{"entity":{"id":"secondary-brain-tumours","kind":"cancer","name":"Brain metastases (secondary brain tumours)","aka":["Brain metastases","Secondary brain cancer","Intracranial metastases","Cerebral metastases","Brain mets"],"tldr":"Brain metastases are cancers that have spread to the brain from elsewhere, most often from the lung, breast or skin. Focused radiation aimed at each spot (radiosurgery) has largely replaced radiation to the whole brain, and for some cancers modern targeted drugs and immunotherapy reach the brain well enough to shrink the deposits on their own.","summary":"Brain metastases seed the grey-white junction and watershed zones through the arterial circulation; they are recognised on contrast MRI and, with a known primary, rarely need biopsy. Prognosis depends on the primary, its molecular subtype, performance status, extracranial disease and number of lesions (graded prognostic assessment). Dexamethasone relieves oedema. Management has moved in twenty years from whole-brain radiotherapy for nearly everyone to a choice among surgery, stereotactic radiosurgery, systemic therapy with brain penetration and, for some, no brain-directed treatment at all.\n\nSurgery is used for a large or symptomatic single lesion or when tissue is needed (Patchell, 1990), followed by radiosurgery to the cavity rather than whole-brain radiotherapy (N107C, 2017). For a limited number of metastases, Alliance N0574 (JAMA 2016) showed that adding whole-brain radiotherapy to radiosurgery worsened cognition at three months in 91.7 percent of patients against 63.5 percent with radiosurgery alone, without lengthening survival, and radiosurgery alone is now standard for up to four lesions and increasingly for more. When whole-brain radiotherapy is still used, NRG CC001 (JCO 2020) showed hippocampal avoidance with memantine preserves cognition. QUARTZ (Lancet 2016) found no meaningful gain in quality-adjusted survival from whole-brain radiotherapy in non-small cell lung cancer patients unsuited to surgery or radiosurgery, so best supportive care alone is legitimate in poor-prognosis patients.\n\nSystemic therapy now controls brain disease in several subtypes: osimertinib in EGFR-mutant and lorlatinib in ALK-positive lung cancer (CROWN), tucatinib with trastuzumab and capecitabine (HER2CLIMB) and trastuzumab deruxtecan (DESTINY-Breast12) in HER2-positive breast cancer, nivolumab plus ipilimumab in melanoma (CheckMate 204) and dabrafenib plus trametinib in BRAF-mutant melanoma (COMBI-MB), so asymptomatic small metastases in these groups are often treated with drugs first and radiosurgery held in reserve. Trials have historically excluded patients with brain metastases; their inclusion, the management of leptomeningeal disease, radionecrosis after radiosurgery, and drugs designed to cross the blood-brain barrier are the open fronts.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Brain_metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Brain_metastasis"},{"label":"Alliance N0574: radiosurgery with or without whole-brain radiotherapy (JAMA 2016)","url":"https://doi.org/10.1001/jama.2016.9839"},{"label":"QUARTZ (Lancet 2016)","url":"https://doi.org/10.1016/S0140-6736(16)30825-X"}],"tags":["subtype-page","cns"],"related":["brain-tumours","metastatic-cancer","nsclc","breast-her2-positive","melanoma"],"cancers":[],"sections":[],"technologies":["radiosurgery-srs","gamma-knife","cyberknife","imrt-igrt","mri","bbb-focused-ultrasound"],"targets":[],"drugs":["dexamethasone","osimertinib","lorlatinib","alectinib","tucatinib","trastuzumab-deruxtecan","nivolumab","ipilimumab","dabrafenib-trametinib"],"companies":[],"institutions":[],"pathways":[],"terms":["brain-metastases","wbrt","stereotactic-radiosurgery","blood-brain-barrier","her2-brain-metastases","leptomeningeal-disease"],"trials":["alliance-n0574","nrg-cc001","quartz","her2climb","destiny-breast12","crown"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"central nervous system","burden":"The commonest intracranial tumour in adults, many times more frequent than primary brain tumours; lung cancer, breast cancer, melanoma, kidney cancer and bowel cancer account for most, and incidence is rising as people live longer with systemic disease.","subtypes":["Brain metastases from non-small cell lung cancer (EGFR, ALK and other driver subsets)","Brain metastases from breast cancer (HER2-positive, triple-negative)","Brain metastases from melanoma","Brain metastases from kidney, bowel and other cancers","Solitary brain metastasis (surgical candidate)","Multiple brain metastases (radiosurgery or whole-brain radiotherapy)","Leptomeningeal metastases (cerebrospinal fluid spread)"],"biomarkers":["Primary tumour type and its driver (EGFR, ALK, HER2, BRAF, PD-L1)","Number, size and location of lesions on contrast MRI","Graded prognostic assessment (age, performance status, extracranial disease, lesion count, molecular subtype)","Cerebrospinal fluid cytology and cell-free DNA for leptomeningeal disease","Distinguishing radionecrosis from progression (perfusion MRI, amino acid PET)"],"standardOfCare":[{"setting":"Symptomatic oedema","approach":"Dexamethasone, tapered as quickly as symptoms allow; anticonvulsants only after a seizure.","refs":["dexamethasone"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Single large or symptomatic lesion, fit patient","approach":"Surgical resection followed by radiosurgery to the cavity (N107C) rather than whole-brain radiotherapy.","refs":["radiosurgery-srs"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Limited number of metastases","approach":"Stereotactic radiosurgery alone (Alliance N0574); whole-brain radiotherapy withheld because it worsens cognition without lengthening life.","refs":["radiosurgery-srs","gamma-knife","cyberknife","alliance-n0574"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Many metastases or leptomeningeal spread","approach":"Hippocampal-avoidance whole-brain radiotherapy with memantine (NRG CC001) where whole-brain treatment is chosen; radiosurgery to many lesions in selected patients; best supportive care alone in poor-prognosis lung cancer (QUARTZ).","refs":["wbrt","nrg-cc001","quartz","imrt-igrt"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Driver-positive lung cancer, asymptomatic metastases","approach":"Brain-penetrant targeted therapy first: osimertinib (EGFR), lorlatinib or alectinib (ALK); radiosurgery for progression.","refs":["osimertinib","lorlatinib","alectinib","crown"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"HER2-positive breast cancer","approach":"Tucatinib with trastuzumab and capecitabine (HER2CLIMB) or trastuzumab deruxtecan (DESTINY-Breast12), with local therapy for symptomatic lesions.","refs":["tucatinib","trastuzumab-deruxtecan","her2climb","destiny-breast12"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}},{"setting":"Melanoma","approach":"Nivolumab plus ipilimumab for asymptomatic metastases (CheckMate 204); dabrafenib plus trametinib for BRAF V600-mutant disease (COMBI-MB); radiosurgery for symptomatic or progressing lesions.","refs":["nivolumab","ipilimumab","dabrafenib-trametinib","radiosurgery-srs"],"guideline":{"version":"NCCN Guidelines: Central Nervous System Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425"}}],"stateOfArt":["Radiosurgery alone has replaced whole-brain radiotherapy for limited disease because it spares cognition without costing survival.","Several targeted drugs and immunotherapy doublets now control brain metastases well enough to be used before radiation.","Whole-brain radiotherapy, once universal, is now reserved for extensive disease and given with hippocampal avoidance and memantine."],"history":[{"year":1954,"title":"Whole-brain radiotherapy reported for brain metastases","note":"Chao and colleagues describe palliative irradiation of cerebral metastases.","refs":["wbrt"]},{"year":1990,"title":"Patchell: surgery plus whole-brain radiotherapy beats radiotherapy alone for a single metastasis (NEJM)","refs":[]},{"year":2004,"title":"RTOG 9508: radiosurgery boost improves function and, for single lesions, survival","refs":["radiosurgery-srs"]},{"year":2016,"title":"Alliance N0574: radiosurgery alone preserves cognition","note":"Brown and colleagues (JAMA): cognitive deterioration at three months in 63.5 percent with radiosurgery alone against 91.7 percent with added whole-brain radiotherapy; no survival difference.","refs":["alliance-n0574","radiosurgery-srs"]},{"year":2016,"title":"QUARTZ: no quality-adjusted survival gain from whole-brain radiotherapy in poor-prognosis lung cancer","refs":["quartz","wbrt"]},{"year":2017,"title":"N107C: radiosurgery to the surgical cavity replaces post-operative whole-brain radiotherapy","refs":["radiosurgery-srs"]},{"year":2018,"title":"CheckMate 204: nivolumab plus ipilimumab active in melanoma brain metastases","refs":["nivolumab","ipilimumab"]},{"year":2020,"title":"NRG CC001: hippocampal-avoidance whole-brain radiotherapy with memantine preserves cognition","refs":["nrg-cc001"]},{"year":2020,"title":"HER2CLIMB: tucatinib triplet benefits patients with HER2-positive brain metastases","refs":["tucatinib","her2climb"]},{"year":2024,"title":"DESTINY-Breast12: trastuzumab deruxtecan active in HER2-positive brain metastases","refs":["trastuzumab-deruxtecan","destiny-breast12"]}],"pipeline":["trastuzumab-deruxtecan","tucatinib","lorlatinib","bbb-focused-ultrasound","radiosurgery-srs"],"openProblems":["Trials still often exclude patients with brain metastases, so drug activity in the brain is learned late.","Leptomeningeal disease has no standard treatment and a survival of months.","Radionecrosis after radiosurgery is hard to tell from progression and hard to treat.","Few drugs are designed from the start to cross the blood-brain barrier."],"parent":"brain-tumours"},"route":"/cancers/secondary-brain-tumours/","neighbours":{"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"braf-v600-melanoma","kind":"cancer","name":"BRAF V600-mutant melanoma","route":"/cancers/braf-v600-melanoma/"},{"id":"brain-tumours","kind":"cancer","name":"Brain and spinal cord tumours (all types)","route":"/cancers/brain-tumours/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"her2-positive-breast-brain-metastases","kind":"cancer","name":"HER2-positive breast cancer with brain metastases","route":"/cancers/her2-positive-breast-brain-metastases/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"cyberknife","kind":"technology","name":"CyberKnife robotic radiosurgery","route":"/technologies/cyberknife/"},{"id":"bbb-focused-ultrasound","kind":"technology","name":"Focused-ultrasound blood-brain barrier opening","route":"/technologies/bbb-focused-ultrasound/"},{"id":"gamma-knife","kind":"technology","name":"Gamma Knife","route":"/technologies/gamma-knife/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"},{"id":"radiosurgery-srs","kind":"technology","name":"Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)","route":"/technologies/radiosurgery-srs/"}],"drug":[{"id":"alectinib","kind":"drug","name":"Alectinib","route":"/drugs/alectinib/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"dexamethasone","kind":"drug","name":"Dexamethasone","route":"/drugs/dexamethasone/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"lorlatinib","kind":"drug","name":"Lorlatinib","route":"/drugs/lorlatinib/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"term":[{"id":"blood-brain-barrier","kind":"term","name":"Blood-brain barrier (BBB)","route":"/terms/blood-brain-barrier/"},{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"her2-brain-metastases","kind":"term","name":"HER2-positive brain metastases","route":"/terms/her2-brain-metastases/"},{"id":"leptomeningeal-disease","kind":"term","name":"Leptomeningeal disease","route":"/terms/leptomeningeal-disease/"},{"id":"stereotactic-radiosurgery","kind":"term","name":"Stereotactic radiosurgery (SRS)","route":"/terms/stereotactic-radiosurgery/"},{"id":"wbrt","kind":"term","name":"Whole-brain radiotherapy (WBRT)","route":"/terms/wbrt/"}],"trial":[{"id":"alliance-n0574","kind":"trial","name":"Alliance N0574 (NCCTG N0574)","route":"/trials/alliance-n0574/"},{"id":"checkmate-204","kind":"trial","name":"CheckMate 204","route":"/trials/checkmate-204/"},{"id":"crown","kind":"trial","name":"CROWN","route":"/trials/crown/"},{"id":"destiny-breast12","kind":"trial","name":"DESTINY-Breast12","route":"/trials/destiny-breast12/"},{"id":"her2climb","kind":"trial","name":"HER2CLIMB","route":"/trials/her2climb/"},{"id":"nrg-cc001","kind":"trial","name":"NRG CC001","route":"/trials/nrg-cc001/"},{"id":"quartz","kind":"trial","name":"QUARTZ","route":"/trials/quartz/"}]}}