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Page 2 of 16 Enrique et al. J Cancer Metastasis Treat 2019;5:54 I http://dx.doi.org/10.20517/2394-4722.2019.20

Keywords: Brain metastases, whole-brain radiation therapy, stereotactic radiosurgery, graded prognostic assessment

INTRODUCTION
Brain metastases are the most common intracranial malign neoplasms in adult patients, with 170,000 new
cases per year reported in the USA alone . The incidence of brain metastasis has been on the rise the last
[1]
20 years, resulting from an increase in the number of cases of lung and breast cancer and the fact that
[2]
cancer survival rates have been increasing thanks to new therapeutic advances and the availability of central
nervous system imaging technologies for diagnosis. More than 40% of patients with cancer develop brain
metastases: specifically, they appear in 50% of patients with lung cancer, more than 25% of patients with
breast cancer, and 20% of patients with melanoma .
[3,4]
Multiple epidemiological studies have been conducted regarding brain metastases. These have had different
methods and limitations; however, a comparison between them can bring an understanding of the incidence
of brain metastasis. Such studies include the initial work done by Goumundsson in Iceland, which reported
an incidence of 2.8 cases per 100,000 people , and Percy et al. , where the incidence found was as high
[6]
[5]
as 11.1 cases per 100,000. The Barnholtz-Sloan et al. 's study derived greater validity from its use of the
[7]
register of the Metropolitan Detroit Cancer Surveillance System from 1973 to 2001, carrying information on
an approximate population of 4.5 million patients, in which the observed incidence of brain metastasis in
patients with any kind of neoplasm was 9.6%.

Considerable variability in the incidence of brain metastasis has been found, which may be attributable to
limited available data, such as autopsy reports or general hospital records; nevertheless, beginning with the
first records of cancer, a similar incidence of brain metastasis has been observed, which may be attributable
to the fact that it is an exclusively oncological population limited to a particular state or region and follow-up
of the same patients .
[8,9]

Generally, lung cancer is the foremost cause of brain metastasis, with studies reporting incidences of 12% to
65% of all patients with primary lung cancer. Among the most commonly associated histologies for brain
[10]
metastasis are small-cell lung cancer and adenocarcinoma. In a high percentage of patients with lung cancer,
diagnosis is performed after the onset of neurological symptoms.

Breast cancer is the main cause of brain metastases in women, with reported incidences between 5% and 30%
of all breast cancer cases. Unlike the case of lung cancer, in breast cancer the diagnosis of brain metastasis
usually follows well after the initial diagnosis of cancer. Diagnoses of melanoma have increased over the last
several years, and this malignant neoplasm has the greatest capacity to develop into brain metastasis, with
incidences from 12% to 90% [Figures 1-3]. Incidences of 7% to 10% of all patients with renal cancer and 1% to
4% of all gastrointestinal tumors have been reported .
[11]

The therapeutic management of patients with brain metastases depends on the localization and number
of brain lesions, primary tumor biology, and disease extension. The overall survival from the moment of
diagnosis for untreated patients is 1-2 months, which can be extended to 6 months in patients who receive
conventional radiotherapy and chemotherapy .
[4]

PATHOPHYSIOLOGY
The genesis of metastasis requires several complex and sophisticated steps to occur first. These include
genetic, epigenetic, and biological changes known as the “metastatic cascade” [12,13] . This process begins
with the detachment of a tumor cell from its primary lesion and the invasion of the surrounding tissue,