Proton Beam Therapy (PBT)

Note: This trial is closed to recruitment now.

The number of cases of cancers arising from the tonsil and back of the tongue is rising worldwide. Even when this type of cancer is large or has spread to lymph nodes in the neck (called locally advanced cancer), it usually responds well to treatment and most people are cured. However, treatment with radiotherapy combined with chemotherapy can cause severe side effects during treatment. In the long-term this has the potential for significant harmful impact on quality of life.     This study includes patients with locally advanced cancers of the tonsil and back of the tongue. It will focus on whether proton beam therapy (a newer form of radiotherapy) can reduce side effects and improve patient-reported quality of life compared with standard radiotherapy (called intensity-modulated radiotherapy). Proton beam therapy can be directed more precisely than standard radiotherapy. This reduces the amount of normal tissue receiving radiation that isn’t wanted. We know from international use of proton beam therapy (e.g. the USA) that it is a safe treatment and is thought to cause less damage to normal tissues.     About 183 patients will take part in the study. Approximately 122 (two thirds) patients will receive proton beam therapy at an NHS proton centre in Manchester or London. The other 61 (one third) patients will receive intensity-modulated radiotherapy at their recruiting cancer centre. The NHS will provide accommodation for the duration of treatment for patients receiving protons and additional funding has been obtained for patient/carer travel costs. Patients will be asked to complete quality of life questionnaires at baseline, during treatment and during 5 years of clinical follow-up, in keeping with routine practice. There are also optional translational studies that patients will be asked to take part in.

Around 33,000 breast cancer patients/year need radiotherapy (RT) as part of their treatment. A small proportion (around 500/year) are not well served by current RT due to the position of their lymph nodes near the breast bone and/or body-shape. This can result in less RT dose where needed and/or unwanted dose to healthy tissue such as the heart, reducing chance of cure and increase risk of serious heart damage many years later. Proton Beam Therapy (PBT) is different from RT as it delivers dose to a defined depth thereby giving better dose coverage where needed with less dose to the heart. Increased skin and rib side effects around 2 years after treatment have however been reported, although this is mostly with older PBT techniques. The NHS now has 2 PBT centres, providing a unique opportunity to compare PBT with RT for this relatively small but important patient group with unmet need.    192 patients with breast cancer who have at least a 2 in 100 predicted lifetime risk of serious heart side effects from their planned RT will receive either PBT or RT. The choice of PBT or RT will be decided randomly by computer to minimise bias. We will assess the average heart dose received with PBT compared with RT as a validated early measure predicting late heart RT damage. Patient-reported side effects in the treated breast will be compared between PBT and RT at 2 years. Outcomes and side effects will be collected up to 5 years and we will use NHS databases for longer term effects. We will assess acceptability of randomisation to PBT v RT and any inequality of access.    Results will be presented at international conferences and published in peer reviewed medical journals; with PPI partners we will produce lay summaries.

We want to improve treatment for people diagnosed with oligodendroglioma (ODG).    ODG is a rare type of brain tumour, and many people continue to live for many years after diagnosis. The standard treatment for ODG involves surgery which will remove as much of the tumour as possible followed by radiotherapy (RT) and chemotherapy treatments. In the UK, standard radiotherapy treatment uses photon radiotherapy. This treatment is given as lots of small doses called fractions, usually on weekdays over 6 weeks. This is the best way to treat the tumour and minimise side effects in normal brain tissue. Sometimes, however, photon RT can cause long-term side effects in normal brain tissue. These side effects can develop many years after the treatment and may include memory problems or difficulties processing information. We call these sorts of problems ‘neurocognitive problems’. Proton Beam Therapy (PBT) is an alternative type of radiotherapy treatment. This treatment is also given on weekdays over 6 weeks. PBT can reduce the dose of RT delivered to normal brain tissue, including some of the parts of the brain that are involved in memory and processing information, and so we think PBT may cause fewer neurocognitive problems. This study will look at whether the lower doses to the normal brain tissue from PBT result in fewer long-term side-effects.

Malignant pleural mesothelioma (MPM) is a cancer which begins in the tissues lining the lungs. Many patients are under initial surveillance after diagnosis and only receive treatment later when deemed suitable when considering the risk and benefits of the NHS approved treatment options and impact on quality of life.  Proton beam therapy (PBT) is a type of radiotherapy which results in less radiation to healthy tissues surrounding the cancer compared to photon radiotherapy. Using PBT to limit these side effects would provide an invaluable way to improve outcomes and life expectancy for these patients whilst maintaining their quality of life.  This trial aims to explore PBT as a treatment option for MPM patients who would routinely be put under initial surveillance in the standard of care pathway after diagnosis; to determine how PBT impacts progression free and overall survival, safety and toxicity, quality of life and health economics.  Patients will be randomly allocated (1:1 ratio) to receive either PBT (the trial arm), or remain in the standard of care surveillance approach for MPM (the control arm). The PBT will be delivered daily (on weekdays) over 5 weeks at the proton centre in London or Manchester.  The trial aims to recruit 148 patients in total. In collaboration with Mesothelioma UK and University of Sheffield, there is also a sub-study for 8-10 patients who are allocated to receive PBT to explore patient expectations and journey with the trial and proton therapy. All patients will be followed up locally at their recruitment centres for two years where tumour assessments with CT scans and blood samples will be collected for biomolecular research.  The evidence from this national trial will support the national guidance on best available treatments for mesothelioma to be updated, and further patients to benefit from this in the future.