A brain metastasis is a

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

that has

metastasized Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

(spread) to the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

from another location in the body and is therefore considered a secondary brain tumor. The metastasis typically shares a cancer cell type with the original site of the cancer. Metastasis is the most common cause of brain cancer, as

primary tumors A primary tumor is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass. Most cancers develop at their primary site but then go on to metastasize or spread to other parts of the body. These fur ...

that originate in the brain are less common. The most common sites of primary cancer which metastasize to the brain are lung, breast, colon, kidney, and skin cancer. Brain metastases can occur in patients months or even years after their original cancer is treated. Brain metastases have a poor

prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...

for cure, but modern treatments are allowing patients to live months and sometimes years after the diagnosis.

Symptoms and signs

Because different parts of the brain are responsible for different functions, symptoms vary depending on the site of metastasis within the brain. However, brain metastases should be considered in any cancer patient who presents with neurological or behavioral changes. Brain metastases can cause a wide variety of symptoms which can also be present in minor, more common conditions. Neurological symptoms are often caused by

increased intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. Th ...

, with severe cases resulting in

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

. The most common neurological symptoms include: * New onset

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

s: headaches occur in roughly half of brain metastasis patients, especially in those with many tumors. * Paresthesias: patients often present with (

hemiparesis Hemiparesis, or unilateral paresis, is weakness of one entire side of the body (''wikt:hemi-#Prefix, hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused ...

), or weakness on only one side of the body, which is often a result of damage to neighboring brain tissue. *

Ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

: when metastasis occurs to the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

, patients will experience various difficulties with spatial awareness and coordination. *

Seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

s: when present, often indicates disease involvement of the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...

Causes

The most common sources of brain metastases in a

case series A case series (also known as a clinical series) is a type of medical research study that tracks subjects with a known exposure, such as patients who have received a similar treatment, or examines their medical records for exposure and outcome. Cas ...

of 2,700 patients undergoing treatment at the

Memorial Sloan–Kettering Cancer Center Memorial Sloan Kettering Cancer Center (MSK or MSKCC) is a cancer treatment and research institution in the borough of Manhattan in New York City, founded in 1884 as the New York Cancer Hospital. MSKCC is one of 52 National Cancer Institute� ...

were: *

Lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...

, 48% *

Breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

, 15% * Genitourinary tract cancers, 11% *

Osteosarcoma An osteosarcoma (OS) or osteogenic sarcoma (OGS) (or simply bone cancer) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) a ...

, 10% *

Melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

, 9% *

Head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...

, 6% *

Neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...

, 5% * Gastrointestinal cancers, especially

colorectal The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being ...

and

pancreatic carcinoma Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of pancre ...

, 3% *

Lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

, 1%

and

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

are most likely to present with multiple metastasis, whereas breast, colon, and renal cancers are more likely to present with a single metastasis.

Diagnosis

Brain imaging (

neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incre ...

such as CT or

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

) is needed to determine the presence of brain metastases. In particular, contrast-enhanced MRI is the best method of diagnosing brain metastases, though detection is primarily done by CT. Biopsy is often recommended to confirm diagnosis. The diagnosis of brain metastases typically follows a diagnosis of a systemic cancer. Occasionally, brain metastases will be diagnosed concurrently with a primary tumor or before the primary tumor is found. In brain metastasis due to malignant melanoma, MRI imaging showed high T1 and low T2 intensity due to the deposition of melanin in the brain. In

susceptibility weighted imaging Susceptibility weighted imaging (SWI), originally called BOLD venographic imaging, is an MRI sequence that is exquisitely sensitive to venous blood, hemorrhage and iron storage. SWI uses a fully flow compensated, long echo, gradient recalled echo ( ...

(SWI), it usually shows abnormal SWI hypointensity in larger proportion than brain metastasis caused by breast carcinoma.

Treatment

Treatment for brain metastases is primarily palliative, with the goals of therapy being reduction of symptoms and prolongation of life. Additionally, there is limited evidence that the treatments that are offered takes account of patient-focused

comparative effectiveness Comparative effectiveness research (CER) is the direct comparison of existing health care interventions to determine which work best for which patients and which pose the greatest benefits and harms. The core question of comparative effectiveness ...

. However, in some patients, particularly younger, healthier patients, aggressive therapy consisting of open

craniotomy A craniotomy is a surgical operation in which a bone flap is temporarily removed from the skull to access the brain. Craniotomies are often critical operations, performed on patients who are suffering from brain lesions, such as tumors, blood clot ...

with maximal excision,

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

, and radiosurgical intervention ( Gamma Knife therapy) may be attempted.

Symptomatic care

Symptomatic care should be given to all patients with brain metastases, as they often cause severe, debilitating symptoms. Treatment consists mainly of: *

Corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...

– Corticosteroid therapy is essential for all patients with brain metastases, as it prevents development of

cerebral edema Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compressio ...

, as well as treating other neurological symptoms such as headaches, cognitive dysfunction, and

emesis Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteriti ...

Dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cav ...

is the

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...

of choice. Although neurological symptoms may improve within 24 to 72 hours of starting corticosteroids, cerebral edema may not improve for up to a week. In addition, patients may experience adverse side effects from these drugs, such as myopathy and opportunistic infections, which can be alleviated by decreasing the dose. *

Anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

s – Anticonvulsants should be used for patients with brain metastases who experience seizures, as there is a risk of status epilepticus and death. Newer generation anticonvulsants including

Lamotrigine Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut synd ...

and

Topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...

are recommended due to their relatively limited side effects. It is not recommended to prophylactically give anti-seizure medications when a seizure has not yet been experienced by a patient with brain metastasis.

Radiotherapy

Radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

plays a critical role in the treatment of brain metastases, and includes whole-brain irradiation, fractionated radiotherapy, and radiosurgery. Whole-brain irradiation is used as a primary treatment method in patients with multiple lesions and is also used alongside surgical resection when patients have single and accessible tumors. However, it often causes severe side effects, including radiation

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

toxic leukoencephalopathy Toxic leukoencephalopathy is a rare condition that is characterized by progressive damage (-pathy) to white matter (-leuko-) in the brain (-encephalo-), particularly myelin, due to causes such as exposure to substance use, environmental toxins, or ...

, partial to complete hair loss, nausea, headaches, and

otitis media Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, ...

. In children this treatment may cause intellectual impairment, psychiatric disturbances, and other neuropsychiatric effects. Results from a 2021 systematic review on radiation therapy for brain metastases found that despite much research on radiation therapy, there is little evidence to inform

and such patient-centered outcomes as quality of life, functional status, or cognitive effects.

Surgery

Brain metastases are often managed surgically if they are accessible. Surgical resection followed by

stereotactic radiosurgery Stereotactic surgery is a minimally invasive form of surgical intervention that makes use of a three-dimensional coordinate system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injec ...

or whole-brain irradiation deliver superior survival compared to whole brain irradiation alone. Therefore, in patients with only one metastatic brain lesion and controlled or limited systemic disease, a life expectancy of at least 3 months and a good

performance status In medicine (oncology and other fields), performance status is an attempt to quantify cancer patients' general well-being and activities of daily life. This measure is used to determine whether they can receive chemotherapy, whether dose adjustment ...

might be expected.

Chemotherapy

Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

is rarely used for the treatment of brain metastases, as chemotherapeutic agents penetrate the

blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the Cell (biology), cells, and transports Metabolic waste, metabolic waste products away from th ...

poorly. However, some cancers such as lymphomas, small cell lung carcinomas (SCLC) and

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

may be highly chemosensitive and chemotherapy may be used to treat extracranial sites of metastatic disease in these cancers. The effectiveness and safety of using chemotherapy to treat a brain metastasis that came from a SCLC is not clear. An experimental treatment for brain metastases is intrathecal chemotherapy, a technique in which a chemotherapeutic drug is delivered via intralumbar injection into the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

. Current research on the treatment of brain metastases includes creating new drug molecules to effectively target the blood-brain barrier and studying the relationship between tumors and various genes. In 2015, the United States

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approved Alecensa (

alectinib Alectinib (INN, marketed as Alecensa) is an oral drug that blocks the activity of anaplastic lymphoma kinase (ALK) and is used to treat non-small-cell lung cancer (NSCLC). It was developed by Chugai Pharmaceutical Co. Japan, which is part of th ...

) for use in patients with a specific type of

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...

(NSCLC; ALK-positive), a type of cancer which often metastasizes to the brain, whose condition worsened after use or were unable to take another medication, Xalkori (

crizotinib Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). It acts as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor. Med ...

Immunotherapy

Immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

, for instance Anti-PD-1 alone or in combination with anti-CTLA-4, appears to be effective in some patients with brain metastases especially when these are asymptomatic, stable and not previously treated.Very recently, OMICs-based approaches such as single-cell and bulk RNA-sequencing revealed molecular subgroups in melanoma brain metastases (MBM) that may explain the variable response of MBM to therapeutic interventions. .

Prognosis

The prognosis for brain metastases is variable; it depends on the type of primary cancer, the age of the patient, the absence or presence of extracranial metastases, and the number of metastatic sites in the brain. For patients who do not undergo treatment the average survival is between one and two months. However, in some patients, such as those with no extracranial metastases, those who are younger than 65, and those with a single site of metastasis in the brain only, prognosis is much better, with

median In statistics and probability theory, the median is the value separating the higher half from the lower half of a data sample, a population, or a probability distribution. For a data set, it may be thought of as "the middle" value. The basic fe ...

survival rates of up to 13.5 months. Because brain metastasis can originate from various different primary cancers, the Karnofsky performance score is used for a more specific prognosis.

Epidemiology

It is estimated that the worldwide

incidence rate In epidemiology, incidence is a measure of the probability of occurrence of a given medical condition in a population within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time peri ...

for brain metastases lies around 9% to 17%, based on the region of diagnosis. However, the baseline incidence rate of brain metastases were found to increase with improvements to brain imaging technology. Approximately 5 - 11% of brain metastasis were found to be deadly at 30 days, and 14 - 23% were found to be deadly at three months. More cases of brain metastases were found in

adult An adult is a human or other animal that has reached full growth. In human context, the term ''adult'' has meanings associated with social and legal concepts. In contrast to a " minor", a legal adult is a person who has attained the age of major ...

s, compared to

child A child ( : children) is a human being between the stages of birth and puberty, or between the developmental period of infancy and puberty. The legal definition of ''child'' generally refers to a minor, otherwise known as a person younger ...

ren. 67% to 80% of all

patients were found to develop brain metastases, as of 2012.

and

patients were found to be at the highest risk of developing brain metastases. However, recent trends in brain metastasis

epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...

have shown an increase in incidence for patients with

renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...

s. Brain metastases are most commonly diagnosed within multiple

intracranial The cranial cavity, also known as intracranial space, is the space within the skull that accommodates the brain. The skull minus the mandible is called the ''cranium''. The cavity is formed by eight cranial bones known as the neurocranium that in ...

areas within the context of extracranial diseases. Both

population studies Population study is an interdisciplinary field of scientific study that uses various statistical methods and models to analyse, determine, address, and predict population challenges and trends from data collected through various data collection met ...

and autopsy studies have historically been used to calculate the incidence of brain metastases. However, many researchers have stated that population studies may express inaccurate data for brain metastases, given that surgeons have, in the past, been hesitant to take in patients with the condition. As a result, population studies regarding brain metastases have historically been inaccurate and incomplete. Recent advances in systemic treatments of brain metastases, such as radiosurgery, whole-brain radiotherapy and

surgical resection Segmental resection (or segmentectomy) is a surgical procedure to remove part of an organ or gland, as a sub-type of a resection, which might involve removing the whole body part. It may also be used to remove a tumor and normal tissue around i ...

has led to an increase in median survival rate of brain metastases patients.

References

{{Authority control Brain tumor