Yuhua Zhao
Limeng Yu
Lili Wang
Qiming Wang
Yufeng Wu- Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China
Malignant pleural effusion (MPE) is a common complication in the late stage of malignant tumors. The appearance of MPE indicates that the primary tumor has spread to the pleura or progressed to an advanced stage. The survival time of the patients will be significantly shortened, with a median survival of only a few months. There are a variety of traditional treatments, and their advantages and disadvantages are relatively clear. There are still many problems that cannot be solved by traditional methods in clinical work. The most common one is intrapleural perfusion therapy with chemotherapy drugs, but it has a large side effect of chemotherapy. At present, with the development of medical technology, there are a variety of treatment methods, and many innovative, significant and valuable treatment methods have emerged, which also bring hope for the treatment of refractory and recurrent MPE patients. Several clinical trials had confirmed that drug-carrying microparticles has less adverse reactions and obvious curative effect. However, there is still a long way to go to completely control and cure MPE, and the organic combination of clinical work and scientific research results is needed to bring dawn to refractory MPE patients.
1 Introduction
With advances in medical technology and in-depth research on the pathogenesis of malignant pleural effusion (MPE), innovative drugs and treatment strategies have been developed. MPE treatment has made many achievements. However, recalcitrant or recurrent MPE currently does not have effective treatment options. Therefore, the treatment of MPE is still a difficult clinical problem, and the current status and progress of MPE treatment are reviewed as follows.
Lung cancer accounts for 18.0% of all cancer deaths according to the latest 2020 Global Cancer Data Report from the World Health Organization’s International Agency for Research on Cancer (IARC) (1). The data show that approximately 50% of malignant tumors can present with malignant pleural effusion (MPE). MPE is more common in lung cancer, breast cancer and lymphoma, with rates as high as 75%, and lung cancer has the highest rate (2). MPE is one of the common complications of advanced malignant tumors, with a median survival of only 3-12 months (3–5).
Pleural fluid cytology is the easiest way to diagnose MPE and the gold standard for diagnosis. However, its sensitivity is limited in cases with few cancer cells, and the rate of positive detection (40%~87%) is relatively low (6); the rate of positive detection can be improved by testing pleural fluid samples multiple times or directly using pleural biopsy to detect cancer cells. For patients with clear primary tumors and asymptomatic MPE, no therapeutic intervention can be performed for the effusion itself (7–10). Once the amount of pleural effusion increases or if substantial pleural effusion is generated within a short period of time, it will cause symptoms such as cough, chest tightness, dyspnea and weakness, which will seriously affect the quality of life of patients. For MPE patients with obvious clinical symptoms, the primary aim of treatment is to relieve dyspnea, chest tightness and other symptoms (11, 12). The presence of MPE indicates that the primary tumor has spread to the pleura or has progressed to an advanced stage, and the survival of patients is significantly shortened. Once MPE is diagnosed in patients with tumors, it should be actively treated; otherwise, the accumulation of fluid will cause pulmonary atelectasis or recurrent lung infections and even threaten the life of the patient (13). With advances in medical technology and in-depth research on the pathogenesis of MPE, innovative drugs and treatment strategies have been developed. For example, the microparticles released by autologous tumor cells can be used to encapsulate chemotherapeutic drugs to achieve antitumor effects through two mechanisms: direct killing of tumor cells and activation of the autoimmune system (14, 15). However, recalcitrant or recurrent MPE does not currently have effective treatment options. Therefore, the treatment of MPE is still a difficult clinical problem, and the current status and progress of MPE treatment are reviewed as follows.
2 Routine clinical treatment modalities
Conventional clinical treatment mainly includes simple chest drainage, pleural fixation, thoracic thermal perfusion and intrathoracic drug infusion. Different treatment options have different indications and contraindications and different advantages and disadvantages, and clinicians usually conduct a comprehensive assessment to choose the most suitable treatment option for each patient.
2.1 Simple thoracentesis for fluid aspiration and tube placement for drainage
In patients with malignant tumors complicated with MPE, the tumor cells have spread or metastasized to the pleura at an advanced stage, and these patients have missed the opportunity for surgical treatment; in this case, internal palliative treatment is most commonly adopted in the clinic (16, 17). The primary task is to relieve respiratory distress and pain, and many clinicians will prioritize simple thoracentesis and aspiration or tube drainage. Thoracentesis alone can quickly relieve the symptoms of dyspnea, but it is a temporary treatment measure. The reason is that the intrathoracic pressure decreases significantly within a short period of time after fluid extraction, which in turn leads to fluid reunion, a faster increase in accumulated pleural fluid, and a higher recurrence rate (18). Repeated drainage of a large amount of pleural fluid can lead to hypoproteinemia, anemia, weakness, electrolyte disorders and other systemic symptoms (19, 20). In severe cases, circulatory collapse and death may occur. Therefore, simple chest puncture and drainage cannot solve the problem of recurrent massive pleural fluid in MPE and can actually accelerate the deterioration induced by the disease and lead to failure of primary tumor systemic treatment or poor efficacy.
2.2 Pleural fixation
Intrathoracic infusion of sclerosing agents, also known as pleural fixation, involves the use of sclerosing agents to chemically irritate and cause pleuritis, which causes adhesional atresia of the visceral and mural pleura and eventually leads to loss of the pleural space, causing a reduction in pleural fluid. The American Thoracic Society (ATS), in its latest edition of its MPE treatment guidelines issued in 2018 (7), recommends placement drainage or chemical pleural fixation as the preferred treatment option to relieve dyspnea in patients with symptomatic MPE without combined pulmonary atelectasis who have never been treated for MPE. The previous guidelines only recommended drainage as an option for patients with MPE combined with pulmonary atelectasis (10). The application of sclerosing agents under video-assisted thoracic surgery (VATS) is a common clinical method. And VATS talc poudrage is recommended for pleurodesis in patients with good performance status. The most commonly used drug in clinical pleural fixation is talcum powder (21–23). A randomized controlled trial has robustly demonstrated that there is no additional clinical effectiveness or cost-effectiveness benefit between talcum powder by thoracoscopy and talc slurry intercostal drainage for MPE patients (24). Therefore, talcum slurry and talcum powder have no difference in efficacy. It has the advantages of low cost and a high success rate compared with other sclerosing agents. The common side effects of talcum powder pleural fixation are fever and chest pain, which can be relieved in most patients but can cause serious adverse reactions in some patients, such as pulmonary edema, acute respiratory distress syndrome (ARDS), and acute respiratory failure (8, 25). In some cases, death can occur. Therefore, the application of talcum powder for pleural fixation for MPE has certain risks.
2.3 Thoracic thermal perfusion therapy
Thoracic thermal perfusion therapy takes advantage of the different tolerances of tumor cells and normal cells to different temperatures (26). Therefore, the key to successful thoracic thermal perfusion is to control the intrathoracic temperature, and conversely, if the temperature is not well controlled, the normal cells of the body will suffer much irreversible damage. Clinically, the intrathoracic temperature is usually maintained at approximately 43°C, which can damage and kill tumor cells without much interference with and impact normal cell function (27). In addition, the increase in intrathoracic temperature caused by thoracic heat perfusion can significantly dilate blood vessels, promote the absorption of chemotherapeutic drugs, significantly increase the concentration of drugs in the thoracic cavity, and increase the ability of drugs to kill tumor cells. Therefore, compared with intratoracic perfusion treatment with chemotherapeutic drugs alone, intratoracic thermal perfusion combined with chemotherapeutic drugs shows more advantages (28–30). On the one hand, chemotherapeutic drugs can directly kill tumor cells, resulting in a reduction in pleural fluid production, and on the other hand, the increase in temperature can expand the pleural blood vessels and promote the absorption of chemotherapeutic drugs by tumor cells, which greatly improves the drug utilization rate and chemotherapeutic drug efficacy. Within 24 h after the end of perfusion, almost all patients showed profuse sweating, hot flashes, elevated body temperature and increased heart rate, which were relieved by symptomatic treatment. However, thoracic thermal perfusion chemotherapy is generally not recommended for patients with a very poor systemic condition or those who are unsuitable for thoracic thermal perfusion, such as patients with obvious liver and kidney failure, severe cardiovascular or cerebrovascular diseases, poor healing of anastomosis after surgery, and extensive adhesions in the thoracic cavity.
2.4 Intrapleural perfusion therapy
The most rapidly advancing and preferred treatment option is intrapleural perfusion therapy (IPT), which is the most widely used strategy in clinical practice due to its obvious efficacy, simplicity and lack of serious adverse effects and is suitable for most patients with MPE (31). It can prolong the survival time and improve the quality of life for most MPE patients. Currently, there are many kinds of drugs used for IPT treatment, including chemotherapeutic drugs, immunomodulators, and Chinese patent medicines. Many innovative drugs are in clinical trials or in the development stage, giving new hope to patients with recalcitrant or recurrent MPE.
2.4.1 Chemotherapy drugs
The chemotherapeutic drugs commonly used in clinical practice alongside thoracic infusion mainly include cisplatin, carboplatin, and bleomycin. Cisplatin, as a first-generation platinum drug, has strong antitumor activity and is thus more widely used in thoracic perfusion (32). Cisplatin can not only directly induce a local antitumor effect but also stimulate the pleura to cause pleurisy and pleural adhesions and cause chest occlusion; in addition, cisplatin can also be absorbed into blood circulation through the blood vessels on the pleura, which can inhibit primary foci and metastases and reduce pleural fluid in many ways (33). Moreover, this mode of drug delivery greatly improves the concentration of drugs in the chest cavity, reduces the toxic side effects caused by systemic chemotherapy, and is tolerated by most patients with mild adverse effects, making it the preferred treatment for MPE. Compared with the second-generation platinum drug carboplatin, the adverse effects of cisplatin mainly include gastrointestinal reactions and nephrotoxicity, with less bone marrow suppression. Typically, only a single chemotherapeutic agent is used clinically, but some investigators have combined multiple chemotherapeutic agents to enhance treatment efficacy by taking advantage of the synergistic effect of various drugs (34, 35). However, the toxic side effects of chemotherapeutic drugs, especially for many patients with advanced tumors who cannot tolerate them, for those who develop drug resistance after multiple doses, or for those with recalcitrant or recurrent MPE with poor response, can lead to the failure of local MPE treatment. Overall, chemotherapeutic agents administered via transthoracic infusion are effective, but resistance may occur after multiple doses, and there is limited overall efficacy and a high rate of pleural fluid recurrence.
2.4.2 Biological response modifiers
The main mechanism of action of biological response modifiers is to stimulate inflammation in the plasma membrane, causing fibrosis of mesothelial cells and adhesions to occlude the pleural space, leading to a decrease in pleural fluid production. The most commonly used clinical biological response modifier is the Nocardia rubra cell wall skeleton (N-CWS). On the one hand, it can inhibit tumor cells and enhance the activity of macrophages, T cells and natural killer (NK) cells (36, 37). On the other hand, it can induce interferon, lymphokine-activated killer cell and tumor necrosis factor production and anticancer effects. Therefore, N-CWS has good clinical efficacy in patients with lung cancer with MPE, can significantly improve the immune function and survival rate of patients, and has mild toxic side effects, so it is worthy of wide clinical application. However, it should be used with caution in patients with MPE who already have high fever and allergic reactions, as it may aggravate existing symptoms and cause deterioration of the patient’s systemic condition.
3 Latest treatment advances
With the continuous development of tumor treatments and advances in antitumor drugs, the MPE treatment paradigm is being constantly modified, and an increasing number of new drugs and technologies are being applied in the clinic, such as antiangiogenic drugs, drug-carrying microparticles, and pleural bladder pumps. A large number of preliminary clinical studies have shown extraordinary efficacy and the ability to overcome some of the shortcomings of traditional treatment modalities and greatly reduce the toxic side effects caused by treatment, bringing new treatment strategies and modalities for MPE, especially for patients with MPE in whom existing treatments have been ineffective, for those with relapsed MPE, and for those who are resistant to traditional treatment methods. For patients with MPE who have relapsed or failed various treatments, indwelling pleural catheters are now clinically available.
3.1 Anti-angiogenic drugs
The generation, invasion and metastasis of malignant tumors and tumor angiogenesis are closely related (38). Therefore, inhibition of tumor neovascularization has become a new strategy for tumor therapy. The main antiangiogenic drugs are bevacizumab and recombinant human vascular endothelial growth factor (VEGF) inhibitors, both of which can be administered by transthoracic perfusion. Both of these antiangiogenic drugs can be combined with platinum agents, and this combination is more effective than platinum agents or antiangiogenic drugs alone, producing greater increases in the inhibition of tumor cells and better reducing the formation of effusion.
3.1.1 Bevacizumab
VEGF is an important proangiogenic mediator, and VEGF/VEGFR-2 is an important signaling pathway for angiogenesis (39–44). The VEGF/VEGFR-2 axis mediates vascular endothelial cell proliferation and neovascularization (45), which leads to the production of pleural fluid (46). Bevacizumab, a human recombinant monoclonal antibody that mediates VEGF signaling, inhibits tumor angiogenesis, growth, and metastasis, reducing the generation and growth of blood vessels in the pleura and ultimately leading to a decrease in pleural fluid production. Tao et al. (47) retrospectively studied 21 patients with lung adenocarcinoma with MPE treated with bevacizumab combined with chemotherapy by intravenous infusion, and the MPE remission rate (RR) was 81.0%. The disease control rate (DCR) at 24 weeks was 89.5%, and 90.5% of patients experienced lung re-expansion after treatment. These results suggest that bevacizumab in combination with chemotherapy has significant efficacy and safety advantages for treating MPE in lung adenocarcinoma and is an option for patients with lung adenocarcinoma with MPE. The results of a study of patients with nonsquamous non-small-cell lung cancer with poorly controlled MPE after drainage tube placement or pleural fixation receiving bevacizumab in combination with chemotherapy showed a pleural effusion control rate (PECR, defined as the percentage of patients with no reaccumulation of MPE at 8 weeks) of 80%, pleural progression-free survival (PPFS) of 16.6 months, and overall survival (OS) of 19.6 months, and patients’ quality of life significantly improved (48).
Many clinical studies (49–52) have also tried to explore the efficacy and safety of intrathoracic injection of bevacizumab combined with platinum-based drugs in the treatment of MPE, and the results of the studies have shown that intrathoracic injection of bevacizumab combined with platinum-based chemotherapeutic drugs showed increased overall efficacy (the difference is statistically significant, P<0.05) compared with administration of platinum-based drugs alone; the RR of the bevacizumab combined with cisplatin group can be as high as 83.33%, significantly higher than the 50.00% of the cisplatin group. In addition, intrapleural injection of bevacizumab reduced the level of VEGF in pleural fluid, with milder, tolerable toxic effects. Single-agent anti-vascular therapy is not ideal (53), and the combination of bevacizumab with platinum drugs in the treatment of MPE significantly increases the therapeutic effect compared with monotherapy. A meta-analysis (54) pooled data from 71 patients with non-small-cell lung cancer with MPE and, for the first time, evaluated the therapeutic effect of intrathoracic injection of different doses of bevacizumab in patients with non-small-cell lung cancer with MPE. The efficacy of low-dose bevacizumab was not inferior to that of high-dose bevacizumab, and the use of low-dose bevacizumab significantly reduced the incidence of adverse events and toxic side effects, suggesting that intrathoracic injection of low-dose bevacizumab can be a suitable treatment for patients with non-small-cell lung cancer with MPE. Currently, there are no uniform standards for the administration, dosing and duration of bevacizumab treatment in patients with MPE, and there are many controversies regarding which specific regimen should be used for the treatment of MPE. Some investigators (55) believe that bevacizumab is effective whether administered intravenously or by thoracic infusion, but the evidence for the use of bevacizumab in the treatment of MPE remains flawed due to study design biases and the small number of subjects.
3.1.2 Recombinant human VEGF inhibitors
Researchers have found that recombinant human VEGF inhibitors can downregulate the expression of VEGF and receptors (56), block VEGF and VEGFR tyrosine phosphorylation, and induce MMP expression (57). A recombinant human VEGF inhibitor was found to inhibit the production of blood vessels and lymphatic vessels in animal models (58). In 2015, Wei et al. (59) found that recombinant human VEGF inhibitors could only inhibit the production of effusion but not cause apoptosis or inhibit tumor growth. However, in recent years, investigators (60, 61) have concluded that recombinant human VEGF inhibitors can also inhibit tumor cell proliferation and induce tumor cell apoptosis. The combination of recombinant human VEGF inhibitors with platinum-based drugs exerts a synergistic effect, and combined administration is better than administration of platinum-based drugs alone (34). Combined administration can improve the quality of life of patients. On the one hand, platinum drugs can directly act on tumor cells and interfere with tumor cell DNA replication and transcription, thus inducing tumor cell necrosis. On the other hand, recombinant human VEGF inhibitors can promote the immune response, improve the local tumor microenvironment (62, 63), promote normalization of tumor vascular function (64), more effectively promote the delivery of platinum drugs to the tumor tissue (65, 66), and more effectively kill tumor cells. In a study evaluating the clinical efficacy and safety of a recombinant human VEGF inhibitor combined with chemotherapy for MPE in lung adenocarcinoma, the treatment group was given chemotherapy and recombinant human VEGF inhibitor via intrathecal administration, and the control group patients were given the same chemotherapy as the treatment group. The efficacy rates were 81.82% and 64.52% in the treatment and control groups, respectively (statistically significant difference, P=0.027). The MPE control rates (DCRs) were 93.94% and 79.03%, respectively (statistically significant difference, P=0.013). Dyspnea symptoms were significantly improved in the treatment group, and side effects were not significantly different between the two groups (67).
3.2 Drug-carrying microparticles
Normally, cellular microparticles in the human body are used to store, transport and digest cellular products and wastes and are important carriers for the transport of various substances (68). Researchers have used autologous tumor cell-derived microparticles (ATMPs) as novel individualized drug carriers (69–73). In other studies, ATMPs have been used as novel individualized drug carriers to deliver chemotherapeutic drugs to tumor cells in a targeted manner (74–76). These drugs can not only directly interfere with the proliferation of tumor cells but also activate antitumor immunity (14, 77–79). In addition, ATMPs can be used to overcome the killing of normal cells by chemotherapeutic drugs and the resistance of tumor cells to chemotherapeutic drugs. The mechanism by which ATMPs encapsulating methotrexate (ATMPs-MTX) activate the neutrophil response as a treatment for MPE has been studied (80). ATMPs-MTX trigger neutrophil recruitment through activation of CXCL1 and CXCL2 released from macrophages (15, 81, 82). ATMPs also reverse drug resistance in cancer stem cells (CSCs). CSCs take up ATMPs-MTX better than do differentiated cancer cells, leading to CSC death (83). Guo et al. (84) demonstrated through mouse models and human experiments that ATMPs encapsulating chemotherapeutic drugs have almost no toxicity and have largely reduced toxic side effects compared with chemotherapeutic drugs in clinical applications. The ORR of 11 patients with advanced lung cancer with MPE treated with ATMPs-MTX was 90.91%, and the median survival time (MST) was 240 days, demonstrating excellent efficacy and only minor side effects. The low level of toxic side effects induced by ATMPs encapsulating chemotherapeutic drugs makes them a promising option for MPE treatment. Currently, many hospitals have used drug-carrying microparticles for MPE treatment. Although their efficacy and safety have been clinically validated, more subjects and clinical studies are needed to further evaluate their efficacy. There are still some concerns regarding the use of drug-carrying microparticles in oncology and MPE treatment. Primarily, the safety of microparticles needs to be determined; for example, ATMPs may contain oncogenic factors that may contribute to tumor progression (85).
3.3 Pleural bladder pump
Astoul et al. (86) performed an in-depth study of a peritoneal bladder pump for the treatment of ascites. The scholars first proposed and designed the pleural bladder pump for the treatment of MPE and named it the pleurapump system, whose specific mechanism is to drive the transfer of accumulated fluid from the pleural cavity to the bladder, from where it can drain from the body via the urinary system. The pump has pressure and position sensors on it to regulate the flow rate and drainage of the effusion and to monitor and record the amount of pleural fluid drained, which is very useful. Previous research on the peritoneal bladder pump (Alfapump system) has yielded some results (87, 88). These successes have inspired researchers to study pleural effusion. However, Astoul et al. conducted only 2 clinical trials, and both subjects experienced varying degrees of dyspnea after implantation of the pleural bladder pump. The investigators suspect that these outcomes may be related to pump dysfunction due to catheter obstruction (86). Studies of the pleurapump system for MPE treatment are still in the exploratory phase, and more subjects and clinical studies are needed to explore the efficacy and safety of this system in the future.
3.4 Indwelling pleural catheter
The currently recommended approaches for recurrent symptomatic MPE are indwelling pleural catheter (IPC) placement and pleural fixation, but IPC placement is significantly superior to repeat thoracentesis or tube placement for drainage and has been shown to be a powerful palliative treatment for patients with recurrent or treatment-resistant MPE. IPCs can be inserted and tunneled through the skin into the pleural cavity, allowing intermittent drainage and promoting pleural fixation. IPC placement is simple to perform and can usually be performed on an outpatient basis (89). IPCs are an effective means of controlling recurrent MPE, especially for patients with pulmonary atrophy and atelectasis who wish to have a shortened hospital stay (90). Thomas et al. (91) conducted a multicenter, randomized controlled clinical trial that included 144 patients with MPE. The researchers showed a reduction in the number of hospital days after IPC treatment compared with after talc pleural fixation, and there was no statistically significant difference in efficacy, in line with the findings of Davies, Ost et al. (92, 93) The results of the study were consistent. Data from a multicenter, randomized, open-label clinical trial suggest that IPCs are more effective in facilitating spontaneous pleural fixation and may improve quality of life (94). Significant improvement of dyspnea symptoms and fewer complications after IPC treatment were seen (95). Compared to talc pleural fixation, IPC placement has a very high safety profile (96): the incidence of pleural infection is <5% (patients usually respond to antibiotic therapy, and catheter removal is usually not necessary); prolonged, intermittent drainage of exudative pleural effusions or celiac disease may cause significant protein loss, leading to systemic malnutrition; and fibrin clots in the catheter lumen can lead to obstruction. In 2018, Bhatnagar et al. (97) studied the treatment of MPE by outpatient IPC placement combined with talcum powder and found that the odds of pleural fusion were significantly higher than those associated with IPC placement alone; in addition, serious adverse effects were rare and generally well tolerated by patients.
4 Summary and outlook
In summary, MPE is a common complication of advanced malignant tumors, and its appearance often indicates poor prognosis and short survival, which seriously affects patient quality of life. Furthermore, poorly controlled MPE can seriously affect the primary tumor systemic treatment plan, so MPE treatment is especially important in tumor treatment. At present, MPE is mainly treated medically, and intrathoracic infusion is the main strategy. With the continuous development of intrathoracic infusion drugs, many kinds of drugs are available, including chemotherapeutic drugs, immunomodulators, traditional Chinese medicines, antiangiogenic drugs and drug-carrying microparticles. MPE patients have benefited greatly from these novel therapies, which have shown good efficacy in clinical application, and clinical symptoms such as dyspnea and wheezing have been greatly improved. Currently, there are many means of MPE treatment, but there is no standard treatment protocol, especially for patients with recalcitrant or relapsed MPE, who suffer from limited overall treatment efficacy, which seriously affects the OS of patients. Therefore, although good results in the treatment of MPE have been achieved, especially via the use of highly beneficial antiangiogenic therapies and immunotherapies, the treatment of MPE, especially recalcitrant or relapsed MPE, is still a clinical challenge, and many issues remain to be solved in the future. Therefore, it is important to explore the pathogenesis of MPE and combine treatment modalities and new therapeutic approaches to improve the quality of life and prolong the survival of MPE patients.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Acknowledgments
The authors would like to thank Dr. Qiming Wang and Dr. Yufeng Wu for helpful and stimulating discussions.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
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References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin (2021) 71(3):209–49. doi: 10.3322/caac.21660
2. Koegelenberg CFN, Shaw JA, Irusen EM, Lee YCG. Contemporary best practice in the management of malignant pleural effusion. Ther Adv Respir disease. (2018) 12:1753466618785098. doi: 10.1177/1753466618785098
3. Bibby AC, Dorn P, Psallidas I, Porcel JM, Janssen J, Froudarakis M, et al. ERS/EACTS statement on the management of malignant pleural effusions. Eur Respir J (2018) 52(1):1800349. doi: 10.1183/13993003.00349-2018
4. Clive AO, Kahan BC, Hooper CE, Bhatnagar R, Morley AJ, Zahan-Evans N, et al. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score. Thorax. (2014) 69(12):1098–104. doi: 10.1136/thoraxjnl-2014-205285
5. Asciak R, Rahman NM. Malignant pleural effusion: From diagnostics to therapeutics. Clinics chest Med (2018) 39(1):181–93. doi: 10.1016/j.ccm.2017.11.004
6. Thomas JM, Musani AI. Malignant pleural effusions: a review. Clinics chest Med (2013) 34(3):459–71. doi: 10.1016/j.ccm.2013.05.004
7. Feller-Kopman DJ, Reddy CB, DeCamp MM, Diekemper RL, Gould MK, Henry T, et al. Management of malignant pleural effusions. an official ATS/STS/STR clinical practice guideline. Am J Respir Crit Care Med (2018) 198(7):839–49. doi: 10.1164/rccm.201807-1415ST
8. Fitzgerald DB, Koegelenberg CFN, Yasufuku K, Lee YCG. Surgical and non-surgical management of malignant pleural effusions. Expert Rev Respir Med (2018) 12(1):15–26. doi: 10.1080/17476348.2018.1398085
9. Shafiq M, Feller-Kopman D. Management of malignant pleural effusions. Clin Chest Med (2020) 41(2):259–67. doi: 10.1016/j.ccm.2020.02.009
10. Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ. Management of a malignant pleural effusion: British thoracic society pleural disease guideline 2010. Thorax. (2010) 65 Suppl 2:ii32–40. doi: 10.1136/thx.2010.136994
11. Porcel JM, Gasol A, Bielsa S, Civit C, Light RW, Salud A. Clinical features and survival of lung cancer patients with pleural effusions. Respirology (Carlton Vic). (2015) 20(4):654–9. doi: 10.1111/resp.12496
12. Azzopardi M, Porcel JM, Koegelenberg CF, Lee YC, Fysh ET. Current controversies in the management of malignant pleural effusions. Semin Respir Crit Care Med (2014) 35(6):723–31. doi: 10.1055/s-0034-1395795
13. Hawkins P, Doyle A, Gavin L, Fabre A, Murphy DJ, Dunican E, et al. A 33-Year-Old man with dyspnea, chest pain, and a massive pleural effusion. Chest. (2021) 159(1):e39–43. doi: 10.1016/j.chest.2020.08.2102
14. Ma J, Zhang H, Tang K, Huang B. Tumor-derived microparticles in tumor immunology and immunotherapy. Eur J Immunol (2020) 50(11):1653–62. doi: 10.1002/eji.202048548
15. Xu P, Tang K, Ma J, Zhang H, Wang D, Zhu L, et al. Chemotherapeutic tumor microparticles elicit a neutrophil response targeting malignant pleural effusions. Cancer Immunol Res (2020) 8(9):1193–205. doi: 10.1158/2326-6066.CIR-19-0789
16. Pilling JE, Dusmet ME, Ladas G, Goldstraw P. Prognostic factors for survival after surgical palliation of malignant pleural effusion. J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. (2010) 5(10):1544–50. doi: 10.1097/JTO.0b013e3181e95cb8
17. Fortin M, Tremblay A. Pleural controversies: indwelling pleural catheter vs. pleurodesis malignant pleural effusions. J Thorac disease. (2015) 7(6):1052–7. doi: 10.3978/j.issn.2072-1439.2015.01.51
18. Olden AM, Holloway R. Treatment of malignant pleural effusion: PleuRx catheter or talc pleurodesis? a cost-effectiveness analysis. J palliative Med (2010) 13(1):59–65. doi: 10.1089/jpm.2009.0220
19. Chen CD, Wang CL, Yu CJ, Chien KY, Chen YT, Chen MC, et al. Targeted proteomics pipeline reveals potential biomarkers for the diagnosis of metastatic lung cancer in pleural effusion. J Proteome Res (2014) 13(6):2818–29. doi: 10.1021/pr4012377
20. Cavazzoni E, Bugiantella W, Graziosi L, Franceschini MS, Donini A. Malignant ascites: pathophysiology and treatment. Int J Clin Oncol (2013) 18(1):1–9. doi: 10.1007/s10147-012-0396-6
21. Xia H, Wang XJ, Zhou Q, Shi HZ, Tong ZH. Efficacy and safety of talc pleurodesis for malignant pleural effusion: a meta-analysis. PLoS One (2014) 9(1):e87060. doi: 10.1371/journal.pone.0087060
22. Clive AO, Jones HE, Bhatnagar R, Preston NJ, Maskell N. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database systematic Rev (2016) 2016(5):Cd010529. doi: 10.1002/14651858.CD010529.pub2
23. Lee YC, Baumann MH, Maskell NA, Waterer GW, Eaton TE, Davies RJ, et al. Pleurodesis practice for malignant pleural effusions in five English-speaking countries: survey of pulmonologists. Chest. (2003) 124(6):2229–38. doi: 10.1378/chest.124.6.2229
24. Bhatnagar R, Luengo-Fernandez R, Kahan BC, Rahman NM, Miller RF, Maskell NA. Thoracoscopy and talc poudrage compared with intercostal drainage and talc slurry infusion to manage malignant pleural effusion: the TAPPS RCT. Health Technol Assess. (2020) 24(26):1–90. doi: 10.3310/hta24260
25. Light RW. Counterpoint: should thoracoscopic talc pleurodesis be the first choice management for malignant pleural effusion? no. Chest (2012) 142(1):17–9. doi: 10.1378/chest.12-1087
26. Li Z, Kawashita M, Kudo TA, Kanetaka H. Sol-gel synthesis, characterization, and in vitro compatibility of iron nanoparticle-encapsulating silica microspheres for hyperthermia in cancer therapy. J materials Sci Materials Med (2012) 23(10):2461–9. doi: 10.1007/s10856-012-4735-y
27. Li J, Yao H, Lei Y, Ye Y. Establishment of a human intrapleural hyperthermic perfusion model and analysis of pleural malignancy treatment depth. Respir Med (2018) 138:144–9. doi: 10.1016/j.rmed.2018.04.004
28. Owusu RA, Abern MR, Inman BA. Hyperthermia as adjunct to intravesical chemotherapy for bladder cancer. BioMed Res Int (2013) 2013:262313. doi: 10.1155/2013/262313
29. Ried M, Potzger T, Braune N, Neu R, Zausig Y, Schalke B, et al. Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience. Eur J cardio-thoracic Surg Off J Eur Assoc Cardio-thoracic Surgery. (2013) 43(4):801–7. doi: 10.1093/ejcts/ezs418
30. Ahmed K, Zaidi SF, Mati Ur R, Rehman R, Kondo T. Hyperthermia and protein homeostasis: Cytoprotection and cell death. J Therm Biol (2020) 91:102615. doi: 10.1016/j.jtherbio.2020.102615
31. Müller H, Guadagni S. Regional chemotherapy for carcinoma of the lung. Surg Oncol Clin N Am (2008) 17(4):895–917. doi: 10.1016/j.soc.2008.04.012
32. Zhong LZ, Xu HY, Zhao ZM, Zhang GM, Lin FW. Comparison of efficacy and toxicity between nedaplatin and cisplatin in treating malignant pleural effusion. Onco Targets Ther (2018) 11:5509–12. doi: 10.2147/OTT.S168391
33. Zhao WY, Chen DY, Chen JH, Ji ZN. Effects of intracavitary administration of endostar combined with cisplatin in malignant pleural effusion and ascites. Cell Biochem biophysics. (2014) 70(1):623–8. doi: 10.1007/s12013-014-9965-9
34. Biaoxue R, Xiguang C, Hua L, Wenlong G, Shuanying Y. Thoracic perfusion of recombinant human endostatin (Endostar) combined with chemotherapeutic agents versus chemotherapeutic agents alone for treating malignant pleural effusions: a systematic evaluation and meta-analysis. BMC Cancer. (2016) 16(1):888. doi: 10.1186/s12885-016-2935-4
35. Wang CQ, Liu FY, Wang W. Thoracic perfusion of lobaplatin combined with endostar for treating malignant pleural effusions: A meta-analysis and systematic review. Med (Baltimore). (2022) 101(40):e30749. doi: 10.1097/MD.0000000000030749
36. Meng Y, Sun J, Wang X, Ma Y, Kong C, Zhang G, et al. The biological macromolecule nocardia rubra cell-wall skeleton as an avenue for cell-based immunotherapy. J Cell Physiol (2019). doi: 10.1002/jcp.28182
37. Wu J, He B, Miao M, Han X, Dai H, Dou H, et al. Enhancing natural killer cell-mediated cancer immunotherapy by the biological macromolecule nocardia rubra cell-wall skeleton. Pathol Oncol Res (2022) 28:1610555. doi: 10.3389/pore.2022.1610555
38. Jayson GC, Kerbel R, Ellis LM, Harris AL. Antiangiogenic therapy in oncology: current status and future directions. Lancet (London England). (2016) 388(10043):518–29. doi: 10.1016/S0140-6736(15)01088-0
39. Qin Y, Takahashi M, Sheets K, Soto H, Tsui J, Pelargos P, et al. Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme. J neuro-oncology. (2017) 134(1):29–40. doi: 10.1007/s11060-017-2507-8
40. Zhang H, Bai M, Deng T, Liu R, Wang X, Qu Y, et al. Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma. Cancer letters. (2016) 375(2):331–9. doi: 10.1016/j.canlet.2016.03.026
41. Wang CQ, Chen L, Dong CL, Song Y, Shen ZP, Shen WM, et al. MiR-377 suppresses cell proliferation and metastasis in gastric cancer via repressing the expression of VEGFA. Eur Rev Med Pharmacol Sci (2017) 21(22):5101–11. doi: 10.26355/eurrev_201711_13826
42. Deng G, Teng Y, Huang F, Nie W, Zhu L, Huang W, et al. MicroRNA-101 inhibits the migration and invasion of intrahepatic cholangiocarcinoma cells via direct suppression of vascular endothelial growth factor-c. Mol Med Rep (2015) 12(5):7079–85. doi: 10.3892/mmr.2015.4239
43. Fang L, Choi SH, Baek JS, Liu C, Almazan F, Ulrich F, et al. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature. (2013) 498(7452):118–22. doi: 10.1038/nature12166
44. Mostmans Y, Cutolo M, Giddelo C, Decuman S, Melsens K, Declercq H, et al. The role of endothelial cells in the vasculopathy of systemic sclerosis: A systematic review. Autoimmun Rev (2017) 16(8):774–86. doi: 10.1016/j.autrev.2017.05.024
45. Bekes I, Friedl TW, Köhler T, Möbus V, Janni W, Wöckel A, et al. Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer? Mol Cancer (2016) 15:13. doi: 10.1186/s12943-016-0497-3
46. Ryu JS, Ryu HJ, Lee SN, Memon A, Lee SK, Nam HS, et al. Prognostic impact of minimal pleural effusion in non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol (2014) 32(9):960–7. doi: 10.1200/JCO.2013.50.5453
47. Tao H, Meng Q, Li M, Shi L, Tang J, Liu Z. Outcomes of bevacizumab combined with chemotherapy in lung adenocarcinoma-induced malignant pleural effusion. Thorac cancer. (2018) 9(2):298–304. doi: 10.1111/1759-7714.12582
48. Noro R, Kobayashi K, Usuki J, Yomota M, Nishitsuji M, Shimokawa T, et al. Bevacizumab plus chemotherapy in nonsquamous non-small cell lung cancer patients with malignant pleural effusion uncontrolled by tube drainage or pleurodesis: A phase II study north East Japan study group trial NEJ013B. Thorac cancer. (2020) 11(7):1876–84. doi: 10.1111/1759-7714.13472
49. Zongwen S, Song K, Cong Z, Tian F, Yan Z. Evaluation of efficacy and safety for bevacizumab in treating malignant pleural effusions caused by lung cancer through intrapleural injection. Oncotarget. (2017) 8(69):113318–30. doi: 10.18632/oncotarget.22966
50. Qi N, Li F, Li X, Kang H, Zhao H, Du N. Combination use of paclitaxel and avastin enhances treatment effect for the NSCLC patients with malignant pleural effusion. Medicine. (2016) 95(47):e5392. doi: 10.1097/MD.0000000000005392
51. Chen D, Song X, Shi F, Zhu H, Wang H, Zhang N, et al. Greater efficacy of intracavitary infusion of bevacizumab compared to traditional local treatments for patients with malignant cavity serous effusion. Oncotarget. (2017) 8(21):35262–71. doi: 10.18632/oncotarget.13064
52. Du N, Li X, Li F, Zhao H, Fan Z, Ma J, et al. Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer−mediated malignant pleural effusion. Oncol Rep (2013) 29(6):2332–40. doi: 10.3892/or.2013.2349
53. Ribatti D. The inefficacy of antiangiogenic therapies. J angiogenesis Res (2010) 2:27. doi: 10.1186/2040-2384-2-27
54. Chen D, Song X, Zhang Y, Kong L, Wang H, Yu J. Optimizing intrapleural bevacizumab dosing in non-small-cell lung cancer-mediated malignant pleural effusion: Less is more. Future Oncol (London England). (2018) 14(21):2131–8. doi: 10.2217/fon-2018-0089
55. Sabang RL, Gandhiraj D, Fanucchi M, Epelbaum O. Role of bevacizumab in the management of the patient with malignant pleural effusion: more questions than answers. Expert Rev Respir Med (2018) 12(2):87–94. doi: 10.1080/17476348.2018.1417042
56. Fischer C, Mazzone M, Jonckx B, Carmeliet P. FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? Nat Rev Cancer (2008) 8(12):942–56. doi: 10.1038/nrc2524
57. Xu Q, Gu J, Lv Y, Yuan J, Yang N, Chen J, et al. Angiogenesis for tumor vascular normalization of endostar on hepatoma 22 tumor-bearing mice is involved in the immune response. Oncol letters. (2018) 15(3):3437–46. doi: 10.3892/ol.2018.7734
58. Ma X, Yao Y, Yuan D, Liu H, Wang S, Zhou C, et al. Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice. PLoS One (2012) 7(12):e53449. doi: 10.1371/journal.pone.0053449
59. Wei H, Qin S, Yin X, Chen Y, Hua H, Wang L, et al. Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites. Oncol letters. (2015) 9(6):2694–700. doi: 10.3892/ol.2015.3134
60. Meng FJ, Wang S, Yan YJ, Wang CY, Guan ZY, Zhang J. Recombined humanized endostatin-induced suppression of HMGB1 expression inhibits proliferation of NSCLC cancer cells. Thorac cancer. (2019) 10(1):90–5. doi: 10.1111/1759-7714.12905
61. Yan H, Guo W, Li K, Tang M, Zhao X, Lei Y, et al. Combination of DESI2 and endostatin gene therapy significantly improves antitumor efficacy by accumulating DNA lesions, inducing apoptosis and inhibiting angiogenesis. Exp Cell Res (2018) 371(1):50–62. doi: 10.1016/j.yexcr.2018.07.040
62. Wu J, Zhao X, Sun Q, Jiang Y, Zhang W, Luo J, et al. Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model. BioMed Pharmacother. (2020) 125:109746. doi: 10.1016/j.biopha.2019.109746
63. Liu X, Nie W, Xie Q, Chen G, Li X, Jia Y, et al. Endostatin reverses immunosuppression of the tumor microenvironment in lung carcinoma. Oncol letters. (2018) 15(2):1874–80. doi: 10.3892/ol.2017.7455
64. Huang Y, Kim BYS, Chan CK, Hahn SM, Weissman IL, Jiang W. Improving immune-vascular crosstalk for cancer immunotherapy. Nat Rev Immunol (2018) 18(3):195–203. doi: 10.1038/nri.2017.145
65. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Sci (New York NY). (2005) 307(5706):58–62. doi: 10.1126/science.1104819
66. Wu JB, Tang YL, Liang XH. Targeting VEGF pathway to normalize the vasculature: an emerging insight in cancer therapy. Onco Targets Ther (2018) 11:6901–9. doi: 10.2147/OTT.S172042
67. Jie Wang X, Miao K, Luo Y, Li R, Shou T, Wang P, et al. Randomized controlled trial of endostar combined with cisplatin/ pemetrexed chemotherapy for elderly patients with advanced malignant pleural effusion of lung adenocarcinoma. J BUON Off J Balkan Union Oncol (2018) 23(1):92–7.
68. van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol (2018) 19(4):213–28. doi: 10.1038/nrm.2017.125
69. Liang Q, Bie N, Yong T, Tang K, Shi X, Wei Z, et al. The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency. Nat Biomed engineering. (2019) 3(9):729–40. doi: 10.1038/s41551-019-0405-4
70. Liang Q, Bie N, Yong T, Tang K, Shi X, Wei Z, et al. Author correction: The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency. Nat Biomed engineering. (2021) 5(5):481. doi: 10.1038/s41551-021-00694-0
71. Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat nanotechnology. (2021) 16(7):748–59. doi: 10.1038/s41565-021-00931-2
72. Rufino-Ramos D, Albuquerque PR, Carmona V, Perfeito R, Nobre RJ, Pereira de Almeida L. Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases. J Controlled release Off J Controlled Release Society. (2017) 262:247–58. doi: 10.1016/j.jconrel.2017.07.001
73. Elsharkasy OM, Nordin JZ, Hagey DW, de Jong OG, Schiffelers RM, Andaloussi SE, et al. Extracellular vesicles as drug delivery systems: Why and how? Advanced Drug delivery Rev (2020) 159:332–43. doi: 10.1016/j.addr.2020.04.004
74. Kalimuthu S, Gangadaran P, Rajendran RL, Zhu L, Oh JM, Lee HW, et al. A new approach for loading anticancer drugs into mesenchymal stem cell-derived exosome mimetics for cancer therapy. Front Pharmacol (2018) 9:1116. doi: 10.3389/fphar.2018.01116
75. Yong T, Wang D, Li X, Yan Y, Hu J, Gan L, et al. Extracellular vesicles for tumor targeting delivery based on five features principle. J Controlled release Off J Controlled Release Society. (2020) 322:555–65. doi: 10.1016/j.jconrel.2020.03.039
76. Buschmann D, Mussack V, Byrd JB. Separation, characterization, and standardization of extracellular vesicles for drug delivery applications. Advanced Drug delivery Rev (2021) 174:348–68. doi: 10.1016/j.addr.2021.04.027
77. Wan C, Sun Y, Tian Y, Lu L, Dai X, Meng J, et al. Irradiated tumor cell-derived microparticles mediate tumor eradication via cell killing and immune reprogramming. Sci Adv (2020) 6(13):eaay9789. doi: 10.1126/sciadv.aay9789
78. Yin Z, Fan J, Xu J, Wu F, Li Y, Zhou M, et al. Immunoregulatory roles of extracellular vesicles and associated therapeutic applications in lung cancer. Front Immunol (2020) 11:2024. doi: 10.3389/fimmu.2020.02024
79. Gao Y, Qin Y, Wan C, Sun Y, Meng J, Huang J, et al. Small extracellular vesicles: A novel avenue for cancer management. Front Oncol (2021) 11:638357. doi: 10.3389/fonc.2021.638357
80. Droste M, Thakur BK, Eliceiri BP. Tumor-derived extracellular vesicles and the immune system-lessons from immune-competent mouse-tumor models. Front Immunol (2020) 11:606859. doi: 10.3389/fimmu.2020.606859
81. Yang Q, Guo N, Zhou Y, Chen J, Wei Q, Han M. The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. Acta Pharm Sin B (2020) 10(11):2156–70. doi: 10.1016/j.apsb.2020.04.004
82. Moore C, Kosgodage U, Lange S, Inal JM. The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy. Int J cancer. (2017) 141(3):428–36. doi: 10.1002/ijc.30672
83. Ma J, Zhang Y, Tang K, Zhang H, Yin X, Li Y, et al. Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles. Cell Res (2016) 26(6):713–27. doi: 10.1038/cr.2016.53
84. Guo M, Wu F, Hu G, Chen L, Xu J, Xu P, et al. Autologous tumor cell-derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion. Sci Trans Med (2019) 11(474):eaat5690. doi: 10.1126/scitranslmed.aat5690
85. Saviana M, Romano G, Le P, Acunzo M, Nana-Sinkam P. Extracellular vesicles in lung cancer metastasis and their clinical applications. Cancers. (2021) 13(22):5633. doi: 10.3390/cancers13225633
86. Astoul P, Laroumagne S, Capel J, Maskell NA. Novel pleural-bladder pump in malignant pleural effusions: from animal model to man. Thorax. (2020) 75(5):432–4. doi: 10.1136/thoraxjnl-2019-214003
87. Bellot P, Welker MW, Soriano G, von Schaewen M, Appenrodt B, Wiest R, et al. Automated low flow pump system for the treatment of refractory ascites: a multi-center safety and efficacy study. J hepatology. (2013) 58(5):922–7. doi: 10.1016/j.jhep.2012.12.020
88. Bureau C, Adebayo D, Chalret de Rieu M, Elkrief L, Valla D, Peck-Radosavljevic M, et al. Alfapump® system vs. large volume paracentesis for refractory ascites: A multicenter randomized controlled study. J hepatology. (2017) 67(5):940–9. doi: 10.1016/j.jhep.2017.06.010
89. Gilbert CR, Wahidi MM, Light RW, Rivera MP, Sterman DH, Thomas R, et al. Management of indwelling tunneled pleural catheters: A modified Delphi consensus statement. Chest. (2020) 158(5):2221–8. doi: 10.1016/j.chest.2020.05.594
90. Demmy TL, Gu L, Burkhalter JE, Toloza EM, D'Amico TA, Sutherland S, et al. Optimal management of malignant pleural effusions (results of CALGB 30102). J Natl Compr Cancer Network JNCCN. (2012) 10(8):975–82. doi: 10.6004/jnccn.2012.0102
91. Thomas R, Fysh ETH, Smith NA, Lee P, Kwan BCH, Yap E, et al. Effect of an indwelling pleural catheter vs talc pleurodesis on hospitalization days in patients with malignant pleural effusion: The AMPLE randomized clinical trial. JAMA (2017) 318(19):1903–12. doi: 10.1001/jama.2017.17426
92. Davies HE, Mishra EK, Kahan BC, Wrightson JM, Stanton AE, Guhan A, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA (2012) 307(22):2383–9. doi: 10.1001/jama.2012.5535
93. Ost DE, Niu J, Zhao H, Grosu HB, Giordano SH. Quality gaps and comparative effectiveness of management strategies for recurrent malignant pleural effusions. Chest. (2018) 153(2):438–52. doi: 10.1016/j.chest.2017.08.026
94. Muruganandan S, Azzopardi M, Fitzgerald DB, Shrestha R, Kwan BCH, Lam DCL, et al. Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial. Lancet Respir Med (2018) 6(9):671–80. doi: 10.1016/S2213-2600(18)30288-1
95. Fysh ETH, Tremblay A, Feller-Kopman D, Mishra EK, Slade M, Garske L, et al. Clinical outcomes of indwelling pleural catheter-related pleural infections: an international multicenter study. Chest. (2013) 144(5):1597–602. doi: 10.1378/chest.12-3103
96. Lui MM, Thomas R, Lee YC. Complications of indwelling pleural catheter use and their management. BMJ Open Respir Res (2016) 3(1):e000123. doi: 10.1136/bmjresp-2015-000123
Keywords: malignant pleural effusion, lung cancer, angiogenesis, IPT, ATMPs-MTX
Citation: Zhao Y, Yu L, Wang L, Wu Y, Chen H, Wang Q and Wu Y (2023) Current status of and progress in the treatment of malignant pleural effusion of lung cancer. Front. Oncol. 12:961440. doi: 10.3389/fonc.2022.961440
Received: 04 June 2022; Accepted: 30 December 2022;
Published: 20 January 2023.
Edited by:
Vamsi Velcheti, New York University, United StatesReviewed by:
Duilio Divisi, University of L’Aquila, ItalyAnastasios D. Giannou, University Medical Center Hamburg-Eppendorf, Germany
Copyright © 2023 Zhao, Yu, Wang, Wu, Chen, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Qiming Wang, cWltaW5nd2FuZzEwMDZAMTI2LmNvbQ==; Yufeng Wu, emx5eXd1eXVmZW5nMzU1OUB6enUuZWR1LmNu