Controversies in the role of radiotherapy in pleural mesothelioma

Our plain-English summary of Controversies in the role of radiotherapy in pleural mesothelioma, by G.G. Hanna, T. John, D.L. Ball (Translational Lung Cancer Research, 2021).

The study

• Authors: G.G. Hanna, T. John, D.L. Ball
• Journal: Translational Lung Cancer Research
• Published: 2021;10(4):2079-2087
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is an uncommon thoracic cancer with a relatively poor outcome, which has only seen modest improvements when compared to non-small cell lung cancer. The mainstays of treatment have been surgery and systemic therapy, with radiation reserved for palliation or as an adjunct. However, there is re-emergent interest in the use of radiotherapy in the treatment of mesothelioma, given recent technical advances in radiotherapy delivery which permit increased treatment accuracy. This overview article reviews the radiobiology of the mesothelioma and whether or not mesothelioma is an inherently radioresistant cancer and the potential impact that hypofractionation may have on different histological subtypes in mesothelioma. This overview also considers the role of radiation in palliation, as adjunct to surgical resection and as adjunct to pleural tract procedures. In particular we review the growing evidence that pleural tract or port site adjuvant radiotherapy provides no clinical benefit. This overview will also consider potential emerging therapeutic strategies such as pre-operative short course hypofractionated radiotherapy. The role of novel radiotherapy techniques such as stereotactic ablative radiotherapy, image guided radiotherapy, proton therapy and the potential role of radiotherapy as an immune stimulating agent in combination of immunotherapy, will also be discussed. Finally, given the many unanswered questions, this review discusses some of the emerging and ongoing clinical trials of radiotherapy in the treatment of mesothelioma.

2021 Translational Lung Cancer Research. All rights reserved.

In plain English

This article reviewed published studies and ongoing trials of radiotherapy for malignant pleural mesothelioma. It studied no patients and mentioned asbestos only as the disease's main cause. The authors described five randomised trials of radiotherapy to biopsy or chest-drain sites. The first, from 1995, reported a benefit; four later trials, including a UK trial of 374 patients, did not. The MARS trial showed no indication of benefit from extrapleural pneumonectomy plus radiotherapy, but only eight of 24 patients assigned to pneumonectomy received the required radical radiotherapy. In SAKK 17/04, adding radiotherapy after surgery made no significant difference to local relapse-free survival. The Toronto group's SMART study gave a week of radiotherapy before surgery and reported median overall survival of 36 months among 62 patients, with 3 treatment-related deaths. The authors concluded that radiotherapy should be used to relieve local symptoms that do not respond to symptomatic measures or systemic therapy, but not to prevent spread along procedure tracts. They concluded that its role alongside surgery remains uncertain, and that short-course radiotherapy before surgery is a potential approach needing more evidence.

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 (overview) of published studies, guidelines and ongoing trials
• Who was studied: No patients of its own; the authors reviewed published studies and registered trials of radiotherapy in patients with malignant pleural mesothelioma
• Exposure: Radiotherapy: palliative, prophylactic to procedure tracts, adjuvant hemithoracic with surgery, short-course before surgery, IMRT, protons and SABR. Asbestos is named only as the main cause of mesothelioma; no fiber types are discussed.
• Main results:
  • Prophylactic radiotherapy to procedure tracts: the 1995 Boutin trial (40 patients) reported a benefit (tract metastases 0% with radiotherapy vs. 40% without, P<0.001). Four later randomised trials did not find a benefit.
  • In the most recent of these trials (PIT, UK, 374 patients randomised), ipsilateral chest wall metastases at 6 months were 3.2% vs. 5.3%, P=0.44, and no benefit was observed
  • In a Netherlands retrospective study of 227 palliative treatments in 189 patients, those treated with 4 Gy per fraction had a higher local response than those receiving fractions of less than 4 Gy (50% vs. 39%)
  • MARS trial (50 randomised): median survival was 14.4 months with extrapleural pneumonectomy plus radiotherapy vs. 19.5 months without pneumonectomy, hazard ratio 1.90 (95% CI: 0.92–3.93)
  • In MARS, only eight (33%) of the 24 patients randomised to pneumonectomy went on to the radical radiotherapy the protocol required
  • SAKK 17/04 (54 patients randomised after surgery): no significant difference in local relapse-free survival. The median was 7.6 months (95% CI: 4.5–10.7) without radiotherapy vs. 9.4 months (95% CI: 6.5–11.9) with radiotherapy.
  • SMART phase II study (62 suitable of 256 patients assessed): no deaths within 30 days of surgery, 3 (4.8%) treatment-related deaths, and median overall survival of 36 months
  • In SMART patients with cT1-3N0M0 disease (n=56), median disease-free and overall survival were 47 and 51 months for the epithelial subtype, vs. 8 and 10 months for the biphasic subtype
  • IMPRINT trial of pleural IMRT with both lungs intact: 45 patients enrolled and 27 evaluable, with two cases (7%) of grade 3 pneumonitis
• The authors' conclusion: The authors concluded that radiotherapy should be used to palliate local symptoms refractory to symptomatic measures or systemic therapy, and should not be used prophylactically on procedure tracts. They concluded that its role as an adjunct to surgery remains uncertain, and that pre-operative short-course hypofractionated radiotherapy is a potential approach needing further evidence.
• Limitations the authors state:
  • The authors state that pre-clinical and clinical data on how mesothelioma responds to radiation, alone or with systemic therapy, are lacking

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Non-Small Cell Lung Cancer, Systemic Therapy, Mesothelioma, Histological Subtype, Surgical Resection, Stereotactic Body Radiation Therapy (SBRT), Proton Therapy.

Related studies

• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)
• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• Current controversies in the management of malignant pleural effusions — M. Azzopardi, J.M. Porcel, et al. (2014)
• Issues and controversies in the plain-film diagnosis of asbestos-related disorders in the chest — W.B. Gefter, E.F. Conant (1988)
• Current controversies regarding the role of asbestos exposure in the causation of malignant mesothelioma: the need for an evidence-based approach to develop medicolegal guidelines — A.M. Marchevsky, M.R. Wick (2003)
• Controversies at international organizations over asbestos industry influence — B.I. Castleman (2001)

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