Hemithoracic Irradiation With Proton Therapy in Malignant Pleural Mesothelioma (HIT-Meso)

Primary Outcome Measures

1. Progression free survival [ Time Frame: From randomisation up to 2 years of follow up ]
   Defined as the time from randomisation to the date of disease progression
2. Overall survival [ Time Frame: From randomisation up to 2 years of follow up ]
   defined as the time from randomisation to the date of death from any cause.

Secondary Outcome Measures

1. Number of PBT-related adverse events as assessed by CTCAE v5.0 [ Time Frame: From start of PBT up to 2 years of follow up, for long term effects ]
   AEs related to proton beam therapy will be collected
2. The EORTC quality of life questionnaire (QLQ), EORTC QLQ-C30 score, scale of 0-100. [ Time Frame: From randomisation up to 2 years of follow up ]

   Participant reported quality of life outcomes. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / quality of life (QoL scale), and six single items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

   Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

3. ED-5D-5L score [ Time Frame: From randomisation up to 2 years of follow up ]
   Participant reported quality of life outcomes. The questionnaire comprises descriptive systems: mobility, self care, usual activities, pain/discomfort, anxiety/depression; scored from, level 1 to 5; level 1 indicating no problem and level 5 indicating unable to/extreme problems. There is also a scale from 0-100 to describe health status, 100 being the best health the patient can imagine, 0 being the worst health they can imagine.
4. Participant reported healthcare resource use from information collected on Client Service Receipt Inventory (CSRI) [ Time Frame: From randomisation up to 2 years of follow up ]
   A tool used to collect participant reported information on the range of healthcare services and supports study participants may use, to calculate the rate of service usage to evaluate resource use as part of health economic analysis.
5. Measurement of costs in economic evaluations using iMTA Valuation of Informal Care (iVICQ) questionnaire [ Time Frame: From randomisation up to 2 years of follow up ]
   Scoring (no scale) to evaluate health economics comparing PBT vs SOC surveillance and other SOC treatments for malignant pleural mesothelioma.

Inclusion Criteria

• Histologically (Biopsy) confirmed malignant pleural mesothelioma
• No previous thoracic surgery
• T1N1, T2N0, T2N1, T3N0, T3N1 disease
• T4 and T4N1 disease if invasion of chest wall and ribs only
• WHO Performance Status 0-1
• Age 18 years or over
• Pulmonary Function Tests:
  • 40% predicted post-FEV1;
  • 40% predicted DLCO (corrected for Hgb)
• Willing to travel to a proton beam therapy centre for treatment (if randomised to experimental arm)

Exclusion Criteria

• Presence of metastatic or contralateral disease, prior thoracic radiotherapy, prior radical surgery for MPM
• Nephrectomy on contralateral side
• Presence of new effusion that is not amenable to drain
• T1N0 disease
• T4 disease with invasion to heart and diaphragm
• M1 disease
• WHO Performance Status ≥ 2
• Severe, active co-morbidity
• Women who are pregnant or breast feeding