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Enrique et al. J Cancer Metastasis Treat 2019;5:54 I http://dx.doi.org/10.20517/2394-4722.2019.20 Page 13 of 16

radiation and pharmacologic approaches to address this syndrome are being studied, and while further data
are needed for any one medical solution to become the standard of care, the results generated to date suggest
a positive outlook for future treatment options .
[70]
As new radiotherapy techniques have appeared, treatment plans have been developed that, in addition to tumor
control, aim to reduce cognitive deterioration through the preservation of the hippocampus. Indeed, the RTOG
0933 trial demonstrated the preservation of cognitive function by reducing the dose to the hippocampus to
[71]
not more than 9 Gy at 100% of the volume and a maximal hippocampal dose of 16 Gy. This was achieved by
manually contouring the hippocampus on a fused MRI-CT image set and expanding by 5 mm to generate
“hippocampal avoidance regions.” The mean relative cognitive decline from baseline to 4 months was 7.0%,
significantly lower than in controls. The study demonstrated that conformal avoidance of the hippocampus
during WBRT was associated with preservation of memory and quality of life. Nonetheless, this procedure
poses a risk of generating new brain metastases within the avoidance regions. However, this risk is not fully
quantified and further data are needed to validate this technique within a phase III setting.

CONCLUSION
Although brain metastasis is the most common malignant intracranial tumor, it is closely linked to
unfavorable outcomes. Its incidence has increased dramatically, due to a greater number of newly diagnosed
cancer patients and the broader therapeutic options available today, which have led to better disease
control and longer overall survival. The majority of patients are not candidates for surgical resection, so
radiotherapy remains the standard of care. The possibility of a cure for an oligometastatic disease has been
gaining increasing attention in recent years. The management of these patients has changed immeasurably
over the past few decades: not many years ago, the prognosis and survival of such patients was for a short
life expectancy, with poor disease control. At present, there are several treatment options available. The
choice among these modalities depends on several factors, such as the functional state of the patient and the
availability of equipment and treatment techniques at the given medical center. Before the 1990s there was
no GPA prognostic scale, much less an RPA, which are quite useful for decision making.

To date, no prospective studies have evaluated the use of SRS relative to WBRT for patients with more than
four brain metastases. However, the current tendency in several hospitals around the world is to avoid
WBRT, due to the toxicity and neurological deterioration attendant on that treatment, especially in developed
countries. Consequently, there has been a shift to highly sophisticated techniques, such as SRS. A randomized
phase III study is currently running at The Odette Cancer Center and the Princess Margaret Cancer Center
(University of Toronto) in patients with 5 to 20 cerebral metastases who are receiving treatment with SRS
without WBRT versus SRS plus WBRT, with the primary outcome being to compare neurocognitive decline
between the approaches, as this is a common late side effect in patients receiving radiotherapy.

DECLARATIONS
Authors’ contributions
All the authors contributed in an equitable way in the conception, bibliographic search and writing of this
review article.

Availability of data and materials
All figures and tables are provided by authors and are available upon request to the corresponding author.

Financial support and sponsorship
None.