Stereotactic radiosurgery is the precise delivery of a lethal dose of radiation to a target while minimizing the radiation exposure of the surrounding tissues. This review discusses the 5 techniques of stereotactic radiosurgery: linear accelerator (LINAC)-based stereotactic radiosurgery, Gamma Knife, tomotherapy, robotic mini-linear accelerator (CyberKnife®), and heavy particle or proton beam stereotactic radiosurgery. The major indications for stereotactic radiosurgery for neurosurgical conditions include metastatic brain and spine tumors, primary brain tumors (eg, meningioma, vestibular schwannoma), arteriovenous malformations, and trigeminal neuralgia, and, more rarely, movement disorders, certain types of intractable epilepsy, and psychiatric disorders such as severe depression. The incorporation of real-time patient movement tracking (CyberKnife) allowed for the extension of stereotactic radiosurgery into the treatment of spinal disease as well as non-nervous system conditions, such as lung and prostate cancer. Stereotactic radiosurgery has assumed a significant role, both as the primary modality and in conjunction with surgery or chemotherapy, in treating a wide variety of disorders both within and outside the central nervous system.
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• Stereotactic radiosurgery is the precise application of a lethal dose of radiation to a localized lesion while exposing nearby normal tissue to a sublethal dose.
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• There are 5 primary techniques for stereotactic radiosurgery delivery: Gamma Knife, LINAC, tomotherapy, CyberKnife®, and heavy particle (proton beam).
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• Radiosurgery is used to treat a variety of pathologies, including brain and spine metastases, vestibular schwannomas, pituitary adenomas, primary central nervous system neoplasms, vascular lesions, including arteriovenous malformations, and functional disorders such tremor, epilepsy, and trigeminal neuralgia.
Historical note and terminology
Stereotactic radiosurgery is the precise application of a lethal dose of radiation to a localized lesion while exposing nearby normal tissue to a sublethal dose. If this radiation is fractionated, the same precise deposition of radiation is delivered over several sessions, allowing for a greater total dose to the target tissue and protection of the surrounding normal structures. The principles underlying stereotactic radiosurgery have been understood for decades, but advances in stereotactic techniques, high-resolution imaging, and computer processing have established stereotactic radiosurgery as a standard neurosurgical technique.
The use of radiation to treat disease is based on the Compton effect, where the collision of a photon with an atom creates free radicals that stop cell cycle replication or cause cell death (136). Medical use of radiation for therapy began in 1922 when Coutard and Hautant treated a case of laryngeal carcinoma with radiation therapy (34). In 1934, Coutard described the concept of fractionation: the total dose of radiation is divided into multiple smaller doses allowing for recovery of normal tissue, repopulation of tumor cells, reoxygenation of tumor cells to increase radiosensitivity, and reassortment of tumor cells within the cell cycle (52). Low-energy emission radiation from early machines made tissue penetration inadequate for anything but superficial lesions. High-voltage machines were developed, producing radiation with energy levels of several million electron volts that could be used to treat intracranial neoplasms. These devices were replaced by cobalt 60 units and linear accelerators in the modern era as sources for high-voltage x-rays (23).
In the 1930s, heavy particles were first used by Lawrence and associates at the University of California, Berkeley, to irradiate small volumes of normal and pathologic tissues (79). The Berkeley cyclotron permitted the use of high-energy alpha particles and proton and deuteron beams to treat deeper brain tissue volumes using the "Bragg peak" rotation technique (137).
Leksell created stereotactic radiosurgery in the early 1950s by combining a stereotactic frame with an orthovoltage x-ray tube (84). He later developed the Gamma Knife using 201 cobalt 60 sources. The early Swedish experience with stereotactic radiosurgery for cerebral arteriovenous malformations led to Gamma Knife centers around the world as additional therapeutic applications were developed. The University of Pittsburgh became the site of the first cobalt 60 Gamma Knife unit for clinical use in North America in 1987. The Gamma Knife improved radiation therapy by providing accelerated treatment times and improved conformation of the radiation dose to the shape of the lesion.
Linear accelerator stereotactic radiosurgery offered 4 major advances:
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(1) A stereotactic system with a movable isocenter.
(2) A secondary collimator system that focused the radiation beams to the narrowest possible peripheral penumbra.
(3) A patient couch that spared body irradiation.
(4) A computerized program that targeted the high-energy photon beams.
By 1987, Winston and Lutz had modified their linear accelerator in Boston to treat neurosurgical patients (146). Available as standard equipment in many radiation therapy departments, only minor modifications were required to convert a standard LINAC to suitability for stereotactic radiosurgery. Ease of fractionation, unlimited field size, and photon delivery flexibility to treat nonspherical lesions were major advantages to this system. Stereotactic radiosurgery requires extensive quality assurance procedures to maintain safety and reliability of radiation dosage and targeting (23).
Commonly used stereotactic radiosurgery systems are the Gamma Knife and the LINAC. Both require rigid fixation of a stereotactic head frame to the patient for optimal spatial accuracy, which is uncomfortable for the patient, is time consuming for the stereotactic radiosurgery team, and makes fractionation difficult. The most current Leksell Gamma Knife systems feature 192 cobalt 60 sources arranged in a cone section configuration with enhanced flexibility in number and diameters of beams intersecting at isocenters compared with previous systems. This allows for treatment of multiple intracranial lesions within a single-session frame placement with submillimeter accuracy (123; 149). The new Leksell Gamma Knife system, approved by the United States Food and Drug Administration in August 2016, uses a cone beam computed tomography scanner and infrared camera to perform Gamma Knife radiosurgery using the thermal plastic mask head immobilization, which is standard for external beam radiation (149; 142). Use of the thermal plastic mask also allows for multiple sessions to be performed without having to apply and reapply a stereotactic frame. One large study of 100 patients who underwent frameless Gamma Knife radiosurgery demonstrated two major improvements: improved workflow and increased number of patients eligible for Gamma Knife due to fractionation. The accuracy of the frameless system is preserved with submillimeter accuracy (142). The use of Gamma Knife has increased rapidly since its inception. A worldwide survey-based study suggested that there appears to be worldwide consensus on its use for meningiomas, metastatic tumors, and arteriovenous malformations; more treatment variation exists for craniopharyngiomas and pituitary tumors (53).
Frameless stereotactic radiosurgery performed on a LINAC system uses optical tracking systems. These systems have a reproducible accuracy of less than 1.0 mm (121). A newer method of LINAC-based radiosurgery known as volumetric arc therapy (VMAT or RapidArc®) delivers radiation in a gantry arc motion, which allows adjustments to both beam dose rate and gantry speed to further customize conformal dose distribution (105). Delivering treatment in this fashion with continuous gantry rotation allows for treatment of multiple intracranial lesions with a few or even a single isocenter set-up and, most importantly, reduces treatment times to 5 to 10 minutes per lesion while maintaining spatial accuracy of less than 1 mm (144; 10).
The CyberKnife® combines a lightweight (130 kg) 6 MeV linear accelerator with a highly maneuverable, articulated robotic arm to position and aim the LINAC. This system improved ease of fractionation, allowed for treatment of young patients without general anesthesia, and had the ability to treat lesions throughout the body. By utilizing real-time image guidance, the need for skeletal fixation for positioning or rigid immobilization of the patient was eliminated. The multiple degrees of freedom afforded by the robotic arm unconstrained the treatment beam and could target nonisocentric beams to any point within the lesion. Maximizing conformation of the treatment beam to the shape of the lesion provided homogenous dosing (23). Treatment with the CyberKnife has proven effective, and with its spatial accuracy and dose homogeneity, it provided the option of stereotactic radiosurgery treatment to patients with lesions in close proximity to critical central nervous system structures.