**2.1 Localization of brain metastases**

Another important aspect is the precise localization of the metastases in the brain (Globus et al. 1942, Tom et al. 1946, Zimm et al. 1981, Tikhtman et al 1995). Approximately the 80% of metastases are localized in the cerebral hemisphere, 17% in the cerebellum and 3% in the brain stem (Tikhtman et al 1995). Delattre and contributors have also analyzed the localization of metastases in the specific regions of the cerebral hemisphere (Delattre et al. 1988). They found that brain metastases involved the frontal area for 21%, the parietal and the temporoparietal-occipital for 19%. These authors have also outlined that metastasis located preferentially at the junction of gray and white matter. Hwang et al. recently reexamined the importance of the vascular border zone and the gray and white matter junction in the distribution of brain metastases and agreed with Delattre and contributors (Hwang et al. 1988). They found in 302 metastatic brain lesions studied, that gray and white matter junction was the preferred site for 64 % of the brain metastases and the vascular border zones were the site of predilection for the 62%. These results support the notion that metastatic emboli tend to lodge in an area of sudden reduction of vascular caliber (gray/white matter junction) and in the most distal vascular field area (Border zone) (Hwang et al. 1988).

#### **2.2 Shape of brain metastases**

Most metastases appear round well-demarcated lesions that displace rather than invade the surrounding brain parenchyma. The lesions can vary in size ranging from microscopic to masses of 1-4 centimeters in diameter. The histopathologic features are similar to that of tumor of origin.

Microinvasion is present although the majority of metastatic lesions appear well demarcated and sometimes with reactive astrocytosis surrounding the metastatic area (Shaffrey et al. 2004). A new vasculature can appear at peripheral zones and is part of the edema. In central areas, necrotic areas are present (Nathoo et al. 2005). Meningeal metastases diffuse into the subarachnoid space with accumulation around blood vessels (Shaffrey et al. 2004).

#### **2.3 Prognosis of brain metastases**

Untreated brain metastases have a dismal prognosis, generally no greater than 1-5 months. Gaspar et al. 2000, studying a RTOG (Radiation Therapy Oncology Group) data base, performed a Recursive – Partitioning Analysis [RPA] on 1200 patients. They identified the factors able to influence the prognosis of these patients (Gaspar et al. 2000, D'Ambrosio et al. 2007). Among the several prognostic factors, Karnofsky Performance Status (KPS) has been identified as the most important. The other important factors were: status of primary tumor, age and the presence or absence of systemic metastases. Stratifying the patients according these criteria they have been able to obtain the following prognostic factors. Patients with KPS = 70%, with age = 65 with controlled primary tumor and absence of systemic metastases had a median survival of 7.1 months, whereas the survival was reduced to 2.3 months for patients with KPS < 70. The presence of uncontrolled tumor and systemic metastases even if with a KPS = 70% reduced the median survival to 4.2 months (Gaspar et al. 1997, 2000). The survival was not different between patients with undiagnosed primary lesion and thosewith diagnosed primary tumor (6 and 4.5 months, respectively; p = 0.097) as reported in a recent study by D'Ambrosio (D'Ambrosio et al. 2007).
