Linear Accelerator Radiosurgery

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CHAPTER 255 Linear Accelerator Radiosurgery

Technical Aspects

Antonio A.F. De Salles, Alessandra A. Gorgulho, Nzhde Agazaryan

The idea of focusing external beam radiation to concentrate the dose on the pathology and spare the peripheral structures appeared in the literature in 1906. It was described by Kohl only 18 years after the discovery of x-rays. During the following years the idea evolved with spiral converging beams, pendulum-directed beams, and finally, rigid hemispheric attached beams directed with stereotactic precision.1 It was Lars Leksell, a practicing functional neurosurgeon at Karolinska University in Stockholm, Sweden, who integrated stereotactic precision with the penetrating capability and radiobiologic effect of the x-ray beam. As widely described, Leksell attached an x-ray tube to his stereotactic frame and performed radiosurgery on the first patient by targeting the trigeminal ganglion for the treatment of trigeminal neuralgia. The term radiosurgery was thus coined.2 This was actually the first application of photon radiosurgery.

Radiosurgery evolved during the last half of the past century in association with the explosion of imaging techniques.3 Because it was dependent on ventriculography, cysternography, and angiography, the applications of radiosurgery were largely limited to the pathologies visualized by these techniques. Functional applications were based on the principles of functional neurosurgical localization, an example being visualization of the anterior commissure and posterior commissure on ventriculography to guide targeting. Cisternography with injection of contrast material into Meckel’s cave provided visualization of targets such as the trigeminal ganglion in Meckel’s cave and prominence of acoustic neuromas in the cerebellopontine angle, previously not seen on plain skull radiographs.4 Angiography provided visualization of arteriovenous malformations (AVMs), and starting in 1972 they became the classic application for radiosurgery.5 The upsurge in radiosurgery applications for structural diseases such as acoustic neuromas and AVMs increased the demand for affordable radiosurgery throughout the world. During the early 1980s there were fewer than 10 radiosurgery devices serving the world’s population: three gamma units and few heavy particle beam facilities. Linear accelerator (LINAC) radiosurgery was therefore developed to make stereotactic radiosurgery (SRS) possible in every hospital capable of treating cancer patients with conventional radiation therapy. During the early 1980s, the LINAC was already the device of choice for producing medically affordable high-energy photons, which progressively replaced cobalt 60 units. This chapter details the development of LINAC radiosurgery, integration of modern imaging techniques for localization of targets, dosimetry, and the most recent advances in the technique with its extension from cranial to extracranial applications. image

imagePlease see the section “Linear Accelerators” on Expert Consult @ www.expertconsult.com

Precision and History of Linear Accelerators

Over the years, radiation oncologists relied on the radiobiology of tissue response to moderate fractions of radiation and thereby decrease complications, hence the name radiotherapy. They did not stress precision of beam delivery. As specialists in cancer, they thought in terms of infiltrative disease, which needed large fields of radiation rather than concentration. Therefore, LINACs were not initially designed for high-precision delivery; the preoccupation was mostly with accuracy of the dose. When neurosurgeons tried to apply the LINAC beam to ablate lesions with a highly concentrated dose, precision of beam delivery became important.

The issue of precision was initially resolved with the description of a gantry correction device by two University of Florida scientists18 and lately by the development of LINACs dedicated to radiosurgery.19 This allowed LINAC radiosurgery to become a competitive technique, not only for lesions but also for functional disorders of the brain, such as trigeminal neuralgia.20-24 LINAC radiosurgery is the most common form of radiosurgery performed today, and its versatility also allows application of the technique to the spine and other sites in the body (Fig. 255-1).16,25,26 Another approach using a LINAC attached to a robot was advanced by the Stanford University group under leadership of the neurosurgeon John Adler.27 This approach is gaining popularity, also because of its ability to reach extracranial targets and obviate the need for a stereotactic frame. image

image

FIGURE 255-1 Example of precision capability and clinical application of linear accelerator radiosurgery in the spine. A, Sagittal T2-weighted magnetic resonance image of an arteriovenous malformation (AVM) treated at the C5 level. The patient recovered almost complete function after tetraparesis secondary to AVM bleeding. B, Radiosurgery performed with 12 Gy delivered to the 90% isodose line encompassing the AVM.

imagePlease see the sections “Stereotactic Precision Requirements” and “Production of the Beam” on Expert Consult.

Dosimetry

The main dosimetric characteristic of radiosurgery is its ability to deliver a high dose of radiation to the target with a low dose to normal tissue in the periphery of the lesion. This can be accomplished when multiple fields converge on a point called an isocenter. The isocenter is generally placed by the LINAC planning software in the geometric center of the lesion. However, as a result of the pass point characteristics of converging beams, the maximum radiation point is usually situated slightly superior to the isocenter when planning intracranial radiosurgery because the multiple radiation fields enter from the top of the head, which brings the “hot spot” to a site slightly above the isocenter.

The limitation of the radiosurgery technique imposed by the beam is the intermediate volume. This is the area outside the lesion where the multiple fields (beams) partially overlap.19 As the target volume increases, the intermediate volume area also increases, which means that more volume of normal parenchyma is exposed to higher doses of radiation; consequently, the target volume in radiosurgery is suggested to be no greater than 3 cm (approximately 12.6 cm3). The target volume also has an impact on the shaping capabilities of LINAC radiosurgery. Modern LINAC conformality approaches, such as intensity-modulated radiosurgery (IMRS), allow the treatment of targets larger than 3 cm in largest diameter (Fig. 255-2).

image

FIGURE 255-2 Intensity-modulated plan to cover a large lesion close to the optic apparatus. A, Representation of the static fields. B, Representation of the beam modulation to achieve the dose distribution in C. Axial T1-weighted magnetic resonance image with gadolinium enhancement. Notice the sharp dose falloff to avoid the optic apparatus and the brainstem (arrow). Recurrence of this skull base meningioma was treated with stereotactic radiotherapy.

Functional Lesion Considerations

The dream of Dr. Lars Leksell of performing functional neurosurgery without violation of the cranium was realized. However, it did not become commonplace in functional neurosurgery. Radiation could not compete with radiofrequency heat generation as the approach of choice to create lesions in the brain42 despite the risks inherent in violating the skull and passing a probe to the depth of the brain. When Dr. Leksell conceptualized radiosurgery in 1951,2 knowledge of the importance of electrophysiology in functional neurosurgery was very incipient and did not allow this perception at the time. Leksell and Larsson designed the first gamma unit with 179 cobalt 60 sources and slit collimators to generate an oval-shaped lesion and thereby mimic the heat lesion made with a radiofrequency probe.1 This dose distribution shape, as used at the University of California, Los Angeles, in the 1980s with Dr. Leksell’s gamma unit, can be achieved with proper LINAC arc determination or cobalt source plugging, at least for the 50% isodose volume.43,44

Functional neurosurgery then grew as a result of the ability of neurosurgeons to make minute and precise lesions in the brain, which is unpredictable with radiation. The technique of choice for making lesions in the nuclei and pathways of the brain is, still today, the heat lesion.45,46 Heat lesions can be graded and monitored because of their radiofrequency attributes. It is possible to glimpse the effects of the lesion by partially increasing the temperature, for example, to 43°C. The lesion is then completed by increasing the temperature beyond the level needed to denaturize protein (i.e., 54°C). Moreover, localization of the target by imaging can be aided by electrical stimulation of the tissue in question. This cannot be accomplished with radiosurgery.

The effects of radiation are achieved slowly, well after the final decision for the lesion’s location is made. Trials of lesion making for the treatment of tremor and other symptoms of Parkinson’s disease fell short of the results expected with radiofrequency lesions because of the unpredictability of the effects of radiation on the target.47-53 Another important drawback of functional radiosurgery is its inability to confirm correct targeting with electrophysiology.54,55 The effects of radiation are not finalized until months to years after its delivery. Radiation has acute, delayed, and late effects,56 a period during which the patient may not experience the benefits of radiosurgery but is actually having to endure its undesirable side effects.57-59 In contrast to radiofrequency lesions, in which the effects are immediate and final in all cell types inside the target volume, the effects of radiation are different in quality and time frame for each cell type. Formation of the lesion after a high dose of radiation takes place in several stages because of the ability of cells to program apoptosis60 and make changes in their machinery to produce neurotransmitters29 and hyaline material.61,62 Such stages range from acute activation of the target area,63 to production of neurotransmitters29 and cytokines,64 and ultimately to thrombosis and ischemia.65

Prescribing to a Point

The dose prescribed for functional neurosurgery is by convention and tradition directed to the isocenter. This means that 100% of the dose (maximal dose) is prescribed to a target point (i.e., to the isocenter). The radiation prescription dose is the same as the maximal dose when prescribing to the maximum. The falloff distance, or the volume of tissue receiving at least 50% of the dose, is proportional to the diameter of the collimator because circular collimators are traditionally used for functional radiosurgery (Fig. 255-3). Application of this concept is nicely seen during targeting of the root entry zone for trigeminal neuralgia in LINAC radiosurgery, where 3-, 4-, and 5-mm collimators are available for use.

image

FIGURE 255-3 Trigeminal neuralgia target in the root entry zone (REZ). A, CISS magnetic resonance imaging sequence to demonstrate the anatomy of the trigeminal nerve (TN), gasserian ganglion (GG), and basilar artery (BA). Notice the dose distributions of the 3-mm collimator (B), 4-mm collimator (C), and 5-mm collimator (D). It is not advisable to use collimators larger than 5 mm for treatment of trigeminal neuralgia with linear accelerator radiosurgery. Note that the 50% isodose line represents the 45-Gy volume. The 100% dose is delivered to a single point inside the target.

Placement of the isocenter while planning radiosurgery for trigeminal neuralgia relies on the isodose line (IDL) to determine the distance from the isocenter to the brainstem. Although some LINAC radiosurgery treatments of trigeminal neuralgia have been delivered with the 5-mm collimator,21,32,49,66-68 the majority of data on trigeminal neuralgia published by gamma unit users has been amassed with the 4-mm collimator.69-73 The dose distributions for treating trigeminal neuralgia very well exemplify the concept of prescribing to a point in LINAC radiosurgery image (Fig. 255-3).

imagePlease see the section “Functional Stereotactic Radiation Therapy for Change in Seizure Focus Firing” on Expert Consult.

Prescribing to a Volume

Considerations of Volumetric Dosimetry

The simplest dose distribution is achieved with a radiosurgery plan involving a single collimator. However, placement of functional lesions only in targets such as the trigeminal nerve and the thalamus, perfectly round metastases/primary tumors, or small round AVMs is amenable to a single isocenter with circular collimators in LINAC radiosurgery. All other lesions do not have a shape that can be covered with a single isocenter without distributing too much radiation to the surrounding brain tissue.

Some fundamental concepts commonly discussed in dose prescription for LINAC radiosurgery are important to present at this point. With regard to brain metastases or small round gliomas, it is desirable to cover the gross contrast-enhancing lesion or gross target volume (GTV) along with some margin, usually 1 or 2 mm. Such a margin may encompass microdissemination of malignant cells surrounding the area defined by the contrast enhancement. This volume is called the clinical target volume (CTV). Besides the CTV, one should account for the uncertainties of the radiation delivery process, which at best approaches 2 mm with any technique (LINAC, Gamma Knife, CyberKnife). The final irradiated volume, defined as the CTV plus generally 2-mm margins, is called the planned target volume (PTV). The minimal radiation dose thought to be clinically safe and effective is prescribed to the PTV. The dose that adequately covers the target is designated the prescription radiation dose. Usually, in LINAC radiosurgery the prescription IDL is high (90%, 80%, or sometimes 70%), which means that the maximal dose is 10%, 20%, or 30% larger than the dose at the periphery of the lesion, depending on whether the prescription was to the 90%, 80%, or 70% IDL, respectively.

The different volumes just discussed are significant when treating malignant or benign recurrent tumors, but its real limits are beyond the contrast-enhancing margins used to determine a target volume. However, in some situations, addition of margins to the GTV is not biologically required. For instance, AVMs are not infiltrative lesions. Tighter plans are the best ones because the brain tissue affected by the AVM is normal and frequently eloquent.84 Therefore, it does not make good sense to use additional margins. The progressive endothelial proliferation triggered by a single dose of radiation will promote cessation of blood flow through the AVM, even though a margin was not added to its boundaries. In the case of functional lesions, as discussed in the section “Prescribing to a Point,” the CTV and PTV concepts do not apply.

Radiation Dose Falloff

The dose falloff in LINAC radiosurgery is very steep. This accounts for the attractiveness of the method because it allows high radiation dose collimation inside the target with very fast radiation dose falloff in the normal brain tissue surrounding the target. Dose falloff varies according to collimator size and the type of planning used, such as multiple isocenter, dynamic arcs, or static beams (Fig. 255-4). This area of radiation falloff is called the penumbra. Consideration of the dosimetric consequences of the penumbra is important because the radiation dose may be still sufficiently high to cause toxicity in eloquent structures neighboring the lesion, such as the brainstem, motor area, and spinal cord.86,87 Conversely, at the margin of a complex lesion, the falloff dose may still be effective in controlling tumor growth, although underdosed in relation to the remaining lesion volume.

image

FIGURE 255-4 A,

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