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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

T. Treasure, L. Lang-Lazdunski, D. Waller, J. Bliss, C. Tan, J. Entwisle, M. Snee, M. O'Brien, G. Thomas, S. Senan, K. O’Byrne, L. Kilburn, J. Spicer, D. Landau, J. Edwards, G. Coombes, L. Darlison, J. Peto
Published 2011 · Medicine

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Summary Background The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study. Methods MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524. Findings Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92–3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21–6·26; p=0·016). Median survival was 14·4 months (5·3–18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group. Interpretation In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients. Funding Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.
This paper references
10.1016/J.LUNGCAN.2007.02.004
Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): Feasibility and results.
F. Rea (2007)
BTS guidelines Guidelines on the selection of patients with lung cancer for surgery British Thoracic Society and Society of Cardiothoracic Surgeons of Great Britain and Ireland Working Party
10.1016/J.RADONC.2003.09.007
Literature-based recommendations for treatment planning and execution in high-dose radiotherapy for lung cancer.
S. Senan (2004)
10.1016/J.ATHORACSUR.2007.04.076
Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma.
D. Rice (2007)
10.1136/thorax.56.2.89
Guidelines on the selection of patients with lung cancer for surgery
T. British (2001)
10.1067/MTC.2001.116560
A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma.
V. Rusch (2001)
MARS Study Investigators and Centre Details Principal and main co-investigators according to centre
Nci Dctd
10.1016/j.jtcvs.2007.10.054
Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients.
R. Flores (2008)
10.1136/BMJ.328.7434.237
Radical surgery for mesothelioma
T. Treasure (2004)
Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI
L D Landau (2003)
10.1016/S1010-7940(02)00273-7
The management of malignant pleural mesothelioma; single centre experience in 10 years.
T. Aziz (2002)
10.1016/S0140-6736(04)17108-0
Pleural mesothelioma: little evidence, still time to do trials
T. Treasure (2004)
10.1016/S0140-6736(95)90462-X
Continuing increase in mesothelioma mortality in Britain
J. Peto (1995)
10.1016/S0022-5223(99)70469-1
Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients.
D. Sugarbaker (1999)
10.1016/J.LUNGCAN.2004.04.019
Considerations for post-operative radiotherapy to the hemithorax following extrapleural pneumonectomy in malignant pleural mesothelioma.
S. Senan (2004)
10.1136/thorax.57.suppl_2.ii36
THE CHANGING PREVALENCE OF ASTHMA?
P. Burney (2002)
10.1097/JTO.0b013e31815608d9
Prognostic Factors in the Treatment of Malignant Pleural Mesothelioma at a Large Tertiary Referral Center
R. Flores (2007)
10.1200/JCO.2008.20.3943
Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma.
L. Krug (2009)
10.1378/CHEST.108.4.1122
A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group.
V. Rusch (1995)
10.1016/S1010-7940(02)00735-2
The management of malignant pleural mesothelioma.
G. Maggi (2003)
10.1016/J.EJCTS.2006.01.015
Incidence and management of complications after neoadjuvant chemotherapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma.
I. Opitz (2006)
10.1016/J.JTCVS.2004.02.021
Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies.
D. Sugarbaker (2004)
Survival in surgically diagnosed patients with malignant mesothelioma in current practice
C. Tan (2002)
10.1016/J.ATHORACSUR.2004.01.034
The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma.
D. Stewart (2004)
The eff ect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma
DJ Stewart (2004)
10.1097/JTO.0b013e3181ed0489
A Systematic Review of Extrapleural Pneumonectomy for Malignant Pleural Mesothelioma
C. Cao (2010)
A phase II trial of surgical resection and adjuvant highdose hemithoracic radiation for malignant pleural mesothelioma
VW Rusch (2001)
10.1093/ANNONC/MDM093
Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma.
W. Weder (2007)
Radiotherapy Group of European Organization for Research and Treatment of Cancer. Literature-based recommendations for treatment planning and execution in high-dose radiotherapy for lung cancer
S Senan (2004)
10.1200/JCO.2008.17.5604
Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma.
M. D. de Perrot (2009)
10.1038/sj.bjc.6602307
The expected burden of mesothelioma mortality in Great Britain from 2002 to 2050
J. Hodgson (2005)
Queens Hospital
S Morgan
10.1016/j.jtcvs.2009.02.046
Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study.
T. R. Tilleman (2009)
10.1097/JTO.0b013e3181ae26ae
The Mesothelioma and Radical Surgery Randomized Controlled Trial: The MARS Feasibility Study
T. Treasure (2009)
10.1183/09031936.00039510
Trimodality therapy for malignant pleural mesothelioma: results from an EORTC phase II multicentre trial
P. V. Van Schil (2010)
Bristol Royal Infirmary (3) A Morgan*; Nottingham City Hospital
10.1038/sj.bjc.6690105
The European mesothelioma epidemic
J. Peto (1999)



This paper is referenced by
10.1016/j.jtcvs.2014.10.083
Fifteen years in the evaluation of extrapleural pneumonectomy: Lessons to be learned.
T. Treasure (2015)
10.1016/j.jtcvs.2015.10.036
Pleurectomy decortication for mesothelioma: The procedure of choice when possible.
R. Flores (2016)
10.1111/crj.13029
Thematic series: Novel insights in pleural diseases
M. Froudarakis (2019)
10.1007/S00761-014-2886-9
Pleuramesotheliome: Multimodales Management als klinische Herausforderung
Rudolf A. Hatz (2015)
10.1080/17476348.2017.1338951
Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma
G. Marulli (2017)
10.1038/nrc.2017.42
Novel insights into mesothelioma biology and implications for therapy
T. Yap (2017)
10.5114/kitp.2017.72232
Malignant mesothelioma as a difficult interdisciplinary problem
W. Rokicki (2017)
10.2174/1573394713666170907160734
Current and Emerging Therapy for Malignant Pleural Mesothelioma: Focus on CD26/Dipeptidyl Peptidase IV as a Therapeutic Target
B. Doonan (2017)
10.1007/s10147-011-0365-5
Early mesothelioma revisited
Seiki Hasegawa (2011)
10.21037/ATM.2020.03.58
Malignant pleural mesothelioma: between pragmatism and hope.
M. Migliore (2020)
10.1002/jso.25260
Short‐term outcomes of pleurectomy decortication and extrapleural pneumonectomy in mesothelioma
M. V. van Gerwen (2018)
10.1159/000486578
Management and Survival of Pleural Mesothelioma: A Record Linkage Study
G. Carioli (2018)
10.1093/ejcts/ezx122
Induction chemotherapy, extrapleural pneumonectomy and adjuvant radiotherapy for malignant pleural mesothelioma
Monica Casiraghi (2017)
10.1016/S1877-1203(13)70384-7
Y a-t-il une place pour la chirurgie ?
Sophie M. Jaillard (2013)
10.1186/s13019-014-0176-7
Extrapleural pneumonectomy plus rib resection for malignant pleural mesothelioma: a case report
Yoshinori Yamashita (2014)
10.1097/JTO.0000000000000614
In Response.
Andrea Billè (2015)
10.1016/j.rpor.2017.07.006
Malignant pleural mesothelioma - Pleural cavity irradiation after decortication with helical tomotherapy.
S. Harrabi (2017)
SYNDECAN-1 INSIGHTS IN MESOTHELIOMA THESIS FOR DOCTORAL DEGREE ( Ph . D . ) By Ghazal
Heidari Hamedani (2017)
10.1016/S0140-6736(14)60418-9
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
R. Rintoul (2014)
10.3389/fonc.2019.01519
Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future
Fabio Nicolini (2019)
10.1007/978-1-4471-7355-7
Tips and Tricks in Thoracic Surgery
Dakshesh H. Parikh (2018)
10.21037/tlcr.2020.01.08
Surgery for pleural mesothelioma, when it is indicated and why: arguments against surgery for malignant pleural mesothelioma.
Gavitt A. Woodard (2020)
Risk factors and biomarkers for malignant mesothelioma
Vasiliki Panou (2019)
10.3389/fonc.2020.00939
Editorial: Emerging Therapies for Malignant Mesothelioma
Nico van Zandwijk (2020)
10.1016/j.ctrv.2015.05.001
The established and future biomarkers of malignant pleural mesothelioma.
V. Panou (2015)
10.21037/atm.2017.04.05
Randomized controlled trials in malignant pleural mesothelioma surgery-mistakes made and lessons learned.
D. Waller (2017)
alignant pleural mesothelioma
F. Honeyball (2013)
10.1136/thoraxjnl-2012-202006
Surgical resection of lung cancer England: more operations but no trials to test their effectiveness
T. Treasure (2012)
10.1111/1754-9485.12291
Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution
A. Bece (2015)
10.1111/php.13067
Modeling Epidermal Growth Factor Inhibitor‐mediated Enhancement of Photodynamic Therapy Efficacy Using 3D Mesothelioma Cell Culture
G. Cramer (2019)
10.1016/J.ARBRES.2014.06.005
Diagnóstico y tratamiento del mesotelioma pleural maligno
Francisco Rodríguez Panadero (2015)
10.1155/2015/282145
Frequency of Surgery in Black Patients with Malignant Pleural Mesothelioma
Emanuela Taioli (2015)
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