Metastatic intracerebral tumours
The primary tumors that most commonly metastasize to the brain include:
- lung cancer,
- breast cancer,
- renal cancer,
- colon cancer.
The majority of metastases (greater than 75%) are found supratentorially with the minority (less than 10%) found in the brainstem.
Multiple metastases to the brain occur in more than 70% of cases, but solitary metastases are not uncommon (Nelson et al. 2000b). Most metastases occur at the corticomedullary junction of the cerebral hemispheres; however, they can be found in any location, with 15% being found in the cerebellum and 3% in the basal ganglia.
As many as 40% to 50% of intramedullary spinal cord metastases originate from primary lung neoplasms. The most common primary cancers causing epidural spinal cord compression include (Patchell 2003):
- breast cancer (22%),
- lung cancer (15%),
- prostate cancer (10%),
- lymphoma (10%).
Leukemias, lymphomas, breast cancer, and gastrointestinal carcinomas are associated with diffuse infiltration of the leptomeninges.
Approximately 35–40% of intracranial neoplasms are metastatic.
Metastases account for 45% of all intracranial tumours and 60% of intracerebral tumours. The frequency of brain metastases varies, depending on the primary tumour, but ranges from 12 to 35% of all cancer patients (Posner and Chernik 1978; Galicich et al. 1996).
Brain metastasis are generally a late manifestation of cancer, and systemic metastases frequently coexist; however, 36% of patients do not have a past history of cancer at initial presentation. It has been estimated that only 19% of patients do not have metastases at other sites at the time of presentation, but this was based on a cancer hospital population (Cairncross et al. 1980).
The frequency of isolated brain metastases is likely to be higher in a general hospital population study. Lung cancer, cancer of unknown origin, breast cancer, and melanoma account for 90% of brain metastases (Grant et al. 1996).
It is very unusual for patients with breast or gastrointestinal tract malignancies to present with brain metastases as the initial manifestation of cancer. If there is no history of malignancy at presentation with brain metastases, the primary site is most commonly lung (55%) or the primary tumour is not identified prior to death (40%) (Grant et al. 1996).
Steroids do reduce the amount of oedema around the tumour and repair a leaky blood–brain barrier, but the symptomatic relief (6–24 hours after starting) antedates any obvious change on CT scan or MRI scan.
Imaging and Location
On MR imaging, cerebral metastases can mimic any cerebral tumor with iso- to hypointense signal on T1- and hyperintensity on T2-weighted imaging (Yuh et al.1995; Davis et al. 1991). In large lesions intensive edema is present, which is frequently absent in small metastatic lesions.
The metastatic foci are well separable from the surrounding edema because of the different signal characteristics that depend on the cellularity, hemorrhage, necrosis etc. Hemorrhage is frequent in metastatic CNS lesions, mainly in lesions from melanoma, lung cancer, hypernephroma, and choriocarcinoma. Hemorrhage can be seen as hyperintensity on unenhanced MRI, representing methemoglobin, but other blood byproducts, e.g., hemosiderin, may also be present.
In MRI, the signal characteristics of brain metastases vary: in most cases, the lesions appear hypointense on T1-weighted and hyperintense on T2-weighted imaging. A hyperintense signal on nonenhanced T1-weighted imaging represents bleeding into the metastasis or high melanin content of the lesion. In some rare cases, e.g., with gastrointestinal adenocarcinoma as the primary tumor, or in massive bleedings into the metastases, the lesions can appear hypointense on T2-weighted imaging.
Besides very small lesions, all cerebral metastases show enhancement. The degrees and patterns of enhancement may vary and can include homogeneous, inhomogeneous, and ring-shaped enhancement. In cases with hemorrhage, the enhancement can be hidden. The degree of enhancement also depends on the amount of contrast medium used and the time-point of imaging after contrast-media application. There have been studies reporting a substantial increase in the detection of metastases with the use of a high dose of contrast media. An optimal dose may be a double dose (Colosimo et al. 2001; Schneider et al. 2001). The use of magnetization transfer technique was also found to be beneficial for detecting small or additional metastatic lesions.
The patients present with signs and symptoms referable to either increased intracranial pressure or focal pathology.
Prognosis in patients with cerebral metastases will depend on the age, primary tumour type and responsiveness to treatment, site of cerebral metastasis (supratentorial versus infratentorial; resectable versus irresectable), presence of systemic metastases, and performance status at diagnosis.
Solitary brain metastasis is uncommon but has a better prognosis, if the brain disease can be controlled. Approximately 30–40 per cent of cerebral metastases are single (Delattre et al. 1988). Metastases from colon, kidney, and breast are more frequently single than metastases from lung or melanoma, but because lung cancer has a higher incidence than colon or kidney, lung cancer remains the most likely cause.
A surgically accessible lesion can be defined as one that is superficial (close to the brain surface or abutting a fissure or sulcus) and can be operated on with minimal parenchymal resection. This type of metastasis can frequently be resected even in eloquent areas of the brain. Surgery has the benefit of removing the lesion, reducing the need for long-term steroids, potentially improving quality of life, and providing a small survival gain in certain situations. Because of the high risk of new cerebral metastatic lesions developing in the brain, it should be followed by cranial radiation.
Technical advances in radiotherapy have re-opened the debate about the value of surgery for single brain metastasis. Stereotactic radiotherapy (SRT), using a linear accelerator with capability for three-dimensional conformal external radiation and a non-invasive removable frame which allows fractionated treatments, or stereotactic radiosurgery (SRS), using multiple cobalt-60 sources and a fixed, rigid, surgically attached stereotactic frame (gamma knife) for single-session treatment, may be as effective as surgical resection for single brain metastasis. Radiosurgery is high-dose, single-fraction external irradiation of a stereotactically well-defined target. For technical reasons the metastasis must be less than 3 cm in diameter and ideally should not border the ventricles, brainstem, or cranial nerves. Radiosurgery is an option for treatment in patients with single metastasis who are unfit for surgery or have a metastasis in a surgically inaccessible site. Highly selected series have demonstrated local control in 80 per cent of treated cases and an incidence of radiation necrosis of approximately 5–10 per cent (Flickinger et al. 1994; Alexander et al. 1995).
Management of young patients with multiple brain metastases is different from those with single metastasis.
First, there is less of a chance of misdiagnosis on CT/MRI scan.
Secondly, there is less of a chance of having two or three metastases at surgically resectable sites.
Thirdly, there is usually less opportunity for stereotactic radiotherapy because the metastases are multiple.
Conventional whole-brain radiation without histological confirmation is almost always the management of choice.
Systemic chemotherapy in a very selected patient group with potentially chemoresponsive tumours (e.g. breast, small cell lung, germ cell tumours) may be offered and may improve systemic disease, but usually the blood–brain barrier will limit the efficacy in patients with brain metastases (Kristjansen and Hansen 1988; Boogerd et al. 1992).
Management of elderly patients with multiple brain metastases and active systemic disease is palliative, with aims being symptomatic control and supportive care. There is no good evidence that radiation extends survival in the elderly.