Radiotherapy for the treatment of malignant pleural mesothelioma

Our plain-English summary of Radiotherapy for the treatment of malignant pleural mesothelioma, by M. de Perrot, L. Wu, M. Wu, et al (The Lancet. Oncology, 2017).

The study

• Authors: M. de Perrot, L. Wu, M. Wu, B.C.J. Cho
• Journal: The Lancet. Oncology
• Published: 2017;18(9):e532-e542
• Type of article: Review
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is an aggressive disease that continues to be associated with poor outcomes. Although, traditionally this disease is considered to be resistant to radiotherapy, more recent evidence suggests that radiotherapy can produce positive outcomes. Over the past 15 years, the development of new, highly conformal radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), has enabled investigators to optimise the delivery of high-dose radiotherapy to the whole of the hemithorax. Prospective single-arm trials have shown that the median survival of patients who have completed high-dose hemithoracic radiotherapy after extrapleural pneumonectomy could reach 23·9-39·4 months independent of the chemotherapeutic response, suggesting that IMRT could potentially have an intrinsic benefit to this subset of patients. These observations have led to a change in practice, with the introduction of adjuvant pleural IMRT after pleurectomy-decortication and the development of induction-accelerated hemithoracic IMRT followed by extrapleural pneumonectomy. This Review focuses on recent observations on the role of radiotherapy in the treatment of malignant pleural mesothelioma, with particular emphasis on the results of clinical trials that evaluate the role of high-dose hemithoracic radiotherapy.

Copyright © 2017 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not a new study. The authors searched PubMed for English-language studies of radiotherapy for malignant pleural mesothelioma published from 1975 to March 2017 and described earlier trials. Asbestos exposure was not discussed. In a small 1995 trial, 8 of 20 patients assigned no radiotherapy developed tumour growth at the procedure site, compared with none of 20 who received preventive radiation. In the larger SMART trial the rates were 9% with immediate and 16% with deferred radiotherapy, a difference that was not statistically significant. In one study, early intensity-modulated radiotherapy to one side of the chest after lung removal led to fatal inflammation of the remaining lung in 6 of 13 patients. In trials combining chemotherapy, lung removal and radiotherapy, median survival was 15.5 to 25.5 months for all enrolled patients and 23.9 to 39.4 months for those completing all three treatments. The authors noted debate over whether this reflected patient selection. In the authors' own program giving radiotherapy before surgery, 90 patients had a median survival of 28.3 months. The authors concluded that radiotherapy's exact role remained to be defined.

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: Narrative review of published studies and clinical trials on radiotherapy for malignant pleural mesothelioma
• Who was studied: Published studies (in vitro, animal and clinical) found by a PubMed search, in English, January 1, 1975 to March 1, 2017, plus ClinicalTrials.gov. The patients in those studies had malignant pleural mesothelioma.
• Exposure: Radiotherapy as a treatment: prophylactic, palliative, adjuvant and induction. Techniques covered were 3D-conformal radiotherapy, intensity-modulated radiation therapy, tomotherapy, VMAT and proton therapy. Asbestos exposure was not studied.
• Main results:
  • In the 1995 randomised trial by Boutin and colleagues, patients were assigned to prophylactic radiotherapy or no radiotherapy. Port-site metastasis developed in 8 (40%) of 20 patients in the control (no radiotherapy) group, compared with none in the radiotherapy group.
  • In the SMART trial (203 patients), procedure-tract metastasis within 12 months occurred in 9% of the immediate radiotherapy group and 16% of the deferred radiotherapy group. This difference was not statistically significant.
  • The authors stated that in their practice they do not currently recommend prophylactic irradiation of surgical port sites.
  • Hemithoracic IMRT after extrapleural pneumonectomy was reported to cause fatal pneumonitis of the contralateral (remaining) lung. Allen and colleagues reported fatal pneumonitis in 6 (46%) of 13 patients.
  • In trimodality trials (chemotherapy, extrapleural pneumonectomy and radiotherapy), median survival by intention-to-treat analysis ranged from 15.5 to 25.5 months.
  • In the same trials, patients who completed all three treatments had median survival ranging from 23.9 to 39.4 months.
  • The randomised SAKK 17/04 trial (54 patients) found no difference in locoregional relapse-free survival or overall survival between adjuvant hemithoracic radiotherapy and no radiotherapy.
  • In the IMPRINT trial of pleural IMRT after lung-sparing surgery, 7% of patients had grade 3 pneumonitis, and no grade 5 pneumonitis was reported.
  • In the authors' own program of induction-accelerated radiotherapy followed by extrapleural pneumonectomy, 90 treatment-naive patients (November 2008 to February 2017) had a median survival of 28.3 months in the intention-to-treat population.
  • In that program, locoregional recurrence occurred in 20 (22%) of 90 patients.
• The authors' conclusion: The authors concluded that increasing evidence supports that mesothelioma is sensitive to radiotherapy, but the exact role radiotherapy will play in treatment remains to be defined.
• Limitations the authors state:
  • The authors stated it remains debated whether the better survival in patients who completed trimodality therapy is a true treatment effect or the result of patient selection bias.
  • The MARS and SAKK 17/04 randomised trials had small sample sizes, and few registered patients completed surgery or radiotherapy.
  • Studies of palliative radiotherapy were retrospective, and the degree of benefit has been difficult to define.
  • A randomised trial would be needed to draw definitive conclusions about the benefit of induction irradiation.

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, Intensity-Modulated Radiation Therapy (IMRT), Hemithorax, Median Overall Survival, Extrapleural Pneumonectomy (EPP), Pleurectomy/Decortication (P/D), Clinical Trial.

Related studies

• Hemithoracic intensity-modulated radiotherapy using helical tomotherapy for patients after extrapleural pneumonectomy for malignant pleural mesothelioma — T. Ebara, H. Kawamura, et al. (2012)
• The Role of Adjuvant Radiotherapy in the Treatment of Pleural Mesothelioma — G.D. Lewis, S.M. Dalwadi, et al. (2019)
• Fast neutron radiotherapy in the treatment of malignant pleural mesothelioma — S.A. Patel, A.S. Kusano, et al. (2015)
• Role of postoperative radiotherapy in the management of malignant pleural mesothelioma : A propensity score matching of the SEER database — O. Abdel-Rahman (2017)
• Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma — A. Chi, Z. Liao, et al. (2011)
• Techniques of surgery and radiotherapy for multimodal treatment of pleural mesothelioma — P. Bonnette (2011)

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