Efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy for malignant pleural effusion: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of intrapleural perfusion with hyperthermic chemotherapy (IPHC) in treating malignant pleural effusion (MPE). METHODS: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Chinese Science and Technology Journal Full-text Database (VP-CSJFD), and Wanfang database were searched by computer from database establishment to January 17, 2024. Relevant randomized controlled articles with IPHC as the observational group and intrapleural perfusion chemotherapy (IPC) as the control group for MPE were included. Then, the methodological quality of the included articles was evaluated and statistically analyzed using Stata 16.0. RESULTS: Sixteen trials with 647 patients receiving IPHC and 661 patients receiving IPC were included. The meta-analysis found that MPE patients in the IPHC group had a more significant objective response rate [RR = 1.31, 95%CI (1.23, 1.38), P < 0.05] and life quality improvement rate [RR = 2.88, 95%CI (1.95, 4.24), P < 0.05] than those in the IPC group. IPHC and IPC for MPE patients had similar incidence rates of asthenia, thrombocytopenia, hepatic impairment, and leukopenia. CONCLUSION: Compared with IPC, IPHC has a higher objective response rate without significantly increasing adverse reactions. Therefore, IPHC is effective and safe. However, this study is limited by the quality of the literature. Therefore, more high-quality, multi-center, large-sample, rigorously designed randomized controlled clinical studies are still needed for verification and evaluation.

Usefulness of thoracic ultrasound in the assessment of removal of indwelling pleural catheter in patients with malignant pleural effusion.

INTRODUCTION: There are no defined criteria for deciding to remove a non-functioning indwelling pleural catheter (IPC) when lung re-expansion on chest X-ray is incomplete. Chest computed tomography (chest CT) is usually used. The objective of this work is to validate the usefulness of chest ultrasound performed by a pulmonologist and by a radiologist compared to chest CT. PATIENTS AND METHODS: Prospective, descriptive, multidisciplinary and multicenter study including patients with malignant pleural effusion and non-functioning IPC without lung reexpansion. Decisions made on the basis of chest ultrasound performed by a pulmonologist, and performed by a radiologist, were compared with chest CT as the gold standard. RESULTS: 18 patients were analyzed, all of them underwent ultrasound by a pulmonologist and chest CT and in 11 of them also ultrasound by a radiologist. The ultrasound performed by the pulmonologist presents a sensitivity of 60%, specificity of 100%, PPV 100% and NPV 66% in the decision of the correct removal of the IPC. The concordance of both ultrasounds (pulmonologist and radiologist) was 100%, with a kappa index of 1. The 4 discordant cases were those in which the IPC was not located on the ultrasound. CONCLUSIONS: Thoracic ultrasound performed by an expert pulmonologist is a valid and simple tool to determine spontaneous pleurodesis and remove a non-functioning IPC, which would make it possible to avoid chest CT in those cases in which lung reexpansion is observed with ultrasonography.

Engineered lactococcus lactis intrapleural therapy promotes regression of malignant pleural effusion by enhancing antitumor immunity.

Intrapleural immunotherapies have emerged as a prominent field in treating malignant pleural effusion (MPE). Among these, bacteria-based intrapleural therapy has exerted an anti-MPE effect by immuno-stimulating or cytotoxic properties. We previously engineered a probiotic Lactococcus lactis (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 and co-stimulator OX40 ligands. FOLactis activates tumor antigen-specific immune responses and displays systemic antitumor efficacy via intratumoral delivery. However, no available lesions exist in the pleural cavity of patients with MPE for intratumoral administration. Therefore, we further optimize FOLactis to treat MPE through intrapleural injection. Intrapleural administration of FOLactis (I-Pl FOLactis) not only distinctly suppresses MPE and pleural tumor nodules, but also significantly extends noticeable survival in MPE-bearing murine models. The proportion of CD103+ dendritic cells (DCs) in tumor-draining lymph nodes increases three-fold in FOLactis group, compared to the wild-type bacteria group. The enhanced DCs recruitment promotes the infiltration of effector memory T and CD8+ T cells, as well as the activation of NK cells and the polarization of macrophages to M1. Programmed death 1 blockade antibody combination further enhances the antitumor efficacy of I-Pl FOLactis. In summary, we first develop an innovative intrapleural strategy based on FOLactis, exhibiting remarkable efficacy and favorable biosafety profiles. These findings suggest prospective clinical translation of engineered probiotics for managing MPE through direct administration into the pleural cavity.

Clinical impact of pleural fluid carcinoembryonic antigen on therapeutic strategy and efficacy in lung adenocarcinoma patients with malignant pleural effusion.

BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. METHODS: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. RESULTS: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. CONCLUSION: High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

[Expert consensus on diagnosis and treatment of malignant pleural effusion caused by lung cancer].

Malignant pleural effusion (MPE) can occur in nearly all types of malignant tumors, with lung cancer being the most prevalent cause. The presence of MPE indicates an advanced stage or distant spread of the tumor, significantly reducing the patient's life expectancy. Particularly, a substantial amount of pleural effusion can impede heart and lung function, impair blood oxygen perfusion levels in the body, and greatly diminish patients' quality of life. Even when systemic treatment has alleviated the primary lung tumor in some patients, effective control over MPE remains challenging and impacts clinical outcomes. Therefore, it is crucial to implement measures for reducing or managing MPE while ensuring standardized treatment for lung cancer. In recent years, significant advancements have been made in diagnosing and treating lung cancer complicated by MPE through extensive basic and clinical research. Based on existing evidence and China's clinical practice experience, relevant experts from the China Association of Health Promotion and Education and Cancer Rehabilitation and Palliative Treatment Professional Committee of China Anti-Cancer Association (CRPC) have summarized key aspects related to diagnosis and treatment consensus opinions for lung cancer complicated by MPE. This aims to establish standardized procedures that will serve as a reference for doctors' clinical practice.

Malignant pleural effusion: current understanding and therapeutic approach.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

Assessing Factors That May Impact Physician-based Decisions for Placing Indwelling Pleural Catheters.

INTRODUCTION: Malignant pleural effusion is a common finding in patients with advanced cancer and is a frequent cause of dyspnea. Current guidelines indicate thoracentesis for symptomatic patients, while indwelling pleural catheters (IPC) are recommended for patients who develop pleural fluid re-accumulation. IPC maintenance, however, requires a significant level of financial and social support. This study aims to analyze potential influencing factors that may play a role in the decision for placing IPCs in patients with recurrent malignant pleural effusions. METHODS: This study retrospectively collected baseline sociodemographic and laboratory data in patients who underwent thoracentesis for malignant pleural effusion from August 2016 to October 2021, and selected patients who presented with re-accumulation of pleural fluid within 30 days or had a pulmonary physician's note documenting that IPC is a potential management option. Of these selected patients (IPC candidates), we stratified patients who underwent IPC placement and those who did not, and performed statistical analysis between these 2 groups. RESULTS: One hundred seventy-six patients who underwent thoracentesis were regarded as IPC candidates. Almost all baseline sociodemographic characteristics, including ethnicity ( P =0.637), sex ( P =0.655), and marital status ( P =0.773) were similar between the 2 groups, but significantly higher ECOG scores ( P =0.049) were noted in the IPC group. No statistically significant differences were noted in age, body mass index, platelet, PTT, international normalized ratio, creatinine, white blood cell, red blood cells, fluid protein, or fluid lactate dehydrogenase. Fluid albumin ( P =0.057) and serum neutrophil:lymphocyte ratio ( P =0.003) were significantly higher in patients without IPC placement. CONCLUSION: This study did not recognize any baseline sociodemographic factors that may contribute to the decision to place IPCs.

The impact of outpatient versus inpatient management on health-related quality of life outcomes for patients with malignant pleural effusion: the OPTIMUM randomised clinical trial.

BACKGROUND: The principal aim of malignant pleural effusion (MPE) management is to improve health-related quality of life (HRQoL) and symptoms. METHODS: In this open-label randomised controlled trial, patients with symptomatic MPE were randomly assigned to either indwelling pleural catheter (IPC) insertion with the option of talc pleurodesis or chest drain and talc pleurodesis. The primary end-point was global health status, measured with the 30-item European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) at 30 days post-intervention. 142 participants were enrolled from July 2015 to December 2019. RESULTS: Of participants randomly assigned to the IPC (n=70) and chest drain (n=72) groups, primary outcome data were available in 58 and 56 patients, respectively. Global health status improved in both groups at day 30 compared with baseline: IPC (mean difference 13.11; p=0.001) and chest drain (mean difference 10.11; p=0.001). However, there was no significant between-group difference at day 30 (mean intergroup difference in baseline-adjusted global health status 2.06, 95% CI -5.86-9.99; p=0.61), day 60 or day 90. No significant differences were identified between groups in breathlessness and chest pain scores. All chest drain arm patients were admitted (median length of stay 4 days); seven patients in the IPC arm required intervention-related hospitalisation. CONCLUSIONS: While HRQoL significantly improved in both groups, there were no differences in patient-reported global health status at 30 days. The outpatient pathway using an IPC was not superior to inpatient treatment with a chest drain.

[Chinese expert consensus on treatment of malignant pleural effusion (2023 Edition)].

Malignant pleural effusion (MPE) is a pleural effusion that is caused by a malignant tumor originating in the pleura or by a metastatic malignant tumor from another site that has invaded the pleura. MPE is associated with poor prognosis. Members of the Pleural and Mediastinal Diseases Working Group (preparatory) of Chinese Thoracic Society and some external experts selected clinical issues related to the management of MPE and conducted rigorous evidence retrieval and evaluation. After several meetings and revisions of the manuscript, recommendations were made. This consensus applies to patients aged≥18 years old with MPE caused by various malignancies except for pleural mesothelioma. It included four chapters: pathogenesis of MPE, prognostic evaluation of MPE, local thoracic treatment, and systemic anticancer therapy for MPE.The main recommendations of this consensus are as follows:1. Prognosis evaluation of MPE was valuable in formulating treatment options. It is suggested to comprehensively evaluate the patient's prognosis by combining the patient's performance status, tumor type, and laboratory examination.2. It is recommended that in patients with symptomatic MPE, therapeutic thoracentesis could be used as the initial therapeutic option. Evaluate whether the lung is expandable after thoracentesis and drainage, and then develop a therapeutic regimen.3. In patients with MPE and known expandable or nonexpandable lung, an indwelling pleural catheter (IPC) is recommended as a first-line pleural management. Daily IPC drainages are recommended. In patients with MPE and expandable lung, talc pleurodesis by talc poudrage or talc slurry is recommended if the drug is accessible. Other pleurodesis agents include povidone iodine, bleomycin, and doxycycline.4. After drainage, it is suggested to consider the option of intrapleural use of recombinant human endostatin or bevacizumab alone or in combination with intrapleural chemotherapy. Intrapleural intervention including electrocautery, argon knife, cryotherapy, laser and radiofrequency ablation, is recommended for use in patients who have undergone rigorous evaluation in eligible hospitals. The use of intrapleural urokinase or streptokinase via pleural catheter is recommended for patients with symptomatic MPE and loculated effusion.5. For patients with good performance status and metastatic malignancies, systemic anti-cancer treatment is recommended as standard of care.

Malignant pleural effusion due to angiosarcoma: A rare entity.

ABSTRACT: Angiosarcoma is a rare and aggressive vascular malignancy that typically originates in the skin or soft tissue of the body. It is known to have a propensity for metastasis to the lung parenchyma in the form of pulmonary nodules and cavitary lesions; however, a less commonly described entity is in the form of a malignant pleural effusion. Management of a malignant pleural effusion due to angiosarcoma presents a unique challenge. This article describes the challenges faced during one patient's diagnostic and treatment course, and the anticipated future complications of his aggressive disease.

Ex vivo pleural effusion cultures to study chimeric antigen receptor T cell cytotoxicity in an immunocompetent environment.

Current in vitro and in vivo assays used to study immunotherapeutic interventions lack human immune components that mimic the tumor microenvironment to investigate drug potency and limitations of efficacy. Herein, we describe an ex vivo pleural effusion culture (ePEC) assay, using malignant pleural-effusion-derived soluble and cellular factors that differentially affected the cytotoxicity of chimeric antigen receptor (CAR) T cells. Following identification of CAR T cell-suppressive factors, blocking of individual factors reveals their contribution to compromising T cell efficacy. ePEC is a human component assay that can be utilized for developing next-generation cell and antibody therapies that counteract immunosuppression.

Reducing hospital admissions in patients with malignant pleural effusion: a quality improvement study.

BACKGROUND: Malignant pleural effusions (MPE) can cause severe dyspnoea leading to greater than 125 000 hospitalisations per year and cost greater than US$5 billion per year in the USA. Timely insertion of tunnelled pleural catheters (TPCs) is associated with fewer inpatient days and emergency department visits. We conducted a quality improvement study to reduce hospital admissions of patients with MPE. METHODS: Key stakeholders were surveyed, including thoracic and breast oncology teams, general pulmonary and interventional pulmonology (IP) to help identify the underlying causes and solutions. Our preintervention group consisted of 51 patients who underwent TPC placement by our IP service. In our first intervention, we reviewed referrals for MPE with the scheduling team and triaged them based on urgency. In the second intervention, we added a follow-up phone call 1 week after the initial thoracentesis performed by IP to assess for the recurrence of symptoms. RESULTS: Demographic and clinical characteristics were summarised across the three groups. We evaluated the rate ratio (RR) of admissions in the intervention groups with the multivariable Poisson regression and adjusted for race, gender and cancer. Compared with the preintervention group, intervention I showed trends towards a 41% lower hospital admission rate (RR 0.59 (0.33-1.07), p=0.11). Compared with the preintervention group, intervention II showed trends towards a 40% lower hospital admission rate (RR 0.6 (0.36-0.99), p=0.07). The results did not reach statistical significance. Exploratory comparisons in readmission rates between interventions I and II showed no difference (RR 0.89 (0.43-1.79), p=0.75). CONCLUSIONS: Both interventions showed trends toward fewer hospital readmissions although they were not statistically significant. Larger-size prospective studies would be needed to demonstrate the continued effectiveness of these interventions.

Efficacy and Safety of Indwelling Catheter for Malignant Pleural Effusions Related to Timing of Cancer Therapy: A Systematic Review

Introduction: To compare the efficacy and safety of indwelling pleural catheters (IPC) in relation with the timing of systemic cancer therapy (SCT) (i.e., before, during, or after SCT) in patients with malignant pleural effusion (MPE). Methods: Systematic review of randomized controlled trials (RCT), quasi-controlled trials, prospective and retrospective cohorts, and case series of over 20 patients, in which the timing of IPC insertion in relation to that of SCT was provided. Medline (via PubMed), Embase, and Cochrane Library were systematically searched from inception to January 2023. The risk of bias was assessed using the Cochrane Risk of Bias (ROB) tool for RCTs and the ROB in non-randomized studies of interventions (ROBINS-I) for non-randomized designs. Results: Ten studies (n=2907 patients; 3066 IPCs) were included. Using SCT while the IPC was in situ decreased overall mortality, increased survival time, and improved quality-adjusted survival. Timing of SCT had no effect on the risk of IPC-related infections (2.85% overall), even in immunocompromised patients with moderate or severe neutropenia (relative risk 0.98 [95%CI: 0.93–1.03] for patients treated with the combination of IPC and SCT). The inconsistency of the results or the lack of analysis of all outcome measures in relation to the SCT/IPC timing precluded drawing solid conclusions about time to IPC removal or need of re-interventions. Conclusions: Based on observational evidence, the efficacy and safety of IPC for MPE does not seem to vary depending on the IPC insertion timing (before, during, or after SCT). The data most likely support early IPC insertion. (AU)

Tract seeding in indwelling pleural catheter placement for the drainage of malignant pleural effusions: Incidence and related clinical and imaging factors.

BACKGROUND: The incidence of tract seeding after the placement of indwelling pleural catheter (IPC) for malignant pleural effusion drainage has been variable in the literature. RESEARCH QUESTION: To evaluate the incidence of IPC-related cancer tract seeding and find out related demographic, clinical or imaging factors to the tract seeding. STUDY DESIGN AND METHODS: This retrospective study included 124 consecutive patients seen between January 2011 and December 2021 who underwent IPC placement for malignant pleural effusion drainage. Chest radiographs before IPC placement and serial chest CT studies were obtained. One patient was diagnosed pathologically, and the other patients were diagnosed as tract seeding radiologically. The incidence of and related factors to tract seeding were assessed by reviewing medical records and imaging studies. RESULTS: The incidence of IPC tract seeding was 21.7% (27 of 124 malignant effusions). Of 27 patients, 15 had primary lung cancer and remaining 12 had extra-thoracic malignancy. Adenocarcinoma (19 of 27, 70.3%) either from the lung (N = 12) or extra-thoracic malignancy (N = 7) was the most common cell type. Mean time elapsed until tract seeding occurrence after IPC placement was 96 days (ranges; 28-306 days). The survival in seeding group after IPC placement was 185 days (ranges, 32-457 days). On odd ratio analysis, the presence of mediastinal pleural thickening (OR [95% CI]; 9.79 (2.67-35.84), p = 0.001) was significantly related to the occurrence of tract seeding. Neither tumor volume within pleural space (p = 0.168), duration of IPC indwelling (p = 0.142), days of survival after IPC placement (p = 0.26), nor pleural effusion amount (p = 0.481) was related to the tract seeding. INTERPRETATION: IPC tract seeding is seen in 27 (21.7%) of 124 malignant pleural effusion patients, particularly with adenocarcinoma cytology. CT features of mediastinal pleural thickening are related to the occurrence of tract seeding.

Efficacy and Safety of Indwelling Catheter for Malignant Pleural Effusions Related to Timing of Cancer Therapy: A Systematic Review.

INTRODUCTION: To compare the efficacy and safety of indwelling pleural catheters (IPC) in relation with the timing of systemic cancer therapy (SCT) (i.e., before, during, or after SCT) in patients with malignant pleural effusion (MPE). METHODS: Systematic review of randomized controlled trials (RCT), quasi-controlled trials, prospective and retrospective cohorts, and case series of over 20 patients, in which the timing of IPC insertion in relation to that of SCT was provided. Medline (via PubMed), Embase, and Cochrane Library were systematically searched from inception to January 2023. The risk of bias was assessed using the Cochrane Risk of Bias (ROB) tool for RCTs and the ROB in non-randomized studies of interventions (ROBINS-I) for non-randomized designs. RESULTS: Ten studies (n=2907 patients; 3066 IPCs) were included. Using SCT while the IPC was in situ decreased overall mortality, increased survival time, and improved quality-adjusted survival. Timing of SCT had no effect on the risk of IPC-related infections (2.85% overall), even in immunocompromised patients with moderate or severe neutropenia (relative risk 0.98 [95%CI: 0.93-1.03] for patients treated with the combination of IPC and SCT). The inconsistency of the results or the lack of analysis of all outcome measures in relation to the SCT/IPC timing precluded drawing solid conclusions about time to IPC removal or need of re-interventions. CONCLUSIONS: Based on observational evidence, the efficacy and safety of IPC for MPE does not seem to vary depending on the IPC insertion timing (before, during, or after SCT). The data most likely support early IPC insertion.