluid were determined by ELISA. In 70 evaluable study subjects, the curative efficacy in the bevacizumab group was significantly higher than that found in the cisplatin group (83.33 vs. 50.00%, respectively; p<0.05). Therapy with combined bevacizumab plus cisplatin significantly reduced VEGF levels in the pleural fluid (p<0.01). In the bevacizumab group, the levels of VEGF in the pleural fluid were significantly lower compared to those of the cisplatin group after treatment, which showed greater efficacy (p<0.01). In addition, combination therapy showed greater efficacy in the patients with high levels of VEGF expression (p<0.01). There was no significant difference in grade III/IV adverse events between the two groups. All procedures were well tolerated by the patients. Combined intrapleural therapy with bevacizumab and cisplatin was effective and safe in managing NSCLC-mediated MPE. We propose that VEGF expression levels in MPE could serve as a prognostic marker for bevacizumab therapy.

Background: Iodopovidone is an alternative agent used to promote pleurodesis in patients with malignant pleural effusion (MPE). However, safety is a concern, and many authors still reject its use. Objectives: Our main objective is to describe the occurrence of common and severe adverse events after pleurodesis with two different doses of iodopovidone in patients with MPE. Our secondary objective is to evaluate dose dependency, efficacy, quality of life, and systemic inflammation. Methods: We conducted a double-blind, randomized clinical trial including patients with recurrent MPE. Patients underwent chest tube insertion and were randomized into two groups according to the doses of iodopovidone: group 1 received 1% iodopovidone, and group 2 received 2% iodopovidone. During follow-up, adverse events, inflammatory markers, quality of life, and imaging exams were systematically evaluated and registered. Results: Sixty patients were analyzed (55 females, 5 males, median age 55.9 years). Overall, 227 adverse events possibly related to pleurodesis were registered, including 47 serious adverse events (in 34 patients). Pleuritic pain and hypertensive peaks were the most frequently observed serious adverse events (11 and 10 episodes, respectively). Grade 3/4 metabolic events such as hyponatremia and an increase in alkaline phosphatase, AST and ALT levels were also common. C-reactive protein (CRP) levels increased substantially and peaked 48 h after pleurodesis. No difference was observed between groups with regard to adverse events, CRP levels, efficacy, or quality of life. Conclusions: Adverse events after iodopovidone pleurodesis in patients with MPE are common and similar in the two doses studied.

The prevalence of malignant pleural effusion is increasing worldwide, but prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. The PROMISE study was designed with the objectives to discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in malignant pleural effusion and build a score that predicts survival. In this multicohort study, we used five separate and independent datasets from randomised controlled trials to investigate potential biomarkers of survival and pleurodesis. Mass spectrometry-based discovery was used to investigate pleural fluid samples for differential protein expression in patients from the discovery group with different survival and pleurodesis outcomes. Clinical, radiological, and biological variables were entered into least absolute shrinkage and selection operator regression to build a model that predicts 3-month mortality. We evaluated the model using internal and external validation. 17 biomarker candidates of survival and seven of pleurodesis were identified in the discovery dataset. Three independent datasets (n=502) were used for biomarker validation. All pleurodesis biomarkers failed, and gelsolin, macrophage migration inhibitory factor, versican, and tissue inhibitor of metalloproteinases 1 (TIMP1) emerged as accurate predictors of survival. Eight variables (haemoglobin, C-reactive protein, white blood cell count, Eastern Cooperative Oncology Group performance status, cancer type, pleural fluid TIMP1 concentrations, and previous chemotherapy or radiotherapy) were validated and used to develop a survival score. Internal validation with bootstrap resampling and external validation with 162 patients from two independent datasets showed good discrimination (C statistic values of 0·78 [95% CI 0·72–0·83] for internal validation and 0·89 [0·84–0·93] for external validation of the clinical PROMISE score). To our knowledge, the PROMISE score is the first prospectively validated prognostic model for malignant pleural effusion that combines biological and clinical parameters to accurately estimate 3-month mortality. It is a robust, clinically relevant prognostic score that can be applied immediately, provide important information on patient prognosis, and guide the selection of appropriate management strategies. European Respiratory Society, Medical Research Funding-University of Oxford, Slater & Gordon Research Fund, and Oxfordshire Health Services Research Committee Research Grants.

Background Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. Methods Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. Results Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228–549; n=43), 130 days (47–467; n=129) and 44 days (22–77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). Conclusions The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.

ObjectiveTumor-related eosinophilia may have extended survival benefits for some cancer patients. However, there has been no report on the prognosis difference between eosinophilic pleural effusion (EPE) and non-EPE in lung cancer patients. Our study aimed to investigate the prognosis difference between EPE and non-EPE due to lung cancer.Patients and methodsWe retrospectively reviewed patients diagnosed with lung cancer who presented with malignant pleural effusion (MPE) between May 2007 and September 2020 at the National Hospital Organization Kochi Hospital. EPE is defined as pleural fluid with a nucleated cell count containing 10% or more eosinophils.ResultsA total of 152 patients were included: 89 were male (59%). The median age was 74.4 years (range 37–101), and all patients were pathologically shown to have MPE. Most patients (140; 92%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0/1. Twenty patients had EPE. The median overall survival (OS) of all 152 lung cancer patients with MPE was 298 days. The median OS of the patients with EPE was 766 days, and the median OS of the patients with non-EPE was 252 days. Kaplan–Meier univariate analysis showed that lung cancer patients with EPE had a significantly better prognosis than patients with non-EPE (P < 0.05). Cox proportional regression analysis showed that EPE, ECOG PS, sex, and the neutrophil-to-lymphocyte ratio in the serum (sNLR) may be independent prognostic factors affecting survival in patients with MPE.ConclusionLung cancer patients with EPE have a better prognosis than those with non-EPE.

Malignant pleural mesothelioma (MPM) is a rare form of thoracic malignancy with a poor prognosis. Pleural effusion (PE) occurs in the majority of patients with MPM; however, its impact on MPM outcomes remains controversial. We searched for eligible patients from the Surveillance, Epidemiology, and End Results (SEER) database, and clinicopathological information and outcomes were collected. Cox proportional hazard regression analyses were utilized to evaluate the association of PE and other factors with overall survival (OS) and cancer-specific survival (CSS) in patients with MPM. A total of 4185 patients were extracted from the SEER database from 2000 to 2021. The median age of the cohort was 73 years, with a predominance of male patients and epithelioid MPM as the main histological subtype. Univariate Cox regression revealed associations between PE, age, sex, marital status, histology, stage, and treatment with both OS and CSS. Besides, multivariate analyses indicated that PE was independently associated with poorer OS and CSS in patients with MPM, regardless of age, sex, histology, stage, and treatment. Subgroup analyses suggested that PE has a remarkable impact on patients undergoing surgery. PE might serve as an independent prognostic factor in patients with MPM, especially in surgery recipients. Consequently, the development of pleural effusion in these patients should receive increased attention. Future studies are needed to validate these findings, particularly concerning the effect of PE in other clinical settings, such as immunotherapy.

Background Patients with lung cancer and malignant pleural effusion (MPE) often have poor prognoses. Accurate prognostic tools are needed to guide interventions and improve outcomes. Methods We retrospectively analyzed clinical and imaging data from MPE patients at two medical centers. A nomogram was developed and externally validated. Clinical and imaging features were refined using least absolute shrinkage and selection operator (LASSO), and independent predictors were identified via multivariate logistic regression. Predictors were integrated into the nomogram, whose predictive performance, calibration, and clinical utility were evaluated using statistical analyses, including receiver operating characteristic (ROC) curves, calibration curves, Hosmer-Lemeshow tests, and decision curve analysis (DCA). Survival curves illustrated prognostic differences among risk groups. Results The final nomogram included five variables: Lactate Dehydrogenase (LDH) levels in pleural fluid, clarity of pleural effusion, treatment regimen, presence of pericardial effusion, and total volume of pleural effusion. In both cohorts, the nomogram demonstrated strong predictive accuracy (Area Under the Curve (AUC): 0.929 and 0.941, respectively) and excellent calibration (Hosmer-Lemeshow test p -values: 0.944 and 0.425, respectively). DCA confirmed the nomogram’s clinical utility. Risk stratification revealed significant survival disparities among patients. Conclusion Our nomogram accurately predicts the prognosis of lung cancer patients with MPE at initial diagnosis, incorporating key variables such as LDH levels in pleural fluid, clarity of pleural effusion, treatment regimen, pericardial effusion, and total volume of pleural effusion. Its robust predictive performance, calibration, and clinical utility support its use in guiding clinical decision-making for this patient population.

Several randomized trials have compared the efficacy of an indwelling pleural catheter (IPC) versus the more traditional chemical pleurodesis in the management of malignant pleural effusion (MPE). As part of the American Thoracic Society's guidelines for management of MPE, we performed a systematic review and a meta-analysis to compare patient-centered outcomes with the use of a tunneled pleural catheter versus chemical pleurodesis for the first-line treatment of malignant pleural effusions. We performed literature searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. We included randomized controlled trials comparing IPC and pleurodesis in adult patients with symptomatic MPE. Risk of bias was assessed with the Cochrane Risk of Bias tool recommended by the Cochrane Methods Bias Group. The meta-analysis was performed with Review Manager software, using a random effects model. We used risk ratios (RRs) with 95% confidence interval (CI) as the effect measure for dichotomous outcomes and mean differences for continuous outcomes. We identified five randomized trials, involving 545 patients, that compared IPC and pleurodesis. Lack of blinding and the inevitable attrition of patients due to death resulted in an overall high risk of bias among the studies. No differences in survival or measures of dyspnea were observed in any of the studies. Total hospital length of stay was shorter, and repeat pleural interventions were less common in the IPC group (RR, 0.32; 95% CI, 0.18-0.55). However, the risk of cellulitis was higher with IPC (RR, 5.83; 95% CI, 1.56-21.8). No differences were noted in other adverse events. Compared with chemical pleurodesis, IPC results in shorter hospital length of stay and fewer repeat pleural procedures but carries a higher risk of cellulitis. Careful assessment of individual patient preferences and costs should be considered when choosing between IPC and pleurodesis.

Malignant pleural effusion (MPE) is a common complication of advanced non-small cell lung cancer (NSCLC), particularly in lung adenocarcinoma, and is associated with poor prognosis. A better understanding of the role of PD-1 CD8 T cells in the pleural environment and their relevance to patient survival could facilitate better clinical decision-making. We performed a cohort study involving NSCLC patients with MPE. The abundance of pleural PD-1 CD8 T cells was measured using flow cytometry. We also assessed the presence of epidermal growth factor receptor (EGFR) mutations and programmed death-ligand 1 (PD-L1) expression in the pleural fluid. The LENT score, a known prognostic tool, was combined with pleural PD-1 CD8 T cell abundance to develop a novel scoring system, the Immuno-LENT score. The model's performance was validated using the bootstrap method and concordance index (C-index) calculation. We found that PD-1 CD8 T cells were present in the pleural fluid of all patients with MPE. Notably, the abundance of these cells was influenced by EGFR mutations, while PD-L1 expression had little effect. Patients with a higher abundance of pleural PD-1 CD8 T cells also exhibited higher LENT scores, correlating with poorer survival. The Immuno-LENT score, incorporating both the LENT score and pleural PD-1 CD8 T cell abundance, was found to be an independent prognostic factor. The model showed strong statistical robustness with a high C-index. The combination of pleural PD-1 CD8 T cells with the LENT score offers a more accurate prognostic tool for survival prediction in NSCLC patients with MPE. Our findings suggest that the Immuno-LENT score could guide clinical management and inform therapeutic decisions for these patients, improving patient outcomes by tailoring interventions based on a more comprehensive biomarker profile.