Central Nervous System Metastases

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Key points

  • Central nervous system (CNS) metastases develop in a substantial subset of cancer patients and a majority of lesions are identified on neuroimaging after pain or neurologic symptoms develop related to tumor location.

  • Radiotherapy is the mainstay of treatment of CNS metastases with a preference for focal radiation in limited disease.

  • Surgery is indicated for solitary and large symptomatic brain metastases or for spinal metastases causing cord compression or that are unstable.

  • Targeted and

Epidemiology

Of all patients that develop brain metastases, 40-50% arise from lung cancers, 15-30% from breast cancer, 5-20% from melanomas, 3-8% from colorectal cancer, and 2-4% from renal cell carcinomas, with other systemic cancer sources being less common.7 There have been several ways in which incidence of CNS metastases historically has been assessed and continues to be measured at the population level. Early autopsy studies from the 1970s and 1980s evaluating rates of intracranial metastasis suggest

Pathophysiology

Given recent epidemiologic trends indicating a rise in CNS metastases, the study of the mechanisms of brain metastasis along with molecular alterations that confer an increased risk or susceptibility to targeted treatment is timely. Understanding the mechanisms that lead to the development of CNS metastasis is one main approach to identifying new prognostic markers and treatment targets. Main routes of spread for cancer cells through the body to reach the CNS include both hematological and

Prevention and early identification

Screening for asymptomatic metastatic CNS lesions remains an area of ongoing debate. A majority of CNS metastases are identified following emergence of neurologic symptoms and not through screening following a cancer diagnosis. Currently, screening for brain metastasis using magnetic resonance imaging (MRI) is recommended for patients with stage II through stage IV NSCLC, stage IV melanoma, and individuals with a new diagnosis of SCLC by the US National Comprehensive Cancer Network.46 For other

Presentation

Patients with CNS metastases may be asymptomatic or present with several different neurologic manifestations, depending on size and location. CNS metastases also may present with acute deterioration typically in the context of hemorrhage or obstruction leading to hydrocephalus.52 Approximately 80% of patients develop brain metastases involving the cerebral hemispheres, typically in the gray and white matter junction, with the remaining lesions occurring in the cerebellum (15%) or brainstem (5%).

Diagnostic evaluation

MRI replaced CT as the gold standard approach to diagnose CNS metastases 4 decades ago. Patients initially presenting with neurologic symptoms commonly obtain CT scans as their first imaging modality due to availability, cost, and efficiency to screen for many conditions. Vasogenic edema caused by CNS metastases appears hypodense compared with adjacent tissue on CT and is enhanced with iodine-based contrast.60 In patients with suspected CNS metastases, it also is recommended to restage systemic

Initial Medical Management

Initial pharmaceutical intervention typically involves the administration of glucocorticoid medication in the setting of symptomatic CNS metastases, such as high doses of dexamethasone, to reduce edema and inflammation surrounding CNS lesions and relieve possible neurologic deficits in advance of definitive treatment.65, 66, 67 Multidisciplinary tumor board discussions are recommended to decide on the individualize patient management strategies between surgery, radiotherapy, and/or systemic

Prognosis and clinical outcomes

The diagnosis of brain metastases continues to relay a relatively poor prognosis. The diagnosis-specific graded prognostic assessment (GPA) is a model developed to understand and quantitatively predict patient prognosis using age, Karnofsky performance scale status, number of brain metastases, burden of extracranial disease, and tumor subtypes. GPA results show that overall survival among patients with brain metastases excluding individuals with LM is improving but remains low across primary

Ongoing research

Liquid biopsies remain a promising technique for early detection and possible characterization of metastatic brain lesions. Although circulating tumor DNA obtained from blood has been used to monitor and sequence tumor burden in patients with metastatic disease, its use in evaluating brain metastases specifically has been more limited.160 One approach to obtain circulating tumor DNA that most closely represents the genomic alterations of brain metastases, in comparison to those of extracanial

Summary and future directions

Although CNS metastases confer a poorer prognosis for cancer patients, recent and ongoing work continues to expand on treatment approaches to improve care for patients with these tumors. There is a growing role for the use of focal radiotherapy in managing CNS metastases along with novel systemic targeted and immunotherapies. Ongoing trials to further evaluate the utility of these treatments in CNS metastasis patients, future work to identify additional therapeutics, increasing representation

Clinics care points

  • Brain metastases are typically screened for in patients with stage II through stage IV NSCLC, stage IV melanoma, and SCLC. CNS metastases should be assessed for with neuroimaging in patients with symptoms that localize to the CNS.

  • Surgery typically is utilized in solitary or large symptomatic brain metastases as well as spinal metastases causing cord compression or spinal instability.

  • Stereotactic radiotherapy is indicated for limited small brain metastases, radioresistant spinal metastases

Disclosure

H. Kluger has the following Institutional Research Grant disclosures: (1) Merck, (2) Bristol-Myers Squibb, and (3) Apexigen. H. Kluger also has the following disclosures related to personal fees over the past 3 years: (1) Nektar, (2) Iovance, (3) Immunocore, (4) Celldex, (5) Array Biopharma, (6) Merck, (7) Elevate Bio, (8) Instil Bio, (9) Bristol-Myers Squibb, (10) Clinigen, (11) Shionogi, (12) Chemocentryx, (13) Calithera, and (14) Signatero. P.K. Brastianos has consulted for Angiochem,

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