Hematogenous spread most common. Skull metastases rarely invade CNS; may compress adjacent brain or cranial nerves or obstruct intracranial venous sinuses. Primary tumors that commonly metastasize to the nervous system are listed in Table 75-1. Brain metastases are well demarcated by MRI and enhance in a ring pattern or diffusely. The radiographic appearance is nonspecific; similar-appearing lesions can occur with infection including brain abscesses, demyelinating lesions, sarcoidosis, radiation necrosis, or a primary brain tumor that is a second malignancy in a pt with systemic cancer. Biopsy rarely necessary for diagnosis because imaging alone in the appropriate clinical situation usually suffices. However, in approximately 10% of pts, a systemic cancer may present with brain metastases; in this situation biopsy of primary tumor or accessible brain metastasis is needed to plan treatment. Brain metastases are single in approximately one-half of pts and multiple in the other half. Treatment is with glucocorticoids, RT, or surgery. Standard treatment has previously been whole-brain RT; approximately 80% of pts improve with glucocorticoids and RT, but it is not curative, is associated with neurocognitive toxicity, and produces median survival of only 4–6 months. If feasible, SRS (gamma knife, linear accelerator, proton beam, or CyberKnife) has become the primary radiation oncology approach to brain metastases. It can sterilize visible lesions and produce local disease control in 80–90% of pts. SRS can effectively treat up to 10 lesions; it is, however, confined to lesions of ≤3 cm and is most effective in metastases of ≤1 cm.

Surgical excision of a single metastasis, or sometimes two lesions, followed by whole-brain RT is another option. Systemic chemotherapy may produce dramatic responses in highly chemosensitive tumor types such as germ cell tumors or small-cell lung cancer harboring specific epidermal growth factor receptor (EGFR) mutations that sensitize them to EGFR inhibitors. Immunotherapy can also be effective against primary tumors that are sensitive to this approach, such as melanoma.