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is reduced favoring the clusters of tumor cells; 80% of
metastases appear in the cerebral hemispheres.
8
Clinical manifestations vary according to the number,
volume, and location of CNS metastases. The main symp-
toms described are headache, nausea, vomiting, focal
neurological dysfunction and cognitive dysfunction.
9
Local treatment for CNS metastases depends primar-
ily on the prognosis of the clinical condition and age of
the patient. There are several tools available to aid in the
classification of patients with brain metastasis regarding
prognostic factors and their possible impact on median
survival. These tools may therefore facilitate the decision
of the most appropriate local treatment for cancer.
10,11
For patients considered to have poor prognosis, treat-
ment should be focused on the control of symptoms caused
by cerebral metastasis aimed at maintaining neurological
functioning and quality of life. For those with good prog-
nosis, local treatment should aim to eradicate and control
metastatic CNS disease. In this scenario, the options avail-
able are surgical resection and radiotherapy (whole brain
radiotherapy or radiosurgery), either alone or combined.
Radiosurgery is a radiotherapy technique that is ca-
pable of delivering high doses of radiation at pre-defined
small target volumes. It is a complex technique that uti-
lizes multiple treatment fields (coplanar and non-coplanar
beam plans) that converge to the desired target(s), allowing
adjacent healthy tissues to be significantly spared and treat-
ment to be performed quickly, non-invasively and safely.
12
1. W
hat
is
the
toxicity
of
radiosurgery
for
brain metastases
?
Toxicity after the use of radiosurgery is generally low.
Patients are unlikely to have side effects that negatively
impact their quality of life.
Fokas et al. showed levels of acute toxicity grade 3 (head-
ache, nausea and vomiting) as low as 3% in patients under-
going radiosurgery. Similarly, rates of chronic toxicity grade
3 (alopecia, headache, motor and neurocognitive deficits,
visual and auditory deficits) of only 6% were observed.
13
(
B
)
Kim et al. used the Common Terminology Criteria for
Adverse Events, version 3.0 to measure the toxicity of 58
patients who underwent radiosurgery for the treatment of
CNS metastases. Ten patients had some degree of toxicity
identified (five patients with grade 1 toxicity, one patient
with grade 2 toxicity, and four patients with grade 3 toxic-
ity). The events observed included headache, vertigo, hemi-
paresis, visual acuity deficit or cerebral necrosis.
14
(
B
)
Flickinger et al. demonstrated that only four patients
out of 116 evaluated developed perilesional edema with
worsening of neurological symptoms requiring the intro-
duction of supportive therapy with steroids. Of the entire
cohort of patients, intracranial tumor hemorrhage oc-
curred in only three (2.5%) patients.
15
(
B
)
Lim et al. conducted a randomized phase 3 clinical
trial with patients diagnosed with non-small cell lung
cancer with 1 to 4 brain metastases who underwent ra-
diosurgery followed by chemotherapy, or chemotherapy
alone. Treatment with radiosurgery was well tolerated
and there was no difference in neurocognitive function
between the two study groups.
16
(
A
)
Even when the tumor is located in critical areas, ra-
diosurgery is feasible. Luther et al. observed that motor
function improves by 31% or remains stable in 50% of
patients with brain metastases located in the motor cor-
tex treated with radiosurgery.
17
(
B
) Other authors have
evaluated the role of radiosurgery in patients with brain-
stem metastases. Asymptomatic perilesional edema oc-
curred in 4%, while 2.4% of the patients developed tumor
hemorrhage at the treatment site.
18,19
(
B
)
Recommendation
Radiosurgery has low morbidity and is associated with
low rates of side effects.
2. W
hat
is
the
maximum
number
and
size
of
metastatic
lesions
in
the
brain
for
radiosurgery
treatment
to
be
performed
?
Empirical doses and volume thresholds were established
for single dose radiosurgery in order to minimize the risks
of side effects. Existing recommendations define up to
four lesions and a maximum diameter of 4 cm as the
ideal group for the indication of primary radiosurgery, or
dose boost after whole brain irradiation
20-23
(
A
) (Table 1).
Nevertheless, there are retrospective series of patients with
up to 15 metastatic lesions treated with radiosurgery who
had clinical progression, complications and responses
similar to those treated with up to four lesions.
24,25
Some
authors suggest that total tumor volume is more impor-
tant than the absolute number of lesions,
26-28
but this
statement requires further investigation. (
B
)
TABLE 1
Main studies recommending adequate number
and size of lesions to indicate radiosurgery.
Study
Grade of
recommendation
Number
of lesions
Size
(diameter)
RTOG 90-05
23
A
1
< 4 cm
RTOG 95-08
20
A
1-3
3 cm
Kondiziolka
21
A
2-4
≤ 25 mm
Mehta
22
A
3-4
4 cm