The MARS feasibility trial: conclusions not supported by data

Our plain-English summary of The MARS feasibility trial: conclusions not supported by data, by W. Weder, R.A. Stahel, P. Baas, et al (The Lancet. Oncology, 2011).

The study

• Authors: W. Weder, R.A. Stahel, P. Baas, U. Dafni, M. de Perrot, B.C. McCaughan, T. Nakano, H.I. Pass, B.W. Robinson, V.W. Rusch, D.J. Sugarbaker, N. van Zandwijk
• Journal: The Lancet. Oncology
• Published: 2011;12(12):1093-4; author reply 1094-5
• Type of article: Letter, Comment
• Cited by: 90 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, the authors disputed the conclusions of the MARS feasibility trial, which compared extrapleural pneumonectomy (EPP) with no EPP in patients with malignant pleural mesothelioma. They summarised six prospective phase 2 studies of neoadjuvant chemotherapy, EPP and postoperative radiotherapy. In these studies around three-quarters of patients underwent EPP, about three-fifths received radiotherapy, median survival ranged from 16.8 to 25.5 months, and operative mortality from EPP ranged from 0% to 5%. They noted that MARS aimed to randomly assign 50 patients within 1 year but took 3 years, and so in their view the feasibility study failed. They also noted that it was not designed to test the benefit of EPP: an estimated 670 patients would be needed, but the survival results were based on only 30 deaths. Of 112 registered patients, 50 (42%) were randomised, and no information was given on the 58% not considered eligible. For this reason, they said, its survival results could not be compared directly with the earlier studies. They also cited several problems: chemotherapy that was not standardised, no data on the time from chemotherapy to EPP, possible treatment delays, and protocol violations, with three patients in the non-surgical group undergoing EPP. Operative mortality among the 17 patients who underwent EPP per protocol was 18%. The authors concluded that the MARS interpretation that EPP offers no benefit and possibly harms patients was inappropriate.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This item is a letter to the editor, not a research study, and did not study asbestos exposure. It criticised the conclusions of the MARS feasibility trial, which compared extrapleural pneumonectomy (EPP) with no EPP after chemotherapy for malignant pleural mesothelioma. The writers argued MARS was designed only to test whether 50 patients could be randomised within 1 year, and failed because this took 3 years. Survival results rested on only 30 deaths, though 670 patients would be needed to detect a survival difference. Of 112 registered patients, 50 were randomised (printed as 42%, though 50 of 112 is about 45%); the report did not give the status of those not deemed eligible. They also pointed to unstandardised chemotherapy and protocol violations. Operative mortality in MARS for the 17 patients who had EPP per protocol was 18%, against 0% to 5% in six earlier trials. They said this could be a statistical anomaly but was a concern. The authors concluded that the MARS interpretation, that limited data suggest EPP within trimodal therapy offers no benefit and possibly harms patients, was inappropriate.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Letter to the editor (correspondence) criticising the published MARS randomised feasibility trial; not an original study
• Who was studied: No study population of its own. The letter discusses the MARS trial, in which 112 patients with malignant pleural mesothelioma were registered and 50 were randomly assigned; the letter prints this as 42%, although 50 of 112 is about 45%. It also tabulates six earlier prospective trimodality therapy studies.
• Exposure: No asbestos exposure was studied. The subject is extrapleural pneumonectomy (EPP) as part of trimodality therapy (chemotherapy, EPP, radiotherapy) for malignant pleural mesothelioma.
• Main results:
  • The writers stated that the MARS feasibility study failed on its own aim: it was meant to randomise 50 patients within 1 year, but enrolling 50 patients took 3 years.
  • MARS investigators estimated 670 patients would be needed to detect an overall survival difference, but the reported MARS survival results were based on only 30 deaths.
  • The writers said the MARS report gave no information about the status of the registered patients not considered eligible for randomisation (printed by the letter as 58%), so its survival results cannot be compared directly with the other trimodality studies.
  • In MARS, chemotherapy before randomisation was not standardised for drug type, dose or number of cycles.
  • In the MARS non-surgical group, three patients underwent EPP and three more had non-EPP surgery. The writers called these protocol violations.
  • In MARS, operative mortality for the 17 patients who underwent EPP per protocol was 18%. The writers compared this with 0% to 5% in the earlier trials they tabulated, and said it could be a statistical anomaly but is a concern.
  • In the six earlier prospective trimodality studies the writers tabulated (other studies, not MARS), median survival ranged from 16.8 to 25.5 months and EPP operative mortality from 0% to 5%.
• The authors' conclusion: The authors concluded that MARS did not show the feasibility of a trial comparing chemotherapy with EPP and radiotherapy. They also concluded that the MARS interpretation was inappropriate, could move mesothelioma research in the wrong direction, and might be harmful to patients seeking advice. That interpretation was that the data, although limited, suggest EPP within trimodal therapy offers no benefit and possibly harms patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Extrapleural Pneumonectomy (EPP), Pleural Mesothelioma, Neoadjuvant Chemotherapy, Median Survival, Chemotherapy.

Related studies

• 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, et al. (2011)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)
• A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma — B.C. Cho, R. Feld, et al. (2014)
• Asbestos-related cancer and the amphibole hypothesis. The hypothesis is still supported by scientists and scientific data — B.T. Mossman, J.B. Gee (1997)
• Surgery for mesothelioma: MARS landing and future missions — T. Treasure (2010)
• Surgery for malignant pleural mesothelioma after radiotherapy (SMART): final results from a single-centre, phase 2 trial — B.C.J. Cho, L. Donahoe, et al. (2021)

Browse more research in The Lancet. Oncology, or return to medical research.