256 Hemi-thoracic irradiation with proton therapy in malignant pleural mesothelioma (HIT-Meso)

Abstract

Introduction Only 15% of UK mesothelioma patients receive radiotherapy and this is predominantly given with palliative intent. Radical hemi-thoracic radiotherapy with conventional radiotherapy has demonstrated an overall survival (OS) benefit, but it has high rates of toxicity. Planning studies have shown that treatment with proton beam therapy (PBT) in malignant pleural mesothelioma (MPM) may be beneficial due to reduced doses to normal tissues, but clinical data is limited. Methods HIT-Meso is a phase III, multicentre, 1:1 randomised controlled trial to determine the benefits of PBT in patients with histologically confirmed MPM confined to one hemi-thorax. Endpoints: (i) progression-free survival and (ii) OS (co-primary using a fixed-sequence approach); time to next treatment, local-failure-free and distant-metastases-free survival, safety and toxicity, quality of life, health and social care resource use, and incremental cost-effectiveness (secondary); translational research (exploratory); participant experience (qualitative sub-study). A sample size of N = 148 is required to detect an OS hazard ratio of 0.58, equivalent to an improvement in 2-year OS from 30% to 50%, with 85% power and 5% two-sided significance level, adjusted for potential dropout and interim analyses of OS benefit at 1.5, 2.0 and 2.5 years. We aim to complete recruitment in 3 years across 20-30 UK centres followed by an additional 2 years of follow-up. Results Recruitment opened 28/03/2024; 9 sites are currently open, predominantly in southern England, with another 12 in set-up (UK-wide). Fifteen patients have been recruited, with 7 randomised to PBT treatment and 4 have completed PBT treatment (06/12/2024). Conclusion HIT-MESO is recruiting ahead of schedule but patients from Scotland remain unable to access PBT trials. If efficacy and safety are demonstrated, PBT will become a standard of care treatment for patients with mesothelioma confined to one hemi-thorax.