When any of the several clinical syndromes caused by metastatic tumor is fully developed, diagnosis is relatively easy. If only headache and vomiting are present, a common problem is to attribute them to migraine or tension headache. One should invoke such explanations only if the patient has the standard symptoms of one of these conditions. CT with contrast will detect practically all sizable (1 cm) metastases though MRI with gadolinium is much more sensitive especially for cerebellar and subcentimeter lesions, and will expose associated leptomeningeal disease. Multiple nodular deposits of tumor in the brain on imaging studies most clearly distinguish metastatic cancer from other tumors but this pattern may also occur with brain abscesses, brain lymphoma, and glioblastoma.
Solitary metastatic disease must be distinguished from a primary tumor of the brain, CNS lymphoma, tumefactive demyelination (see Chap. 35), and from infective abscess. Multiple brain metastases must not be confused with the syndromes associated paraneoplastic neurologic syndromes that sometimes accompany carcinoma. The latter include sensory neuronopathies and the Lambert-Eaton myasthenic syndrome (usually with carcinoma of the lung), cerebellar degeneration (ovarian and other carcinomas and Hodgkin disease), necrotizing myelopathy (rare), limbic encephalitis, and the opsoclonus–myoclonus syndrome. These paraneoplastic syndromes are discussed further on, under “Remote Effects of Neoplasia on the Nervous System (Paraneoplastic Disorders).”
In addition to the aforementioned conditions, there are many patients with cancer who exhibit symptoms of an altered mental state without evidence of metastases or a recognizable paraneoplastic disorder. These symptoms usually have their basis in systemic metabolic disturbances (hypercalcemia in particular), drugs, and psychologic reactions, some of which have yet to be clearly delineated. Problems of this type were noted in a high percentage of cancer patients seen in consultation at the Memorial Sloan-Kettering Cancer Center (Clouston et al) and are seen almost daily on the wards of our hospital. Once chemotherapy or brain radiation has been administered, the secondary effects of these treatments further cloud the picture.
Treatment The treatment of metastatic tumors of the nervous system undergoes frequent change. Current programs utilize various combinations of corticosteroids, radiation therapy (focal or whole brain treatment), surgical removal, and chemotherapy and immune modulating treatment. Corticosteroids produce prompt improvement, probably on the basis of a reduction in the edema surrounding the lesion(s), but sustained use is restricted by side effects and eventual loss of efficacy. Most patients with multiple metastases also temporarily benefit from the use of whole-brain irradiation, usually administered over approximately a 2-week period, in multiple doses. Various studies report a response rate, albeit temporary, in 50 to 70 percent of patients with multiple metastases but the type of tumor also determines the likelihood of response. High-dose and focused radiotherapy (radiosurgery) is now considered the main alternative for single or several cerebral metastases.
One randomized trial comparing stereotactic radiotherapy alone, or combined with whole-brain radiation for 1 to 4 metastases, found no difference in survival but there was a reduction in the frequency of recurrence at other sites in the brain when whole-brain treatment was added (Aoyama et al). Several other studies have suggested that control of local symptoms related to a metastasis is better with focused radiotherapy. However, with the exception of a single lesion from small cell lung cancer, there does not seem to be an advantage to either approach. If focused treatment has been used, whole-brain radiation can still be instituted at the time of a recurrence. Whether there is evidence to justify the routine implementation of this approach is not clear, especially as overall measures of the quality of life are not generally improved. An arbitrary limit of stereotactic treatment of four metastases arose as the field evolved but it appears that the results are similar with even greater numbers.