Brain metastasis
Encyclopedia
A brain metastasis is a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 that has metastasized
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 (spread) to the brain from another location in the body. Brain metastases are the most common cause of intracranial mass lesions, and up to 45% of cancer patients eventually develop brain metastases during the course of their illness, with 98,000 to 170,000 new cases diagnosed each year in the US. As primary cancer treatments such as surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

, radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

 and chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 have become more effective in the past few decades, people with cancer are living longer after initial treatment than ever before. However, brain metastases still occur in many patients months or even years after their original cancer treatment. Brain metastases have a poor prognosis for cure, but modern treatments are allowing patients to live months and sometimes years after the diagnosis.

Symptoms

Often, patients have no obvious symptoms to alert them that their cancer has spread to the brain. Follow-up doctor visits and brain scans may be needed to determine the presence of brain metastases.

Brain metastases can cause a wide variety of symptoms, many of which are also present in minor, more common conditions. They include:
  • Vertigo
    Vertigo
    Vertigo is a form of dizziness.Vertigo may also refer to:* Vertigo , a 1958 film by Alfred Hitchcock**Vertigo , its soundtrack** Vertigo effect, or Dolly zoom, a special effect in film, named after the movie...

  • New onset headaches
  • Cognitive, personality, and behavioral changes.
  • Nausea and vomiting
    Vomiting
    Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

  • Memory loss
    Memory loss
    Memory loss can be partial or total and it is normal when it comes with aging. Sudden memory loss is usually a result of brain trauma and it may be permanent or temporary. When it is caused by medical conditions such as Alzheimers, the memory loss is gradual and tends to be permanent.Brain trauma...

  • Increased intracranial pressure
  • Paraesthesias
  • Visual changes
  • Bells palsy
  • Ataxia
    Ataxia
    Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

  • Seizure
    Seizure
    An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

    s

Causes

The most common sources of brain metastases in a case series
Case series
A case series is a medical research descriptive study that tracks patients with a known exposure given similar treatment or examines their medical records for exposure and outcome. It can be retrospective or prospective and usually involves a smaller number of patients than more powerful...

 of 2,700 patients undergoing treatment at the Memorial Sloan–Kettering Cancer Center were:
  • Lung cancer
    Lung cancer
    Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

    , 48%
  • Breast cancer
    Breast cancer
    Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

    , 15%
  • Genitourinary tract cancers
    Urogenital neoplasm
    A urogenital neoplasm is a tumor of the urogenital system.Types include:* Cancer of the breast and female genital organs:...

    , 11%
  • Osteosarcoma
    Osteosarcoma
    Osteosarcoma is an aggressive cancerous neoplasm arising from primitive transformed cells of mesenchymal origin that exhibit osteoblastic differentiation and produce malignant osteoid...

    , 10%
  • Melanoma
    Melanoma
    Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

    , 9%
  • Head and neck cancer
    Head and neck cancer
    Head and neck cancer refers to a group of biologically similar cancers that start in the upper aerodigestive tract, including the lip, oral cavity , nasal cavity , paranasal sinuses, pharynx, and larynx. 90% of head and neck cancers are squamous cell carcinomas , originating from the mucosal lining...

    , 6%
  • Neuroblastoma
    Neuroblastoma
    Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...

    , 5%
  • Gastrointestinal cancer
    Gastrointestinal cancer
    Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract, including the esophagus, stomach, biliary system, pancreas, bowels, and anus. The symptoms relate to the organ affected, and can include obstruction , abnormal bleeding, or other associated problems...

    s, especially colorectal and pancreatic carcinoma, 3%
  • Lymphoma
    Lymphoma
    Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

    , 1%

Treatment

Treatment for brain metastases is primarily palliative, with the goals of therapy being reduction of symptoms and prolongation of life. However, in some patients, particularly younger, healthier patients, aggressive therapy consisting of open craniotomy with maximal excision, aggressive chemotherapy, and radiosurgical intervention (gamma knife radiosurgery) 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 - Corticosteroid therapy is essential for all patients with brain metastases, as it prevents development of cerebral edema (swelling of the brain tissue), as well as treating other neurological symptoms such as headaches, cognitive dysfunction, and emesis. Dexamethasone
    Dexamethasone
    Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

     is the corticosteroid of choice.
  • Anticonvulsants - Anticonvulsants should be used in all of the 30-40% of patients with brain metastases who experience seizures, as there is a risk of status epilepticus and death, as is the case with other patients with possibly severe seizure types (particularly generalized tonic- clonic, or grand mal, seizures, where the entire brain, not just one local focus or lobe, is pathologically affected). Phenytoin
    Phenytoin
    Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

     is the most commonly used drug in this setting, but valproic acid and other anticonvulsants can also be used; newer anticonvulsants generally have the advantage of fewer toxic side effects.

Radiotherapy

Radiotherapy plays a critical role in the treatment of brain metastases, and includes whole-brain irradiation, fractionated radiotherapy, and radiosurgery. For decades, whole brain irradiation has been advocated for patients with multiple lesions, a life expectancy of less than three months, or a low Karnofsky performance score, and it does appear at least somewhat effective. However, it often causes severe side effects, including radiation necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

, dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

, leukoencephalopathy
Leukoencephalopathy
The term Leukoencephalopathy is a broad term for leukodystrophy-like diseases . It is applied to all brain white matter diseases, whether their molecular cause is known or not...

, partial to complete hair loss, nausea, headaches, and otitis media
Otitis media
Otitis media is inflammation of the middle ear, or a middle ear infection.It occurs in the area between the tympanic membrane and the inner ear, including a duct known as the eustachian tube. It is one of the two categories of ear inflammation that can underlie what is commonly called an earache,...

. In children this treatment may cause mental retardation, psychiatric disturbances, and other neuropsychiatric effects.

Surgery

Brain metastases are often managed surgically, with maximum surgical resection followed by stereotactic radiosurgery or whole-brain irradiation delivering superior survival compared to whole brain irradiation alone. Therefore, in patients with one metastatic brain lesion, limited, absent, or controlled systemic disease, a life expectancy of at least 3 months and good performance status might be expected.

Sterotactic Radiosurgery

Stereotactic radiosurgery is being increasingly utilized for the treatment of a limited number of brain metastases. Stereotactic radiosurgery alone or with whole brain radiation therapy has been shown to achieve excellent local tumor control. Addition of stereotactic radiosurgery to whole brain radiation can increase the control rate and functional status of patients.

Chemotherapy

Chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 is rarely used for the treatment of brain metastases, as chemotheraputic agents penetrate the blood brain barrier poorly. However, some cancers such as lymphomas,small cell lung carcinomas and breast cancer are highly chemosensitive and chemotherapy may be used to treat extracranial sites of metastatic disease in these cancers. Intrathecal chemotherapy is an experimental but promising treatment for brain metastases that involves an intralumbar injection of a chemotheraputic drug into the cerebrospinal fluid. However, it is not approved by the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

(FDA) for the treatment of brain metastases.

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 all patients combined, median survival is only 2.3 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 survival rates of up to 13.5 months.
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