Controversies in the role of radiotherapy in pleural mesothelioma

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.

Contemporary management of mesothelioma

“…The highest quality evidence for palliative radiotherapy comes from the phase II SYSTEMS trial, which reported pain improvement in only 35% using 20 Gy in five fractions [ 59 ]. Since PM has a low α/β ratio, predicting better responses to dose-escalated hypofractionated regimes [ 60 ], the SYSTEMS trial was followed by the phase III RCT, SYSTEMS-2, which compared 36 Gy in six fractions to 20 Gy in five fractions [ 61 ]. Mature data from this trial are expected during 2024.…”

Effects of Photon Radiation on DNA Damage, Cell Proliferation, Cell Survival, and Apoptosis of Murine and Human Mesothelioma Cell Lines

“…Localised radiotherapy is used for multiple purposes in treating mesothelioma -ranging from treatment of procedure tract metastases, adjuvant hemi-thoracic radiation as part of aggressive multimodality therapy, and as palliative therapy to individual lesions 7 . However, high dose radiotherapy for local control can have toxicities, and does not palliate symptoms in a wholly effective manner [8][9][10] .…”

“… 6 However, high-dose RT for local control can have toxic effects and does not palliate symptoms in a wholly effective manner. 7 , 8 , 9 …”