Topic of the month.... The role of gamma knife in the management of brain metastasis
Metastatic disease to the brain occurs in a significant percentage of patients with cancer and can
limit survival and worsen quality of life. Glucocorticoids and whole-brain radiation therapy
(WBRT) have been the mainstay of intracranial treatments, while craniotomy for tumor resection
has been the standard local therapy. In the last few years however, stereotactic radiosurgery (SRS)
has emerged as an alternative form of local therapy. Studies completed over the past decade have
helped to define the role of stereotactic radiosurgery. The authors review the evolution of the
techniques used and the indications for stereotactic radiosurgery use to treat brain metastases.
Stereotactic radiosurgery, compared with craniotomy, is a powerful local treatment modality
especially useful for small, multiple, and deep metastases, and it is usually combined with whole-
brain radiotherapy for better regional control.
Brain Metastasis is the most common intracranial tumor, with an estimated annual incidence of
more than 100,000 cases. In 20 to 40% of patients with cancer, metastatic lesions travel to the
brain.[8,44] On the basis of historical studies, medical treatment with glucocorticoids alone yields a
life expectancy of less than 3 months. The addition of whole-brain radiotherapy improves survival
to 3 to 6 months.[6,27] Aggressive local treatments such as resection and radiosurgery in
combination with whole-brain radiotherapy can achieve median survival times of 9 to 12 months in
The Radiation Therapy Oncology Group has conducted multiple studies that have helped to
delineate several predictive variables for patients with metastatic brain disease. Among the most
important predictive factors is the general medical and oncological condition of a patient. Gaspar
and colleagues evaluated 1200 patients from previous Radiation Therapy Oncology Group
studies and used RPA to identify three major variables predictive of outcome: patient age greater
than or equal to 65 years, functional independence as defined by a KPS score greater than or equal
to 70, and controlled compared with uncontrolled extracranial disease. The authors then stratified
the patients into RPA Classes 1, 2, or 3 according to these variables. The single most important
predictor of out come was functional status, and patients with KPS scores less than 70 (RPA Class
3) had the worst prognosis. Young and functionally independent patients with controlled
extracranial disease (RPA Class 1) had the best prognosis ( Table 1 )
Table 1. Determination of RPA Class Based on KPS Score, Age, and Extracranial Disease Status*
KPS Score Age (yrs) Primary Disease Control RPA Class Survival (mos)
70–100 <50 good 1 7.1
70–100 65 bad 2 4.2
<70> irrelevant irrelevant 3 2.3
* The RPA class is correlated with mean survival. Based on data from Gaspar et al., 1997..
Although RPA class is the most important predictor of survival, aggressive local therapy (such as
resection) for metastatic foci in addition to regional therapy (whole-brain radiotherapy) improves
survival in selected patients.[35,40] In a surgical trial conducted at a single medical center in the
United States, Patchell et al. randomly assigned 48 patients with single brain metastases to two
treatment groups and demonstrated a median survival of 40 weeks in the patients that underwent
resection and whole-brain radiotherapy compared with 15 weeks in patients who underwent whole-
brain radiotherapy alone. Similarly, Noordjik and coworkers showed a statistically significant
survival advantage in their European study of patients with single brain metastases who underwent
resection. One study of 83 patients failed to prove a survival benefit in patients who underwent
resection. The lack of benefit in this last study has been attributed to the overwhelming
influence of RPA class on survival, especially in terms of control of extracranial disease. Patient
selection is crucial, therefore, to realizing benefit from aggressive local management of patients
with brain metastasis.
Stereotactic Radiosurgery for Brain Metastases
Because of the success of aggressive local control with resection for a single metastasis,
neurosurgeons have pursued a complementary approach with the use of stereotactic radiosurgery
to control single and multiple brain metastases. In a relatively short time, stereotactic radiosurgery
has emerged as an important noninvasive option in the neurosurgical armamentarium against
brain metastasis. Brain metastases are discrete and often semispherical, thus making attractive
The largest and most influential study conducted to date in patients with brain metastasis treated
with stereotactic radiosurgery comes from Radiation Therapy Oncology Group 95-08 by Andrews
and colleagues. This was a multiinstitutional clinical trial in which 333 patients were randomly
assigned to two treatment groups. The patients in one group underwent both stereotactic
radiosurgery and whole-brain radiotherapy and those in the other group underwent whole-brain
radiotherapy alone. Study inclusion criteria were the presence of one to three brain metastases,
patient age older than 17 years with no history of previous cranial irradiation, and a KPS score
greater than 70. In contrast to the patients who participated in the studies of resection alone,
patients with multiple brain metastases (one to three lesions) were eligible to participate. The
primary end point was survival. Two major groups of patients benefitted from radiosurgery: those
with a single metastasis (regardless of RPA class) and those in RPA Class 1 with up to three brain
metastases. An intent-to-treat analysis was used to control for both known and unknown biases. It
is important to note that 31 of 164 patients assigned to the stereotactic radiosurgery group did not
actually undergo stereotactic radiosurgery, and 28 of 167 patients in the whole-brain radiotherapy
arm received salvage stereotactic radiosurgery. Hence, a quot;per protocolquot; analysis probably would
have demonstrated an even greater survival advantage for the same groups. On the basis of this
randomized trial, stereotactic radiosurgery has been established as an important tool in the local
management of brain metastasis.
In an earlier randomized clinical trial, Kondziolka et al. examined local control as the primary
end point in their study of patients with multiple metastases. The authors compared local control in
patients with two to four metastases who underwent either whole-brain radiotherapy alone or
whole-brain radiotherapy and stereotactic radiosurgery. The study was stopped after 60% accrual
because the interim analysis showed a dramatic advantage to adding stereotactic radiosurgery.
Median time to local failure was 6 months in patients who received whole-brain radiotherapy alone
and 36 months in patients who received both whole-brain radiotherapy and stereotactic
radiosurgery. Because the study was stopped early, the survival difference between the two groups
was not statistically significant. Nevertheless, the authors demonstrated that stereotactic
radiosurgery improves local control.
Stereotactic Radiosurgery Technique
Stereotactic radiosurgery is performed with either a linear accelerator or a Co-60 gamma source
unit. Masks or cranial pin frames provide immobilization. Regardless of technique, preoperative
imaging is paramount. Gadolinium-enhanced T1-weighted MR imaging is standard. Contrast-
enhanced computed tomography scans can be used if MR imaging is not possible. Tailored MR
imaging techniques are available to increase detection of small and emerging metastases. Triple-
dose Gd and MT magnetization transfer can be used to detect lesions not seen on single-dose
images. Triple-dose imaging can help clarify any equivocal findings on single-dose imaging, but
it is more expensive, is time consuming, carries an increased false-positive rate, and is probably not
justified for routine use.
Dose and Tumor Size
Radiation dosing is usually described in terms of Gy delivered to the prescription isodose line. This
allows a simple understanding of the minimum amount of radiation delivered to every tumor cell.
The prescription dose refers to the radiation dose, usually specified in Gy or cGy, delivered to the
tumor margin. Hence, the general goal is to include the entire gross tumor volume within the
prescribed tumor volume. The prescription dose is often referenced as a percentage of the
maximum dose (Fig. 1). To achieve effective local control and the survival benefit of stereotactic
radiosurgery requires the delivery of a tumoricidal radiation dose to all neoplastic cells within the
prescription dose line while minimizing the radiation dose to the surrounding brain parenchyma.
Modern stereotactic radiosurgery systems can contour isodoses to the tumor volume precisely, but
large tumor volumes present difficulties. A large tumor volume results in a higher integral
radiation dose to the surrounding brain. Thus, larger tumors must generally be treated with a
lower dosage in order to avoid radiation toxicity. Because of the corresponding decrease in
dose, the ability to achieve local control may be compromised.
Figure 1. Screen
snapshot from planning
targeting of a left
mass in a patient with
isodose curves show
50% (yellow) and 35%
Dose escalation studies conducted by the Radiation Therapy Oncology Group outlined maximum
tolerated doses in patients undergoing stereotactic radiosurgery after whole-brain radiotherapy or
fractionated external-beam radiation. The study population included patients with primary
gliomas and brain metastases and was not subdivided. The primary stratification variable was size.
The tumors were divided into groups of less than 2 cm, 2 to 3 cm, or 3 to 4 cm ( Table 2 ). The
maximum tolerated dose was not reached for tumors larger than 2 cm. This study provides a
guideline for dosing but does not account for other variables, such as location of delivery. For
example, the optic nerve and brainstem are more sensitive to radiation-induced edema than the
frontal lobe. The dose prescription must be reduced if necessary to protect such structures.
Clinical judgment and experience remain important in dose prescription.
Table 2. Final Recommendation of the RTOG Protocol 90-05 Study for Recurrent Metastases*
Tumor Size (cm) Recommended Dose (Gy) 1-Year Local Control Rate (95% CI)
<2 24 85 (78–92)
2–3 18 49 (30–68)
3–4 15 45 (23–67)
* Tumor size is based on the maximum measured tumor diameter in cm. Dose is delivered to the 50% isodose line. Based on
data from Shaw et al. and Vogelbaum and Suh. CI = confidence interval.
The authors of several studies have demonstrated differences in local tumor control based on size.
One study demonstrated a 78% response rate in tumors 2 cm3 or smaller compared with a 50%
response rate in tumors 10 cm3 or greater. In a study of 103 patients with melanoma
metastases, local control rates after stereotactic radiosurgery were 75.2% for lesions less than 2 cm
in diameter compared with 42.3% in larger lesions. The same authors studied another 135
patients with tumors of various histological types and found local 1- and 2-year control rates of 86
and 78% for tumors less than 1 cm in diameter compared with 56 and 24% for tumors of larger
diameters. A systematic analysis of this topic comes from a recent publication in which the
established dosing schedule outlined by Radiation Therapy Oncology Group 90-05 was used. A
three-part grouping of 1-year local control rates based on size is presented in Table 2 .
Local control has been used as a surrogate end point in some trials but does not necessarily
correlate with survival. Two studies found no significant effect of tumor size on survival,[18,48]
whereas another found it to be the most important factor predicting survival.
The size of the brain metastasis must influence the choice of treatment modality. Local control of
larger tumors with stereotactic radiosurgery is compromised because of the need to limit the
prescription dose. Larger tumors with mass effect, especially if single and superficial, should be
resected if the patient is young, has good systemic disease control, and a high KPS score. Tumors
that are small, multiple, deep, or that have a minimal mass effect should be managed with
stereotactic radiosurgery. Clinical judgment and patient preference must help guide treatment
decisions for the many patients with conditions between the two extremes.
Radioresistance and Radiosensitivity to stereotactic radiosurgery
Traditional concepts of radioresistance and radiosensitivity to fractionated external beam radiation
may not correlate with the response of brain metastasis to stereotactic radiosurgery. For example,
brain metastases from melanomas and sarcomas have traditionally been considered radioresistant
based on their response to whole-brain radiotherapy (3 Gy per fraction). In contrast, Mehta et al.
 evaluated volumetric response rates based on the histological characteristics of the lesions.
They found complete response to treatment in 100% of lymphomas, 67% of melanomas and
sarcomas, 50% of non-small cell lung cancers, 33% of breast cancers, and 11% of renal cell
carcinomas. Again, tumor stabilization or shrinkage noted radiologically did not correlate with
clinical outcome. Patients with more radioresistant tumor types often fared better after stereotactic
radiosurgery than those with radiosensitive types. In a multiinstitutional review, patients with
melanomas, breast cancer, and renal cell carcinomas treated with stereotactic radiosurgery
survived longer than patients with other lesion types. In a review of studies assessing
radiological regression and local control, Boyd and colleagues noted that traditionally
radiosensitive tumors did show more complete radiographic regression than the radioresistant
tumors. However, clinically relevant local control rates were as good or better for the
quot;radioresistantquot; types as the quot;radiosensitivequot; types.
The deviation of stereotactic radiosurgery responses from the traditional definition of radiation
resistance may have to do with the different mechanism of killing cells compared with fractionated
methods.[34,37] This may be due to a different impact on tumor vasculature. A single high dose
of radiation delivered by stereotactic radiosurgery can provide local control for tumors that are
resistant to standard radiation therapy.
Complications of stereotactic radiosurgery
Reported complications of stereotactic radiosurgery include peritumoral edema, radiation-induced
necrosis, tumoral hemorrhage, and radiation-induced neoplasia. In a review of 264 brain
metastases treated in 189 patients, Chang and coworkers reported a 6.4% rate of hemorrhage
within 2.5 months of treatment with stereotactic radiosurgery. In half of these cases of hemorrhage
corrective surgical treatment was required. The authors also noted a 3.8% rate of significant
peritumoral edema, and in half of these cases, too, the patients had to undergo resection. The study
by Chang et al. included renal cell carcinomas, melanomas, and sarcomas only.
Lutterbach et al. evaluated responses to treatment with stereotactic radiosurgery in 101
patients harboring metastases of various histological subtypes and noted complications in 13
patients. Some of these complications occurred within the first month (worsened seizures or
transiently worsened neurological deficits) and some arose between 5 and 26 months posttreatment
(such as fixed neurological deficits or radiation necroses). Radiation-induced necrosis can be
difficult to manage because standard imaging characteristics do not distinguish reliably between
necrosis and residual or recurrent tumor at the treatment site. Advanced imaging modalities, such
as MR spectroscopy, can help differentiate between the two and may assist in further treatment
Radiation-induced neoplasia has been described after stereotactic radiosurgery. Meningiomas have
been documented to grow in arteriovenous malformation treatment beds. Malignant
progression of benign lesions treated with stereotactic radiosurgery is another problem, although
deciphering treatment effect from natural history can be difficult. Although radiation-induced
neoplasia must be considered when recommending stereotactic radiosurgery for benign tumors or
curable vascular lesions, it is less important for patients with brain metastases. These lesions are
already malignant, and the patient's life expectancy is short relative to the normal time frame for
this complication. One case report describes the development of an anaplastic astrocytoma 5 years
after stereotactic radiosurgery treatment of metastatic melanoma. The authors reiterate the very
low incidence of radiation-induced neoplasia after stereotactic radiosurgery.
Craniotomy Compared with stereotactic radiosurgery
Resection of a single accessible brain metastasis in addition to whole-brain radiotherapy has been
the standard of care for single metastases in patients with other favorable prognostic factors.
However, stereotactic radiosurgery is becoming more commonly available and a number of studies
have demonstrated efficacy comparable with craniotomy, making the decision as to which is the
optimal treatment more complex. Indeed, some authors have even suggested that stereotactic
radiosurgery may supplant craniotomy as the new gold standard.
One obvious disadvantage to stereotactic radiosurgery is the lack of histological confirmation of
diagnosis. Among patients with known systemic cancer and a new brain lesion, up to 11% may
be harboring an alternative pathological entity such as a primary brain tumor, abscess, or even a
hemorrhage. Resection provides both the treatment and the opportunity for diagnosis.
Therefore, resection—or at least biopsy sampling—should be considered for any patient without a
Several investigators have initiated randomized controlled trials to compare the efficacy of these
two treatments. Patient accrual has been difficult, and the results are not yet available. In place of
prospective data, one can try to glean data from the multiple retrospective studies that have been
performed. There are three single-center retrospective analyses comparing stereotactic
radiosurgery to craniotomy. Bindal et al. studied 31 retrospectively matched patients treated
with stereotactic radiosurgery and 62 patients treated with craniotomy. These authors found a
median survival period of 7.5 months in the stereotactic radiosurgery group compared with 16.4
months in the craniotomy group (p = 0.0018). This study has been criticized because of an overt
selection bias and differences in radiosurgical techniques and outcomes in comparison to other
groups. Muacevic et al. retrospectively reviewed 108 patients and compared a group of patients
who underwent craniotomy and whole-brain radiotherapy compared with those who underwent
stereotactic radiosurgery alone. These authors found no significant difference in 1-year survival, 1-
year local control, or morbidity and mortality rates. O'Neill et al. studied 97 patients with
single brain metastases, of whom 74 underwent craniotomy and 23 underwent stereotactic
radiosurgery. Their rate of local failure for surgery was unusually high at 58%. None of the
stereotactic radiosurgery patients had local failure. Regardless, they found no difference in 1-year
Several authors have attempted to review the existing literature to determine the role of
stereotactic radiosurgery compared with conventional craniotomy and resection. Sperduto
undertook a literature review and reached several conclusions: patients with a single accessible
metastasis should undergo craniotomy; patients with one to three tumors and a KPS score greater
than 70 should receive both stereotactic radiosurgery and whole-brain radiotherapy; patients with
more than three tumors and a KPS score less than 70 should undergo whole-brain radiotherapy
only. Boyd and colleagues studied 21 reports of stereotactic radiosurgery for brain metastasis.
Although they were unable to perform a definitive analysis due to data inhomogeneity, they found
an average local control rate of 83% and median survival of 9.6 months. As noted in their report,
this is comparable to the results of recent surgical series. Boyd and colleagues note the following
characteristics that make metastasis amenable to stereotactic radiosurgery: lesion tendency toward
spherical shape, gray-white junction location allowing the application of a large radiation dose with
minimal toxicity, and frequent presentation at less than 3 cm diameter. In a literature review and
commentary, Alexander and Loeffler concluded that stereotactic radiosurgery is comparable to
surgery and therefore surgery should be restricted to the minority of patients for whom the brain
metastasis is immediately life threatening.
In summary, there is no confirmed clear advantage of one treatment over the other. The
discomfort, risks, and costs of surgery must be justified to recommend this treatment to a patient.
The two modalities have some complementary aspects. Stereotactic radiosurgery seems clearly
preferable for small, multiple, and deep lesions, and in patients unlikely to tolerate general
anesthesia well. Craniotomy should be recommended for single, large lesions causing herniation or
a posterior fossa mass effect. For tumors that could reasonably be treated using either modality,
patient and physician preference will play a large role and both modalities remain accepted
Cost-effectiveness of stereotactic radiosurgery
Most studies demonstrate that stereotactic radiosurgery is a cost-effective treatment for patients
with brain metastasis. Mehta et al. undertook a cost-effectiveness analysis of patients with
brain metastases, among whom 46 underwent resection, 135 received stereotactic radiosurgery,
and 454 received whole-brain radiotherapy alone. The authors found that surgery and stereotactic
radiosurgery were similarly effective and superior to the use of whole-brain radiotherapy alone.
The net cost of surgery was 1.8-fold higher. The average cost per week of survival was $310 for
whole-brain radiotherapy, $524 for surgery and whole-brain radiotherapy, and $270 for
stereotactic radiosurgery and whole-brain radiotherapy.
Rutigliano et al. reviewed the literature on the economic efficiency of stereotactic radiosurgery
or surgery with whole-brain radiotherapy from 1974 to 1994 and had similar (although less
dramatic) findings, stating the cost as $24,811/life year ($477/week) for stereotactic radiosurgery
combined with whole-brain radiotherapy compared with $32,149/life year ($618/week) for
craniotomy. Thus, craniotomy is 1.3 times more expensive for the additional survival time offered
com pared to 1.8 times more expensive as reported by Mehta et al.
In a Munich study, 127 patients with various diagnoses were treated with craniotomy or
stereotactic radiosurgery. The stereotactic radiosurgery costs were determined by the global
operating costs for the gamma knife surgery center divided by the number of patients treated.
Craniotomy costs included the costs of surgery, the intensive care unit, and inpatient and ancillary
services. The costs of treating meningiomas, vestibular schwannomas, brain metastases, and
arteriovenous malformations less than 3 cm in diameter averaged 15,242 euros for craniotomy and
7,920 euros for stereotactic radiosurgery.
Compared with conventional craniotomy, stereotactic radiosurgery is a cost-effective treatment for
brain metastasis. The decision to pursue craniotomy or stereotactic radiosurgery as a treatment in
a particular patient should not be determined by economics. However, because cost, access, and
resource management are increasingly important, these factors must be included in professional
discussions of treatment algorithms.
Is whole-brain radiotherapy Needed After stereotactic radiosurgery?
Whole brain radiation therapy is an accepted treatment modality for brain metastases. As
mentioned, the addition of whole-brain radiotherapy improves patient survival from 1 to 2 months
to 3 to 6 months after the original diagnosis.[6,27] The community standard regimen is 30 Gy
delivered in 10 fractions, although other protocols have been investigated. An Radiation
Therapy Oncology Group study using hyperfractionation demonstrated improved survival and
neurological function. How ever, a follow-up randomized trial in which patients received 1.6
Gy twice a day and 54.4 Gy total could not conclusively show improved survival.
Radiation-induced dementia is a serious side effect of whole-brain radiotherapy. This complication
occurs 6 to 12 months after irradiation and can be very debilitating.[4,14] This raises the question
whether whole-brain radiotherapy should be used more judiciously. Patients with good KPS scores
are likely to live longer and are more likely to benefit from improved cerebral tumor control but
are also more likely to suffer delayed dementia after whole-brain radiotherapy.
Aoyama and colleagues recently published a randomized controlled trial of 132 patients with up
to four metastases each who underwent stereotactic radiosurgery or stereotactic radiosurgery
followed by whole-brain radiotherapy. The primary end point was survival. Secondary end points
included functional preservation and radiation toxicity. The Mini Mental Status Examination was
used for assessment. This is a rapid but not thorough neuropsychological tool. Consistent with
previous retrospective studies,[20,50] Aoyama and colleagues found that stereotactic radiosurgery
alone does not provide as good local or distant control as stereotactic radiosurgery with whole-
brain radiotherapy. The elimination of whole-brain radiotherapy did not, however, result in
shortened survival or an altered level of functional independence. This is similar to the results of a
surgical trial published by Patchell et al. in 1998 in which patients were randomly assigned to
groups that received resection with or without whole-brain radiotherapy. This study also failed to
demonstrate a survival advantage with the addition of whole-brain radiotherapy. Neither trial was
designed as an equivalency study and should not be interpreted as such. Instead, we can conclude
that within the power of the predetermined criteria, both studies failed to show a survival
advantage with the addition of whole-brain radiotherapy if patients are treated with stereotactic
radiosurgery initially or even with resection.
The major reason for withholding whole-brain radiotherapy is to avoid the late onset of radiation-
induced dementia. Unfortunately, Aoyama et al. used an effective but perhaps insensitive tool to
study functional status—the KPS score. The ability to determine radiation-induced dementia and
complications may require a more sensitive measure than KPS score. It remains unproven,
although intuitive, that an stereotactic radiosurgery-only treatment plan would reduce the
incidence of radiation-induced dementia.
An alternative strategy for treatment of new brain metastases is stereotactic radiosurgery alone
initially and whole-brain radiotherapy given only to those with treatment failure. Sneed et al.
concluded that patients with single metastasis are most likely to benefit from whole-brain
radiotherapy. However, they noted that stereotactic radiosurgery without whole-brain
radiotherapy led to salvage (delayed) whole-brain radiotherapy in only 26% of their patients, thus
sparing 74% the loss of time, the expense, and the risk of dementia.
Deinsbeger et al. studied 110 patients with new brain metastases and found a local control rate
of stereotactic radiosurgery without whole-brain radiotherapy of 89.4% and a median survival of
12.5 months. Based on this high rate of control with the single modality, they recommended that
whole-brain radiotherapy be reserved for cases of numerous metastases or used in a delayed
fashion for recurrence. Conversely, Aoyama et al. found a significantly higher need for salvage
whole-brain radiotherapy in patients who had undergone stereotactic radiosurgery alone
compared with those treated with stereotactic radiosurgery and whole-brain radiotherapy initially.
Further evaluation is needed to clarify the proper use and timing of whole-brain radiotherapy in
patients treated with stereotactic radiosurgery. The North Central Cancer Treatment Group Is
currently treating patients harboring one to three brain metastases with stereotactic radiosurgery
alone and with stereotactic radiosurgery followed by whole-brain radiotherapy. Overall survival
duration, central nervous system control, quality of life, and toxicity are among the end points.
Such data from a large study may help the clinician in the future with this decision.
Which stereotactic radiosurgery System is Best?
There are two fundamental types of stereotactic radiosurgery systems. The prototype radiosurgical
system is the Gamma Knife (Elekta) which uses 201Co-60 sources semispherically arranged around
a geometric center. The basic engineering design concepts of the Gamma Knife have not changed
since its development in 1967; design changes have increased usability and efficiency. This modality
relies on forward planning with the delivery of quot;shotsquot; to the tumor. It relies on the stereotactic
Leksell G frame for rigid skull fixation and accurate dose delivery. The nomenclature quot;stereotactic
radiosurgeryquot; was coined by Lars Leksell, the Swedish neurosurgeon who invented the current
Leksell arc-centered frame and the Gamma Knife. The precision and accuracy of gamma knife
surgery remain the standards by which intracranial stereotactic radiosurgery is defined.
The second type of radiosurgical system is based on linear accelerators, or linear accelerators,
which are standard radiation oncology tools. The radiation source is mounted on a robotic arm and
moves around the patient. Such systems include the Cyberknife (Accuray), X-Knife (Radionics),
Trilogy (Varian), and Novalis (BrainLab). Early linear accelerator machines did not have the
sophisticated features seen on modern units such as multileaf collimators, reverse planning
software, and image-guided capabilities with cone-beam computed tomography scanners. Early
versions were imperfectly adapted for precise cranial anatomy, resulting in poor quality assurance
and, consequently, poor clinical outcomes compared with gamma knife surgery.[43,46] Modern
linear accelerators have gained sophistication. Some units allow non-frame-based stereotaxis, using
a molded face mask or similar device. This alternative may appeal to patients who wish to avoid
cranial pins and is more amenable to hypofractionated treatment regimens. Additionally,
extracranial targets (such as spinal lesions) may also be targeted.
Most of the radiosurgical literature does not distinguish between gamma knife surgery and linear
accelerator stereotactic radiosurgery. The efficacy and safety of the two modalities are likely
similar with the modern systems, although there is clearly a higher central dose, and thus more
dose inhomogeneity, with gamma knife surgery. Depending on the situation, this may serve as
either an advantage or disadvantage. Choosing a particular stereotactic radiosurgery system is
often based on institutional, financial, and administrative factors.
Stereotactic radiosurgery has emerged as a noninvasive and effective means of improving patient
survival as well as local control in patients with brain metastases. Two evidence-based management
strategies that can be justified on the basis of randomized clinical trials are resection followed by
whole-brain radiotherapy or whole-brain radiotherapy followed by stereotactic radiosurgery.
Stereotactic radiosurgery and resection are overlapping and complementary techniques. Single,
large, and superficial lesions in noneloquent brain regions in patients with favorable prognostic
factors should be resected. Multiple deep lesions in the medically frail patient should be treated
with stereotactic radiosurgery. Between these two extremes lie the majority of patients, and thus
the art of medical management requires an understanding of the strengths and weaknesses of the
three tools in the armamentarium: whole-brain radiotherapy, stereotactic radiosurgery, and
GKS = gamma knife surgery; KPS = Karnofsky Performance Scale; LINAC = linear accelerator;
MR = magnetic resonance; RPA = recursive partitioning analysis; RTOG = Radiation Therapy
Oncology Group; SRS = stereotactic radiosurgery; WBRT = whole-brain radiotherapy.
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The author: Professor Yasser Metwally, professor of neurology, Ain Shams university, Cairo,