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The prognostic indices certainly play an important role symptomatic CNS metastases. New surgical modalities
in assessing the risk/benefit ratio and providing realistic have expanded the indication and spectrum of tumors
advice and expectations to patients. For example, patients that can be successfully removed. Since the introduction
with poor prognosis can be offered supportive care, and of intraoperative monitoring and development of less
those with good prognosis can be offered multimodality invasive strategies (e.g. microsurgery, endoscopic surgery,
treatment. The prognostic scores might play a vital role in intraoperative navigation, ultrasound, and intraoperative
designing clinical trials as well. MRI), surgical removal of brain metastases even in deep-
seated and elusive areas has become feasible without
Information about variables on neuroimaging, in addition increased morbidity. To date, the strongest evidence
to the pure number of brain metastases, might be valuable for a survival benefit from surgery is for single CNS
extensions to currently established prognostic scores. metastases. In 1996, Mintz et al. did not confirm a
[53]
[54]
Spanberger and colleagues found a significant correlation positive impact of surgery on overall survival in these
between a small brain edema with an invasive tumor patients. However, only 21.4% of patients in this study had
growth pattern, a low neo-angiogenic activity, and a low a controlled extracerebral disease, and none of the patients
expression of HIF1a. These findings were associated had brain MRI assessment; therefore, comparability
with a shorter overall survival. Further, high DW-MRI with other studies is rather limited. In a retrospective
[50]
hyperintensity correlated significantly with a high amount study of treatment modalities in 1,292 patients with CNS
of interstitial reticulin deposition, and this was again metastasis of lung cancer, breast cancer, and melanoma,
associated with lower survival. Similarly, pre-operative Lagerwaard et al. demonstrated an increase of median
[55]
[51]
DW-MRI characteristics of cerebral metastases and their OS of 1.3 months in patients who received best supportive
peritumoral region in 76 patients were related to patient care only, 3.6 months in patients who received RT, and
outcome. [52] 8.9 months in patients who received a combination of
surgery and RT. Similar median OS benefits were also
THERAPEUTIC APPROACHES shown in a retrospective study of 1,137 melanoma patients
TO CENTRAL NERVOUS SYSTEM who received best supportive care (2.1 months), RT (3.4
METASTASIS months), surgery (8.7 months), or combined RT and
surgical resection. [56]
CNS metastases are, of course, a heterogeneous group with
varied response to treatment and survival. Conventional Benefits of surgery include the ability to establish a tissue
treatment options usually include a combination of diagnosis and an immediate decrease of tumor mass,
steroids, surgery, and radiation. Cytotoxic chemotherapy particularly of masses in the posterior fossa. Nevertheless,
has had a limited role in the treatment of brain metastases, patients who might benefit from surgical resection must
probably because CNS metastases often arise from heavily be carefully selected. Predictors that favor a surgical
pretreated primary tumors and may thus have already benefit include: single or few metastases, tumor location,
acquired resistance to chemotherapeutics. In addition, the surgical accessibility, KPS > 70, patient age < 65 years,
impaired blood-brain barrier penetration of some agents local mass effect, control of extracranial disease, and
might further reduce their bioavailability in the CNS. absence of leptomeningeal involvement. Based on the
[57]
Therapeutic decisions mainly depend on several factors therapy oncology group database, patients of RPA class
related to patient clinical status (neurological deficit, I are likely to benefit from surgery, whereas patients of
neurocognitive deficit, general condition, comorbidities, RPA class III are not. The primary goal of surgery is
[40]
etc.), primary disease status, extracranial metastatic disease, either macroscopic gross total resection or decompression
and CNS tumor characteristics (number, radiological dependent on the aforementioned predictors. Intraoperative
aspect, size, and location). Median overall survival times neurosurgical techniques to maximize resection (e.g.
[40]
after occurrence of CNS metastases might be predicted by image-guided surgery, [58] ultrasonography, [59] and
[60]
biomarkers as shown for LDH elevation in melanoma CNS introduction of fluorescence-guided surgery ) and to
metastases. All relevant clinical factors need to be taken minimize neurological deficits by electrophysiological
[48]
[58]
into account to identify the best therapeutic strategy among techniques improved the likelihood of complete and
the available therapeutic options. We outline the currently safe removal of metastases. A combination of surgery plus
available local and systemic therapeutic options in the radiation in patients with up to three CNS metastases can
following paragraphs. improve survival and preserve functional independence,
as outlined in two prospective studies [61,62] and three
LOCAL THERAPEUTIC STRATEGIES: retrospective studies. [63-65] Several criteria -- including
NEUROSURGICAL INTERVENTION AND tumor location, medical comorbidities, extracranial
RADIATION THERAPY disease, and performance status -- may impact individual
consideration and risk assessment for surgical resection.
Neurosurgical intervention and radiation therapy This is particularly relevant because evidence from
are currently the main modalities in the therapy of studies in high-grade glioma surgery indicates that a new

Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ May 20, 2016 ¦ 167