PRESTO: A Phase III Randomised Controlled Trial of Dose-escalated Proton Beam Therapy Versus Standard of Care Radiotherapy for Functioning Pituitary Tumours

PRESTO: A Phase III Randomised Controlled Trial of Dose-escalated Proton Beam Therapy Versus Standard of Care Radiotherapy for Functioning Pituitary Tumours

The goal of this clinical trial is to evaluate whether a higher dose of radiotherapy can lead to better outcomes for participants with functioning pituitary tumours. The main question it aims to answer is whether a greater proportion of participants will achieve normal hormone levels with the higher dose of proton beam radiotherapy than with standard radiotherapy treatment doses.

Following randomisation, participants will receive approximately 6 weeks of either standard dose radiotherapy (intensity-modulated radiation therapy or proton beam therapy, depending on age) OR escalated dose proton beam therapy. Following this, participants will be followed up for at least 2 years to monitor their condition. This includes pituitary, hormone level, tumour, neurocognitive, and ophthalmology assessments, as well as patient-reported quality of life outcomes and health economic measures.

Inclusion Criteria:

1. Neuropathological confirmation of growth hormone (acromegaly) or ACTH (Cushing's disease) secreting pituitary adenoma after neurosurgical intervention.
2. Ongoing hormonal hypersecretion as defined by local and age-specific normal range values without hormone supressing medication (may need washout).
3. Multidisciplinary team meeting recommendation for fractionated radiotherapy.
4. Karnofsky performance status ≥70.
5. Age ≥18 years.
6. Agreement to travel to a proton beam therapy centre (i.e. UCLH or The Christie) as required.
7. Written informed consent.
8. Agreement to be followed up at a local PRESTO trial site.

Exclusion Criteria:

1. Women who are pregnant or breast feeding.
2. Prior cranial or head and neck radiotherapy treatment, including Stereotactic radiosurgery (SRS).
3. Unsuitability or intolerability of MRI scans.
4. Severe active comorbidities that limit compliance with trial requirements.
5. Prior invasive malignancy unless disease free interval of ≥3 years.
6. Unable to travel to the PBT centres as per trial requirements.