The limitation on the delivery of radiation to the central nervous system (CNS) is the radiation tolerance of the normal brain and spinal cord. Radiation doses beyond conventional tolerance are associated with complications, and these are described as acute, early delayed and delayed reactions based on the time of appearance after treatment completion.
Acute reactions during radiotherapy for pituitary adenoma in the form of acute edema are extremely rare and reversible. Early delayed reactions in the brain are characterized by a transient period of exhaustion, drowsiness, and anorexia, and this is described as the somnolence syndrome (1). The severity relates to the intensity of radiotherapy and the volume irradiated. Apart from tiredness, the full somnolence syndrome after small-volume pituitary irradiation is relatively uncommon.
Delayed normal tissue reaction is attributable to the damage to target cell lineages, which include the oligodendroglia and vascular endothelium. Late delayed damage to the brain from the combination of oligodendroglia loss and endothelial damage leads to demyelination and vascular occlusion, causing necrosis. Lower radiation doses may cause diffuse injury to the white matter with atrophy. Wide field irradiation to the developing brain of children can be associated with cognitive impairment, and this is of particular relevance in children under 5 yr of age. There are no data to suggest that such effect occurs in adults receiving small-volume irradiation to the pituitary.
The estimates of dose fractionation limits for brain necrosis are in the region of 60-62 Gy in 30 fractions (2-4). The risk of brain necrosis after a dose of 64 Gy in 32 fractions to normal temporal lobes as part of curative radiotherapy for nasopharyngeal carcinoma is 5% (5). The risk is highly dependent on fraction size, with most reported cases of damage to the optic apparatus developing after radiation fraction sizes of >2 Gy (6-8). After conventional external beam radiotherapy for pituitary adenoma, there should be negligible or no risk of necrosis or white matter damage.
The CNS is particularly vulnerable to single large doses of irradiation. After single-fraction radiosurgery to parasellar region lesions, including pituitary adenoma, the risk of optic neuropathy has been reported as 27% after doses of 10-15 Gy and 78% after doses of more than 15 Gy to the optic nerve and chiasm (9). Similar risk (24%) has been reported after a single dose of 8 Gy or more (10). Although there is no clear dose response relationship for nerves in the cavernous sinus, single doses between 10-40 Gy have been associated with an 11% risk of neuropathy (10). Single fraction radiosurgery for pituitary adenoma has also been associated with a 25% risk of temporal lobe necrosis (11) not seen after conventional fractionated irradiation.
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