With persistently poor survival and restricted treatment options for pleural mesothelioma, a UK-first trial aims to determine whether highly targeted proton beam therapy can improve survival and quality of life in selected patients with the condition, as this horizon-scanning feature explains.
Mesothelioma remains one of the most difficult thoracic malignancies to treat. Primarily linked to asbestos exposure, although non-occupational causes are rising, it has a median survival of only 12–18 months.
There is currently no cure and treatment options remain limited. Key treatment guidelines from the European Society for Medical Oncology and the British Thoracic Society emphasise a multidisciplinary and comprehensive management approach.
First-line systemic treatment options include platinum–pemetrexed chemotherapy and combination treatment with the immune checkpoint inhibitors nivolumab and ipilimumab.
Proton beam therapy rationale in mesothelioma
Conventional radiotherapy can help to control small areas of mesothelioma, such as painful tumour deposits, but is not generally suitable for treating the full lining of the lung.
The target area is large and close to critical structures, meaning standard radiotherapy risks clinically significant exposure to the heart, healthy lung tissue and the liver.
Proton beam therapy offers a more targeted approach to radiotherapy delivery. By depositing most of its energy within the tumour, rather than beyond it, researchers believe it may reduce radiation exposure to healthy tissue and lead to fewer side effects.
As such, the first randomised UK clinical trial to investigate proton beam therapy for mesothelioma has been launched by University College London (UCL) and University College London Hospitals NHS Foundation Trust (UCLH).
HIT-MESO trial design and potential impact
This phase 3, multicentre, randomised HIT-MESO trial will test whether the approach can delay the need for systemic anti-cancer therapy and increase two-year overall survival from around 30% to 50%.
The trial is sponsored by UCL and funded by Asthma + Lung UK, with treatment being delivered at either UCLH or The Christie NHS Foundation Trust in Manchester. As travel and accommodation can be major practical barriers for patients with advanced thoracic disease, the charity Mesothelioma UK is providing funding to support these costs.
HIT-MESO aims to recruit up to 148 patients from 23 NHS centres across England and Wales. Around 50 patients have already been recruited.
Eligible participants have histologically confirmed mesothelioma confined to one hemithorax and have not yet received anti-cancer treatment and will receive daily proton beam therapy over five days for five weeks.
Final words: the expert perspective
HIT-MESO highlights a broader direction for mesothelioma care: using advanced radiotherapy technology not only for palliative care but also as part of active disease control in carefully selected patients.
Dr Crispin Hiley, clinical associate professor and honorary consultant at UCL Cancer Institute and HIT-MESO chief investigator, said: ‘Mesothelioma is one of the most challenging cancers we treat. Conventional radiotherapy simply cannot safely cover the full area affected by the disease without causing unacceptable harm to healthy tissue.
‘Proton beam therapy allows us to deliver high-dose radiation far more precisely, sparing critical organs like the heart and healthy lung. Through this trial, we hope to show that this approach can significantly improve survival and quality of life for patients.
If successful, it is hoped that the HIT-MESO trial could fundamentally change how mesothelioma is treated in the UK, with proton beam therapy becoming a new standard treatment for selected mesothelioma patients.