Epidemiology, Treatment, and Complications of Central Nervous System Metastases

Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival.

Targeted therapies with tyrosine kinase inhibitors and immune checkpoint inhibitors and cytotoxic therapies directed at disease-specific chemosensitivity patterns have dramatically improved the prognosis of non-small cell lung cancer, melanoma, and breast cancer, but have led to some novel complications and altered recurrence patterns. Clinical trials suggest the superiority of hippocampal-avoidance radiation fields and the use of stereotactic radiosurgery over whole-brain radiation therapy to minimize long-term cognitive consequences of radiation therapy. Emerging data document tolerable safety when brain radiation is combined with immunotherapy. Chemotherapy can be a first-line treatment for some inoperable brain metastases, eliminating or deferring whole-brain radiation therapy. Stereotactic body radiation therapy is a new technique of radiation used for spinal and epidural metastases that spares spinal cord tissue while ablating tumors.

Metastases to the nervous system remain devastating, but their prognosis and therapies are more heterogeneous than previously appreciated. Neurologists now can offer more personalized prognostic information based on new stratification criteria, can predict drug complications relevant to the nervous system, and can provide critical partnership in the multidisciplinary effort to balance effective longer-term disease control with treatment-related adverse consequences.