NcXHF

RADIOTHERAPY AND RADIOSURGERY EVIDENCE IN BRAIN METASTASES
tastases performed in 23 hospitals in Japan, no difference
in overall survival was demonstrated in patients who had
two to four brain metastases versus fıve or more brain metastases
when treated with SRS alone. 11 The median overall
survival after SRS was 13.9 months in patients who had
a single brain metastasis, 10.8 months in patients who had
two to four brain metastases, and 10.8 months in patients
who had fıve to 10 brain metastases. This suggests that SRS
may be a reasonable approach in selected patients with up
to 10 brain metastases, further broadening the horizon of
use of SRS in these patients. This also supports the hypothesis
that the volume, and not the number, of metastases
may be the driver in determining the outcomes in brain
metastases. 12 An ongoing prospective trial, NAGKC 12-
01, is comparing the neurocognitive outcomes and survival
in patients with fıve or more brain metastases treated
either with SRS or WBRT (NCT01731704); this trial will
further defıne the role of SRS in this patient population.
Another active area of interest is utilization of SRS in lieu of
WBRT to prevent local recurrence after resection. Resection
bed SRS targeting is more complex because of uncertainties
about the interpretation of postoperative MRI. Soltys et al 13
showed a 1-year local control rate of 94% with the addition of
a 2-mm margin around the defıned tumor bed versus 78%
when there was no margin. 13 The median overall survival
time was 17 months, and 72% of patients were able to avoid
WBRT, although intracranial relapse and salvage with other
therapies (such as SRS) was required in a substantial proportion
of patients. Concerns with this approach include the
possibility of leptomeningeal spread secondary to the resection,
especially for patients who have breast cancer and those
who have posterior fossa disease. 14 The North Central Cancer
Treatment Group (NCCTG) study N107C is an ongoing
intergroup study of patients who have one to four brain
metastases that compares WBRT versus SRS after resection
(NCT01372774).
An approach to potentially minimize leptomeningeal spread
is to perform neoadjuvant SRS before surgery to sterilize the
tumor cells before surgical resection. Neoadjuvant SRS in 47
patients, who were undergoing preoperative SRS with a median
dose of 14 Gy (range, 11.8 to 18 Gy), was reported by
Asher et al. 15 Surgical resection performed after SRS resulted
in control in 86% at 1 year, and only 15% of the patients eventually
required WBRT. Signifıcantly, no leptomeningeal failures
were observed in this study.
There is no level-1 evidence to support use of SRS in lieu of
surgery. More than one randomized effort to answer this
question has failed because of poor accrual. In a retrospectively
matched series of 75 patients treated by surgery and
SRS, a median survival time of 7.5 months with SRS versus
16.4 months in the surgical group was reported. 16 However,
the dosing regimen for SRS in this study resulted in the use of
lower prescriptions to the tumor margin than would be considered
standard according to the widely accepted RTOG dosing
schema. 5,17 Auchter et al 18 reported a multi-institutional
data set of SRS in 122 highly selected patients who had one
resectable brain metastases. The median survival was 56
weeks in this retrospective series, which was comparable to
the results of most surgical series. 18 Schoggl et al 19 performed
a retrospective case-control analysis with 133 patients who
were treated with either SRS (67 patients) or surgery (66 patients)
along with WBRT. There was no difference in median
survival (SRS vs. surgery, 12 vs. 9 months; p 0.19), but the
local control rate was superior with SRS. 19 In a retrospective
study that compared surgery and SRS for the treatment of a
solitary brain metastasis, no signifıcant difference was found
in patient survival. However, the difference in the local tumor
control rate was signifıcant (100% after SRS vs. 58% after surgery).
20 Muacevic et al 21 compared surgery and WBRT with
SRS in patients who had single brain metastases. 21 The approaches—of
surgery and WBRT, or of SRS—resulted in
similar 1-year survival rates (53% vs. 43%; p 0.19), 1-year
local control rates (75% vs. 83%; p 0.49), and 1-year neurologic
death rates (37% vs. 39%; p 0.8).
THE ABANDONMENT OF WHOLE-BRAIN
RADIOTHERAPY
The randomized studies discussed above demonstrate that
postoperative WBRT clearly improves intracranial control
of brain metastases, but they also demonstrate that this
benefıt has not categorically translated into an overall survival
benefıt. Further, there are concerns regarding the potential
for cognitive decline in patients receiving WBRT.
More importantly, there are emerging data presented by
Sahgal et al 22 showing an overall survival advantage of SRS
alone over WBRT (10 vs. 8.2 months) for patients age 50 or
younger who have one to four brain metastases, on the
basis of a meta-analysis of three phase III studies. 22 Collectively,
these factors, as well as the ability to salvage intracranial
relapses with further application of SRS (an
opportunity afforded in abundance by withholding
WBRT), recently have led to the wholesale abandonment
of WBRT, with its use reserved largely for patients who
have multiple brain metastases and are not deemed favorable
SRS candidates.
This approach requires thoughtful scrutiny. The analysis
by Sahgal et al 22 was conducted by merging the EORTC
22952-26001, JROSG99-1, and MDACC NCT00460395
data sets. Collectively, these three trials included patients
who had one to four brain metastases, who were treated
with SRS with or without WBRT, and who had variable
entry criteria for each trial and considerable variability in
terms of systemic therapies, enrollment eras, SRS dose,
follow-up imaging, and re-treatment considerations. Further,
the EORTC trial also included patients undergoing
resection at physician discretion. A total of 364 patients is
available in this collated data set, of whom 51% (185 patients)
were treated with SRS alone and only 19% (69 patients)
were younger than age 50. The results demonstrate
a curious blend of outcomes; for the post hoc–defıned
subset of these patients younger than age 50, the overall
survival was superior with the SRS-alone arm (10 vs. 8.2
months), but the time to distant brain failure was shorter
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK
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