Management Of Malignant Pleural Effusion Research Articles

Effect of Chemotherapy on Removal of Indwelling Pleural Catheters in Breast Cancer Patients with Malignant Pleural Effusions

Background: Indwelling pleural catheters (IPC) are commonly used in the management of malignant pleural effusions (MPE). The effect of systemic chemotherapy on IPC removal has not been reported previously. Objectives: The purpose of this study is to identify the effect of chemotherapy on the removal of IPCs in breast cancer patients with MPEs. Methods: In this retrospective cohort study at an academic tertiary-care center, patients with breast cancer and MPE who received an IPC between 2006 and 2016 were identified from a prospectively collected database. Patient chemotherapy data were obtained, as well estrogen receptor (ER) and human epidermal growth factor receptor-2 status at the time of diagnosis. Patients receiving chemotherapy while their IPC was in situ were compared to those who did not. The primary outcome was time to IPC removal. All patients were followed until IPC removal or death. Results: A total of 207 patients and 216 IPCs were included in the analysis. There was no difference in time to IPC removal between the chemotherapy and no-chemotherapy groups (HR 0.73, 95% CI 0.50–1.07, p = 0.10) or rate of IPC removal (OR 1.16, 95% CI 0.68–1.98, p = 0.59). The risk of IPC infection was not different between patients who received chemotherapy and those who did not (RR 0.57, 95% CI 0.06–5.39, p = 0.48). Conclusions: Treatment with chemotherapy with an IPC in situ was not associated with a reduced time to IPC removal in our breast cancer population. IPC insertion in patients receiving chemotherapy is safe and not associated with an increased risk of infection.

ERS/EACTS statement on the management of malignant pleural effusions.

Malignant pleural effusions (MPE) are a common pathology, treated by respiratory physicians and thoracic surgeons alike. In recent years, several well-designed randomized clinical trials have been published that have changed the landscape of MPE management. The European Respiratory Society (ERS) and the European Association for Cardio-Thoracic Surgery (EACTS) established a multidisciplinary collaboration of clinicians with expertise in the management of MPE with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified, including the optimum management of symptomatic MPE, management of trapped lung in MPE, management of loculated MPE, prognostic factors in MPE, whether there is a role for oncological therapies prior to intervention for MPE and whether a histological diagnosis is always required in MPE. The literature revealed that talc pleurodesis and indwelling pleural catheters effectively manage the symptoms of MPE. There was limited evidence regarding the management of trapped lung or loculated MPE. The LENT score was identified as a validated tool for predicting survival in MPE, with Brims' prognostic score demonstrating utility in mesothelioma prognostication. There was no evidence to support the use of oncological therapies as an alternative to MPE drainage, and the literature supported the use of tissue biopsy as the gold standard for diagnosis and treatment planning.Management options for malignant pleural effusions have advanced over the past decade, with high-quality randomized trial evidence informing practice in many areas. However, uncertainties remain and further research is required http://ow.ly/rNt730jOxOS.

Malignant Pleural Effusions—Personalised Management

Malignant pleural effusions (MPEs) are frequent and are associated with significant morbidity and mortality. This article reviews the most recent literature on the management of MPE. With an increasing focus on personalised medicine, the primary treatment aims have changed from the primary aim of recurrence prevention to symptom control and quality of life improvement. Dependent on patient preference, options available to achieve such targets include repeated aspiration, talc pleurodesis (either through a small-bore chest drain or at thoracoscopy), and indwelling pleural catheters (IPCs). There is a consensus regarding the use of IPC in cases of trapped lung and failed talc pleurodesis, but two recent randomised controlled trials have proposed the use of IPCs as first-line therapy. MPE management should be personalised, considering factors such as predicted survival, performance status, social support, local expertise and, most importantly, patient preference. IPCs are now more widely available as a treatment option and should be explored as a first-line treatment in selected patients.

Nitric oxide suppresses formation of malignant pleural effusion

In the present study, we were prompted to investigate the effect of NO signaling on the formation of malignant pleural effusion (MPE) and determined whether NO affects Th1/Th17 response in MPE. The development of MPE and survival of MPE mice were compared between wild-type and NOS2 ‒/‒ mice. The effect of NOS2 on vascular permeability of pleura and differentiation of Th1 and Th17 in MPE was also explored. Our current data show that production of NO is significantly enhanced in MPE as compared with peripheral circulation, and that nitric oxide synthase-2 (NOS2) deficiency increases pleural vascular permeability and thus promotes the development of MPE, and reduces the survival of mice bearing MPE. NOS2 deficiency inhibits Th1 cell differentiation and promotes Th17 cell differentiation. Our data provide the first evidence that NO inhibits MPE formation by inhibiting fluid extravasation into the pleural space and by promoting Th1 cell differentiation and suppressing Th17 cell differentiation. Overall, our results shed light on the mechanisms by which NO suppresses MPE formation, providing a promising therapeutic strategy in the management of MPE.

A comparison between two types of indwelling pleural catheters for management of malignant pleural effusions

Malignant pleural effusion (MPE) is a common cause of quality of life deterioration in patients with advanced cancer. Management options include chemical pleurodesis with a sclerosing agent such as doxycycline or talc powder, surgery, and also the placement of tunneled indwelling pleural catheters (IPCs). Two different IPC types are mostly used in the USA. We conducted a single-center retrospective study with the objective to compare the efficacy and safety profiles of two IPC systems. Patients with a diagnosis of malignancy, who received IPCs by the interventional radiology department of our hospital from January 2013 to March 2015, were identified in the local database and a chart review was performed to record characteristics and outcomes. Patients without a diagnosis of malignancy or with pleural effusions of cardiac origin were excluded from the study. We identified 27 patients with a median age of 59.0 years. Eighty patients received Aspira catheter while nine patients received PleurX catheter, and seven patients achieved spontaneous pleurodesis. The median length of stay (LOS) was 9 days for the Aspira group (AG), as compared to 13 days for the PleurX group (PG) (overall median LOS was 10 days; range, 2-62 days). The rate of catheter-related complications (pain, obstruction, loculations, infection, hemorrhage) was 39% (seven patients) for the AG and 33% (three patients) for the PG (overall ten patients, 37%). In our study, outcomes and safety were similar for patients receiving either type of IPC, Aspira or PleurX.

The role of VEGF in the diagnosis and treatment of malignant pleural effusion in patients with non‑small cell lung cancer (Review).

Malignant pleural effusion (MPE) is a severe medical condition, which can result in breathlessness, pain, cachexia and reduced physical activity. It can occur in almost all types of malignant tumors; however, lung cancer is the most common cause of MPE, accounting for ~1/3 of clinical cases. Although there are numerous therapeutic approaches currently available for the treatment of MPE, none are fully effective and the majority can only alleviate the symptoms of the patients. Vascular endothelial growth factor (VEGF) has now been recognized as one of the most important regulatory factors in tumor angiogenesis, which participates in the entire process of tumor growth through its function to stimulate tumor angiogenesis, activate host vascular endothelial cells and promote malignant proliferation. Novel drugs targeting VEGF, including endostar and bevacizumab, have been developed and approved for the treatment of various tumors. Data from recent clinical studies have demonstrated that drugs targeting VEGF are effective and safe for the clinical management of MPE. Therefore, VEGF-targeting represents a promising novel strategy for the diagnosis and treatment of MPE. The present review summarized recent advances in the role of VEGF in the pathogenesis, diagnosis and clinical management of MPE in patients with non-small cell lung cancer.

Contemporary best practice in the management of malignant pleural effusion.

Malignant pleural effusion (MPE) affects more than 1 million people globally. There is a dearth of evidence on the therapeutic approach to MPE, and not surprisingly a high degree of variability in the management thereof.We aimed to provide practicing clinicians with an overview of the current evidence on the management of MPE, preferentially focusing on studies that report patient-related outcomes rather than pleurodesis alone, and to provide guidance on how to approach individual cases.A pleural intervention for MPE will perforce be palliative in nature. A therapeutic thoracentesis provides immediate relief for most. It can be repeated, especially in patients with a slow rate of recurrence and a short anticipated survival. Definitive interventions, individualized according the patient’s wishes, performance status, prognosis and other considerations (including the ability of the lung to expand) should be offered to the remainder of patients. Chemical pleurodesis (achieved via intercostal drain or pleuroscopy) and indwelling pleural catheter (IPC) have equal impact on patient-based outcomes, although patients treated with IPC spend less time in hospital and have less need for repeat pleural drainage interventions. Talc slurry via IPC is an attractive recently validated option for patients who do not have a nonexpandable lung.

Effect of chest tube size on pleurodesis efficacy in malignant pleural effusion: a meta-analysis of randomized controlled trials.

Malignant pleural effusion (MPE) develops in approximately 50% of all patients with metastatic cancer. The efficacy of small- vs. large-bore chest tube for pleurodesis in patients with MPE is still not clear. We performed a meta-analysis to evaluate the efficacy and safety of chest tube size in the management of MPE. A systematic search of Medline (Ovid) and Embase (from 1980 to March 2016) was performed. Randomized clinical trials (RCTs) evaluating the effect of small (≤14 French) vs. large (>14 French) chest tube size on successful pleurodesis for patients with MPE. Of 708 potentially relevant publications, four matched the selection criteria and were included in the meta-analysis. Overall relative risk (RR) with 95% confidence intervals (CI) was pooled using a random-effects model. Heterogeneity was assessed using Q statistic (significant at P<0.1). In the 231 patients, the success proportion of pleurodesis as well as complication proportion were comparable between large and small chest tube groups with a pooled RR of 0.90 (95% CI, 0.77-1.05; P=0.19; I2 =17.4%) and 0.95 (95% CI, 0.42-2.15; P=0.90; I2 =0.9%) respectively. Successful pleurodesis and complication proportion for small vs. large chest tubes were 73.8% vs. 82.0% and 13.0% vs. 10.5%, respectively. This meta-analysis suggests that small and large chest tubes are both effective treatment for MPE with similar successful pleurodesis and complication proportion. Further RCTs are needed to more clearly determine which size tube is superior.

Tunneled pleural catheters for management of malignant pleural effusions: a 2-year review of outcomes at a high-volume center

Background: Report outcomes of patients receiving tunneled pleural catheters (TPCs) for malignant pleural effusions (MPE) over a 2-year period. Methods: TPCs were placed by one interventional pulmonologist under moderate sedation using PleurX TM catheters between September 2014 and August 2016. Retrospective data was collected from electronic medical records of adult patients, with malignant etiology, MPE evidence, with no previous talc pleurodesis. Two study groups were defined as reaching autopleurodesis indicated by TPC removal date or failure to reach autopleurodesis indicated by death prior to TPC removal. Results: Total sample size was 83, where 33 were male and 50 were female. The mean age was 63.1 years. The most common type of cancer was lung (n=36, 43.4%). By September 2016, 60.2% (n=50) patients were deceased, and 8 of 83 patients were alive with continued TPC drainage. In total, 94 TPCs placed in 83 patients, which included five patients with bilateral placements. Only 75 patients were included in the final calculations, where 41 (54.7%) reached autopleurodesis, and 34 (45.3%) expired with TPC in place. It took a median of 50.0 days to reach autopleurodesis and a median of 52.5 days to expire with TPC. Conclusions: Our exploratory study reviewing the clinical outcomes and complications of TPCs in a high-volume institution represents a significant addition to the growing body of literature describing these catheters. Results show TPC use for the treatment of MPEs significantly aid in accomplishing autopleurodesis with minimal risk of complication.

34 - Ambulatory management of malignant pleural effusion using indwelling pleural catheters

34 - Ambulatory management of malignant pleural effusion using indwelling pleural catheters

Video-assisted thoracic surgery ( conventional and single-port ) - place and role in the improved management of malignant pleural effusions: review article

MPE management has been changing over the years as this is due both to the technological advancement of mini-invasive surgical methods and to the change in our knowledge about this manifestation of oncology disorder. Advanced cancer disease and poor general condition in most cases do not allow large-volume and duration of surgical procedures. VATS is becoming an increasingly large share of the operating methods of treatment of spontaneous pneumothorax, thoracic trauma, acute pleural empyema, pleural effusion, benign pleural and pulmonary lesions, secondary metastatic and primary malignant lesions - pleural, pulmonary, mediastinal and bilateral location. Diagnostic and therapeutic capabilities of VATS for simultaneous diagnosis and palliative surgical treatment make it the optimal procedure in MPE management. It should be noted that the preliminary assessment of the patient’s condition and local status with an estimate of survival time often undergoes a radical change after the video-assisted surgical procedure. Improvement is reported with an increase of predetermined survival time and improved performance status, which supports the application of more minimally invasive, non-intubated, “awake” single-port VATS.

24 - Clinical follow up in ambulatory management of malignant pleural effusion

24 - Clinical follow up in ambulatory management of malignant pleural effusion

Role of bevacizumab in the management of the patient with malignant pleural effusion: more questions than answers

ABSTRACTIntroduction: Malignant pleural effusion (MPE) is a feature of metastatic cancer associated with significant morbidity and cost. The typical management of MPE is systemic chemotherapy and mechanical intervention. Vascular endothelial growth factor (VEGF), an inducer of vascular permeability, has been shown to mediate fluid formation. Therefore, bevacizumab, an inhibitor of VEGF, offers theoretical promise for abolishing fluid formation in MPE.Areas covered: This review begins with a summary of VEGF physiology and evidence of its role in MPE pathogenesis. This is followed by an overview of bevacizumab and major trials that put it on the map of non-small cell lung cancer (NSCLC). The majority of the article is devoted to a review of the current evidence base for the use of bevacizumab for MPE control in metastatic pleural malignancy. The review concludes with considerations of patient selection and toxicity.Expert commentary: Evidence in support of bevacizumab administration for MPE management remains flawed. Small studies suggest efficacy of both intravenous and intrapleural routes, but their design raises bias concerns. Bevacizumab appears to be safe in properly selected cases. The future of MPE management may de-emphasize VEGF inhibition in favor of precise molecular therapeutics that could address the root cause of tumorigenesis.

P2.01-041 Pemetrexed plus Platinum Chemotherapy with or Without Immuno Responses of Bevacizumab plus Cisplatin for the Non-Squamous Non-Small-Cell Lung Cancer Patients with Malignant Pleural Effusions Therapy in Non-Squamous NSCLC: Descriptive Safety Analysis

To explore the efficacy and safety of intrapleural bevacizumab plus cisplatin for malignant pleural effusions (MPEs) of non-squamous non-small-cell lung cancer (NSCLC) patients. We retrospectively analyzed 14 patients with MPEs who received intrapleural bevacizumab (200mg) plus cisplatin (60mg) from May, 2015 to March, 2017. Treatment response was assessed according to RECIST 1.1 The patients included 6 (42.6%) men and 8 (57.1%) women, with a median age of 54 years (ranged, 41-71 years). Five (35.7%) patients had smoking history. Thirteen (92.9%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2. Driver gene alterations were detected in 4 (28.6%) patients, among them, 3 epidermal growth factor receptor mutations and 1 anaplastic lymphoma kinase arrangement. Four (28.6%) patients received first-line intravenous chemotherapy, and 10 (71.4%) had second or later line chemotherapy. In the management of MPEs, 8 (57.1%) patients achieved partial response (PR), 2 (14.3%) patients showed stable disease (SD) and 4 (28.6%) patients experienced progressive disease (PD). No one was seen complete response (CR). The overall response rate (ORR) and disease control rate (DCR) was 57.1% and 71.4%, respectively. There were 7 (50.0%) cases treated with bevacizumab and cisplatin as initial intrapleural therapy, another 7 (50.0%) patients as subsequent treatment. There were 4 (57.1%) PR for group with bevacizumab plus cisplatin as initial treatment and 4 (57.1%) PR for group with bevacizumab plus cisplatin as subsequent treatment. No significant difference was observed in the two groups (P=1.00). In addition, the adverse events we seen were myelosuppression (7.1%), nausea and emesis (28.5%), mainly in grade 1-2. No thrombosis or bleeding occurred in this study. Combined intrapleural therapy with bevacizumab and cisplatin was found to be effective for the non-squamous NSCLC patients with MPEs, and the adverse events were well tolerable.

445P - Phase II study of efficacy of bevacizumab plus chemotherapy in management of malignant pleural effusion in non-squamous non-small cell lung cancer patients with malignant pleural effusion (MPE) unsuccessfully controlled by tube drainage or pleurodesis (NEJ-13-2 trial)

Background: Prospective and retrospective studies on intrapleural therapy of malignant pleural effusion (MPE) have reported that the success rate for controlling pleural effusion is 50% at 2.5 months. When pleurodesis is unsuccessful, the lung is not fully expanded after drainage before receiving effective chemotherapy. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of MPE. Here, a multicenter phase II trial was conducted to evaluate bevacizumab therapy in non-squamous NSCLC patients with unsuccessful management of MPE. Methods: Non-squamous NSCLC patients with MPE who had received unsuccessful tube drainage or pleurodesis received chemotherapy with bevacizumab (15 mg/kg) every 3 weeks. The primary endpoint was pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE for 8 weeks. The secondary endpoint was pleural Progression-free survival (PPFS), defined as PFS without reaccumulation of MPE. Results: Fifteen of 20 patients entered received a median of 4 cycles of carboplatin plus paclitaxel or pemetrexed including maintenance therapy with bevacizumab. The PECR was 80% of treated patients. PPFS was 16.6 months. The response rate and disease control rate were 45% and 80%, respectively, and the median PFS and overall survival (OS) were 9.8 months and 19.6 months, respectively. The patients with high VEGF (<1000pg/ml) in MPE had shorter PPFS (P = 0.01) and OS (P < 0.01). Toxicities of grade ≥3 included neutropenia (50.0%), thrombocytopenia (10.0%), proteinuria (10.0%) and hypertension (2.0%). Global QOL score investigated by EORTC QLQ-C30 favored in the patients without reaccumulation of MPE. Conclusions: The combination of bevacizumab with chemotherapy demonstrated efficacy with acceptable toxicities as a standard therapy in controlling MPE in patients with non-squamous NSCLC whose MPE was unsuccessfully controlled by tube drainage or pleurodesis. Clinical trial indentification: trial protocol number (NIH or European equivalent) is UMIN000006868. The release data is 10/12/2011. Legal entity responsible for the study: North East Japan Study Group Funding: None Disclosure: Y. Hosomi: Research funding from Chugai, MSD, Boheringer and Astrazeneca, H. Okamoto: Reserch funding from Chugai MSD Taiho AstraZeneca, Merck, Eli Lilly, Bristol and Astellas. K. Hagiwara: Patents, Royalties from LSI Medience, K. Kubota: Research funding from Chugai, Astrazeneca, Bheringer and Lilly. A. Gemma: Research fundung from Astrazeneca, Taiho, Chugai, MSD, Lilly and Bheringer. All other authors have declared no conflicts of interest.

P3.12-002 Patients with Malignant Pleural Effusion who Succeeded Pleurodesis have a Longer Survival Rate - A 10-year Follow-Up

Pleurodesis is often used to prevent re-accumulation of malignant pleural effusions (MPE). Intrapleural urokinase (IPUK) therapy facilitates lung re-expansion for patients with loculated MPE or trapped lung and allows subsequent pleurodesis. The MPE management has been traditionally regarded as a symptomatic treatment with rare mention of its impact on survival. Our preliminary study involved 26 patients showed successful pleurodesis translates into a longer survival. (BMC Cancer 2016; 16:463) The successfully induced inflammatory response by sclerosing agent is supposed to prohibit tumor invasion and metastasis. Part I. Three hundred and eighty-nine consecutive patients with symptomatic MPE underwent minocycline pleurodesis with (n = 184) and without (n = 205) antecedent IPUK therapy between September 2005, and August 2015, were recruited for pleurodesis outcome and survival analysis. Part II. The pleural fluid pro-inflammatory (IL-6, TNF-α), or anti-inflammatory (IL-1β, IL-10, TGF-β) cytokines before and after pleurodesis in fifteen patients with MPE between September 2015 and April 2016 were measured using Bio-Plex® Multiplex assays and correlated with the pleurodesis outcome and patient survival. Part I. Patients numbering 109 (59.2%) responded to the IPUK therapy. The success rate of the subsequent pleurodesis was similar to that of the simple pleurodesis group (70.5% vs 69.0%; p = 0.804). In both groups, the patients who succeeded pleurodesis had a longer survival rate than those that failed (median, 259 vs 102 days; p <.001 and 414 vs 100 days; p <0.001 respectively). Multivariate analysis showed that successful pleurodesis was an independent prognosticator (hazard ratio, 0.374; p <0.001 and 0.271; p <0.001 respectively). The differences remained when lung and breast cancer patients were studied separately. Part II. After instillation of sclerosing agent, pleural fluid IL-1β and IL-10, with a lesser degree were elevated in the group of successful pleurodesis. There was no discrimination in the TGF-β1, and IL-6 level between those succeeded and failed pleurodesis. No consistent change of TNF-α was observed in either group. Successful pleurodesis translates into a better survival rate promotes performing pleurodesis on lung re-expansion. The selective elevation of anti-inflammatory cytokines following pleurodesis suggests an anti-tumor effect. The change of TGF-β1 correlated with its dual role in cancer. While chronic inflammation might promote tumor formation, therapy induced acute inflammation might well hamper the process, and is indeed used therapeutically to inhibit tumor. Further studies are warranted to clarify the mechanism and provide opportunities to develop novel therapeutic strategies.

Malignant Pleural Mesothelioma: Spotlight on Recent Advances in Diagnosis and Treatment

Pleural malignancies constitute either primary pleural malignancies, such as malignant pleural mesothelioma (MPM), or secondary pleural tumours, either from pleural metastasis or direct extension of adjacent tumours. Mesothelioma is a rare aggressive tumour of the pleural surfaces associated with prior asbestos exposure. Mesothelioma is also a challenging disease from a diagnostic staging, and treatment perspective and is rarely cured despite multimodal treatment. With incidence continuing to rise, this disease represents a serious global problem that needs urgent attention. This review provides an in-depth review of MPM. Recent advances in diagnostic approaches, such as imaging techniques and the role of immunohistochemistry and biomarkers, are discussed. Treatment modalities, including chemotherapy, radiotherapy, and surgery as part of a multimodal approach, are reviewed, as well as the management of malignant pleural effusions.

Diagnosis and management of malignant pleural effusions: state of the art in 2017.

Malignant pleural effusion (MPE) is a known complication of both thoracic and extra thoracic malignancies. The presence of MPE regardless of the primary site translates into advanced stage disease. Diagnosis and management of MPE with the goals of palliation and improving quality of life poses a challenge for chest physicians. Recently, multiple studies have made attempts to answer questions regarding optimal management in various clinical scenarios. We will review the current evidence and available options for the management of MPE.

Asymptomatic malignant pleural effusion: to observe or to manage.

The malignant pleural effusion (MPE) incidence in the United States is estimated to be more than 150,000 cases annually (1). Most of the MPEs are symptomatic and commonly present with dyspnea, dry cough, dull chest pain and constitutional symptoms (2). While there is a fair amount of data about symptomatic MPEs, including epidemiology, clinical presentation and treatment options, the management of asymptomatic MPEs is mostly through observation (3,4).

Advances in the management of malignant pleural effusion.

The current review describes the latest evidence in the management of malignant pleural effusions (MPE). Daily drainage of indwelling pleural catheters achieved auto-pleurodesis at a higher rate compared with every-other-day drainage [0.47 vs. 0.24; difference in proportion of 0.23; 95% confidence interval (CI) 0.08-0.38; P = 0.003]. In patients with MPE undergoing talc pleurodesis, a large multicenter randomized clinical trial found that pain control with opiates vs. nonsteroidal anti-inflammatory drugs (NSAID) group were not significantly different (mean visual analog scale of 23.8 vs. 22.1 mm, respectively, adjusted difference -1.5 mm; 95% CI 1.3-3.4; P = 0.40). NSAID use was found to be noninferior to opiates with respect to the rate of pleurodesis failure at 3-month follow-up (prespecified noninferiority margin 15%, failure rates 20% opiates vs. 23% NSAIDS, respectively, difference -3%, 95% CI -10% to ∞; P = 0.004 for noninferiority). Talc remains the most effective sclerosing agent based on multiple systematic reviews and meta-analyses. More prospective studies are needed to determine the optimal frequency of indwelling pleural catheters drainage. NSAIDS can be used for pain control and do not adversely impact the chance of successful pleurodesis.