Radiotherapy for the treatment of pain in malignant pleural mesothelioma
MacLeod, Nicholas James Lewis
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Aims: The primary aim of this thesis was to explore the role of palliative radiotherapy in the treatment of pain in malignant pleural mesothelioma (MPM). The effect of radiotherapy on other symptoms was also examined. Biomarkers which might predict response to radiotherapy (Quantitative Sensory Testing – QST) were explored and objective evidence of response was sought via interpretation of Computed Tomography (CT) scans. The thesis also examined the role of Positron Emission Tomography (PET)-CT in radiotherapy planning and characterising pain in MPM. Methods: A narrative review of the challenges of pain management in MPM and a systematic review of the evidence supporting the use of palliative radiotherapy for pain control in MPM, were undertaken. In addition, a multi-centre, single arm phase II trial was conducted which examined the role of radiotherapy in pain control in MPM. This trial also assessed the role of PET-CT in radiotherapy planning and allowed for a characterisation of MPM-related pain. These components form the basis of this thesis. Results: Palliative radiotherapy at a dose of 20 Gy in five daily fractions using 6 Megavoltage (MV) photons improves pain in a significant proportion of patients with MPM. It does not have a beneficial effect on other symptoms or on quality of life. QST does not appear to be a useful clinical biomarker indicating likelihood of response to radiotherapy. Objective evidence of response via CT is low. Incorporation of PET-CT in the radiotherapy planning process alters the anatomical location of the target volume in patients with MPM. There is also an association between the Standard Uptake Value (SUV) uptake and pain, with the areas with highest SUV uptake being associated with the areas of pain. PET-CT results in upstaging of a significant proportion of patients. Pain is often severe and debilitating for patients with MPM and it has often a combination of neuropathic and nociceptive mechanisms. The presence of a neuropathic component to the pain is not associated with an increased likelihood of response to radiotherapy. Conclusions: Radiotherapy is effective at relieving pain in a proportion of patients with MPM and should be considered for all patients with MPM-related pain. PET-CT improves multiple parameters in the radiotherapy planning process compared with CT alone. QST parameters have not been shown to predict those patients who are likely to respond to radiotherapy.