Eosinophilic pleural effusion due to lung cancer has a better prognosis than non-eosinophilic malignant pleural effusion.

OBJECTIVE: Tumor-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 METHODS: We 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. RESULTS: A 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. CONCLUSION: Lung cancer patients with EPE have a better prognosis than those with non-EPE.

Evaluation of prognostication scores and proposal for refinement in malignant pleural effusion in Asians.

BACKGROUND AND OBJECTIVE: Prognostication of malignant pleural effusion (MPE) guides treatment strategies but existing prognostication scores are yet to be validated in Asians. We aimed to evaluate the performance of these scores in an Asian population. A refined score was also proposed based on the impact of EGFR mutation on survival. METHODS: Survival and clinical data of histocytologically-confirmed MPE patients from a Hong Kong hospital were analyzed with the LENT, modified-LENT, PROMISE and SELECT (converted from its original model) scores. A refinement of the LENT score for Asians was proposed by inclusion of EGFR status (EGFR-LENT), which was compared with the LENT score and validated in an independent patient cohort. RESULTS: All prognostication scores performed well on risk stratification by Kaplan-Meier curve (log rank p < 0.0001) in 368 MPE patients except for LENT in low-risk group. C-statistics for LENT, modified-LENT, PROMISE and SELECT in predicting 3-month mortality were 0.77, 0.80, 0.80 and 0.82, respectively. The proposed LENT score refinement (EGFR-LENT) improved stratification among low-risk patients; with a higher C-statistic (0.83) in 3-month mortality prediction than LENT (0.77, p = 0.0121), PROMISE (0.80, p = 0.3713), and SELECT (0.82, p = 0.7908) scores. Validation of EGFR-LENT in an independent cohort (124 patients) confirmed good performance in predicting 3-month mortality (C-statistic 0.87, vs 0.79 in LENT, p = 0.0444). CONCLUSION: All existing scores had reasonable performance in prognosticating MPE, and LENT score refinement by inclusion of EGFR mutation status improved its performance among Asian MPE patients.

Prediction modeling using routine clinical parameters to stratify survival in malignant pleural mesothelioma patients complicated with malignant pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) is common in malignant pleural mesothelioma (MPM). The survival of patients with MPM and MPE is heterogeneous. The LENT and BRIMS scores using routine clinical parameters were developed to predict the survival of patients with unselected MPE and MPM, respectively. This study aimed to stratify the survival of selected MPM patients with MPE. METHODS: Data were collected from subjects diagnosed with MPM and MPE. The LENT and BRIMS scores were applied using a combination of clinical variables to stratify subjects and compare survival characteristics. RESULTS: In total, 101 patients with MPM complicated by MPE were included in the study. The median follow-up time was 71 months (interquartile range: 24-121 months). Overall median survival was 24 (interquartile range: 12-52 months). Based on the LENT score, the low-, moderate-, and high-risk groups accounted for 65.3% (66 cases), 34.7% (35 cases), and 0%, respectively. The cumulative survival rates of the two groups were statistically significant (p = 0.031). The area under the curve (AUC) of the LENT score was 0.662. Based on the BRIMS score, the first, second, third, and fourth risk groups accounted for 1.0% (1 case), 42.9% (35 cases), 28.7% (29 cases), and 19.4% (36 cases), respectively. Survival was significantly higher in patients in the risk groups 1 and 2 than in patients in the risk groups 3 and 4 (p  = 0.037). The AUC of the BRIMS score was 0.605. CONCLUSIONS: Using routinely available clinical variables, both LENT and BRIMS scores could stratify selected MPM and MPE patients into risk groups with statistically different survival.

Neutrophil-to-lymphocyte ratio in malignant pleural fluid: Prognostic significance.

Predicting survival of patients with malignant pleural effusions (MPEs) is notoriously difficult. A robust prognostic marker can guide clinical decision making. The neutrophil-to-lymphocyte ratio (NLR) in blood has been shown to predict survival in many cancers. Pleural fluid bathes the malignant pleural tissues, thus the NLR of the pleural fluid may reflect more closely the local tumour environment. The objective of this study was to explore the prognostic significance of pleural effusion NLR for MPE. We analysed matched effusion and blood from 117 patients with malignant and 24 with benign pleural effusions. Those who had received recent chemotherapy or had a pleurodesis were excluded. Neutrophil and lymphocyte counts in effusions were performed by manual review of cytospin cell preparations by trained observers. Clinical data were extracted from a state-wide hospital database. We found significantly fewer neutrophils (expressed as percentage of total leukocyte count) in pleural fluid than in corresponding blood (9% vs 73%; p<0.001). The NLR was an order of magnitude lower in pleural fluid than in corresponding blood: median [IQR] = 0.20 [0.04-1.18] vs 4.9 [3.0-8.3], p<0.001. Correlation between blood and pleural fluid NLR in MPE patients was moderate (rs = 0.321, p<0.001). In univariate analysis, NLR (>0.745)) in malignant pleural fluid was predictive of poorer survival (HR = 1.698 [1.0054-2.736]; p = 0.030), and remained significant after adjustment for age, sex, presence of a chest drain, cancer type, concurrent infection and subsequent treatment with chemotherapy (HR = 1.786 [1.089-2.928]; p = 0.022). Patients with pleural fluid NLR > 0.745 had a significantly shorter median survival of 130 (95% CI 0-282) days compared to 312 (95% CI 195-428) days for pleural NLR < 0.745, p = 0.026. The NLR in blood was also predictive of poorer survival in MPE patients (HR = 1.959 [1.019-3.096]; p<0.001). The proportion of neutrophils in pleural fluid was predictive of prognosis more strongly than lymphocytes. This study provides evidence that NLR in malignant effusions can predict survival, and therefore may provide prognostic information for this cohort. This prognostic association in the fluid is driven by the presence of neutrophils.

Breast and Lung Effusion Survival Score Models: Improving Survival Prediction in Patients With Malignant Pleural Effusion and Metastasis.

BACKGROUND: Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. RESEARCH QUESTION: Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? STUDY DESIGN AND METHODS: Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell's C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vs continuous predictors' performances. RESULTS: The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P < .0001), pleural fluid lactate dehydrogenase (P = .029), and bilateral effusion (P = .002). DSMs for lung, breast, and hematologic malignancies showed C-statistics of 0.72, 0.72, and 0.62, respectively; the combined model's C-statistics was 0.67. LENT-D (C-statistic, 0.60) and LENT-C (C-statistic, 0.65) models underperformed. INTERPRETATION: EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.

Long-Term Treatment Results for Ovarian Tumors with Malignant Effusion in Seven Dogs.

Surgery and platinum-based chemotherapy are highly efficacious for treating advanced ovarian cancers in humans, but their efficacy is less known in dogs. We evaluated the long-term treatment outcomes of seven dogs with malignant ovarian tumors with malignant abdominal effusion. Ovariohysterectomies (OVHs) were performed on all dogs; four had ovarian adenocarcinoma (AC) with gross dissemination in the peritoneum (two with pleural effusion), and three had a granulosa cell tumor (GCT) with no gross dissemination in the peritoneal cavity, although one showed pleural effusion. Effusion resolved after the OVH in all dogs. Six dogs (three ACs, three GCTs) received postoperative IV carboplatin therapy. Two dogs with GCT had no postoperative recurrence or metastasis, and one dog with GCT had recurrence 1811 days postoperatively. All dogs with AC developed recurrent effusion 171-584 days postoperatively, which resolved after intracavitary administration of cisplatin or carboplatin, with a subsequent disease-free interval of 155-368 days. Overall survival was longer for dogs with GCTs (822-1840 days) than for those with ACs (617-841 days). These results suggest that dogs with ovarian tumors with malignant effusion can survive relatively long after platinum-based chemotherapy in addition to OVH, with a more favorable prognosis for GCT than AC.

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.

Novel therapies for malignant pleural effusion: Anti­angiogenic therapy and immunotherapy (Review).

Patients with a variety of malignancies can develop malignant pleural effusion (MPE). MPE can cause significant symptoms and result in a marked decrease in quality of life and a poor prognosis. MPE is primarily considered as an immune and vascular manifestation of pleural metastases. In the present review, the existing evidence supporting the applicability of anti­angiogenic therapy and immunotherapy for the treatment of MPE was summarized. Patients with MPE have benefited from anti­angiogenic agents, including bevacizumab and endostar; however, no relevant prospective phase III trial has, thus far, specifically analyzed the benefit of anti­angiogenic therapy in MPE. Immunotherapy for MPE may be sufficient to turn a dire clinical situation into a therapeutic advantage. Similar to anti­angiogenic therapy, more clinical data on the efficiency and safety of immunotherapy for controlling MPE are urgently required. The combined use of anti­angiogenic therapy and immunotherapy may be a promising strategy for MPE, which requires to be further understood.

High frequency of exon 20 S768I EGFR mutation detected in malignant pleural effusions: A poor prognosticator of NSCLC.

BACKGROUND: Lung cancer is the cause of a fourth of all cancer-related deaths. About a third of all lung adenocarcinoma tumours harbour mutations on exons 18 to 21 of the epidermal growth factor receptor (EGFR) gene. Detection of these mutations allows for targeted therapies in the form of EGFR Tyrosine kinase inhibitors. Recently, "liquid biopsies" have emerged as an alternative to conventional tissue mutation detection. AIM: In this pilot study, we attempted to optimize EGFR mutation detection from malignant pleural effusions (MPEs) as "liquid biopsies" when tissue biopsies were unavailable. Resulting mutations were then to be mapped on the EGFR gene and explored using cBioPortal, a public cancer genomic database. METHODS AND RESULTS: We first attempted a direct sequencing approach and showed that single nucleotide variants (SNVs) were likely to be missed in MPEs. We then switched to and optimized an EGFR mutant-specific quantitative polymerase chain reaction-based assay. This assay was piloted on n = 10 pleural effusion samples (one non-malignant pleural effusion as a negative control). 5/9 (55.55%) samples harboured EGFR mutations with 2/9 (22.22%) being exon 19 deletions and 3/9 (33.33%) the S768I mutation. The frequency of the S768I SNV in our study was significantly higher than that observed in other studies (~0.2%). Utilizing cBioPortal data, we report that patients with S768I have a shorter median survival time (6 months vs 38 months), progression-free survival time (8 months vs 44 months) and lower tumor mutation count compared to patients with other EGFR mutations. CONCLUSIONS: The shorter survival of patients with the S768I SNV predicts aggressive disease and poor prognosis as a result of this mutation. Studies in larger cohorts and/or animal models are necessary to confirm these findings.

Platelet factor 4 regulates T cell effector functions in malignant pleural effusions.

Malignant pleural effusion (MPE) is defined as the presence of tumor cells in pleural fluid and it is a fatal complication of advanced lung adenocarcinoma (LAC). To understand the immune response to the tumor in MPE, we compared the concentration of immunomodulatory factors in MPE of LAC and pleural effusion of heart failure (HF) patients by ELISA, and the proliferation and cytotoxic phenotype of T cells stimulated in the presence of LAC and HF pleural fluids by cytometry. Platelet factor 4 (PF4), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-ß) and P-selectin levels were higher in LAC than in HF pleural fluids. However, plasmatic PF4 and P-selectin levels were similar in LAC and HF. VEGF positively correlated with TGF-ß and sPD-L1 in LAC but not in HF pleural fluids. LAC pleural fluids also inhibited T lymphocyte proliferation and cytotoxicity and reduced IL-17 production. PF4 levels inversely correlated with T cell function. The high content of PF4 in MPE was associated with poor prognosis. Our findings suggest that an impaired response of T lymphocytes induced by PF4 provides a significant advantage for tumor progression.

LENT Score: Predicting the Survival of Malignant Pleural Effusion - A Prospective Study of Three Years / Score LENT: prediciendo la supervivencia del derrame pleural maligno - un estudio prospectivo de tres años

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Thoracoscopy and talc poudrage compared with intercostal drainage and talc slurry infusion to manage malignant pleural effusion: the TAPPS RCT.

BACKGROUND: There are around 40,000 new cases of malignant pleural effusion in the UK each year. Insertion of talc slurry via a chest tube is the current standard treatment in the UK. However, some centres prefer local anaesthetic thoracoscopy and talc poudrage. There is no consensus as to which approach is most effective. OBJECTIVE: This trial tested the hypothesis that thoracoscopy and talc poudrage increases the proportion of patients with successful pleurodesis at 3 months post procedure, compared with chest drain insertion and talc slurry. DESIGN: This was a multicentre, open-label, randomised controlled trial with embedded economic evaluation. Follow-up took place at 1, 3 and 6 months. SETTING: This trial was set in 17 NHS hospitals in the UK. PARTICIPANTS: A total of 330 adults with a confirmed diagnosis of malignant pleural effusion needing pleurodesis and fit to undergo thoracoscopy under local anaesthetic were included. Those adults needing a tissue diagnosis or with evidence of lung entrapment were excluded. INTERVENTIONS: Allocation took place following minimisation with a random component, performed by a web-based, centralised computer system. Participants in the control arm were treated with a bedside chest drain insertion and 4 g of talc slurry. In the intervention arm, participants underwent local anaesthetic thoracoscopy with 4 g of talc poudrage. MAIN OUTCOME MEASURES: The primary outcome measure was pleurodesis failure at 90 days post randomisation. Secondary outcome measures included mortality and patient-reported symptoms. A cost-utility analysis was also performed. RESULTS: A total of 166 and 164 patients were allocated to poudrage and slurry, respectively. Participants were well matched at baseline. For the primary outcome, no significant difference in pleurodesis failure was observed between the treatment groups at 90 days, with rates of 36 out of 161 (22%) and 38 out of 159 (24%) noted in the poudrage and slurry groups, respectively (odds ratio 0.91, 95% confidence interval 0.54 to 1.55; p = 0.74). No differences (or trends towards difference) were noted in adverse events or any of the secondary outcomes at any time point, including pleurodesis failure at 180 days [poudrage 46/161 (29%), slurry 44/159 (28%), odds ratio 1.05, 95% confidence interval 0.63 to 1.73; p = 0.86], mean number of nights in hospital over 90 days [poudrage 12 nights (standard deviation 13 nights), slurry 11 nights (standard deviation 10 nights); p = 0.35] and all-cause mortality at 180 days [poudrage 66/166 (40%), slurry 68/164 (42%); p = 0.70]. At £20,000 per quality-adjusted life-year gained, poudrage would have a 0.36 probability of being cost-effective compared with slurry. LIMITATIONS: Entry criteria specified that patients must be sufficiently fit to undergo thoracoscopy, which may make the results less applicable to those patients presenting with a greater degree of frailty. Furthermore, the trial was conducted on an open-label basis, which may have influenced the results of patient-reported measures. CONCLUSIONS: The TAPPS (evaluating the efficacy of Thoracoscopy And talc Poudrage versus Pleurodesis using talc Slurry) trial has robustly demonstrated that there is no additional clinical effectiveness or cost-effectiveness benefit in performing talc poudrage at thoracoscopy over bedside chest drain and talc slurry for the management of malignant pleural effusion. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47845793. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 26. See the NIHR Journals Library website for further project information.

In patients with cancer, fluid can build up in the space between the chest wall and lung, causing breathlessness. The fluid can be drained using a small tube inserted between the ribs under local anaesthetic. However, it often recurs. To avoid this, doctors usually inject talc powder (mixed into a slurry) back down the drainage tube to try to 'stick' the lung to the inside of the chest wall. If successful, this prevents the fluid reforming. This procedure is called pleurodesis. An alternative is to insert a camera into the chest under light sedation and local anaesthetic (a 'thoracoscopy') and spray talc directly onto the inside of the chest wall (poudrage). This may be more effective, although this has not been proven and it is a slightly more complex procedure. Therefore, this trial was conducted to see if poudrage was more effective than slurry. A total of 330 patients were recruited from 17 UK hospitals who had chest fluid due to cancer. They were divided evenly, with half receiving standard drainage and slurry and the other half receiving a thoracoscopy and poudrage. They were followed up for 6 months. We measured how many experienced a recurrence in fluid build-up 3 months after treatment, as well as other impacts, including if there was any difference in the long-term costs. No difference in clinical effectiveness was found between talc poudrage and talc slurry. Poudrage was unlikely to be cost-effective. In summary, the researchers conclude that slurry is likely to be the preferable method.

Death domain-associated protein (DAXX) expression is associated with poor survival in metastatic high-grade serous carcinoma.

The objective of this study was to analyze the expression and clinical role of mitosis regulators α-thalassemia/mental retardation syndrome X-linked (ATRX) and death-domain-associated protein (DAXX) in metastatic high-grade serous carcinoma (HGSC). ATRX and DAXX protein expression by immunohistochemistry was analyzed in 400 HGSC effusions. DAXX expression was additionally studied in 15 cancer cell lines, including 4 ovarian carcinoma lines, and in 81 of the 400 HGSC effusions using Western blotting. ATRX and DAXX were expressed in HGSC cells in 386/400 (96%) and 348/400 (87%) effusions, respectively. Western blotting showed DAXX expression in all 15 cell lines and in 70/81 (86%) HGSC effusions. DAXX expression by immunohistochemistry was higher in pleural compared to peritoneal effusions (p = 0.006) and in post-chemotherapy compared to pre-chemotherapy effusions (p = 0.004), and its expression was significantly associated with poor overall survival in univariate of the entire cohort (p = 0.014), as well as analysis limited to chemo-naïve effusions tapped at diagnosis (p = 0.038). The former association retained its prognostic role in Cox multivariate survival analysis (p = 0.011). ATRX expression was unrelated to clinicopathologic parameters or survival. In conclusion, DAXX is associated with disease progression and could be a prognostic marker in metastatic HGSC. Silencing this molecule may have therapeutic relevance in this cancer.

MiR-200c-3p suppression is associated with development of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer via a mediating epithelial-to-mesenchymal transition (EMT) process.

BACKGROUND: EGFR-mutant lung cancer inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). OBJECTIVE: To investigate the clinical relevance of microRNAs (miRNAs) in TKI therapy response and resistance. METHODS: We performed a miRNA PCR array analysis and used The Cancer Genome Atlas (TCGA) database to identify potential miRNAs related to EGFR TKIs resistance. We then correlated miRNA expression in 70 surgical and 50 malignant pleural effusion specimens with patient outcomes in those with non-small cell lung carcinoma. Molecular manipulation was performed in EGFR mutant lung cancer cells to assess the effect of miR-200c-3p on cell migratory ability and EGFR-TKI sensitivity. RESULTS: We identified miR-200c-3p and miR-203a-3p as potential EGFR TKI resistance regulators via their modulation of epithelial-to-mesenchymal transition (EMT). MiR-200c-3p and miR-203a-3p were down-regulated in EGFR TKI-resistant cell lines. Progression-free survival (PFS) with EGFR-TKI treatment of patients with high miR-200c-3p expression, but not miR-203a-3p, in the specimens was significantly longer than that of patients with low expression. MiR-200c-3p overexpression inhibited the EMT process in EGFR TKI resistance cell lines and promoted cell death. MiR-200c-3p silencing in EGFR TKI sensitive cell lines increased drug resistance. CONCLUSION: MiR-200c-3p plays a role in sensitivity to EGFR TKIs via modulating EMT process.

Malignant pleural effusion survival prognostication in an Asian population.

BACKGROUND AND OBJECTIVE: LENT and PROMISE scores prognosticate survival in patients with MPE. Prognostication guides the selection of interventions and management. However, the predictive value of these scores and their refinements (modified-LENT) in Asians remain unclear. We aim to evaluate the performance of LENT, modified-LENT and clinical PROMISE scores; identify predictors of survival; and develop an alternative prognostication tool should current scores lack accuracy. METHODS: Retrospective medical record review of an Asian pleuroscopy database from 2011 to 2018 of patients with MPE was conducted. The prognostic capability of current available scores were evaluated using C-statistics. Demographic and clinical variables as predictors of survival were assessed, and an alternative model was developed using logistic regression. RESULTS: In 130 patients, the C-statistics for modified-LENT was not significantly different from LENT (0.59 (95% CI: 0.52-0.67) vs 0.56 (95% CI: 0.49-0.63); P = 0.403). In 57 patients, the PROMISE C-statistics was 0.72 (95% CI: 0.53-0.91). In our alternative prognostication model (n = 147), Sex, Eastern Cooperative Oncology Group status, Leukocyte count, EGFR mutation, Chemotherapy and primary Tumour type (SELECT) were predictors of 90-day mortality (C-statistic = 0.87 (95% CI: 0.79-0.95)). SELECT sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios using a predicted probability of 90-day mortality cut-off point of 10% were 0.91, 0.68, 0.34, 0.98, 2.83 and 0.13, respectively. CONCLUSION: The LENT, modified-LENT and PROMISE scores have poor accuracy of survival prognostication in Asian patients with MPE undergoing pleuroscopy. The proposed SELECT prognostication model is accurate at identifying patients with high probability of survival at 90 days.

Interventions for the management of malignant pleural effusions: a network meta-analysis.

BACKGROUND: Malignant pleural effusion (MPE) is a common problem for people with cancer and usually associated with considerable breathlessness. A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid, including administration of a pleurodesis agent (via a chest tube or thoracoscopy) or placement of an indwelling pleural catheter (IPC). This is an update of a review published in Issue 5, 2016, which replaced the original, published in 2004. OBJECTIVES: To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success and to quantify differences in patient-reported outcomes and adverse effects between interventions. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and three other databases to June 2019. We screened reference lists from other relevant publications and searched trial registries. SELECTION CRITERIA: We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE, comparing types of sclerosant, mode of administration and IPC use. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, characteristics, outcome measures, potential effect modifiers and risk of bias. The primary outcome was pleurodesis failure rate. Secondary outcomes were adverse events, patient-reported breathlessness control, quality of life, cost, mortality, survival, duration of inpatient stay and patient acceptability. We performed network meta-analyses of primary outcome data and secondary outcomes with enough data. We also performed pair-wise meta-analyses of direct comparison data. If we deemed interventions not jointly randomisable, or we found insufficient available data, we reported results by narrative synthesis. For the primary outcome, we performed sensitivity analyses to explore potential causes of heterogeneity and to evaluate pleurodesis agents administered via a chest tube only. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified 80 randomised trials (18 new), including 5507 participants. We found all except three studies at high or unclear risk of bias for at least one domain. Due to the nature of the interventions, most studies were unblinded. Pleurodesis failure rate We included 55 studies of 21 interventions in the primary network meta-analysis. We estimated the rank of each intervention's effectiveness. Talc slurry (ranked 6, 95% credible interval (Cr-I) 3 to 10)  is an effective pleurodesis agent (moderate certainty for comparison with placebo) and may result in fewer pleurodesis failures than bleomycin and doxycycline (bleomycin versus talc slurry: odds ratio (OR) 2.24, 95% Cr-I 1.10 to 4.68; low certainty; ranked 11, 95% Cr-I 7 to 15; doxycycline versus talc slurry: OR 2.51, 95% Cr-I 0.81 to 8.40; low certainty; ranked 12, 95% Cr-I 5 to 18). There is little evidence of a difference between the pleurodesis failure rate of talc poudrage and talc slurry (OR 0.50, 95% Cr-I 0.21 to 1.02; moderate certainty). Evidence for any difference was further reduced when restricting analysis to studies at low risk of bias (defined as maximum one high risk domain in the risk of bias assessment) (pleurodesis failure talc poudrage versus talc slurry: OR 0.78, 95% Cr-I 0.16 to 2.08). IPCs without daily drainage are probably less effective at obtaining a definitive pleurodesis (cessation of pleural fluid drainage facilitating IPC removal) than talc slurry (OR 7.60, 95% Cr-I 2.96 to 20.47; rank = 18/21, 95% Cr-I 13 to 21; moderate certainty). Daily IPC drainage or instillation of talc slurry via IPC are likely to reduce pleurodesis failure rates. Adverse effects Adverse effects were inconsistently reported. We performed network meta-analyses for the risk of procedure-related fever and pain. The evidence for risk of developing fever was of low certainty, but suggested there may be little difference between interventions relative to talc slurry (talc poudrage: OR 0.89, 95% Cr-I 0.11 to 6.67; bleomycin: OR 2.33, 95% Cr-I 0.45 to 12.50; IPCs: OR 0.41, 95% Cr-I 0.00 to 50.00; doxycycline: OR 0.85, 95% Cr-I 0.05 to 14.29). Evidence also suggested there may be little difference between interventions in the risk of developing procedure-related pain, relative to talc slurry (talc poudrage: OR 1.26, 95% Cr-I 0.45 to 6.04; very-low certainty; bleomycin: OR 2.85, 95% Cr-I 0.78 to 11.53; low certainty; IPCs: OR 1.30, 95% Cr-I 0.29 to 5.87; low certainty; doxycycline: OR 3.35, 95% Cr-I 0.64 to 19.72; low certainty). Patient-reported control of breathlessness Pair-wise meta-analysis suggests there is likely no difference in breathlessness control, relative to talc slurry, of talc poudrage ((mean difference (MD) 4.00 mm, 95% CI -6.26 to 14.26) on a 100 mm visual analogue scale for breathlessness; studies = 1; participants = 184; moderate certainty) and IPCs without daily drainage (MD -6.12 mm, 95% CI -16.32 to 4.08; studies = 2; participants = 160; low certainty). Overall mortality There may be little difference between interventions when compared to talc slurry (bleomycin and IPC without daily drainage; low certainty) but evidence is uncertain for talc poudrage and doxycycline. Patient acceptability Pair-wise meta-analysis demonstrated that IPCs probably result in a reduced risk of requiring a repeat invasive pleural intervention (OR 0.25, 95% Cr-I 0.13 to 0.48; moderate certainty) relative to talc slurry. There is likely little difference in the risk of repeat invasive pleural intervention with talc poudrage relative to talc slurry (OR 0.96, 95% CI 0.59 to 1.56; moderate certainty). AUTHORS' CONCLUSIONS: Based on the available evidence, talc poudrage and talc slurry are effective methods for achieving a pleurodesis, with lower failure rates than a number of other commonly used interventions. IPCs provide an alternative approach; whilst associated with inferior definitive pleurodesis rates, comparable control of breathlessness can probably be achieved, with a lower risk of requiring repeat invasive pleural intervention.  Local availability, global experience of agents and adverse events (which may not be identified in randomised trials) and patient preference must be considered when selecting an intervention. Further research is required to delineate the roles of different treatments according to patient characteristics, such as presence of trapped lung. Greater attention to patient-centred outcomes, including breathlessness, quality of life and patient preference is essential to inform clinical decision-making. Careful consideration to minimise the risk of bias and standardise outcome measures is essential for future trial design.

Management of Respiratory Symptoms in Those with Serious Illness.

Respiratory symptoms are common in patients living with serious illness, both in cancer and nonmalignant conditions. Common symptoms include dyspnea (breathlessness), cough, malignant pleural effusions, airway secretions, and hemoptysis. Basic management of respiratory symptoms is within the scope of primary palliative care. There are pharmacologic and nonpharmacologic approaches to treating respiratory symptoms. This article provides clinicians with treatment approaches to these burdensome symptoms.

Clinical course of non-small cell lung cancer patients with dry pleural dissemination: Retrospective observational study.

We investigated the prognosis of patients with dry pleural dissemination (DPD) of non-small cell lung cancer (NSCLC) and the risk factors of developing to malignant pleural effusion (MPE).We retrospectively reviewed 104 patients with NSCLC and DPD, confirmed surgically from 1996 to 2016. Incidence rate and risk factors of MPE were analyzed statistically. The prognosis of NSCLC patients with MPE was evaluated using the Kaplan-Meier method.The most common histologic type was adenocarcinoma in 95 (91.3%) patients. The median follow-up duration was 65.5 months and the median survival time was 37.7 months. MPE developed in 51 (49%) patients, and the median effusion-free interval was 41.9 months. The median survival time of the patients with and without MPE was not different (41.3 vs 31.7 months, P = .16). No predictive factors for the development of MPE were identified. Fifteen (14.4%) patients underwent invasive procedures for the management of MPE.Almost half of all patients with NSCLC and DPD experienced MPE, and 14.4% patients developed symptomatic MPE requiring invasive procedures. MPE in DPD did not affect the survival in NSCLC patients.

Impacto clínico de una unidad de patología pleural en un hospital de tercer nivel / Clinical Impact of a Pleural Unit in a Tertiary Level Hospital

INTRODUCCIÓN: La enfermedad pleural conlleva un gran número de ingresos y elevadas estancias hospitalarias. Con el fin de mejorar esto, se creó en nuestro hospital una unidad de patología pleural (UPP). Nuestro objetivo es analizar el impacto clínico de dicha unidad. MATERIAL Y MÉTODOS: Estudio prospectivo en el que incluimos a los pacientes ingresados en la UPP del Hospital Universitario Central de Asturias por neumotórax espontáneo primario (NEP), secundario (NES), derrame pleural paraneumónico complicado (DPPC) y derrame pleural maligno (DPM), entre enero de 2015 y diciembre de 2018. Analizamos parámetros descriptivos, estancias medias, reingresos al mes, necesidad de cirugía y, en los DPPC, también la mortalidad hospitalaria. Los datos se compararon con los de los pacientes ingresados por la misma enfermedad en neumología durante los 2 años previos (2013-2014). Describimos además todos los procedimientos realizados en la UPP, tanto ambulatorios como en pacientes ingresados. RESULTADOS: Se incluyeron 741 pacientes. Objetivamos una disminución progresiva de los ingresos totales por enfermedad pleural y de la estancia media (días) en dichas afecciones, excepto en el DPM: NEP de 6,2 a 4,2 (p = 0,004), NES de 13,2 a 8,6 (p = 0,005), DPM de 10,3 a 12,3 (p = 0,05) y DPPC de 18,3 a 11,3 (p = 0,001). Existió una reducción de los reingresos al mes y de la mortalidad hospitalaria por DPPC en el periodo de la UPP (14,9% al 5,5%) (p = 0,021). CONCLUSIONES: La creación de una UPP podría disminuir el número de ingresos innecesarios, favoreciendo una reducción de las estancias medias y, en los DPPC, también la mortalidad hospitalaria

INTRODUCTION: Pleural disease involves a large number of admissions and long hospital stays. In order to improve this situation, a Pleural Unit (PU) was created in our hospital. Our aim was to analyze the clinical impact of this unit. MATERIAL AND METHODS: In this prospective study, we included patients admitted to the PU of the Hospital Universitario Central de Asturias for primary spontaneous pneumothorax (PSP), secondary spontaneous pneumothorax (SSP), complicated parapneumonic pleural effusion (CPPE), and malignant pleural effusion (MPE) between January 2015 and December 2018. We analyzed descriptive parameters, mean length of stay, readmissions at 1 month, need for surgery, and in the CPPE group, in-hospital mortality. The data were compared with those of patients admitted to the respiratory medicine department for the same diseases during the previous two years (2013-2014). We also describe all procedures performed in the PU, in both inpatients and outpatients. RESULTS: A total of 741 patients were included, We observed a progressive decrease in total admissions for pleural diseases and mean length of stay (days) (with the exception of MPE), as follows: PSP: from 6.2 to 4.2 (P = .004); SSP: 13.2 to 8.6 (P = .005), MPE: 10.3 to 12.3 (P = .05); and CPPE: 18.3 to 11.3 (P = .001) There was a reduction in hospital readmissions at 1 month and in in-hospital mortality due to CPPE in the PU period (14.9% to 5.5%) (P = .021). CONCLUSIONS: The creation of a PU could decrease the number of unnecessary admissions, and reduce mean lengths of stay and, in the case of CPPE, in-hospital mortality

Analysis of Quality of Life after Pleurodesis in Patients with Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion is one of the most important complications of metastatic cancer, and recurrent pleural effusions do not only have an impact on survival but also cause a huge repercussion on a patient's quality of life. OBJECTIVES: The main objective was to describe quality of life status before and after pleurodesis in patients with malignant pleural effusion. Secondary, we aimed to find predictors of quality of life improvement in such a population. METHODS: Retrospective analysis of a database collected prospectively. We included patients who underwent pleurodesis from June 2004 to July 2014. Quality of life was evaluated through the WHOQOL-BREF questionnaire and applied before and 30 days after pleurodesis. We used a paired t test and the Wilcoxon rank-sum to compare pre-/post-pleurodesis results, Kaplan-Meier curves for survival analysis, and multiple linear regressions to find predictors of quality of life improvement. RESULTS: 183 patients were included (145 were women). Mean age was 58.3 ± 12.3 years, the most numerous primary tumor was breast cancer. Median survival time was 9 months. Dyspnea was the most prevalent symptom. Baseline results showed that patients had low quality of life scores. After pleurodesis, there was a significant improvement in respiratory symptoms, physical domain, and general health. Linear regression showed an improvement in physical domain with the sclerosing agent nitrate (p = 0.005). Male gender (p = 0.002) and a higher lymphocyte count (p = 0.01) were inversely associated with improvement in physical domain. CONCLUSIONS: Pleurodesis improved symptoms and quality of life in patients with malignant pleural effusion. Gender, lymphocyte count, and sclerosing agent might interfere with quality of life improvement.