Cranial irradiation is used to treat patients with primary or metastatic brain tumors and as prophylaxis for selected patients at high risk of neoplastic involvement of the nervous system. A full understanding of the potential consequences associated with cranial irradiation is needed both to manage potential complications and to properly counsel patients and/or families prior to treatment.
The primary factors influencing the likelihood of developing complications include the volume of normal brain tissue treated, the total radiation dose, and the fractionation schedule. The likelihood of brain damage also increases in the young (ie, <5 years old) and the elderly. Furthermore, the use of concurrent or sequential chemotherapy can significantly affect the incidence and severity of radiation-induced toxicity. In addition, the underlying tumor often can impair neurologic function, making it difficult to assess accurately the separate effect of radiation. Finally, genetic factors may make certain individuals more susceptible to otherwise safe doses of radiation. For example, a study of 15 families with radiation-induced meningiomas after treatment for tinea capitis identified several genes as potential risk factors . Other genetic markers have been found to enhance susceptibility when specific organs are irradiated .
The complications of radiation therapy (RT) are usually divided into acute effects that can occur during the course of radiation, early-delayed effects that appear two to four months after radiation, and late effects that can develop more than 90 days after the initiation of RT. The Radiation Therapy Oncology Group (RTOG) has established specific grading criteria for acute and delayed toxicities (table 1 and table 2) .
Complications that might occur many months or even years following cranial irradiation are generally not important as a consideration for patients with brain metastases or grade IV primary brain tumors, where a median survival in the range of 6 to 15 months is expected. Late effects are a more important consideration for patients with a much longer life expectancy (eg, low-grade glioma and primary CNS lymphoma patients or pediatric patients with acute lymphocytic leukemia) [4,5]. The distinction between early and late complications is also important since acute and early-delayed complications are usually reversible while late reactions often are not.
Both the acute and late complications of fractionated cranial irradiation will be reviewed here. Complications of spinal cord and peripheral nerve irradiation and complications of single-fraction cranial radiosurgery are discussed elsewhere. (See "Complications of spinal cord irradiation" and "Complications of peripheral nerve irradiation" and "Complications of cranial stereotactic radiosurgery".)