Brain metastases (secondary brain tumours)
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.
Overview
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.
Surgery 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.
Systemic 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.
State of the art
- 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.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Radiosurgery alone has replaced whole-brain radiotherapy for limited disease because it spares cognition without costing survival.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowSkin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
- Call the 24-hour line nowInterstitial lung disease or pneumonitis
Any new or worsening cough, breathlessness or fever. The label says to interrupt treatment for any suspected ILD and to permanently discontinue for grade 2 or higher.
- Check before combiningLorlatinib with Tucatinib: major interaction
CYP3A4: Tucatinib (strong inhibitor) raises Lorlatinib exposure (sensitive substrate).. Avoid; if unavoidable, reduce from 100 mg to 75 mg daily.
- Check before combiningFood and drink: Alectinib
Take with food; exposure roughly triples with a high-fat meal, and the trials dosed with food.
See all on the product pages:AlectinibDabrafenib + trametinibIpilimumabLorlatinibNivolumabOsimertinibTrastuzumab deruxtecanTucatinib·Printable cards in the navigator
Anatomy and lymph node drainage
- Frontal lobe (glioblastoma commonest)
- Temporal lobe
- Corpus callosum (butterfly glioma)
- Lower-grade IDH-mutant glioma
- Cerebellum (medulloblastoma)
- Brainstem and spinal cord (diffuse midline glioma, cord tumours)
- Ventricles and ependymal lining (ependymoma)
- Sella and pituitary (pituitary tumours, craniopharyngioma)
- Deep periventricular tissue (CNS lymphoma)
- Meninges and convexity (meningioma)
- Grey-white junction (brain metastases)
- Cerebellopontine angle and eighth nerve (vestibular schwannoma)
- Pineal and suprasellar midline (germ cell tumours)
Gliomas infiltrate along white matter and can cross the corpus callosum, medulloblastoma sits in the cerebellum, and CNS lymphoma favours deep periventricular tissue; none spread through lymph nodes.
- Frontal lobe (glioblastoma commonest)Brain metastases from non-small cell lung cancer (EGFR, ALK and other driver subsets)
- Temporal lobe
- Corpus callosum (butterfly glioma)
- Lower-grade IDH-mutant glioma
- Cerebellum (medulloblastoma)
- Brainstem and spinal cord (diffuse midline glioma, cord tumours)Leptomeningeal metastases (cerebrospinal fluid spread)
- Ventricles and ependymal lining (ependymoma)
- Sella and pituitary (pituitary tumours, craniopharyngioma)
- Deep periventricular tissue (CNS lymphoma)
- Meninges and convexity (meningioma)Leptomeningeal metastases (cerebrospinal fluid spread)
- Grey-white junction (brain metastases)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)
- Cerebellopontine angle and eighth nerve (vestibular schwannoma)
- Pineal and suprasellar midline (germ cell tumours)
No conventional lymphatics: gliomas spread along white matter tracts and, rarely, through cerebrospinal fluid; medulloblastoma can seed the spine.
Same organ: Glioma & glioblastoma, Primary CNS lymphoma, Medulloblastoma, Paediatric low-grade glioma, Diffuse midline glioma, H3 K27-altered (including DIPG), Atypical teratoid/rhabdoid tumour (ATRT), Ependymoma, Craniopharyngioma, Pituitary tumours (pituitary neuroendocrine tumours) and pituitary carcinoma, Brain and spinal cord tumours (all types), Astrocytoma, IDH-mutant (grades 2 to 4), Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, Paediatric high-grade glioma (excluding diffuse midline glioma), Meningioma, Vestibular schwannoma (acoustic neuroma), Central nervous system germ cell tumours (germinoma and non-germinomatous), Spinal cord tumours (intramedullary and intradural)
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.
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Dexamethasone, tapered as quickly as symptoms allow; anticonvulsants only after a seizure.
Surgical resection followed by radiosurgery to the cavity (N107C) rather than whole-brain radiotherapy.
Stereotactic radiosurgery alone (Alliance N0574); whole-brain radiotherapy withheld because it worsens cognition without lengthening life.
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).
Brain-penetrant targeted therapy first: osimertinib (EGFR), lorlatinib or alectinib (ALK); radiosurgery for progression.
Tucatinib with trastuzumab and capecitabine (HER2CLIMB) or trastuzumab deruxtecan (DESTINY-Breast12), with local therapy for symptomatic lesions.
Nivolumab plus ipilimumab for asymptomatic metastases (CheckMate 204); dabrafenib plus trametinib for BRAF V600-mutant disease (COMBI-MB); radiosurgery for symptomatic or progressing lesions.
Subtypes & biomarkers
top- 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)
- 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)
How often this target appears
- 1954Whole-brain radiotherapy reported for brain metastases
Chao and colleagues describe palliative irradiation of cerebral metastases.
- 1990Patchell: surgery plus whole-brain radiotherapy beats radiotherapy alone for a single metastasis (NEJM)
- 2004RTOG 9508: radiosurgery boost improves function and, for single lesions, survival
- 2016Alliance N0574: radiosurgery alone preserves cognition
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.
- 2016QUARTZ: no quality-adjusted survival gain from whole-brain radiotherapy in poor-prognosis lung cancer
- 2017N107C: radiosurgery to the surgical cavity replaces post-operative whole-brain radiotherapy
- 2018CheckMate 204: nivolumab plus ipilimumab active in melanoma brain metastases
- 2020NRG CC001: hippocampal-avoidance whole-brain radiotherapy with memantine preserves cognition
- 2020HER2CLIMB: tucatinib triplet benefits patients with HER2-positive brain metastases
- 2024DESTINY-Breast12: trastuzumab deruxtecan active in HER2-positive brain metastases
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 20 changes by month →- 2026-09-17This recordBrain metastases (secondary brain tumours)Facts on this page last checked
When this page itself was last checked or edited.
- 2024Trial resultDESTINY-Breast12DESTINY-Breast12 reported
CNS ORR 71.
- 2024MilestoneTrastuzumab deruxtecanDESTINY-Breast12: trastuzumab deruxtecan active in HER2-positive brain metastases
A milestone in how this cancer is treated.
- 2020-04-17RegulatoryTucatinibTucatinib: approval (US)
HER2+ metastatic breast cancer including brain metastases, with trastuzumab and capecitabine (HER2CLIMB)
- 2020ApprovalTucatinibTucatinib approved in US
HER2+ metastatic breast cancer including brain metastases, with trastuzumab and capecitabine
- 2020Trial resultCROWNCROWN reported
5-year PFS 60% vs 8%, HR 0.
What is in development for Brain metastases (secondary brain tumours), drawn from the whole corpus: 8 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Technologies being tested · 1
Trials reported · 7
- Alliance N0574 (NCCTG N0574) · phase 3 · 2016 · positive
- CheckMate 204 · phase 2 · 2018 · positive
- CROWN · phase 3 · 2020 · positive
- DESTINY-Breast12 · phase 3 · 2024 · positive
- HER2CLIMB · phase 2 · 2019 · positive
- NRG CC001 · phase 3 · 2020 · positive
- QUARTZ · phase 3 · 2016 · negative
Open problems and what is being done
Trials still often exclude patients with brain metastases, so drug activity in the brain is learned late.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- Gamma KnifeEstablished
- IMRT / IGRT (modern external beam)Standard of care
- MRIStandard of care
- Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Established
- Trastuzumab deruxtecanApproved
- TucatinibApproved
In trials- Alliance N0574 (NCCTG N0574)Positive
- CheckMate 204Positive
- DESTINY-Breast12Positive
- Focused-ultrasound blood-brain barrier openingPhase 2
- HER2CLIMBPositive
Ideas and roadmapsNothing recorded yet.
Background: Blood-brain barrier (BBB), HER2-positive brain metastases. Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Leptomeningeal disease has no standard treatment and a survival of months.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- Gamma KnifeEstablished
- IMRT / IGRT (modern external beam)Standard of care
- MRIStandard of care
- Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)Established
- Trastuzumab deruxtecanApproved
- TucatinibApproved
In trials- Alliance N0574 (NCCTG N0574)Positive
- CheckMate 204Positive
- DESTINY-Breast12Positive
- Focused-ultrasound blood-brain barrier openingPhase 2
- HER2CLIMBPositive
Ideas and roadmapsNothing recorded yet.
Background: Blood-brain barrier (BBB), HER2-positive brain metastases. Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
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.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Houston · cancer center | United States | 0 | 6,724 | 95,007 | #2 | ||
Seoul · hospital | South Korea | none recorded | 0 | 1,312 | 17,172 | #3 | |
Rochester, MN · hospital | United States | 0 | 4,511 | 44,748 | #5 | ||
Villejuif · cancer center | France | none recorded | 0 | 1,855 | 31,182 | #6 | |
Seoul · hospital | South Korea | none recorded | 0 | 1,607 | 24,676 | #8 | |
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Berlin · university | Germany | none recorded | 0 | 1,563 | 17,749 | #12 | |
Tokyo · government | Japan | none recorded | 0 | 1,599 | 21,937 | none recorded | #13 |
Boston · hospital | United States | 0 | 3,582 | 54,857 | #16 | ||
Cleveland · hospital | United States | 0 | 2,264 | 29,412 | #20 | ||
Seoul · hospital | South Korea | none recorded | 0 | 464 | 3,248 | #22 | |
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
San Francisco · cancer center | United States | 0 | 2,800 | 46,704 | #33 | ||
Stockholm · university | Sweden | none recorded | 0 | 987 | 12,440 | #39 | |
Philadelphia, PA · consortium | United States | none recorded | 1 | 87 | 2,130 | none recorded | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Brain metastases but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Brain metastases
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Primary tumour type and its driver, Number, size and location of lesions on contrast MRI, Graded prognostic assessment, Cerebrospinal fluid cytology and cell-free DNA for leptomeningeal disease, Distinguishing radionecrosis from progression), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Brain metastases from non-small cell lung cancer, Brain metastases from breast cancer, Brain metastases from melanoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Symptomatic oedema
- For my situation (symptomatic oedema), which of the standard options do you recommend and why?Why: Guideline options include: Dexamethasone, tapered as quickly as symptoms allow; anticonvulsants only after a seizure.
- Am I a candidate for Dexamethasone, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Single large or symptomatic lesion, fit patient
- For my situation (single large or symptomatic lesion, fit patient), which of the standard options do you recommend and why?Why: Guideline options include: Surgical resection followed by radiosurgery to the cavity (N107C) rather than whole-brain radiotherapy.
Limited number of metastases
- For my situation (limited number of metastases), which of the standard options do you recommend and why?Why: Guideline options include: Stereotactic radiosurgery alone (Alliance N0574); whole-brain radiotherapy withheld because it worsens cognition without lengthening life.
- How do the results of Alliance N0574 (NCCTG N0574) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Many metastases or leptomeningeal spread
- For my situation (many metastases or leptomeningeal spread), which of the standard options do you recommend and why?Why: Guideline options include: 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).
- How do the results of NRG CC001 and QUARTZ apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Driver-positive lung cancer, asymptomatic metastases
- For my situation (driver-positive lung cancer, asymptomatic metastases), which of the standard options do you recommend and why?Why: Guideline options include: Brain-penetrant targeted therapy first: osimertinib (EGFR), lorlatinib or alectinib (ALK); radiosurgery for progression.
- Am I a candidate for Osimertinib, Lorlatinib, Alectinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CROWN apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
HER2-positive breast cancer
- For my situation (her2-positive breast cancer), which of the standard options do you recommend and why?Why: Guideline options include: Tucatinib with trastuzumab and capecitabine (HER2CLIMB) or trastuzumab deruxtecan (DESTINY-Breast12), with local therapy for symptomatic lesions.
- Am I a candidate for Tucatinib, Trastuzumab deruxtecan, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of HER2CLIMB and DESTINY-Breast12 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Melanoma
- For my situation (melanoma), which of the standard options do you recommend and why?Why: Guideline options include: Nivolumab plus ipilimumab for asymptomatic metastases (CheckMate 204); dabrafenib plus trametinib for BRAF V600-mutant disease (COMBI-MB); radiosurgery for symptomatic or progressing lesions.
- Am I a candidate for Nivolumab, Ipilimumab, Dabrafenib + trametinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Trastuzumab deruxtecan, Tucatinib, Lorlatinib, Focused-ultrasound blood-brain barrier opening?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Trials still often exclude patients with brain metastases, so drug activity in the brain is learned late”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Leptomeningeal disease has no standard treatment and a survival of months”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Brain metastases, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
12targets
6drugs
9companies
6terms
6trials
7Latest papers
topQuery for this cancer: (TITLE:"Brain metastases" OR ABSTRACT:"Brain metastases" OR TITLE:"secondary brain tumours" OR ABSTRACT:"secondary brain tumours" OR TITLE:"Secondary brain cancer" OR ABSTRACT:"Secondary brain cancer" OR TITLE:"Intracranial metastases" OR ABSTRACT:"Intracranial metastases" OR TITLE:"Cerebral metastases" OR ABSTRACT:"Cerebral metastases" OR TITLE:"Brain mets" OR ABSTRACT:"Brain mets") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Brain metastases (secondary brain tumours), not a curated reading list.
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