Dr Kirsten Hopkins
Bristol Haematology & Oncology Hospital

Pituitary Radiotherapy can now be better localised and some of the previous fears of using this treatment for a benign disease can be dispelled. It is offered either to prevent recurrent growth or to diminish excess secretion of hormones. If a Pituitary tumour re-grows after surgery, a second operation can be associated with side effects and risks. Studies confirm that radiotherapy can prevent recurrent growth in 80-90% of cases. However, when the aim of treatment is to lower hormone levels, the effect of radiotherapy is slow and less satisfactory. Levels may take between 6 months and 2 years to drop. Treatment is most often successful in Acromegaly (70-90%) but disappointing results are seen in Cushing's disease (50-83%) and macroprolactinomas (40-70%).

This leaves debate about when patients should be referred for radiotherapy and there has been considerable regional and inter-disciplinary variation in the advice given. Nowadays, multi-disciplinary team meetings where endocrinologists, neurosurgeons and clinical oncologists meet up every few months and discuss cases, help to combine the skills of the whole team to optimise individual management decisions. Generally, radiotherapy may be recommended:

• After sub-total resection of macroadenomas;
• After total resection of active tumours where hormone levels are persistently elevated; or
• For recurrent tumours.

To prepare for radiotherapy, the patient has a plastic shell made from a plaster of Paris impression of their head. A computed tomography (CT) scan is performed in the shell and the target volume is marked on the scans. This is larger than the tumour to allow for movement. Physicists calculate the size and angle of beams to give a uniform dose of radiation to the target. The beams must pass through normal brain to reach the pituitary and consequently with conventional radiotherapy the total volume of brain treated may be considerably larger than the target volume. A dose of 45 Gray (joules of radiation energy per kilogram) is delivered in 25 treatments to the target volume over 5 weeks. Immediate side effects are very rare. In adults, the brain tissue is relatively resistant and although concern has been raised in the past that there may be significant late effects, a recent study, which analysed 1388 adult patients who had previously received pituitary radiotherapy, was very reassuring. Low instances of serious side effects were recorded as follows:

• Deterioration of vision - 1.7%
• Vascular damage - 6.3%
• Brain necrosis - 0.2%
• Second malignancy - 0.8%
• Neuro-psychological disorder - 0.7%

The risk of vascular damage (strokes or transient ischaemic (lack of blood to a body region) attacks) is concerning but must be balanced against the risks associated with repeated surgery if radiotherapy is not offered and tumours recur. The risks of memory impairment seem to be greatest when surgery and radiotherapy are both needed but this includes patients who have had large tumours and multiple procedures. In practice, one 'optimal' operation followed by well-planned radiotherapy is unlikely to cause demonstrable memory loss.

Sadly, very young children are much more sensitive to radiotherapy and when they require treatment - often for craniopharyngiomas - learning and developmental difficulties are common. These side effects result in part from damage to adjacent healthy brain that has also been treated. Stereotactic radiotherapy is a new technique where treatment is delivered in a relocatable metal frame secured using a dental mouth-bite. This is extremely accurate, permitting smaller margins to be used around the target volume, and treatment to be planned in a way that spares more normal brain.

Similar technology with a surgically applied, 'fixed' frame has also been used to deliver high-dose single shots of radiation for resistant conditions such as Cushing's disease. This is true 'surgery' as all the tissue in the high dose volume is ablated. Theoretically this could carry risk to adjacent visual nerves, but initial studies suggest treatment can be delivered safely and carries promise in a condition that has previously been difficult to treat.