Author's Accepted Manuscript
Surgical management of malignant pleural mesothelioma: an update of clinical evidence Christopher Cao MBBS BSc, Ben Fu MDS, Chloe Wilcox MBBS, Elan Novis MBBS, David H. Tian MBBS, Tristan D. Yan MBBS BSc MD MS PhD
www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1043-0679(15)00011-8 http://dx.doi.org/10.1053/j.semtcvs.2015.02.007 YSTCS723
To appear in:
Semin Thoracic Surg
Cite this article as: Christopher Cao MBBS BSc, Ben Fu MDS, Chloe Wilcox MBBS, Elan Novis MBBS, David H. Tian MBBS, Tristan D. Yan MBBS BSc MD MS PhD, Surgical management of malignant pleural mesothelioma: an update of clinical evidence, Semin Thoracic Surg, http://dx.doi.org/10.1053/j.semtcvs.2015.02.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Article type: Editorial Title: Surgical management of malignant pleural mesothelioma: An update of clinical evidence Running head: Surgical Clinical Evidence for MPM Authors: Christopher Cao MBBS BSc1,2, Ben Fu MDS1, Chloe Wilcox MBBS1, Elan Novis MBBS1, David H. Tian MBBS1, Tristan D. Yan MBBS BSc MD MS PhD1,3 Affiliations: The Systematic Review Unit, The Collaborative Research (CORE) Group, Macquarie University, Sydney, Australia1; Department of Cardiothoracic Surgery, Prince of Wales Hospital, Sydney, Australia2; Department of Cardiothoracic Surgery, the Royal Prince Alfred Hospital, Sydney, Australia3 Keywords: Malignant pleural mesothelioma, pleurectomy, pleurodesis, randomized controlled trial Main text word count: 1237 Corresponding Author: Christopher Cao, The Systematic Review Unit, The Collaborative Research (CORE) Group, Macquarie University, Sydney, Australia; email: [email protected]; Phone: +61291131111 Fax: +61291133393 Disclaimers: No potential conflicts of interest. Ultramini abstract: Two randomized controlled trials have been completed to investigate the surgical management of malignant pleural mesothelioma. We hereby discuss the findings from these trials and the current evidence of various surgical techniques to treat this challenging disease.
The MesoVATS Collaborators recently published the second ever randomized controlled trial on the surgical management of malignant pleural mesothelioma (MPM) in The Lancet.1 This trial recruited 196 patients from 12 hospitals over a decade to undergo either video-assisted thoracoscopic partial pleurectomy (VAT-PP, n = 98) or talc pleurodesis (n = 98). The primary endpoint was 12-month survival, and secondary outcomes included lung function tests, presence or absence of pleural effusions, quality-of-life measurements, cost analyses and perioperative complications. Results of the study found that overall survival at 1-year was not statistically significantly different between the two treatment groups. Complete data for secondary endpoints were available for less than half of the randomized patients. Patients who underwent VAT-PP were reported to result in more complications and longer hospitalization, but morbidities were not standardized according to any grading system. More patients were likely to achieve resolution of pleural effusion on imaging after undergoing VAT-PP at 1-month and 6-months, but no differences were found at 3-months and 12-months. The estimated mean cost for VAT-PP treatment and follow-up care at 12 months was approximately ₤3800 more than talc pleurodesis, with a calculated incremental cost effectiveness ratio of ₤109,028 per quality-adjusted life year gained. No clear advantages were found for either treatment arm in regards to quality-of-life outcomes and lung function tests from the limited data available. Overall, the authors concluded that VAT-PP should not be recommended to improve the overall survival outcomes of patients presenting with pleural effusions secondary to MPM.
The immense logistical challenges of completing a clinical trial for a rare disease such as MPM were demonstrated by Treasure et al. in the Mesothelioma and
Radical Surgery (MARS) trial,2 and the MesoVATS Collaborators should be congratulated on their efforts to complete the second ever randomized study related to MPM. The primary objective of the MARS trial was to assess the feasibility of randomizing 50 patients within a 12-month period to undergo either extrapleural pneumonectomy (EPP) versus no EPP. At the completion of the trial, 16 out of 24 patients assigned to the EPP arm completed the procedure after a 3-year recruitment period. From the available data, authors of the MARS trial concluded that EPP ‘offers no benefit and possibly harms patients,’ a controversial statement that has drawn criticism from some members of the thoracic surgical community.3 It was claimed that the MARS trial violated the fundamental principles of clinical trial reporting by retrospectively analysing a feasibility-testing study.4 Objectively, with an operative mortality rate of 18% for patients who underwent EPP per protocol, the clinical outcomes of the MARS trial represented one of the worst results in the existing literature.5, 6 Nonetheless, authors of the MARS trial emphasized the benefits of a randomized controlled trial with intention to treat analysis to circumvent potential biases in case selection, reporting and interpretation, stating that ‘some unbiased evidence is clearly better than none’.7, 8
A number of comments can be made regarding the clinical design, technical performance and methodological analysis of the MesoVATS trial. Unlike the MARS trial, this study did not mandate histological confirmation prior to randomization, and VAT-PP was performed for 11% of patients who had benign disease or nonmesothelioma malignancies. Although these patients were excluded from analysis, their exposure to potential complications without significant benefit from a partial
pleurectomy procedure may have posed a clinical dilemma. From a technical perspective, the pleurodesis arm included a combination of talc slurry (n=35) and thoracoscopic poudrage (n=34) techniques. It should be acknowledged that both clinical and economic endpoints may differ significantly between these two distinct therapeutic approaches. Thoracoscopy would generally require an operating theatre and general anaesthesia, as well as associated personnel requirements and costs. However, this procedure does offer an opportunity to directly visualise tumour involvement and perform biopsies for unconfirmed cases of MPM. On the other hand, previous studies have demonstrated that talc slurry may be associated with higher recurrences of pleural effusions, but it can be performed in more frail candidates at a lower cost.9 Finally, the MesoVATS trial performed a retrospective subgroup analysis by stratifying patients according to the European Organisation for Research and Treatment of Cancer (EORTC) prognostic score, which involved a combination of white cell count, gender, ECOG score and histological subtype. More recent studies have demonstrated that nodal involvement, staging, and (neo)adjuvant therapy may be more predictive of survival in patients with MPM.10
From a broader perspective, outcomes of the MesoVATS study should be considered in the context of a spectrum of surgical procedures performed for MPM, ranging from radical surgeries that aim for macroscopic complete resection to minimally invasive procedures that are palliative, as summarized in Figure 1. The authors of the MesoVATS study concluded from their findings that VAT-PP conferred no survival benefit over talc pleurodesis at 12-months, which was the primary endpoint of the trial. This was further emphasized by the accompanying commentary by Lee11, who stated that VAT-PP failed to demonstrate survival benefits through
‘cytoreduction’, and that there is no evidence to suggest cytoreduction is effective for MPM. However, it should be recognized that neither procedures primarily aimed to improve survival, but rather to improve symptomatic relief and quality-of-life. Arguably, these endpoints should have been given more focus in the MesoVATS trial to compare the two palliative procedures. Unfortunately, only 71 out of 171 analysed patients completed their functional scale scores at 1-year due to missed appointments, consent withdrawals or deaths. In regards to ‘cytoreduction’, the term ‘complete macroscopic cytoreduction’ is usually associated with radical procedures such as EPP that are performed with a curative intent and an aim of prolonging longterm survival. Lee cited a general review published 15 years ago and claimed that surgical resection for mesothelioma is an evidence-free practice.11, 12 In fact, recent systematic reviews have identified prospective studies on trimodality therapy involving patients treated with standardized neoadjuvant chemotherapy regimens, EPP and adjuvant radiotherapy that resulted in a median survival of 16.8 – 25.5 months, with a perioperative mortality of 0 – 5%.6, 13-16 Apart from EPP, another form of ‘cytoreductive surgery’ for MPM includes extended pleurectomy/decortication (P/D), which was recently defined by the International Mesothelioma Interest Group as ‘parietal and visceral pleurectomy to remove all gross tumour with resection of the diaphragm and/or pericardium as required.’17 A systematic review of the current literature found that extended P/D can achieve a median overall survival of 11.5 – 31.7 months, with an inter-quartile range of 15 – 25 months, although there is a paucity of randomized controlled data with this treatment modality, and survival benefits may be multi-factorial.18
In conclusion, the MesoVATS Collaborators have again demonstrated that highquality randomized controlled trials are feasible to assess surgical outcomes in the treatment of MPM. However, their study design, analysis and interpretation should be viewed with caution, and patients who require partial pleurectomy/decortication, particularly in cases that require liberation of the underlying lung, should not be declined VAT-PP based on this trial. Currently, clinical outcomes for surgical procedures performed in the treatment of MPM remain controversial. A large number of observational studies have presented encouraging results for EPP and extended P/D, indicating that prolonged survival can be achieved for highly selected patients in tertiary referral centres.14, 19, 20 Perhaps the challenge in the future is not to prove whether surgery should be performed at all for MPM, but rather which patients should undergo which form of surgery based on yet to be determined prognostic factors that will help facilitate patient selection and minimize unnecessary morbidity and mortality. REFERENCES 1.
Rintoul RC, Ritchie AJ, Edwards JG, Waller DA, Coonar AS, Bennett M, et al. Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial. Lancet. 2014.
2.
Treasure T, Lang-Lazdunski L, Waller D, Bliss JM, Tan C, Entwisle J, 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. The lancet oncology. 2011;12:763-72.
3.
Weder W, Stahel RA, Baas P, Dafni U, de Perrot M, McCaughan BC, et al. The MARS feasibility trial: conclusions not supported by data. The lancet oncology. 2011;12:1093-4; author reply 4-5.
4.
Rusch VW, Kindler HL. MARS: a sense of perspective and an inconvenient truth. Journal of thoracic oncology. 2013;8:e49-50.
5.
Cao CQ, Yan TD, Bannon PG, McCaughan BC. A systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma. Journal of thoracic oncology. 2010;5:1692-703.
6.
Cao C, Tian D, Manganas C, Matthews P, Yan TD. Systematic review of trimodality therapy for patients with malignant pleural mesothelioma. Annals of cardiothoracic surgery. 2012;1:428-37.
7.
Bliss JM, Coombes G, Darlison L, Edwards J, Entwisle J, Kilburn LS, et al. The MARS feasibility trial: conclusions not supported by data ? Authors' reply. The lancet oncology. 2011;12:1094-5.
8.
Treasure T, Utley M, O'Byrne K. MARS: a sense of perspective and an inconvenient truth. Journal of thoracic oncology. 2013;8:e48-9.
9.
Tan C, Sedrakyan A, Browne J, Swift S, Treasure T. The evidence on the effectiveness of management for malignant pleural effusion: a systematic review. European journal of cardio-thoracic surgery. 2006;29:829-38.
10.
Cao C, Yan TD, Bannon PG, McCaughan BC. Summary of prognostic factors and patient selection for extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. Annals of surgical oncology. 2011;18:29739.
11.
Lee YC. Surgical resection of mesothelioma: an evidence-free practice. Lancet. 2014;384:1080-1.
12.
Lee YC, Light RW, Musk AW. Management of malignant pleural mesothelioma: a critical review. Current opinion in pulmonary medicine. 2000;6:267-74.
13.
Van Schil PE, Baas P, Gaafar R, Maat AP, Van de Pol M, Hasan B, et al. Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial. The European respiratory journal. 2010;36:1362-9.
14.
Krug LM, Pass HI, Rusch VW, Kindler HL, Sugarbaker DJ, Rosenzweig KE, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. Journal of clinical oncology. 2009;27:3007-13.
15.
Weder W, Stahel RA, Bernhard J, Bodis S, Vogt P, Ballabeni P, et al. Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. Annals of oncology. 2007;18:1196-202.
16.
Rea F, Marulli G, Bortolotti L, Breda C, Favaretto AG, Loreggian L, et al. Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): Feasibility and results. Lung cancer. 2007;57:89-95.
17.
Rice D, Rusch V, Pass H, Asamura H, Nakano T, Edwards J, 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. Journal of thoracic oncology. 2011;6:1304-12.
18.
Cao C, Tian DH, Pataky KA, Yan TD. Systematic review of pleurectomy in the treatment of malignant pleural mesothelioma. Lung cancer. 2013;81:319-27.
19.
Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD. A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung cancer. 2014;83:240-5.
20.
Bolukbas S, Manegold C, Eberlein M, Bergmann T, Fisseler-Eckhoff A, Schirren J. Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy. Lung cancer. 2011;71:75-81.
Figure Legend Figure 1: Overview of surgical procedures performed in the curative and palliative treatment of malignant pleural mesothelioma *includes 30-day and in-hospital mortality
Fig 1
Surgical management of malignant pleural mesothelioma: an update of clinical evidence Christopher Cao MBBS BSc, Ben Fu MDS, Chloe Wilcox MBBS, Elan Novis MBBS, David H. Tian MBBS, Tristan D. Yan MBBS BSc MD MS PhD
www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1043-0679(15)00011-8 http://dx.doi.org/10.1053/j.semtcvs.2015.02.007 YSTCS723
To appear in:
Semin Thoracic Surg
Cite this article as: Christopher Cao MBBS BSc, Ben Fu MDS, Chloe Wilcox MBBS, Elan Novis MBBS, David H. Tian MBBS, Tristan D. Yan MBBS BSc MD MS PhD, Surgical management of malignant pleural mesothelioma: an update of clinical evidence, Semin Thoracic Surg, http://dx.doi.org/10.1053/j.semtcvs.2015.02.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Article type: Editorial Title: Surgical management of malignant pleural mesothelioma: An update of clinical evidence Running head: Surgical Clinical Evidence for MPM Authors: Christopher Cao MBBS BSc1,2, Ben Fu MDS1, Chloe Wilcox MBBS1, Elan Novis MBBS1, David H. Tian MBBS1, Tristan D. Yan MBBS BSc MD MS PhD1,3 Affiliations: The Systematic Review Unit, The Collaborative Research (CORE) Group, Macquarie University, Sydney, Australia1; Department of Cardiothoracic Surgery, Prince of Wales Hospital, Sydney, Australia2; Department of Cardiothoracic Surgery, the Royal Prince Alfred Hospital, Sydney, Australia3 Keywords: Malignant pleural mesothelioma, pleurectomy, pleurodesis, randomized controlled trial Main text word count: 1237 Corresponding Author: Christopher Cao, The Systematic Review Unit, The Collaborative Research (CORE) Group, Macquarie University, Sydney, Australia; email: [email protected]; Phone: +61291131111 Fax: +61291133393 Disclaimers: No potential conflicts of interest. Ultramini abstract: Two randomized controlled trials have been completed to investigate the surgical management of malignant pleural mesothelioma. We hereby discuss the findings from these trials and the current evidence of various surgical techniques to treat this challenging disease.
The MesoVATS Collaborators recently published the second ever randomized controlled trial on the surgical management of malignant pleural mesothelioma (MPM) in The Lancet.1 This trial recruited 196 patients from 12 hospitals over a decade to undergo either video-assisted thoracoscopic partial pleurectomy (VAT-PP, n = 98) or talc pleurodesis (n = 98). The primary endpoint was 12-month survival, and secondary outcomes included lung function tests, presence or absence of pleural effusions, quality-of-life measurements, cost analyses and perioperative complications. Results of the study found that overall survival at 1-year was not statistically significantly different between the two treatment groups. Complete data for secondary endpoints were available for less than half of the randomized patients. Patients who underwent VAT-PP were reported to result in more complications and longer hospitalization, but morbidities were not standardized according to any grading system. More patients were likely to achieve resolution of pleural effusion on imaging after undergoing VAT-PP at 1-month and 6-months, but no differences were found at 3-months and 12-months. The estimated mean cost for VAT-PP treatment and follow-up care at 12 months was approximately ₤3800 more than talc pleurodesis, with a calculated incremental cost effectiveness ratio of ₤109,028 per quality-adjusted life year gained. No clear advantages were found for either treatment arm in regards to quality-of-life outcomes and lung function tests from the limited data available. Overall, the authors concluded that VAT-PP should not be recommended to improve the overall survival outcomes of patients presenting with pleural effusions secondary to MPM.
The immense logistical challenges of completing a clinical trial for a rare disease such as MPM were demonstrated by Treasure et al. in the Mesothelioma and
Radical Surgery (MARS) trial,2 and the MesoVATS Collaborators should be congratulated on their efforts to complete the second ever randomized study related to MPM. The primary objective of the MARS trial was to assess the feasibility of randomizing 50 patients within a 12-month period to undergo either extrapleural pneumonectomy (EPP) versus no EPP. At the completion of the trial, 16 out of 24 patients assigned to the EPP arm completed the procedure after a 3-year recruitment period. From the available data, authors of the MARS trial concluded that EPP ‘offers no benefit and possibly harms patients,’ a controversial statement that has drawn criticism from some members of the thoracic surgical community.3 It was claimed that the MARS trial violated the fundamental principles of clinical trial reporting by retrospectively analysing a feasibility-testing study.4 Objectively, with an operative mortality rate of 18% for patients who underwent EPP per protocol, the clinical outcomes of the MARS trial represented one of the worst results in the existing literature.5, 6 Nonetheless, authors of the MARS trial emphasized the benefits of a randomized controlled trial with intention to treat analysis to circumvent potential biases in case selection, reporting and interpretation, stating that ‘some unbiased evidence is clearly better than none’.7, 8
A number of comments can be made regarding the clinical design, technical performance and methodological analysis of the MesoVATS trial. Unlike the MARS trial, this study did not mandate histological confirmation prior to randomization, and VAT-PP was performed for 11% of patients who had benign disease or nonmesothelioma malignancies. Although these patients were excluded from analysis, their exposure to potential complications without significant benefit from a partial
pleurectomy procedure may have posed a clinical dilemma. From a technical perspective, the pleurodesis arm included a combination of talc slurry (n=35) and thoracoscopic poudrage (n=34) techniques. It should be acknowledged that both clinical and economic endpoints may differ significantly between these two distinct therapeutic approaches. Thoracoscopy would generally require an operating theatre and general anaesthesia, as well as associated personnel requirements and costs. However, this procedure does offer an opportunity to directly visualise tumour involvement and perform biopsies for unconfirmed cases of MPM. On the other hand, previous studies have demonstrated that talc slurry may be associated with higher recurrences of pleural effusions, but it can be performed in more frail candidates at a lower cost.9 Finally, the MesoVATS trial performed a retrospective subgroup analysis by stratifying patients according to the European Organisation for Research and Treatment of Cancer (EORTC) prognostic score, which involved a combination of white cell count, gender, ECOG score and histological subtype. More recent studies have demonstrated that nodal involvement, staging, and (neo)adjuvant therapy may be more predictive of survival in patients with MPM.10
From a broader perspective, outcomes of the MesoVATS study should be considered in the context of a spectrum of surgical procedures performed for MPM, ranging from radical surgeries that aim for macroscopic complete resection to minimally invasive procedures that are palliative, as summarized in Figure 1. The authors of the MesoVATS study concluded from their findings that VAT-PP conferred no survival benefit over talc pleurodesis at 12-months, which was the primary endpoint of the trial. This was further emphasized by the accompanying commentary by Lee11, who stated that VAT-PP failed to demonstrate survival benefits through
‘cytoreduction’, and that there is no evidence to suggest cytoreduction is effective for MPM. However, it should be recognized that neither procedures primarily aimed to improve survival, but rather to improve symptomatic relief and quality-of-life. Arguably, these endpoints should have been given more focus in the MesoVATS trial to compare the two palliative procedures. Unfortunately, only 71 out of 171 analysed patients completed their functional scale scores at 1-year due to missed appointments, consent withdrawals or deaths. In regards to ‘cytoreduction’, the term ‘complete macroscopic cytoreduction’ is usually associated with radical procedures such as EPP that are performed with a curative intent and an aim of prolonging longterm survival. Lee cited a general review published 15 years ago and claimed that surgical resection for mesothelioma is an evidence-free practice.11, 12 In fact, recent systematic reviews have identified prospective studies on trimodality therapy involving patients treated with standardized neoadjuvant chemotherapy regimens, EPP and adjuvant radiotherapy that resulted in a median survival of 16.8 – 25.5 months, with a perioperative mortality of 0 – 5%.6, 13-16 Apart from EPP, another form of ‘cytoreductive surgery’ for MPM includes extended pleurectomy/decortication (P/D), which was recently defined by the International Mesothelioma Interest Group as ‘parietal and visceral pleurectomy to remove all gross tumour with resection of the diaphragm and/or pericardium as required.’17 A systematic review of the current literature found that extended P/D can achieve a median overall survival of 11.5 – 31.7 months, with an inter-quartile range of 15 – 25 months, although there is a paucity of randomized controlled data with this treatment modality, and survival benefits may be multi-factorial.18
In conclusion, the MesoVATS Collaborators have again demonstrated that highquality randomized controlled trials are feasible to assess surgical outcomes in the treatment of MPM. However, their study design, analysis and interpretation should be viewed with caution, and patients who require partial pleurectomy/decortication, particularly in cases that require liberation of the underlying lung, should not be declined VAT-PP based on this trial. Currently, clinical outcomes for surgical procedures performed in the treatment of MPM remain controversial. A large number of observational studies have presented encouraging results for EPP and extended P/D, indicating that prolonged survival can be achieved for highly selected patients in tertiary referral centres.14, 19, 20 Perhaps the challenge in the future is not to prove whether surgery should be performed at all for MPM, but rather which patients should undergo which form of surgery based on yet to be determined prognostic factors that will help facilitate patient selection and minimize unnecessary morbidity and mortality. REFERENCES 1.
Rintoul RC, Ritchie AJ, Edwards JG, Waller DA, Coonar AS, Bennett M, et al. Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial. Lancet. 2014.
2.
Treasure T, Lang-Lazdunski L, Waller D, Bliss JM, Tan C, Entwisle J, 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. The lancet oncology. 2011;12:763-72.
3.
Weder W, Stahel RA, Baas P, Dafni U, de Perrot M, McCaughan BC, et al. The MARS feasibility trial: conclusions not supported by data. The lancet oncology. 2011;12:1093-4; author reply 4-5.
4.
Rusch VW, Kindler HL. MARS: a sense of perspective and an inconvenient truth. Journal of thoracic oncology. 2013;8:e49-50.
5.
Cao CQ, Yan TD, Bannon PG, McCaughan BC. A systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma. Journal of thoracic oncology. 2010;5:1692-703.
6.
Cao C, Tian D, Manganas C, Matthews P, Yan TD. Systematic review of trimodality therapy for patients with malignant pleural mesothelioma. Annals of cardiothoracic surgery. 2012;1:428-37.
7.
Bliss JM, Coombes G, Darlison L, Edwards J, Entwisle J, Kilburn LS, et al. The MARS feasibility trial: conclusions not supported by data ? Authors' reply. The lancet oncology. 2011;12:1094-5.
8.
Treasure T, Utley M, O'Byrne K. MARS: a sense of perspective and an inconvenient truth. Journal of thoracic oncology. 2013;8:e48-9.
9.
Tan C, Sedrakyan A, Browne J, Swift S, Treasure T. The evidence on the effectiveness of management for malignant pleural effusion: a systematic review. European journal of cardio-thoracic surgery. 2006;29:829-38.
10.
Cao C, Yan TD, Bannon PG, McCaughan BC. Summary of prognostic factors and patient selection for extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. Annals of surgical oncology. 2011;18:29739.
11.
Lee YC. Surgical resection of mesothelioma: an evidence-free practice. Lancet. 2014;384:1080-1.
12.
Lee YC, Light RW, Musk AW. Management of malignant pleural mesothelioma: a critical review. Current opinion in pulmonary medicine. 2000;6:267-74.
13.
Van Schil PE, Baas P, Gaafar R, Maat AP, Van de Pol M, Hasan B, et al. Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial. The European respiratory journal. 2010;36:1362-9.
14.
Krug LM, Pass HI, Rusch VW, Kindler HL, Sugarbaker DJ, Rosenzweig KE, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. Journal of clinical oncology. 2009;27:3007-13.
15.
Weder W, Stahel RA, Bernhard J, Bodis S, Vogt P, Ballabeni P, et al. Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. Annals of oncology. 2007;18:1196-202.
16.
Rea F, Marulli G, Bortolotti L, Breda C, Favaretto AG, Loreggian L, et al. Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): Feasibility and results. Lung cancer. 2007;57:89-95.
17.
Rice D, Rusch V, Pass H, Asamura H, Nakano T, Edwards J, 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. Journal of thoracic oncology. 2011;6:1304-12.
18.
Cao C, Tian DH, Pataky KA, Yan TD. Systematic review of pleurectomy in the treatment of malignant pleural mesothelioma. Lung cancer. 2013;81:319-27.
19.
Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD. A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung cancer. 2014;83:240-5.
20.
Bolukbas S, Manegold C, Eberlein M, Bergmann T, Fisseler-Eckhoff A, Schirren J. Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy. Lung cancer. 2011;71:75-81.
Figure Legend Figure 1: Overview of surgical procedures performed in the curative and palliative treatment of malignant pleural mesothelioma *includes 30-day and in-hospital mortality
Fig 1
