190
Stereotactic Radiosurgery
for Treatment of Posterior Fossa
Metastasis
Traditionally, most brain metastases were treated
with fractionated radiotherapy, in which patients
receive small, fractionated doses of radiation
daily for 10–15 days to the whole brain (WBRT).
Within the last few decades, there has been a
trend to move to newer models of radiation deliv-
ery focused on higher doses delivered to smaller
target volumes. SRS defines the application of
one to five doses of radiation to a precise loca-
tion, with high-dose delivery to the site of inter-
est, yet minimal dose toxicity in the surrounding
tissue. Today this is achieved through a number
of different systems. The first was the Gamma
Knife system, which was introduced in 1967 by
Leksell [ 63 ]. This system utilizes a series of 192
or 201 cobalt (60) decay sources whose beams of
radiation are mechanically focused at a single
site to achieve high-dose delivery with good pre-
cision and rapid falloff of radiation dosage in the
adjacent tissues [ 64 ]. Newer methods of delivery
have been developed that rely on the use of a lin-
ear accelerator (LINAC) and the robot-based
delivery LINAC system called the CyberKnife.
LINAC systems function through the same basic
principle as Gamma Knife and rotate around a
patient’s head to deliver “arcs” of radiation at
varying, nonoverlapping points of incidence—all
targeting a defined site to produce high-dose
delivery to the tumor with minimal extralesional
tissue toxicity and necrosis. These methods have
proven to have similar complications and tumor-
treating efficacy [ 65 , 66 ].
The first cases of SRS for cerebral metastasis
were described in 1987 by Sturm et al., who used
a LINAC system [ 67 ]. Gamma Knife therapy has
been demonstrated in numerous studies to pro-
vide an average local tumor control rate ranging
from 84% to 97% [ 68 ]. There have been numer-
ous prospective and retrospective studies exam-
ining the clinical utility of SRS versus WBRT
versus surgical resection [ 69 – 72 ]. An exhaustive
review of this literature is outside the scope of
this chapter but we review a few key studies and
summarize the use of SRS in the context of pos-
terior fossa metastasis. This first began with the
demonstration that WBRT in addition to surgical
resection was superior to WBRT alone. Patients
had better functional outcomes as well as better
median survival rates [ 33 ]. Follow-up studies
confirmed these findings [ 73 ].
Subsequently, a number of studies compared
the efficacy of SRS with that of surgery. In these
studies, surgery with postoperative WBRT was
compared with SRS with follow-up WBRT, and
the authors found no difference between the SRS
or surgical resection arms of the studies [ 74 – 76 ].
These data suggest that surgery and SRS have
equal efficacy for lesions with little to no mass
effect. It is not clear whether this is always the
case in the posterior fossa, where smaller volume
tumors can cause more mass effect than within
the supratentorial space. The biggest limitation of
SRS is that although local control rates are very
good, distant brain metastasis control is not
included. This is overcome in studies that dem-
onstrate SRS + WBRT offers a better 1-year local
and distant tumor control and survival when
compared with SRS-only treatments but at the
expense of neurocognitive decline [ 77 , 78 ]. There
are a couple of tumor biological considerations
associated with radiosurgery treatment. The rela-
tive radiosensitivity of metastatic lesions is an
important caveat when considering the results of
these trials. Many tumors that are relatively
radioresistant to WBRT (such as renal cell carci-
noma or melanoma) may be treated successfully
with SRS [ 79 , 80 ].
Although radiotherapy and radiosurgery have
been appreciated as a cytotoxic therapy histori-
cally, recently uncovered molecular mecha-
nisms of cell death after radiotherapy point
toward an intersecting role with the tumor
immune response. Immune evasion is necessary
for clinically significant tumors [ 81 ]. Ionizing
radiation has a demonstrated ability to increase
proinflammatory cascades such as interferon
gamma release and to promote recruitment of
effector and helper T-cells [ 82 – 84 ]. Current data
support the hypothesis that radiation treatments
can create novel epitopes to be leveraged for
immune cell activation, in essence creating an
in vivo vaccine.B.D. Weaver and R.L. Jensen