13 / 99
T
reatment
of
brain
metastases
R
ev
A
ssoc
M
ed
B
ras
2016; 62(5):389-394
393
for those not treated with radiotherapy
vs.
9.5 months for
patients undergoing RT (95CI 7.8-11.9), p=0.71 (level of
evidence
1B
).
Aoyama et al. (1996) did not find benefit in function-
al prognosis (p=0.53) or preservation of neurological func-
tion (p=0.99) at 12 months with combined treatment (lev-
el of evidence
1B
).
Evidence summary
Radiotherapy combined with holocranial radiotherapy does
not increase the time of functional independence com-
pared with radiosurgery
(A)
. However, compared to patients
treated with radiotherapy, the combined treatment is supe-
rior in terms of functional independence at 6 months
(B)
.
O
utcome
: T
umor
control
4) C
linical
question
Does radiosurgery combined with holocranial radiother-
apy improve tumor control compared with radiosurgery
or holocranial radiotherapy alone?
Results
The study by Kondziolka et al. (1997) ended prematurely
after an interim analysis identified considerable benefit in
terms of local tumor control with combined treatment
compared to radiotherapy alone. The median time to lo-
cal recurrence was 36 months for the first and 6 months
for radiotherapy alone (p=0.005) (level of evidence
2B
).
In the study by Kocher et al. (2004), combined treat-
ment led to better local control of tumors at 2 years com-
pared with radiosurgery alone: reduction from 31% (95CI
22-40%) to 19% (95CI 11-27%; p=0.04). There was also bet-
ter control of tumors in other locations: a reduction from
48% (95CI 38-58%) to 33% (95CI 24-43%; p=0.023).
In the study by Chang et al. (2009), tumor control at
1 year occurred in 100% of the patients undergoing com-
bined treatment
versus
67% of tumor control with radio-
surgery alone (p=0.012).
In the study by Aoyama et al. (1996), tumor control
at 12 months reached 88.7% (95CI 80.1-97.3%) in the
group of combined treatment
versus
72.5% (95CI 60.3-
84.7%) in the group undergoing radiosurgery alone
(p=0.002). Tumor control at 1 year in other sites of the
brain was also more favorable than under combined treat-
ment. There was a decline from 73% to 45% (p=0.02).
Evidence summary
Radiosurgery combined with holocranial radiotherapy
reduces the likelihood of local tumor recurrence and the
development of new brain lesions
(A)
.
O
utcome
: C
ognitive
decline
5) C
linical
question
Is radiosurgery combined with holocranial radiotherapy
associated with greater cognitive decline compared with
radiosurgery or holocranial radiotherapy alone?
Results
The study by Chang et al. (2009) had cognitive function as
the primary endpoint, which was evaluated by a set of neu-
ropsychological tests covering various domains. This study
was terminated early after an interim analysis demonstrat-
ed that the possibility of deterioration of learning andmem-
ory at 4 months was significantly higher in patients under-
going combined treatment (52%) than in patients treated
with radiosurgery alone (24%) (level of evidence
1B
).
Aoyama et al.
13
(2007) used the mini-mental state ex-
amination to assess cognitive function, and found that
the main factor related to cognitive function is tumor
control. Cognitive worsening was earlier the single treat-
ment group (7.6 months
vs.
16.5 months, p=0.05). How-
ever, after 36 months, only 14.7% of patients who under-
went combined treatment had no cognitive worsening
(level of evidence
2B
).
Evidence summary
Radiosurgery combined with holocranial radiotherapy
leads to significant worsening of cognition compared
with radiosurgery alone
(A)
.
O
utcome
: Q
uality
of
life
6) C
linical
question
Is radiosurgery combined with holocranial radiotherapy
associated with poorer quality of life compared to radio-
surgery or holocranial radiotherapy alone?
Results
Soffietti et al. (2013) analyzed the aspects of quality of
life based on the EORTC QLQ-C30 scale in patients un-
dergoing radiosurgery/surgery alone or combined treat-
ment. Patients who underwent combined treatment had
poorer overall quality of life at 9 months (p=0.014) (lev-
el of evidence
2B
).
Evidence summary
Radiosurgery combined with holocranial radiotherapy is
associated with poorer quality of life
(B)
.
N
ote
The different treatment modalities, either combined or
alone, produce different effects on various outcomes. The