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Malignant Pleural Mesothelioma

February 14, 2023 - read ≈ 25 min



Richard S. Whitlock, MD

Department of Surgery, Division of Thoracic Surgery, Baylor College of Medicine, Houston, TX


Bryan M. Burt, MD

Department of Surgery, Division of Thoracic Surgery, Baylor College of Medicine, Houston, TX



Malignant pleural mesothelioma (MPM) is an aggressive primary malignancy of the pleural surface. Most cases of MPM are associated with previous asbestos exposure with a reported latency period of approximately 40 years.[1, 2] Within the United States the current incidence of MPM is reported to be between 2,000 and 3,000 cases per year.[3] It is also noted that the global incidence of MPM has steadily risen over the past decade with an estimated 14,000 cases worldwide every year.[4]

Despite surgical adjuncts and medical advances including the incorporation of bicavitary heated chemotherapy and immunotherapy, prognosis in cases of MPM remains poor overall with reported median survival times of 8-14 months from the time of diagnosis.[1, 5]


The most commonly reported presenting symptoms of patients with MPM are shortness of breath and chest pain.[6,7]  Shortness of breath is often the result of malignant pleural effusion from the pleural malignancy, present in approximately 70% of cases.[7] Interestingly, with disease progression, the frequency and amount of pleural effusions tend to decrease secondary to obliteration of the pleural space by tumor progression.[8]  Other associated symptoms of MPM include constitutional symptoms of fatigue, anorexia, malaise, sweats, and weight loss which are resultant of systemic responses to malignancy primarily to upregulation of pro-inflammatory cytokines such as IL-1 and TNF-alpha.[6]


Given the high mortality and paucity of early symptoms in cases of MPM, there has remained a high level of interest regarding early detection in mesothelioma in efforts to improve outcomes and reduce mortality.  However, given the low incidence of MPM, there currently exists no standard generalized screening guidelines or criteria for mesothelioma.

However, some patients with a personalized history of significant environmental exposure, namely asbestosis exposure, may be considered for screening in a personalized fashion.[9,10]  As early as 1973, the United States Occupational Safety and Health Administration has mandated monitoring and specific screening for high risk individuals with a documented history of occupational airborne asbestosis exposure.[9]

As it relates to environmental exposure risk association with MPM, asbestos exposure and its association with mesothelioma carcinogenesis is derived from epidemiologic studies as well as confirmatory studies.[11]  Carcinogenesis from asbestos fibers is hypothesized to be linked to free radical generation and release as well as the cycle of repeated inflammation and fibrosis that inhaled fibers incite within the pleural space.  Worldwide use and consumption of asbestos and containing products remains surprisingly high despite nationwide banning in many parts of the world.  As such, a decrease in the number of new cases of MPM in Western countries is predicted.[12]


The diagnosis of MPM can be challenging.  To date, the use of biomarkers has been evaluated in identification of MPM however they remain of limited clinical use without established levels of benefit.  Biomarkers that have been evaluated in the pathogenesis and diagnosis of MPM include mesothelin[13], megakaryocyte potentiating factor[14], and fibulin-3[15].

Elements that are key in the diagnosis of MPM include clinical history and imaging findings that include computed tomography (CT) with or without the adjunct of positron emission tomography (PET).  The characteristic imaging findings of MPM include nodular thickening or a pleural-based mass[8,16]

Histopathologic classification of diffuse MPM on microscopic examination and the most widely utilized classification categorizes MPM subtypes as epithelial, sarcomatoid, or mixed.[17]

Accurate histopathologic classification of MPM is necessary as it can assist to predict prognosis as well as aid in delineating treatment pathways for patients.  Currently, patients with epithelial type MPM hare noted to have the best survival with cases demonstrating sarcomatoid features having the worst. Interestingly, cases with sarcomatoid pathology are unlikely to have positive cytology on pleural fluid analysis during staging workup. Part of the investigatory process of MPM will involve video assisted thoracoscopic surgery (VATS) biopsy of the suspected affected pleura for tissue diagnosis.


Establishment of a universal and generalizable staging system for malignant pleural mesothelioma has been difficult owing to a multitude of factors: low tumor incidence, anatomic complexity, tumor heterogeneity, and limited treatment options.  Additionally, accurate staging of MPM is further complicated due to limitations in current imaging techniques, specifically in accurate tumor characterization and evaluation of lymph nodal involvement[18].

Conceptually, this is manifested as MPM typically spreads in a nodular fashion tangentially along the pleural surfaces and as such, MPM tumors can grow to considerable bulky disease that is not accurately characterized radiographically.  Additionally, lymph node involvement is not accurately assessed using current imaging techniques as nodal size does not necessarily correlate with the presence of metastatic disease.  Also, clinically relevant nodal stations, particularly hilar and internal thoracic stations, are typically located in areas that commonly involve primary MPM tumors.[7,19,20]

Finally, there is a noted lack of correspondence between preoperative clinical stage and final pathologic stage in cases of MPM.  Due to these complexities, pre-treatment clinical staging has been challenging in MPM as related to prognosis stratification or to inform treatment decisions as in other thoracic malignancies, especially evaluation as to whether the treatment modality of surgical resection should be incorporated.  Surgical thoracoscopy with additional mediastinoscopy to assess nodal disease may also be utilized for staging assessment in cases of malignant pleural mesothelioma.[21]

There are a number of staging classifications schema for MPM, all of which have limitations in clinical practice.[4,5]  Currently, modified TNM classification and stage grouping criteria proposed by the International Mesothelioma Interest Group (IMIG) were adopted by The American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC).[22]  Radiographic imaging is a cornerstone in the staging of patients with MPM and include chest computed topography (CT) scan, and fluorodeoxyglucose positron emission tomography(FDG-PET).

Magnetic resonance imaging (MRI) can be useful to investigate invasion of the local structures including the diaphragm and pericardium. Pathologic mediastinal staging includes cervical mediastinoscopy or endoscopic ultrasound.Pathological staging is obtained for patients undergoing surgery for MPM, and upstaging commonly occurs. As it relates to clinical staging and correspondence to pathologic staging, previous studies have demonstrated only a 46% rate of staging accuracy across 164 patients with resected MPM and completed staging data.[23]

To summarize, apart the identification of overt extra thoracic disease, current clinical staging of MPM is highly variable with very low predictive value for the outcome of patients with MPM under consideration for surgical therapy.

Historically, T classification of malignancies is based primarily on tumor size with associated upstaging when invasion of structures is noted.  By comparison, due to the diffuse and heterogeneous growth pattern of MPM, tumor size is not easily established in mesothelioma.  As such, tumor size is not currently considered when establishing MPM stage.

  • According to current AJCC/UICC criteria, T1 MPM tumors remain confined within the ipsilateral pleural surfaces.[24]
  • T2 tumors extending into the interlobar fissures or showing involvement of the lung parenchyma or diaphragm are classified as T2.
  • Tumors showing extension into the endothoracic fascia or mediastinal adipose tissue but pericardial involvement that is not transmural are classified as  T3.
  • Finally, tumors showing direct extension into the chest wall soft tissue or adjacent mediastinal organs or involvement of the contralateral pleura or pericardium/diaphragm are classified as T4.

Currently, regional lymph node staging of MPM uses the same classification schema as lung cancer which helps to simplify lymph node staging.[25]

  • As such, cases with identified hilar and intraparenchymal lymph nodes are classified as N1.
  • Tumors with associated subcarinal and ipsilateral mediastinal or internal mammary nodal involvement are N2.
  • And finally, contralateral internal mammary/mediastinal nodes or the involvement of supraclavicular nodes are N3

Even though the staging classification for nodal disease in MPM is similar to that of the nodal staging system for lung cancer, the relationship for nodal drainage is more complex as direct lymphatic drainage from the diaphragmatic pleura to the mediastinal nodal chains allows MPM tumors to arrive directly to N2 lymph nodes without first affecting N1 stations.[26] 

It is well established that nodal metastasis is associated poor prognosis in MPM which has been demonstrated in studies on multivariate analysis in patients treated with extrapleural pneumonectomy (EPP) who were able to undergo complete pathologic analysis following surgical resection.[27,28] As related to M status, interestingly, despite the aggressive local growth patterns associated with MPM, rare distant metastases are rare.[29]  Distant organ involvement can be difficult to determine as a result of caused by either direct extension through the diaphragm or hematogenous metastases.[30]


Due to the complexity of MPM, treatment of these tumors involves a multidisciplinary approach.  The broad strokes of treatment for primary MPM tumors can be divided into systemic chemotherapy/radiation, targeted therapy, immunotherapy, and surgery.

Systemic chemotherapy

In cases of unresectable disease, systemic chemotherapy should be considered as it has been shown to improve survival and quality of life in select MPM cases.  Standard first line therapy remains a combination of cisplatin and pemetrexed and continues to be the only FDA-labeled treatment option in MPM.

The EMPHACIS trial demonstrated efficacy in terms of response rate, median time to progression of disease, and median overall survival31.  Due to the results of this study, this chemotherapy combination became the standard first line therapy in mesothelioma.  They are delivered intravenously once every 21 days at doses of cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 with associated vitamin B12 (1000 ug intramuscularly) and folic acid (400 ug by mouth daily).

Optimum length of therapy for chemotherapy in unresectable MPM has not yet been defined, however current guidelines recommend for four to six cycles of therapy32.  Recently, while not currently FDA approved, vascular endothelial growth factor (VEGF) blockade of receptors VEGFR1 & VEGFR2 utilizing addition of the VEGF inhibitor bevacizumab to platinum and pemetrexed combination therapy, has been included in the NCCN guidelines for consideration in front-line therapy in MPM.[33, 34]


Immunotherapy has shown promise in the treatment of MPM.  An early focus on the implementation of immunotherapy in MPM management has involved the use of checkpoint inhibitors such as nivolumab and pembrolizumab.  Programmed cell death protein 1 (PD-1) is expressed in activated T & B lymphocytes as well as natural killer cells.  The binding between PD-1 and its ligands PD-L1/L2 leads to decreased T cell activity.[35]

The results from the recent Checkmate 743 trial demonstrate encouraging results for the use of immunotherapy in the care of malignant pleural mesothelioma.  Checkmate 743 represents an open label randomized phase 3 study evaluating the efficacy and safety of first-line nivolumab with the addition of ipilimumab versus platinum plus pemetrexed chemotherapy in unresectable MPM.[36]  Findings from Checkmate 743 demonstrate clinically and significant meaningful improvement in overall survival in patients treated with immunotherapy versus standard-of-care platinum-based chemotherapy[36] without additional safety profile concerns.  At a follow-up of 29.7 months, nivolumab plus ipilimumab significantly extended overall survival as compared to standard of care chemotherapy (18.1 months vs 14.1 months).[36]  Based on these findings from this landmark study, nivolumab plus ipilimumab has been supported as first line therapy in previously untreated unresectable cases of MPM.[36]


Whilst a tenant of the management of the vast majority of solid organ tumors, the benefit and feasibility of surgical resection in the management of MPM has been an area of debate. The two main procedures for resection of MPM can be simplified to include extrapleural pneumonectomy (EPP) and pleurectomy and decortication (P/D).  Currently, as established by the International Association for the Study of Lung Cancer (IASLC), the term P/D is denoted to attempted removal of all macroscopic tumor from the visceral and parietal pleura with the term extended P/D used if the involved diaphragm and pericardium are removed with the aforementioned pleura.[37]  EPP includes resection of the entire lung, visceral pleura, parietal pleura, and involved pericardium and diaphragm.  Original reports of EPP reported improved survival but with prohibitively high rates of associated morbidity and mortality.[38]  In subsequent years with adaptations of multimodality therapy, morbidity rates of EPP improved with resultant mortality reductions.[39]

Given the morbidity associated with EPP, extended P/D has become the most common operation for resection of MPM.  P/D is generally better tolerated and has reported mortality rates of 1% to 2% at high volume tertiary centers.  There currently exists no randomized trial data determining whether P/D extends survival as compared to no surgery however studies such as the multicenter MARS-2 trial is currently evaluating this.[40]

HIPEC (hyperthermic intraperitoneal chemotherapy)

Perioperative adjuncts combined with surgery have also been evaluated in the operative management of MPM.  In cases of MPM treated either with EPP or P/D, the adjunct of heated intraoperative chemotherapy (HIOC) has championed by some groups.  HIOC, which involves intracavitary administration of heated chemotherapy (42oC) with purpose to increase the intracellular uptake of drugs in an effort to decrease systemic side effects while maximizing effect.[41]  Traditionally, thoracic HIOC has been undertaken with platinum-based chemotherapy (cisplatin) with doses of sodium thiosulfate and amifostine to provide added renal protection during heated chemotherapy administration.[42-44]

Certain non-randomized studies in carefully selected patients have reported median survival times of up to 29 months in patients treated with EPP with subsequent HIOC following induction chemotherapy.[45]  HIOC has also been studied in use in patients undergoing P/D with intraoperative chemotherapy with median survival rates of 11.5-13 months.[42, 46] Alternatively, recent groups have evaluated administration of PVP-I (iodine bound to carrier molecule poly-(1-vinyl-2-pyrrolidone)).  Due to its lower side effect profile as compared to HIOC, hyperthermic pleural lavage with PVP-I has been studied as a surgical adjunct during P/D instead of HIOC.  Previous studies evaluating patients treated with P/D and heated intraoperative PVP-I and prophylactic radiotherapy in patients with MPM demonstrated 0% mortality rate with an overall median survival of 24 months.[47]

Targeted therapy

Owing to the increased understanding of biology of MPM disease, targeted therapy has been investigated in combination with systemic chemotherapy for certain cases.  Due to the aforementioned identification of high expression of angiogenic growth factors and receptors in MPM tumors and positive results from the MAPS trial with the utilization of bevacizumab,[33, 34] the implementation of anti-angiogenic agents continue to be an active area of research in mesothelioma.  Results of previous trials have only demonstrated modest results.

Additionally, cediranib and nintedanib are oral small molecule inhibitors of VEGF that have been evaluated in phase I & II clinical trials who experienced MPM disease progression.[48-50]  In addition to angiogenic inhibition, mesothelin, a glycoprotein involved in cell adhesion has been found to have high expression rates in MPM as compared to normal surrounding tissue, and mesothelin inhibitors such as amatuximab have been studied in clinical trials (NCT02357147) with some preliminarily favorable results.[51]

Additional areas of investigation as related to targeted therapy include mammalian target of rapamycin (mTOR) inhibition, oral epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors, histone deacetylase inhibitors (HDACi), and proteosome inhibition are still being evaluated as supplemental therapy in cases of MPM with standard of care systemic chemotherapy.

Management of Malignant Pleural Effusions

The majority of patients diagnosed with MPM will experience a disease related pleural effusion at some point.  Drainage of these effusions improves symptoms and attempts at prevention of re-accumulation can help to improve quality of life in patients diagnosed with MPM.  Simple aspiration and drainage can provide immediate symptomatic relief in cases of malignant effusions, however, fluid will inevitably re-accumulate and as such, a definitive procedure is generally preferable.[52]

Definitive control of recurrent effusions can be accomplished via chemical pleurodesis via a minimally invasive approach, a number of chemical agents have been evaluated and found to be effective that include talc, doxycycline, and bleomycin.  Talc pleurodesis is successful in approximately 60% of patients in providing long term relief from recurrent effusion accumulation.[53]

An alternative to chemical pleurodesis in the management of recurrent pleural effusion from MPM is the placement of a long-term indwelling pleural drainage catheter.  Indwelling pleural catheters have demonstrated efficacy in the management in a number of thoracic malignancies, including MPM.[16, 52]  The decision whether to proceed with either pleurodesis or placement of a pleural drainage catheter should be made with the patient’s input and quality of life in mind.


Due to the low incidence of MPM and the high associated early disease mortality even in patients who have received medical/surgical therapy, there are no currently established post-treatment patient surveillance protocols.  Currently, MPM post-surgery are monitored for disease recurrence with center-specific followup protocols that include regular history and physical exams, monitoring for a decrease in pulmonary function, and interval established radiologic imaging to evaluate for disease recurrence.  Given the high recurrence rates of MPM, oftentimes development of symptoms often precedes radiologic identification of disease recurrence. 


Currently, the only reported data from a randomized clinical trial directly comparing MPM cases undergoing surgery vs no surgery are findings from the United Kingdom- based Mesothelioma and Radical Surgery Feasibility Study (MARS) that demonstrated a higher morbidity and in-fact lower overall survival (14.4 vs 19.5 months).[54]

However, these findings should be taken into specific context in that many have argued that this study was not sufficiently powered for survival determination, and that previous studies, albeit lower powered, have exceedingly demonstrated the potential negative impact that EPP can have in the overall outcomes of MPM patients when not performed in high-volume centers or amongst poorly selected candidates.[38, 39]   Conversely, other studies, often limited to single center experiences, have demonstrated more acceptable rates of morbidity and mortality as related to surgical resection.[39, 41]

The balance of literature suggests to maximize the benefit of surgical resection, it should be performed in a multimodal setting with adjuvant and/or adjuvant modalities such as systemic therapy inlcuding chemotherapy, and/or radiotherapy. In our experience and in the experiences of other tertiary high-volume centers, incorporated as a component of multimodal treatment that also includes immunotherapy, systemic chemotherapy, and radiation therapy protocols, surgical resection may provide enhanced survival in appropriately selected mesothelioma patients with acceptable rates of morbidity and complications.

An additional controversy in the surgical management of malignant pleural mesothelioma relates to the selection for cytoreductive surgery technique.  This controversy directly relates to the main crux of criticism of surgery in MPM patients that is often muddied by the morbidity and mortality with which extrapleural pneumonectomy can be associated.[38]  As previously mentioned, providers have begun to evaluate whether extended pleurectomy and decortication can yield comparable oncologic results as the more cardiopulmonary high-risk EPP.  It is well established that EPP can contribute to hazard mortality ratios of greater than 1.4 as compared to P/D.  Because of these issues, the implementation of P/D which is a significantly less radical procedure than EPP, is currently being assessed in conjunction with standard of care chemotherapy in the randomized phase 3 MARS-2 trial.[40]

Summary and recommendations

MPM is an aggressive pleural malignancy that is associated in most cases with exposure to asbestos.

First line systemic therapies for patients with unresectable MPM include platinum-based therapy and pemetrexed (plus/minus bevacizumab) and immune checkpoint blockade

The CheckMate 743 trial was recently published and shows that immumotherapy with nivolumab plus iplimumab increased overall survival in patients with unresectable MPM when compared with chemotherapy

Surgical resection for MPM, in the setting of multimodal therapy, may be associated with extended survival in selected patients. The role of EPP versus P/D is not determined


  1. British Thoracic Society Standards of Care C. BTS statement on malignant mesothelioma in the UK, 2007. Thorax 2007; 62 Suppl 2:ii1-ii19.
  2. Clement A, de Blic J, Epaud R, et al. Management of children with interstitial lung diseases: the difficult issue of acute exacerbations. Eur Respir J 2016; 48(6):1559-1563.
  3. Connelly RR, Spirtas R, Myers MH, et al. Demographic patterns for mesothelioma in the United States. J Natl Cancer Inst 1987; 78(6):1053-60.
  4. Scherpereel A, Opitz I, Berghmans T, et al. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. Eur Respir J 2020; 55(6).
  5. Sinn K, Mosleh B, Hoda MA. Malignant pleural mesothelioma: recent developments. Curr Opin Oncol 2021; 33(1):80-86.
  6. Clayson H, Seymour J, Noble B. Mesothelioma from the patient’s perspective. Hematol Oncol Clin North Am 2005; 19(6):1175-90, viii.
  7. Rudd RM. Malignant mesothelioma. Br Med Bull 2010; 93:105-23.
  8. Bibby AC, Tsim S, Kanellakis N, et al. Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment. Eur Respir Rev 2016; 25(142):472-486.
  9. Pass HI, Carbone M. Current status of screening for malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg 2009; 21(2):97-104.
  10. Roberts HC, Patsios DA, Paul NS, et al. Screening for malignant pleural mesothelioma and lung cancer in individuals with a history of asbestos exposure. J Thorac Oncol 2009; 4(5):620-8.
  11. Godleski JJ. Role of asbestos in etiology of malignant pleural mesothelioma. Thorac Surg Clin 2004; 14(4):479-87.
  12. Price B, Ware A. Time trend of mesothelioma incidence in the United States and projection of future cases: an update based on SEER data for 1973 through 2005. Crit Rev Toxicol 2009; 39(7):576-88.
  13. Chang K, Pai LH, Batra JK, et al. Characterization of the antigen (CAK1) recognized by monoclonal antibody K1 present on ovarian cancers and normal mesothelium. Cancer Res 1992; 52(1):181-6.
  14. Creaney J, Yeoman D, Demelker Y, et al. Comparison of osteopontin, megakaryocyte potentiating factor, and mesothelin proteins as markers in the serum of patients with malignant mesothelioma. J Thorac Oncol 2008; 3(8):851-7.
  15. Pass HI, Levin SM, Harbut MR, et al. Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma. N Engl J Med 2012; 367(15):1417-27.
  16. Clive AO, Jones HE, Bhatnagar R, et al. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev 2016(5):CD010529.
  17. DeLellis RA, Caton M. The AFIP/ARP Atlases of Pathology Past, Present, and Future. Am J Surg Pathol 2018; 42(3):e28-e32.
  18. Scherpereel A, Astoul P, Baas P, et al. [Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma]. Zhongguo Fei Ai Za Zhi 2010; 13(10):C23-45.
  19. Patz EF, Jr., Rusch VW, Heelan R. The proposed new international TNM staging system for malignant pleural mesothelioma: application to imaging. AJR Am J Roentgenol 1996; 166(2):323-7.
  20. Pilling JE, Stewart DJ, Martin-Ucar AE, et al. The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma. Eur J Cardiothorac Surg 2004; 25(4):497-501.
  21. Heelan RT, Rusch VW, Begg CB, et al. Staging of malignant pleural mesothelioma: comparison of CT and MR imaging. AJR Am J Roentgenol 1999; 172(4):1039-47.
  22. Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest 1995; 108(4):1122-8.
  23. Nakas A, Black E, Entwisle J, et al. Surgical assessment of malignant pleural mesothelioma: have we reached a critical stage? Eur J Cardiothorac Surg 2010; 37(6):1457-63.
  24. Boutin C, Rey F, Gouvernet J, et al. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 2: Prognosis and staging. Cancer 1993; 72(2):394-404.
  25. Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997; 111(6):1718-23.
  26. Edwards JG, Stewart DJ, Martin-Ucar A, et al. The pattern of lymph node involvement influences outcome after extrapleural pneumonectomy for malignant mesothelioma. J Thorac Cardiovasc Surg 2006; 131(5):981-7.
  27. de Perrot M, Uy K, Anraku M, et al. Impact of lymph node metastasis on outcome after extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2007; 133(1):111-6.
  28. Sugarbaker DJ, Strauss GM, Lynch TJ, et al. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993; 11(6):1172-8.
  29. Nauta RJ, Osteen RT, Antman KH, et al. Clinical staging and the tendency of malignant pleural mesotheliomas to remain localized. Ann Thorac Surg 1982; 34(1):66-70.
  30. Finn RS, Brims FJH, Gandhi A, et al. Postmortem findings of malignant pleural mesothelioma: a two-center study of 318 patients. Chest 2012; 142(5):1267-1273.
  31. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003; 21(14):2636-44.
  32. Kindler HL, Ismaila N, Armato SG, 3rd, et al. Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36(13):1343-1373.
  33. Konig J, Tolnay E, Wiethege T, et al. Co-expression of vascular endothelial growth factor and its receptor flt-1 in malignant pleural mesothelioma. Respiration 2000; 67(1):36-40.
  34. Zalcman G, Mazieres J, Margery J, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet 2016; 387(10026):1405-1414.
  35. Zhang Y, Huang S, Gong D, et al. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol 2010; 7(5):389-95.
  36. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet 2021; 397(10272):375-386.
  37. Rice D, Rusch V, Pass H, et al. Recommendations for uniform definitions of surgical techniques for malignant pleural mesothelioma: a consensus report of the international association for the study of lung cancer international staging committee and the international mesothelioma interest group. J Thorac Oncol 2011; 6(8):1304-12.
  38. Butchart EG, Ashcroft T, Barnsley WC, et al. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 1976; 31(1):15-24.
  39. Sugarbaker DJ, Jaklitsch MT, Bueno R, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg 2004; 128(1):138-46.
  40. Lim E, Darlison L, Edwards J, et al. Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma. BMJ Open 2020; 10(9):e038892.
  41. Sugarbaker PH, Chang D, Stuart OA. Hyperthermic intraoperative thoracoabdominal chemotherapy. Gastroenterol Res Pract 2012; 2012:623417.
  42. Lee JD, Perez S, Wang HJ, et al. Intrapleural chemotherapy for patients with incompletely resected malignant mesothelioma: the UCLA experience. J Surg Oncol 1995; 60(4):262-7.
  43. Markman M, Howell SB, Green MR. Combination intracavitary chemotherapy for malignant pleural disease. Cancer Drug Deliv 1984; 1(4):333-6.
  44. Ratto GB, Civalleri D, Esposito M, et al. Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study. J Thorac Cardiovasc Surg 1999; 117(4):759-65.
  45. Krug LM, Pass HI, Rusch VW, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol 2009; 27(18):3007-13.
  46. Rice TW, Adelstein DJ, Kirby TJ, et al. Aggressive multimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1994; 58(1):24-9.
  47. Lang-Lazdunski L, Bille A, Belcher E, et al. Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine followed by adjuvant chemotherapy in patients with malignant pleural mesothelioma. J Thorac Oncol 2011; 6(10):1746-52.
  48. Garland LL, Chansky K, Wozniak AJ, et al. Phase II study of cediranib in patients with malignant pleural mesothelioma: SWOG S0509. J Thorac Oncol 2011; 6(11):1938-45.
  49. Grosso F, Steele N, Novello S, et al. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial. J Clin Oncol 2017; 35(31):3591-3600.
  50. Tsao AS, Moon J, Wistuba, II, et al. Phase I Trial of Cediranib in Combination with Cisplatin and Pemetrexed in Chemonaive Patients with Unresectable Malignant Pleural Mesothelioma (SWOG S0905). J Thorac Oncol 2017; 12(8):1299-1308.
  51. Hassan R, Kindler HL, Jahan T, et al. Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma. Clin Cancer Res 2014; 20(23):5927-36.
  52. Davies HE, Mishra EK, Kahan BC, 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.
  53. Walker-Renard PB, Vaughan LM, Sahn SA. Chemical pleurodesis for malignant pleural effusions. Ann Intern Med 1994; 120(1):56-64.
  54. Treasure T, Lang-Lazdunski L, Waller D, et al. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study. Lancet Oncol 2011; 12(8):763-72.
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