Systemic therapy for brain metastases
- Jan Drappatz, MD
Jan Drappatz, MD
- Associate Director
- Adult Neuro-Oncology Program
- Associate Professor
- Departments of Neurology and Medicine
- University of Pittsburgh
- Section Editor
- Patrick Y Wen, MD
Patrick Y Wen, MD
- Section Editor — Neurooncology
- Professor of Neurology
- Harvard Medical School
- Deputy Editors
- April F Eichler, MD, MPH
April F Eichler, MD, MPH
- Senior Deputy Editor — Neurology and Sleep Medicine
- Assistant Professor of Neurology
- Harvard Medical School
- Diane MF Savarese, MD
Diane MF Savarese, MD
- Senior Deputy Editor — UpToDate
- Deputy Editor — Oncology and Palliative Care
- Clinical Instructor of Medicine
- Harvard Medical School
Metastases account for more than one-half of all intracranial tumors in adults. Brain metastases are being diagnosed more often, due to both improved detection of small metastases by magnetic resonance imaging (MRI) and a true increase in incidence resulting from improved systemic therapy of extracranial disease. (See "Epidemiology, clinical manifestations, and diagnosis of brain metastases".)
The primary approaches to the treatment of patients with brain metastases include whole brain radiation therapy (WBRT), surgery, and stereotactic radiosurgery (SRS). There is only limited evidence documenting the superiority of these approaches compared to systemic chemotherapy in the treatment of patients with brain metastases.
The roles of various factors that determine responsiveness to systemic treatment will be reviewed here, along with the efficacy and risks of such treatment in the tumors that most commonly metastasize to the brain. The use of WBRT, SRS, and surgery in the management of brain metastases are discussed elsewhere, as is the treatment of leptomeningeal carcinomatosis. (See "Overview of the treatment of brain metastases" and "Treatment of leptomeningeal metastases (carcinomatous meningitis)".)
FACTORS AFFECTING RESPONSIVENESS
Blood brain barrier — The blood-brain barrier limits the passage of large molecules and hydrophilic drugs into normal brain. Whereas hydrophilic chemotherapy agents generally do not penetrate primary brain tumors because of this, several studies suggest that such drugs can reach brain metastases [1,2]. The observed contrast enhancement of metastases on computed tomography (CT) and magnetic resonance imaging (MRI) also suggests that the blood-brain barrier is at least partially disrupted in metastases  and also high-grade primary brain tumors that contrast enhance.
The responsiveness of some brain metastases to conventional chemotherapy also indicates that the blood-brain barrier is not always impermeable. However, there are only limited data on the potential enhanced delivery of chemotherapeutic agents via intraarterial infusion and blood brain barrier disruption in patients with brain metastases, and this approach cannot be recommended [4,5]. (See "Experimental treatment approaches for high-grade gliomas", section on 'Blood-brain barrier'.)
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- FACTORS AFFECTING RESPONSIVENESS
- Blood brain barrier
- SMALL CELL LUNG CANCER
- NON-SMALL CELL LUNG CANCER
- Cytotoxic chemotherapy
- Targeted agents
- - EGFR tyrosine kinase inhibitors
- - ALK tyrosine kinase inhibitors
- - Bevacizumab
- Chemotherapy plus RT
- - Temozolomide
- - Other agents
- BREAST CANCER
- GERM CELL TUMORS
- GESTATIONAL TROPHOBLASTIC DISEASE
- NON-HODGKINS LYMPHOMA
- OTHER TUMORS
- RISK OF CNS HEMORRHAGE WITH ANTIANGIOGENIC AGENTS
- SUMMARY AND RECOMMENDATIONS