Chapter 49 - Brain metastases

Abstract

Brain metastases occur in 20–40% of patients with cancer and their frequency has increased over time. Lung, breast, and skin (melanoma) are the commonest sources of brain metastases, and in up to 15% of patients the primary site remains unknown. After the introduction of magnetic resonance imaging (MRI), multiple lesions have outnumbered single lesions. Contrast-enhanced MRI is the gold standard for the diagnosis. There are no pathognomonic features on computed tomography or MRI that distinguish brain metastases from primary malignant brain tumors or non-neoplastic conditions; therefore, a tissue diagnosis by biopsy should be always obtained in patients with an unknown primary tumor before undergoing radiotherapy and/or chemotherapy. Some factors are prognostically important: a high Karnofsky Performance Status, a solitary brain metastasis (absence of systemic metastases and controlled primary tumor), and a younger age. Based on these factors, subgroups of patients with different prognosis have been identified (recursive partitioning analysis (RPA) class I, II, III). Symptomatic therapy includes corticosteroids to reduce vasogenic cerebral edema and anticonvulsants to control seizures. In patients with newly diagnosed brain metastases, prophylactic anticonvulsants should not be used routinely. The combination of surgery and whole-brain radiotherapy (WBRT) is superior to WBRT alone for the treatment of single brain metastasis in patients with limited or absent systemic disease and good neurological condition. Complete surgical resection allows relief of intracranial hypertension, seizures, and focal neurological deficits. Radiosurgery, alone or in conjunction with WBRT, yields results that are comparable to those reported after surgery followed by WBRT, provided the diameter of the lesion does not exceed 3–3.5 cm. Radiosurgery offers the potential of treating patients with surgically inaccessible metastases. Still controversial is the need for WBRT after surgery or radiosurgery; local control is better with the combined approach, but overall survival does not improve. Late neurotoxicity in patients with a long survival after WBRT is not negligible; to avoid this complication, patients with favorable prognostic factors must be treated with conventional schedules of radiation therapy, and monitoring of cognitive functions is important. WBRT alone is the treatment of choice in patients with a single brain metastasis not amenable to surgery or radiosurgery, and with active systemic disease, and in patients with multiple brain metastases. A small subgroup of the latter patients may benefit from surgery. The response rate of brain metastases to chemotherapy is similar to that of the primary tumor and extracranial metastases, some tumor types being more chemosensitive (small-cell lung carcinoma, germ cell tumors, breast carcinoma). New radiosensitizers, targeted agents, and innovative techniques of drug delivery are being investigated.