Neurotoxicity of Radiation Therapy
Section snippets
Acute encephalopathy
Brain injury by radiation therapy (RT) has traditionally been classified according to its time of onset into acute, early delayed, and late forms. The acute reaction to fractionated RT usually occurs during the first several days of treatment and consists of headache, nausea, fever, somnolence, and worsening of preexisting focal symptoms. Acute RT encephalopathy tends to occur more frequently and to be more severe among patients with increased intracranial pressure. Acute toxicity occurs in
Early delayed encephalopathy
“Early delayed” encephalopathy is a broad designation referring to reversible clinical and/or radiographic worsening occurring from a few weeks up to several months after brain irradiation. This includes a number of clinical scenarios, which may have differing pathophysiologies.
The “somnolence syndrome” occurs in about one-half of children given whole-brain RT for a primary tumor or leukemia prophylaxis. The syndrome is probably more frequent and more severe in children younger than 3 years. It
Focal cerebral necrosis
Focal cerebral radiation necrosis can occur after treatment of primary or metastatic brain tumors, or following incidental irradiation of the brain during treatment of extraneural tumors such as pituitary adenoma, nasopharyngeal carcinoma,7 or skull base tumors.8 Among patients with glioblastoma or anaplastic glioma who receive standard fractionated external beam RT (6000 cGy in daily fractions of 180–200 cGy), the actuarial incidence of focal necrosis is 10% to 15% in persons surviving at
Diffuse cerebral injury in adults
The most frequent neurotoxic effect of cranial RT at any patient age is not focal necrosis but diffuse cerebral injury. For adults with glioblastoma or other malignant primary brain tumors, only a small minority survives long enough for delayed diffuse cerebral injury to become an issue. Among anaplastic glioma patients surviving longer than 18 to 24 months, serial CT or MR scans in the majority show diffuse cortical atrophy, ventricular dilatation, and signal abnormalities in the hemispheric
Diffuse cerebral injury in children
The developing brain is clearly more sensitive to irradiation than the adult brain. Prospective studies have consistently found mean full-scale IQ scores to be at least 10 points below normal among disease-free survivors of childhood medulloblastoma or other primary brain tumors who received whole-brain RT.39, 40 This is believed to be because of deficits in the “core functions” of memory, attention, and processing speed. IQ scores often continue to decline over several years, as children fall
Cerebrovascular disease
Stenosis or occlusion of the extracranial or intracranial cerebral arteries can occur after RT given for tumors of the neck, head, or brain.58, 59 Transient ischemic attacks or cerebral infarcts usually occur at least 5 to 10 years after RT, but shorter latent periods are possible. Angiography shows stenosis or occlusion, often multifocal, of one or more major arteries lying within the RT ports. The pathology of RT-induced large-vessel disease resembles “ordinary” atherosclerosis. Many of the
Radiation-induced central nervous system tumors
Radiation-induced intracranial tumors most commonly occur in survivors of childhood medulloblastoma, other brain tumors, or leukemia.71 Among 14,000 survivors of childhood cancer who received brain RT, the relative risk of developing subsequent meningioma was increased by nearly 10-fold, and the risk of glioma by nearly 7-fold.72 Most gliomas occurred within 5 years after the initial RT, whereas the latency time for meningiomas was at least 15 years in two-thirds of cases. There was a
Cranial nerve injury
Radiation injury to the optic nerve and chiasm most often occurs in patients treated for tumors of the orbit, paranasal sinus, nasopharynx, pituitary adenoma, or craniopharyngioma,83 or less commonly following whole-brain RT for primary or metastatic brain tumors. In most reported patients, the optic nerve exposure after fractionated RT was 5000 cGy or more.84 Optic neuropathy may also occur after stereotactic radiosurgery for treatment of pituitary adenoma or meningioma.85 Radiation-induced
Myelopathy
Radiation-induced spinal cord injury most often occurs after “incidental” irradiation of the spinal cord as part of treatment for an extraneural primary tumor, and less often among patients in whom the spinal cord itself is targeted in treatment of a glioma or as part of craniospinal axis RT for medulloblastoma. The most common form of radiation myelopathy is a transient syndrome usually occurring within 4 to 6 months after treatment. This syndrome consists solely of paresthesias or “electric
Brachial plexopathy
Breast carcinoma is the tumor most often associated with radiation brachial plexopathy, accounting for 40% to 75% of reported patients, followed by lung carcinoma and then by lymphoma.101, 102 Radiation-induced brachial plexopathy may rarely occur as a relatively mild reversible syndrome, or much more commonly as a delayed and progressive syndrome. Delayed radiation brachial plexopathy occurs after a latent interval varying from a few months up to more than 10 years, with peak onset of
Lumbosacral plexopathy and polyradiculopathy
RT injury to the lumbosacral plexus or cauda equina most commonly occurs after treatment of pelvic tumors, testicular tumors, or tumors involving para-aortic lymph nodes.113, 114, 115 Injury may occur after external beam photon therapy, interstitial or intracavitary radiation implants, or combined photon and proton beam RT.115, 116 Relatively mild, reversible lumbosacral plexopathy may rarely occur within a few months after RT.117 Delayed, severe plexopathy occurs after a median latent interval
Summary
Clinicians need to be aware of the many ways in which radiation-induced neurotoxicity can manifest itself, so that they carry out the appropriate steps in differential diagnosis and management. Future efforts will hopefully refine the uses and techniques of therapeutic irradiation further, leading to improved efficacy and reduced toxicity.
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