Isolation of tumor-specific T cells and their antigen receptors (TCRs) from malignant pleural effusions (MPE) may facilitate the development of TCR-transduced adoptive cellular immunotherapy products for advanced lung cancer patients. However, the characteristics and markers of tumor-specific T-cells in MPE are largely undefined. To this end, to establish the phenotypes and antigen specificities of CD8+ T cells, we performed single-cell RNA and TCR sequencing of samples from three advanced lung cancer patients. Dimensionality reduction on a total of 4,983 CD8+ T cells revealed 10 clusters including naïve, memory, and exhausted phenotypes. We focused particularly on exhausted T cell clusters and tested their TCR reactivity against neoantigens predicted from autologous cancer cell lines. Four different TCRs specific for the same neoantigen and one orphan TCR specific for the autologous cell line were identified from one of the patients. Differential gene expression analysis in tumor-specific T cells relative to the other T cells identified CXCL13, as a candidate gene expressed by tumor-specific T cells. In addition to expressing CXCL13, tumor-specific T cells were present in a higher proportion of T cells co-expressing PDCD1(PD-1)/TNFRSF9(4-1BB). Furthermore, flow cytometric analyses in advanced lung cancer patients with MPE documented that those with high PD-1/4-1BB expression have a better prognosis in the subset of 57 adenocarcinoma patients (p = .039). These data suggest that PD-1/4-1BB co-expression might identify tumor-specific CD8+ T cells in MPE, which are associated with patients\' prognosis. (233 words).

UNASSIGNED: Malignant pleural effusion (MPE) is a common and debilitating condition seen in advanced cancer disease, and life-expectancy is short. Symptoms include pain and severe shortness of breath. Current first-line treatment options include pleural drainage using catheters as well as pleurodesis. However, these treatment modalities are often inefficient and patients need repeated procedures. Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive procedure, where antineoplastic agents are nebulized under pressure into the pleural space.
UNASSIGNED: We present the preliminary safety, feasibility, and response assessment data for PITAC based on a comprehensive literature review.
UNASSIGNED: Five retrospective studies reported data on 38 PITACs in 21 patients. Data were heterogeneous and incomplete on several important aspects such as procedure, safety, local effect and long-term outcomes. PITAC seems technically feasible with a low risk of complications and may provide some reduction in MPE in selected cases.
UNASSIGNED: PITAC seems feasible, but prospective phase I and II studies are needed to define safety, indications, and efficacy.

UNASSIGNED: Malignant pleural effusion (MPE) is prevalent among cancer patients, indicating pleural metastasis and predicting poor prognosis. However, accurately identifying MPE in clinical settings is challenging. The aim of this study was to establish an innovative nomogram-derived model based on clinical indicators and serum metal ion levels to identify MPE.
UNASSIGNED: From July 2020 to May 2022, 428 patients diagnosed with pleural effusion (PE) were consecutively recruited. Comprehensive demographic details, clinical symptoms, imaging data, pathological information, and laboratory results, including serum metal ion levels, were systematically collected. The nomogram was created by incorporating the most significant predictors identified through LASSO and multivariate logistic regression analysis. The predictors were assigned weighted points based on their respective regression coefficients, allowing for the calculation of a total score that corresponds to the probability of MPE. Internal validation using bootstrapping techniques assessed the nomogram\'s performance, including calibration, discrimination, and clinical applicability.
UNASSIGNED: Seven key variables were identified using LASSO regression and multiple regression analysis, including dyspnea, fever, X-ray/CT compatible with malignancy, pleural carcinoembryonic antigen(pCEA), serum neuron-specific enolase(sNSE), serum carcinoembryonic antigen(sCEA), and pleural lactate dehydrogenase(pLDH). Internal validation underscored the superior performance of our model (AUC=0.940). Decision curve analysis (DCA) analysis demonstrated substantial net benefit across a probability threshold range > 1%. Additionally, serum calcium and copper levels were significantly higher, while serum zinc levels were significantly lower in MPE patients compared to benign pleural effusion (BPE) patients.
UNASSIGNED: This study effectively developed a user-friendly and reliable MPE identification model incorporating seven markers, aiding in the classification of PE subtypes in clinical settings. Furthermore, our study highlights the clinical value of serum metal ions in distinguishing malignant pleural effusion from BPE. This significant advancement provides essential tools for physicians to accurately diagnose and treat patients with MPE.

BACKGROUND: Malignant pleural effusion (MPE) is frequently observed in patients with advanced lung adenocarcinoma (LUAD). Pleural fluid cytology is a less invasive procedure compared to pleural biopsy. Therefore, it is crucial to identify novel effective biomarkers for LUAD-associated pleural fluid cytology.
METHODS: The RNA sequencing (RNA-Seq) and clinical data of LUAD cases were downloaded from TCGA and OncoSG databases. Differential gene expression analysis, survival analysis and immune cell infiltration analysis were performed on the LUAD datasets. The expression levels of FAM83A, TFF-1, and NapsinA in 94 paired LUAD and adjacent normal tissues, and in the pleural effusion specimens of 40 LUAD and 21 non-neoplastic patients were evaluated by immunohistochemistry.
RESULTS: FAM83A expression levels were significantly different between the LUAD and normal tissue datasets, and correlated with overall or disease-free survival, and histological grade of the tumors. Furthermore, the in-situ expression of FAM83A was higher in 89/94 LUAD tissues compared to the paired normal tissues. FAM83A expression was significantly correlated with immune cell infiltration, and showed a positive association with macrophage infiltration. In addition, FAM83A staining was positive in 37 LUAD pleural effusion samples, and negative in 20 non-neoplastic pleural effusion samples. The expression pattern of FAM83A in the pleural effusion of LUAD patients was relatively consistent with that of TFF-1 and NapsinA, and even stronger in some specimens that were weakly positive or negative for TTF1/NapsinA.
CONCLUSIONS: FAM83A is a promising immune-related biomarker in LUAD biopsy specimens and pleural fluid, and can distinguish between malignant and benign pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) affects up to 15% of patients with malignancy, and the prevalence is increasing. Non-expandable lung (NEL) complicates MPE in up to 30% of cases. However, it is not known if patients with malignant pleural effusion and NEL are more symptomatic in activities of daily living compared to patients with MPE with expandable lung.
METHODS: This was an observational study on consecutively recruited patients with MPE from our pleural clinic. Before thoracentesis, patients completed patient-reported outcomes on cancer symptoms (ESAS), health-related quality of life (5Q-5D-5L), and dyspnoea scores. Following thoracentesis, patients scored dyspnoea relief and symptoms during thoracentesis. Data on focused lung ultrasound and pleural effusion biochemistry were collected. The non-expandable lung diagnosis was made by pleural experts based on radiological and clinical information.
RESULTS: We recruited 43 patients, including 12 with NEL (28%). The NEL cohort resembled those from previous studies concerning ultrasonography, pleural fluid biochemistry, and fewer cases with high volume thoracentesis. Patients with and without NEL were comparable concerning baseline demography. The 5Q-5D-5L utility scores were 0.836 (0.691-0.906) and 0.806 (0.409-0.866), respectively, for patients with and without NEL. We observed no between-group differences in symptom burden or health-related quality of life.
CONCLUSIONS: While the presence of NEL affects the clinical management of recurrent MPE, the presence of NEL seems not to affect patients\' overall symptom burden in patients with MPE.

UNASSIGNED: The definitive etiology of nonspecific pleuritis (NSP), the influence of the type of pleural biopsy on clinical results and the minimum duration of follow-up is controversial.
UNASSIGNED: A retrospective, observational study of patients ≥ 18 years with NSP confirmed by closed pleural biopsy (CPB), local anesthesia pleuroscopy (LAP), or video-assisted thoracic surgery (VATS).
UNASSIGNED: A total of 167 patients were included (mean follow-up, 14.4 months), of which 25 (15%) were diagnosed within one month; [15 (60%) malignant]. Of the remaining 142 pleural effusions (PEf), 69 (48.6%) were idiopathic; 49 (34.5%) not-malignant and 24 (16.9%) malignant (4 mesotheliomas and 20 metastasic). The diagnosis of NSP was established by CPB (7; median time to diagnosis, 9.4 months), LAT (5; 15.8 months), and VATS (8; 13.5 months) (p = 0.606). Sixty-eight patients (40.7%) died during follow-up (mean time, 12 months).
UNASSIGNED: In a substantial percentage of patients diagnosed with NSP, a definitive diagnosis will not be obtained, a relevant number of patients will develop a malignant PEf. The diagnostic procedure used for the diagnosis of NSP does not seem to influence delay in the diagnosis of malignant PEf. The data obtained suggest that follow-up should be maintained for at least 24 months.

Imaging continues to gain a greater role in the assessment and clinical management of patients with mesothelioma. This communication summarizes the oral presentations from the imaging session at the 2023 International Conference of the International Mesothelioma Interest Group (iMig), which was held in Lille, France from June 26 to 28, 2023. Topics at this session included an overview of best practices for clinical imaging of mesothelioma as reported by an iMig consensus panel, emerging imaging techniques for surgical planning, radiologic assessment of malignant pleural effusion, a radiomics-based transfer learning model to predict patient response to treatment, automated assessment of early contrast enhancement, and tumor thickness for response assessment in peritoneal mesothelioma.

BACKGROUND: Malignant pleural effusion (MPE) is a common cancer complication. Clinical and economic implications of different recurrent MPE treatment pathways have not been evaluated fully.
OBJECTIVE: What clinical outcomes, complications, health care resource use, and costs are associated with various rapidly recurrent MPE treatment pathways?
METHODS: This retrospective cohort study using Surveillance, Epidemiology and End Results Medicare data (2011-2015) included patients 66 to 90 years of age with rapidly recurrent MPE. Rapid recurrence was defined as receipt of a second pleural procedure within 14 days of the first thoracentesis, including nondefinitive repeated thoracentesis or a definitive treatment option including chest tube, indwelling pleural catheter (IPC), or thoracoscopy.
RESULTS: Among 8,378 patients with MPE, 3,090 patients (36.9%) had rapidly recurrent MPE (mean ± SD age, 75.9 ± 6.6 years; 45.6% male; primary cancer, 62.9% lung and 37.1% other). Second pleural procedures were nondefinitive thoracentesis (62.3%), chest tube (17.1%), IPC (13.2%), or thoracoscopy (7.4%). A third pleural procedure was required more frequently if the second pleural procedure was nondefinitive thoracentesis vs chest tube placement, IPC placement, or thoracoscopy (70.3% vs 44.1% vs 17.9% vs 14.4%, respectively). The mean number of subsequent pleural procedures over the patient\'s lifetime varied significantly among the procedures (1.74, 0.82, 0.31, and 0.22 procedures for patients receiving thoracentesis, chest tube, IPC, and thoracoscopy, respectively; P < .05). Average total costs after the second pleural procedure to death adjusted for age at primary cancer diagnosis, race, year of second pleural procedure, Charlson comorbidity index, cancer stage at primary diagnosis, and time from primary cancer diagnosis to diagnostic thoracentesis were lower with IPC ($37,443; P < .0001) or chest tube placement ($40,627; P = .004) vs thoracentesis ($47,711). Patients receiving thoracoscopy ($45,386; P = .5) incurred similar costs as patients receiving thoracentesis.
CONCLUSIONS: Early definitive treatment was associated with fewer subsequent procedures and lower costs in patients with rapidly recurrent MPE.

UNASSIGNED: To investigate the clinical value of combined detection of carcinoembryonic antigen(CEA) and CA125 in the diagnosis of non-small cell lung cancer(NSCLC) combined with malignant pleural effusion.
UNASSIGNED: This was retrospective research. Fifty-six NSCLC patients combined with malignant pleural effusion in Baoding No.1 Hospital, China, from January 2020 to January 2022 were recruited as the malignant group, and another 56 NSCLC patients combined with pleural effusion in the same period were recruited as the benign group. Pleural effusion and serum specimens were collected from both groups and their carcinoembryonic antigen (CEA), carbohydrate antigen 125(CA125) and SP70 antigen levels were measured respectively. The differences in index levels between the two groups were compared, and the value of the index in diagnosing NSCLC combined with malignant pleural effusion was analyzed.
UNASSIGNED: The positive rates of CEA, CA125 and SP70 antigen in pleural effusion were higher in the malignant group than in the benign group (p>0.05); The positive rates of CEA and CA125 in the malignant group were higher than those in the benign group (p>0.05), with no statistically significant difference between the two groups in the positive rates of SP70 antigen (p>0.05). ROC curve analysis revealed the value of serum CEA and CA12 in the diagnosis of NSCLC combined with malignant pleural effusion, while serum SP70 antigen had no diagnostic value (p>0.05).
UNASSIGNED: The combined detection of CEA, CA125 and SP70 antigen boasts a higher diagnostic value for NSCLC-mediated pleural effusion, with higher diagnostic value than the combined detection of serum indexes.

OBJECTIVE: Malignant pleural effusion (MPE) is a common complication of lung cancer with poor prognosis. Benign pleural effusion (BPE), such as tuberculous and pneumonic pleural effusion, usually has a good prognosis. Differential diagnosis between MPE and BPE remains a clinical challenge.
METHODS: 52 MPE, 93 BPE, and their corresponding serum samples were analyzed by hydrogen nuclear magnetic resonance (1HNMR) based metabolomics.
RESULTS: The 1HNMR study showed that some amino acids and betaine in MPE are significantly altered in pleural effusion and serum compared to BPE patients. Levels of serum glucose and glutamine have strong positive correlation with those in pleural effusion (r>0.6) for MPE patients. The area under the receiver operating characteristic curve (AUROC) values of metabolites in pleural effusion or serum were less than 0.805 in differentiating MPE from BPE. Improved an AUROC value of 0.901 was observed using pleural effusion-serum ratios of glutamic acid in differentiating MPE from BPE, which was further validated by 15 double-blind samples.
CONCLUSIONS: Compared with BPE patients, amino acids and betaine in MPE are significantly altered in pleural effusion and serum. Pleural effusion-serum ratio of glutamic acid may contribute to the rapid diagnosis of MPE from BPE by 1HNMR analysis.