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What is the clinical scope and management for brain metastases?

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Key concept

Brain metastases are common sequelae of solid tumors (lung, breast, melanoma, renal, and colorectal). Lung cancer has the highest number of brain metastases; however, melanoma has the highest propensity to metastasize to brain. Although their exact incidence is unknown, about 8%–10% of patients with cancer will manifest brain metastasis, with an expected growing incidence as a function of increased life expectancy.1,2

Management is primarily local, owing to limited penetration of most systemic agents through the blood-brain barrier. The historical standard of care (whole-brain radiation therapy [WBRT]) is being rapidly replaced by focal techniques such as stereotactic radiosurgery (SRS) and surgical resection, alone or in combination.1,3

Clinical scenario

A 48-year-old woman with a history of stage 2 triple-negative (ER– PR– Her-2-Neu–) breast cancer treated 3 years prior presents with headache and seizure. Imaging demonstrates a solitary 2-cm lesion in the left motor cortex.

Action items
  • Assess prognosis; although the historical expected survival duration for patients with brain metastases is <1 year, at present multiple factors are used to assess prognosis, including

    • the extent of intracranial disease (number and volume of metastases)

    • the extent of extracranial disease (primary site control and/or presence of extracranial metastases)

    • histology and radiosensitivity

    • performance status1,3

  • A customized treatment plan should be tailored for each patient based on the above factors and should be discussed in a multidisciplinary team including medical oncology, radiation oncology, and neurosurgery1,3


SRS offers a convenient method for the treatment of brain metastases that differs from traditional fractionated WBRT in both scope and adverse-effect profile. Published studies describe local control rates ranging from 70% to 90% for brain tumors smaller than 2 cm, dependent on histology. The control rates are lower for larger lesions, and sometimes a decision is made to combine surgery with SRS for such tumors.1,3

SRS is preferred to WBRT due to comparable long-term overall survival,3 as well to decreased neurocognitive decline. Studies, including the most recent North Central Cancer Treatment Group N0574 trial, have demonstrated a decline in cognitive function in patients who received WBRT and SRS versus SRS alone.4 A recently published meta-analysis denoted decreased overall survival for patients receiving WBRT versus SRS alone, presumably due to neurocognitive dysfunction.5

Trials are being performed to determine the maximum number of lesions that can safely be treated with SRS. At present, the number is typically 4, but recent series have described a favorable safety profile in treating up to 10 brain metastases.6

  • SRS is an emerging option for the treatment of brain metastases

  • Palliative WBRT remains the standard of care for widely disseminated central nervous system disease, leptomeningeal disease, or poor performance status1,3

  1. National Comprehensive Cancer Network (NCCN) guidelines for central nervous system cancers. Version 1.2017. Available at:

  2. Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence ...

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