Stereotactic Radiosurgery
Decades of experience have proven stereotactic radiosurgery to be an effective means of local tumor control in carefully selected patients. Studies specific to the pediatric population support its use as well, although numbers of patients and length of follow-up for most tumor types are meager compared with those in studies on the adult population. One must understand both the strengths and limitations of stereotactic radiosurgery to yield the best results.
The History of Stereotactic Radiosurgery
Stereotactic radiosurgery was developed in 1951 by Lars Leksell and Borje Larsson.1–3 Using converging proton beams coupled with stereotactic frame-based guidance, they were able to create intracranial lesions noninvasively. In 1968, the first Gamma Knife unit became operational.3 Like the modern Gamma Knife, this predecessor used multiple cobalt-60 sources. It was first intended as a tool for functional neurosurgery; however, it was soon being used to treat intracranial tumors and arteriovenous malformations (AVMs).3
Over the decades, several technical improvements have allowed for more accurate and efficient treatment delivery of stereotactic radiosurgery. As imaging modalities (computed tomography [CT] and then magnetic resonance imaging [MRI]) developed and improved, targeting was revolutionized. In addition, early efforts required tedious manual repositioning of the patient and frame relative to the isocenter. Current Gamma Knife units are equipped with robotic automatic positioning systems (APSs) that allow for much faster delivery of care.4
The Gamma Knife was introduced in the United States in 1987 by Dade Lunsford′s group at the University of Pittsburgh.5 Lunsford, Douglas Kondziolka, and John Flickinger continue to amass large numbers of patients with meticulous tracking of results as well as complications, including an extensive pediatric experience.6–15
In late 1990s, John R. Adler developed the CyberKnife as an alternative way of delivering highly focused stereotactic radiation to intracranial lesions.16 Unlike the Gamma Knife, which is a frame-based system, the CyberKnife moves the radiation source relative to the patient via a large robotic arm. The patient is not rigidly fixed, but is tracked by X-ray. Adjustments are made to the position of the source based on moment-to-moment feedback. Small shifts in patient position are accommodated while maintaining accuracy; however, the patient is required to be relatively still. Because the CyberKnife does not require a frame, its use is not limited to intracranial lesions and treatments can be hypofractionated.17
Basics of Stereotactic Radiosurgery
Regardless of the equipment used, the concept of stereotactic radiosurgery remains the same.1–3,16 By using multiple weak converging beams, a field of radiation is created that sharply conforms to the borders of a lesion. The field has a steep drop-off so that the treated area can receive a relatively high dose of radiation while the surrounding area receives a relatively low dose. This is advantageous in many clinical scenarios, in comparison with other forms of radiation therapy, in that it facilitates maximal therapeutic benefit with minimal toxicity ( Table 12.1 ).
Stereotactic radiosurgery involves acquiring images that show the target tumor, defining the borders of that lesion, and then creating a treatment plan that best matches the lesion in shape and location ( Fig. 12.1 ). A radiation dose is selected based on tumor type as well as its proximity to potentially radiosensitive structures. The dose may be decreased if the patient has undergone previous radiation therapy. Radiation is then delivered to the planned treatment area with a high degree of accuracy using stereotactic guidance (based on the imaging studies).
For a tumor to be treated with stereotactic radiosurgery, it must be clearly visible on either CT or MRI. Ideally the tumor should well circumscribed. Because of the steep drop-off of high-dose radiation, treating an infiltrative lesion will result in either undertreating parts of the tumor or over-radiating areas of normal brain. Radiosurgery is a highly focal treatment. As such, it loses effectiveness when one tries to treat a diffuse or disseminated process.
Across different tumor types, a smaller target results in a better response to treatment with lower complication rates.8,10–12,18,19 In addition to size, the location of the tumor is relevant to the safety and efficacy of treatment. Specifically, structures such as the optic chiasm have a higher risk of injury from stereotactic radiosurgery when they are less than 2 mm from the target.
Special Considerations for Children
For the majority of adults, stereotactic radiosurgery can be performed with either local anesthesia or conscious sedation. This is often not the case for pediatric patients. When planning a stereotactic radiosurgery procedure, one must keep in mind the length of the entire process (which is typically several hours) and the degree of immobilization required. Depending on the age, a pediatric patient may need general anesthesia for frame placement and image acquisition, as well as treatment delivery.20 There will be times when the anesthesia team has limited access to the patient. When in doubt, intubate to fully control the airway.
Small, well-circumscribed tumors that are easily defined on imaging studies |
Tumors not amenable to further surgical resection |
Tumors located at least 2 mm from radiosensitive structures (such as the optic chiasm) |
Tumors that are predominantly solid rather than cystic |
Tumors that have not disseminated |
The thickness of the skull may limit the use of the stereotactic frame in very young children. The feasibility of frameless stereotactic radiosurgery for pediatric patients has been demonstrated in several small series with patients ranging in age from 8 months to 19 years.21–23 Although it is possible to deliver conformal radiation that is likely to cause fewer side effects than conventional radiation therapy, the efficacy of stereotactic radiosurgery is yet to be demonstrated in very young patients. In fact, in a preliminary report, three of five infants treated with radiosurgery for malignant brain tumors died either from progressive local disease or distant recurrence.23
When considering any form of radiation therapy in a pediatric population, one must keep in mind that the developing brain is more at risk for damage from radiation than is the adult brain. Due to limited dosage to regions beyond the treatment area, however, stereotactic radiosurgery is less likely to cause intellectual decline in young patients when compared with whole-brain radiation.23,24 Long-term studies are needed to confirm this.
Pediatric Tumors
Stereotactic radiosurgery is used to treat several types of pediatric tumors ( Table 12.2 ). They are discussed in the following subsections.
Pilocytic Astrocytoma
A role for stereotactic radiosurgery has been established in adults7,25 and children8,18,19,24,25 with pilocytic astrocytomas. In some ways, these tumors are ideal targets for this form of therapy because they are typically discrete and brightly enhancing on MRI. In addition, they rarely metastasize, so local control can result in a good long-term outcome. Thus, the first line of treatment for a newly diagnosed or recurrent pilocytic astrocytoma remains surgery whenever possible.
The University of Pittsburgh group has looked at the results of 50 pediatric patients who underwent Gamma Knife radiosurgery for pilocytic astrocytomas between 1987 and 2006.8 The 5-year progression-free survival after treatment was 70.8% with one death. The Pittsburgh group noted that the best responses occurred when treating tumors with small volumes, and concluded that stereotactic radiosurgery should be considered when resection is not feasible.8 Similar statistics have been shown in other groups with a trend toward improved outcome when stereotactic radiosurgery was compared with external beam radiation.19,26
Pilocytic tumors |
Ependymomas |
Craniopharyngiomas |
Pituitary tumors |
Vestibular schwannomas |
Meningiomas |
Focal brainstem gliomas |
Given that almost a third of the treated patients showed tumor progression in 5 years (a short time period for a slow-growing tumor), radiosurgery is by no means a cure-all for these tumors. In addition, residual tumor can remain dormant or spontaneously regress.27,28 Radiosurgery should be reserved for progressively enlarging residual or recurrent pilocytic tumors not amenable to further surgery.
Ependymoma
Like pilocytic astrocytomas, recurrent ependymomas have been treated with stereotactic radiosurgery with various degrees of success ( Fig. 12.2 ).10,11,24,29,30 These tumors can be difficult to manage. With surgery, a greater extent of resection offers a better prognosis; however, gross total resection is not always possible. Even with a gross total resection, these tumors can recur both locally and with distant disease. Chemotherapy either after initial surgery or at the time of recurrence has not proven successful.31 With recurrence, most patients have already received some form of radiation therapy, which can further limit treatment options.
Stereotactic radiosurgery offers a means to deliver additional radiation in an area that was previously radiated. In different series, local control of ependymomas treated with stereotactic radiosurgery ranged from 29 to 45% at 3 years.10,30 More importantly (and less promising) is that even in the setting of local control, a high rate of distant tumor relapse has been noted (80% at 3 years).10 This distant disease often resulted in overall failure of treatment and death.
There are factors linked with a potential for better outcome. In recurrent pediatric ependymomas, small tumors that have homogeneous contrast enhancement appear to respond best to stereotactic radiosurgery.10 In addition, a later recurrence or a longer interval between conventional radiation therapy and stereotactic radiotherapy is also linked with a better response.11
Primitive Neuroectodermal Tumors
The role of stereotactic radiosurgery is less well defined in the treatment of primitive neuroectodermal tumors (PNETs). Case series are small, and use is limited to palliative therapy after failure of multimodal treatment.12,21,30 In the Pittsburgh group′s recent series, all patients died of either local or distant disease progression following stereotactic radiosurgery.12 Given that these patients received other therapies, it is difficult to determine if radiosurgery extended life or improved quality of life in any way. There may be an advantage in treating recurrence with repeat surgery followed by stereotactic radiosurgery to the re-section bed.12,32 However, with a poor ultimate response, some have questioned the cost-effectiveness of this focal treatment for what is, by behavior, a systemic disease.32
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