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Brain metastasis
What's new
The Congress of Neurological Surgeons (CNS) has released an update on emerging therapies for brain metastases. For targeted therapy, icotinib is recommended for brain metastases from EGFR-mutant non-small cell lung carcinoma (NSCLC), lorlatinib for ALK-mutant NSCLC, dabrafenib plus trametinib for metastases from BRAFV600E+ melanoma, and trastuzumab for metastases from HER2+ breast cancer. Temozolomide is recommended as a radiosensitizer in patients with metastases from NSCLC undergoing whole-brain radiotherapy (WBRT). .
Background
Overview
Definition
Brain metastases are secondary malignant tumors that originate from extracranial primary cancers and spread to the brain via hematogenous dissemination.
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Pathophysiology
Tumor cells gain access to the brain via the bloodstream, often crossing the blood-brain barrier at sites of disrupted vascular integrity. Transendothelial migration depends on adhesion molecules such as integrins, selectins, and chemokines. Once within the brain parenchyma, metastatic cells adapt to the unique microenvironment through interactions with resident astrocytes, immune cells, and endothelial cells, facilitating proliferation, angiogenesis, and immune evasion. The resulting peritumoral edema, neuronal damage, and vascular permeability changes contribute to the neurological symptoms and complications associated with brain metastases.
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Epidemiology
Brain metastases occur in approximately 30% of patients with solid tumors, making them the most common intracranial neoplasms in adults. Lung cancer accounts for 40-50% of cases, followed by breast cancer (15-30%), melanoma (5-20%), CRC (3-8%), and renal cell carcinoma (2-4%).
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Risk factors
Patients with advanced-stage malignancies, particularly lung cancer, breast cancer, and melanoma, are at the highest risk of developing brain metastases, with additional factors including tumor biology, genetic mutations, and systemic disease burden.
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Disease course
Brain metastases often present with progressive neurological symptoms, including headache, cognitive impairment, focal deficits, and seizures, which depend on the location and number of lesions. Symptoms may develop gradually or acutely due to peritumoral edema, hemorrhage, or increased ICP. Without treatment, neurological decline typically progresses, leading to significant morbidity and reduced functional status, though interventions such as corticosteroids, radiation therapy, and systemic treatments can provide symptomatic relief and prolong survival.
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Prognosis and risk of recurrence
The prognosis for patients with brain metastases is variable and depends on factors such as the number and size of lesions, primary tumor type, performance status, and available treatment options. The esimated 5-year survival is 2.4%. Without treatment, median survival is typically less than 6 months, but advances in systemic therapies, stereotactic radiosurgery, and targeted treatments have improved survival in select patient populations.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of brain metastasis are prepared by our editorial team based on guidelines from the Congress of Neurological Surgeons (CNS 2025,2019), the American Society for Radiation Oncology (ASTRO 2022), the Society for Neuro-Oncology (SNO/ASTRO/ASCO 2022), and the European Association of Neuro-Oncology (EANO/ESMO 2021).
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Diagnostic investigations
Diagnostic imaging: as per EANO/ESMO 2021 guidelines, consider screening for brain metastases in patients with lung cancer (except potentially in stage I non-small cell lung cancer), stage IV melanoma, and potentially in patients with metastatic HER2+ and triple-negative breast cancer.
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Cell-free tumor DNA
Diagnostic procedures
Histopathology: as per EANO/ESMO 2021 guidelines, obtain histopathological and immunohistochemical evaluation of brain metastases according to local institutional protocols.
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CSF analysis
Medical management
General principles: as per ASCO/ASTRO/SNO 2022 guidelines, offer local therapy, including radiosurgery, radiotherapy, and/or surgery, in patients with symptomatic brain metastases regardless of the systemic therapy used for the systemic disease.
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Systemic therapy (non-small cell lung cancer)
Systemic therapy (small cell lung cancer)
Systemic therapy (breast cancer)
Systemic therapy (colon cancer)
Systemic therapy (melanoma)
Management of increased ICP
Antiseizure prophylaxis
Thromboprophylaxis
Therapeutic procedures
Radiotherapy, intact metastases, indications
As per ASTRO 2022 guidelines:
Offer upfront local therapy in patients with symptomatic brain metastases eligible for local therapy and CNS-active systemic therapy.
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Consider engaging in multidisciplinary decision-making to determine if local therapy may be safely deferred for patients with asymptomatic brain metastases eligible for CNS-active systemic therapy, taking into account brain metastasis size, parenchymal brain location, number of metastases, likelihood of response to specific systemic therapy, access to close neuro-oncologic surveillance, and availability of salvage therapies.
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Radiotherapy (intact metastases, stereotactic radiosurgery)
Radiotherapy (intact metastases, whole-brain radiotherapy)
Radiotherapy (resected metastases)
Interstitial therapies
High-intensity focused ultrasound
Surgical interventions
Surgical resection: as per ASTRO 2022 guidelines, consider offering surgery in patients with intact brain metastases measuring > 4 cm in diameter. Consider offering multifraction stereotactic radiosurgery instead of single-fraction stereotactic radiosurgery if surgery is not feasible. Avoid performing stereotactic radiosurgery for tumor sizes > 6 cm due to limited evidence.
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