The role of radical radiotherapy in the management of malignant pleural mesothelioma: A systematic review

Our plain-English summary of The role of radical radiotherapy in the management of malignant pleural mesothelioma: A systematic review, by M. Ashton, N. O'Rourke, S. Currie, et al (Radiotherapy and Oncology, 2017).

The study

• Authors: M. Ashton, N. O'Rourke, S. Currie, A. Rimner, A. Chalmers
• Journal: Radiotherapy and Oncology
• Published: 2017;125(1):1-12
• Type of article: Systematic review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a devastating disease with limited treatment options and a dismal prognosis. Attempts to employ radical radiotherapy in this disease have been limited by the complex shape of the pleura and the dose restrictions necessitated by the close proximity of radiosensitive structures. Recent shifts towards a 'lung sparing' surgical approach in MPM have further heightened these challenges. The aim of this systematic review is to assess recent advances in radiotherapy planning and delivery, to ascertain how these developments have impacted on the feasibility of delivering photon-based, high-dose radiotherapy with radical intent in MPM. Three electronic databases were searched and a total of 249 articles reviewed. The challenge of generating high quality, practice-defining data for diseases such as MPM was highlighted by the identification of just two randomised studies. Much of the literature consisted of low quality, retrospective data with small cohorts and inconsistent reporting on radiotherapy techniques and dosimetry. Nevertheless, a number of prospective phase II studies were identified to suggest that radical doses of radiotherapy can be delivered safely after a lung sparing procedure in MPM, reporting encouraging survival data and acceptable levels of toxicity.

Copyright © 2017 Elsevier B.V. All rights reserved.

In plain English

This article was a systematic review. The authors searched three electronic databases and reviewed 249 articles in detail, including letters, reviews and technical planning studies, to assess high-dose radiotherapy given with radical (curative) intent for malignant pleural mesothelioma. It covered techniques such as intensity modulated radiotherapy (IMRT) after lung removal (extrapleural pneumonectomy) or lung-sparing pleurectomy/decortication. Asbestos exposure was not studied. Much of the literature consisted of retrospective single-centre reports, often with few patients. Only two randomised trials of radical treatment had been done. One reviewed randomised trial gave radiotherapy after lung removal and had locoregional relapse-free survival as its main outcome. In that trial, relapse-free survival was 9.4 months (95% CI 6.5–11.9) with radiotherapy and 7.6 months (95% CI 4.5–10.7) without, a difference that was not statistically significant. In three early centre reports of IMRT after lung removal, fatal lung toxicity ranged from 1 of 13 to 6 of 13 patients. The authors concluded that several prospective phase II studies suggested radical radiotherapy doses can be delivered safely after lung-sparing surgery. They noted that firm conclusions were difficult to draw from studies without control groups or randomisation.

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: systematic review of published literature
• Who was studied: 249 articles on radiotherapy in malignant pleural mesothelioma (MPM), reviewed in detail. They were found by searching Embase, MEDLINE (1946 to present) and PubMed, plus hand-searching. They included retrospective case series and case reports, prospective studies, letters to the editor, systematic reviews, general reviews and technical/radiotherapy planning studies.
• Exposure: Photon-based high-dose radiotherapy with radical intent for malignant pleural mesothelioma. Techniques included conventional methods, IMRT, volumetric modulated arc radiotherapy (VMAT) and helical tomotherapy, given after extrapleural pneumonectomy (EPP), after pleurectomy/decortication (PD), or before surgery. Asbestos exposure was not the subject of the review.
• Main results:
  • Only two randomised trials of radical treatment in MPM had been undertaken, and the validity of the outcomes of both had been challenged.
  • Much of the literature consisted of retrospective reviews of single-centre practice. Of the 249 articles, 46 were prospective studies combining radiotherapy, surgery and chemotherapy, and 14 of these were multicentre.
  • The reviewed randomised trial by Stahel et al. recruited 54 patients to its second part, after EPP. The primary endpoint of that part was locoregional relapse-free survival. The review reported relapse-free survival of 9.4 months (95% CI 6.5–11.9) in the radiotherapy group and 7.6 months (95% CI 4.5–10.7) in the group without radiotherapy. The difference was not statistically significant.
  • Toxicity data were tabulated from three early institutional reports of IMRT after EPP. The fatal pulmonary toxicity rate was 6/63 (9.5%) at MD Anderson, 6/13 (46%) at Dana-Farber Institute/Brigham & Women's Hospital, and 1/13 (7.7%) at Duke University Medical Centre. A later retrospective report of 86 patients treated with post-operative IMRT gave a fatal pulmonary toxicity rate of 5.81%.
  • In a reviewed two-centre phase II study of IMRT after chemotherapy and PD, 27 patients commenced radiotherapy. There were 2 cases of grade 3 radiation pneumonitis and no grade 4 or 5 toxicities.
  • In reviewed long-term data on helical tomotherapy for 20 patients, all of whom had undergone PD, median overall survival was 33 months and median progression-free survival was 29 months.
• The authors' conclusion: The authors concluded that a number of prospective phase II studies suggested that radical doses of radiotherapy can be delivered safely after a lung-sparing procedure in MPM, with encouraging survival data and acceptable levels of toxicity. They also stated that the future role of radiotherapy in MPM remains unclear.
• Limitations the authors state:
  • Firm conclusions were difficult to draw from the trimodality studies because they lacked control groups and randomisation, and patients chosen for surgery were often highly selected.
  • Studies reported outcomes such as median overall survival in different ways, measuring survival from different starting points. This made comparisons of retrospective datasets very difficult.
  • Conference abstracts included in the review are subject to less robust peer review than journal articles, and they often gave limited information on technique, dosimetry and toxicity.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Systematic Review, Prognosis, Pleura.

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