Abstract
Major complications after contemporary SRS are uncommon and most can be well managed by experienced physicians. The risk of ARE are greater in patients with a history of prior radiation treatment, large treatment volumes, and non-conformal dose plans. Late ARE can occur after both AVM and benign tumor SRS, emphasizing the need for ongoing MRI follow-up many years after SRS. The risk of radiation-induced tumors after single-fraction SRS is very low and should not be used as a reason to choose alternative treatment strategies for appropriate patients.
Keywords
complication, radiation, stereotactic radiosurgery
Highlights
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Complications after stereotactic radiosurgery relate primarily to either temporary or permanent radiation injury to the structures adjacent to the irradiated target.
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Risk factors are history of prior irradiation, lesion size, lesion location, nonconformal dose planning, and radiation dose.
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Reversible imaging changes (areas of increased signal on T2-weighted magnetic resonance imaging) are common and generally occur in the first 6 to 12 months after stereotactic radiosurgery. Most are asymptomatic and resolve without treatment, whereas patients with symptomatic reversible imaging changes can usually be managed with corticosteroid therapy.
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Radiation necrosis (persistent areas of enhancement with adjacent edema) is much less common and represents permanent vascular damage with resultant immune response. Treatment of symptomatic patients can include corticosteroids, bevacizumab, hyperbaric oxygen therapy, or surgical resection.
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Late adverse radiation effects develop 5 or more years after stereotactic radiosurgery and are characterized by perilesional edema or cyst formation. Symptomatic late adverse radiation effects frequently require surgical removal to improve the patient’s neurologic condition.
Introduction
The concept of stereotactic radiosurgery (SRS) was developed by Lars Leksell from the Karolinska Institute in Stockholm, Sweden in 1951. SRS utilizes the principles of stereotactic localization combined with the precise delivery of radiation to an imaging-defined target. In the past 40 years, SRS has experienced exponential growth and has become an integral part of both neurosurgery and radiation oncology. Advances in neuroimaging and dose-planning software, together with the accumulated clinical experience of more than 1,000,000 treated patients to date, have made SRS safer and more effective for a wide variety of clinical indications. Whereas once SRS was available in only a few academic centers, now SRS is available to patients at both academic and community medical centers around the world.
The goal of SRS is to deliver a clinically effective radiation dose to an imaging-defined target. At first, SRS was a single-fraction technique limited to the brain. Now SRS is defined as stereotactically delivered radiation in 1 to 5 fractions to both intracranial and extracranial targets. As with any radiation treatment, SRS aims to damage the target more than the adjacent normal tissues. Two primary approaches are used to increase the therapeutic ratio in different types of radiation treatment. One, dose fractionation, exploits the differential radiosensitivity of normal and abnormal tissues. Typically, normal tissues are better able to repair sublethal DNA damage than tumors because of aberrant cell cycle control mechanisms in tumors. This is the rationale behind external beam radiation therapy (EBRT), whereby multiple small doses of radiation are delivered to the target and the adjacent normal tissue. Two, and in contrast to EBRT, single-fraction SRS achieves its therapeutic effect by minimizing the radiation delivered to the nearby normal structures by using highly conformal dose plans. Within several millimeters of the edge of the target, the radiation dose drops from a therapeutic level (10–25 Gy) to doses that approximate a single fraction of EBRT (2 Gy). Multisession SRS (2–5 fractions) theoretically takes advantage of both of these approaches by using conformal dose planning delivered in a small number of sessions.
Types of Radiation Complications
Parenchymal Injury
Imaging changes noted after SRS are common and can be divided into three categories. First, reversible imaging changes (RIC) (areas of increased signal on T2-weighted magnetic resonance imaging [MRI]) generally occur in the first 6 to 12 months after SRS ( Fig. 35.1 ). Most are asymptomatic and resolve without treatment. Second, radiation necrosis (persistent areas of enhancement with adjacent edema) is much less common and represents permanent vascular damage with resultant immune response. Distinguishing between RIC, radiation necrosis, and tumor growth after SRS is important, and no imaging technique is perfect at guiding clinical decision-making. For small areas in asymptomatic patients, observation with repeat imaging is preferred. Comparison of the area on gadolinium-enhanced T1-weighted and T2-weighted MRI is commonly used after brain metastases SRS. Third, late adverse radiation effects (ARE) develop 5 or more years after SRS and are characterized by perilesional edema or cyst formation.
Cranial Neuropathy
Cranial nerve deficits after SRS of skull base lesions are uncommon. Most occur within the first year after SRS, but delayed injury can occur. Special somatic sensory nerves (optic, vestibulo-cochlear) are the most radiation sensitive, followed by the general somatic sensory nerves (trigeminal). The motor nerves are particularly radiation resistant.
Vascular
Large vessel injury is uncommon after SRS, although cases of internal carotid artery occlusion and stroke have been reported after SRS of cavernous sinus meningiomas, and focal morphologic changes and aneurysm formation have been seen in the superior cerebellar artery in patients after trigeminal neuralgia SRS.
Secondary Tumor Formation
The most significant complication of any radiation-based procedure is the development of secondary tumors caused by irradiation. Cahan et al. reported 11 cases of bone sarcomas that arose after radiation treatment and outlined four criteria that are required before a secondary tumor could be deemed radiation induced. First, the second tumor must arise within the prior radiation field. Second, there must be an adequate latency between the radiation exposure and the development of the second tumor. Third, the secondary tumor must be histologically different from the original tumor. Fourth, the patient must not have a genetic predisposition for tumor development. Often it is difficult to separate cases that are more likely coincidental than radiation induced. The risk of radiation-induced tumors after SRS has been reported between 0% and 2.6% at 15 years and should not be used as a justification for choosing other treatment approaches over SRS for appropriate patients.
Risk Factors for Radiation Complications
The primary risk factors for ARE after SRS are a history of prior irradiation, large treatment volume, target location, poor (nonconformal) dose planning, and higher radiation doses. Numerous studies have correlated the chance of RIC after SRS with some measure of the radiation dose to the surrounding tissue and the location of the target. The most commonly cited parameter is the 12-Gy volume that is the total volume in the treatment field that receives a radiation dose of 12 Gy or more. Patients with lesions in deep parenchymal locations (thalamus, basal ganglia, and brainstem) are more likely to develop neurologic deficits secondary to imaging changes noted on MRI. Advances in SRS technique including improved neuroimaging, better dose-planning software, and more precise radiation delivery devices have all contributed to a reduction in the incidence of ARE after SRS. In addition, medical knowledge based on the last 40 years has been instrumental in guiding clinical decision-making and proper patient selection for SRS. Patients with large lesions with symptomatic mass effect are rarely good candidates for SRS.
One area that has received a great deal of attention is the risk of radiation-induced optic neuropathy (RION) after single-fraction SRS in the parasellar region. Early studies concluded that the risk of RION was increased if the radiation dose to the anterior visual pathways (optic nerves or chiasm) exceeded 8 Gy. However, more recent studies have shown that radiation doses of 10 to 14 Gy are well tolerated and have a low risk of RION ( Fig. 35.2 ). Acceptance of this higher dose threshold for the anterior visual pathways increases the applicability and likely the effectiveness of single-fraction SRS for patients with lesions in the parasellar region.
