RAMB - Agosto 2016

ima

FMT

392

ssoc

ras

2016; 62(5):389-394

ly calculated considering 124 patients per group and

eventually adjusted to 326 patients. The analysis of loss

to follow-up was done based on intention-to-treat. There

is no data on extraction of results.

Kondziolka

(1B)

(1999) was a single-center trial dis-

continued after the interim analysis of 27 patients that

revealed significant benefit in the rate of local metastat-

ic control with whole brain radiotherapy plus radiosur-

gery. This study included patients with 2 to 4 brain me-

tastases sized 25 mm or less. Local tumor control was

also assessed as a primary outcome. No other results were

presented. MRI scans were read by an independent ob-

server blinded for treatments.

Aoyama et al.

(1B)

(2006) studied patients aged 18

years or older with 1 to 4 brain metastases measuring a

maximum of 3 cm in diameter on MRI divided into two

groups: stereotactic radiosurgery alone

versus

stereotac-

tic radiosurgery combined with whole brain radiothera-

py. Eligible patients should have a Karnofsky performance

score of 70 or more. The study was conducted at the Hok-

kaido University (Japan) and ten other centers. Random-

ization was centralized at the Hokkaido University, in

blocks of four. The patients were stratified based on the

number of brain metastases (single

vs.

2-4), extent of ex-

tracranial disease (active

vs.

stable), and location of the

primary tumor (lung

vs.

other sites).

The study by Chang et al.

(1B)

(2009) considered el-

igible patients who were treated at the Departments of Ra-

diation Oncology and Neurosurgery of MD Anderson Can-

cer Center, Houston, aged 18 years or older, Karnofsky =

70 or more, with 1-3 brain metastases. Randomization was

done by computer (1:1) between the group of stereotactic

radiosurgery combined with radiotherapy and stereotac-

tic radiosurgery alone, in blocks of 2, 4, 6, or 8 patients.

The sequence was hidden until all interventions were des-

ignated. Intention-to-treat analysis was conducted.

Kocher et al.

(1B)

studies the role of whole brain ra-

diotherapy after surgery or radiosurgery in a limited num-

ber of brain metastases in patients in good conditions

with stable systemic cancer. The trial was randomized by

center, organized by the European Organisation for Re-

search and Treatment of Cancer. The study was designed

to detect a difference of 11% in the proportion of live pa-

tients, with strength of 80% and 5% of two-tailed signifi-

cance. 340 patients were planned to be recruited.

Soffietti R et al.

(1B):

This was a multicenter, ran-

domized, international, phase III trial comparing patients

undergoing radiosurgery or surgery with whole brain ra-

diotherapy as adjuvant treatment or monitoring.

Results

Outcome: Survival

Andrews et al.

(1B)

(2004) studied 333 patients evaluat-

ing the effects of the “boost” of radiosurgery in the tu-

mor bed after radiotherapy. There was no benefit in sur-

vival between the groups. However, in patients with single

metastasis, combined treatment proved to be superior

(6.5 months

vs.

4.9 months, p=0.03)

(1B)

Kondziolka et al.

(1B)

(1997) studied 27 patients

and found no significant differences with respect to sur-

vival. The mean survival in the group undergoing com-

bination treatment was 11 months, while the group treat-

ed with radiotherapy alone had a survival of 7.5 months

(p=0.22). This study was terminated early because an in-

terim analysis showed significant benefit in terms of lo-

cal tumor control in favor of the combined treatment (ev-

idence level

Aoyama et al. (2006), in 132 patients, obtained a 7.5

month survival with the combined treatment, and 8

months in the group undergoing radiosurgery alone

(p=0.42) (level of evidence

Chang et al. (2009) compared the combined treat-

ment with radiosurgery alone in 58 patients. In the ra-

diosurgery group, survival was 15.2 months

versus

5.7 in

the combined treatment group (p=0.003) (level of evi-

dence

). This study was terminated at 4 months after

an interim analysis showed cognitive decline in the com-

bined treatment group.

Evidence summary

Compared to radiosurgery alone, it is not possible to de-

termine whether the combination treatment is superior

or not in terms of survival

(A)

utcome

: F

unctional

independence

3) C

linical

question

Does radiosurgery combined with holocranial radiother-

apy increase the time of functional independence com-

pared with radiosurgery or holocranial radiotherapy alone?

Results

Andrews et al. (2004) found that combination treatment

provides less possibility of functional worsening at 6

months (RR=0.78, 95CI 0.61-1, p=0.05) compared with

holocranial radiotherapy alone (level of evidence

Kocher et al. (2011) showed that adjuvant radiother-

apy does not improve functional outcome of patients un-

dergoing radiosurgery alone. The mean time of worsen-

ing of functional status was 10 months (95CI 8.1-11.7)