Intracerebral metastases medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Overview

The optimal therapy for intracerebral metastases depends on the number, size, and location of the metastatic lesions. The various treatment options for intracerebral metastases include symptomatic treatment (corticosteroids and anticonvulsants), whole brain radiotherapy, chemotherapy, stereotactic radiosurgery, and surgery.

Medical Therapy

The treatment options for intracerebral metastases include the following:

Treatment for brain metatases

Symptomatic treatment

Definitive treatment

Corticosteroids

Anticonvulsants

Whole brain radiotherapy

Surgery

Stereotactic radiosurgery

Chemotherapy

Symptomatic Treatment

• Corticosteroid therapy is essential for all patients with intracerebral metastases, as it prevents the development of cerebral edema, as well as treating other neurological symptoms such as headaches, cognitive dysfunction, and emesis. Dexamethasone is the corticosteroid of choice.
• Anticonvulsants should be used in patients with intracerebral metastases who experience seizures, as there is a risk of status epilepticus and death. Phenytoin is the most commonly used drug, but valproic acid and other anticonvulsants can also be used. Newer anticonvulsants have the advantage of fewer toxic side effects.
• Hyperosmolar agents (i.e., mannitol) can be given to reduce intracranial pressure.
• Recently, methylphenidate and donepezil have been used to improve cognition, mood, and quality of life.

Radiation Therapy

• The most widely used treatment for patients with multiple intracerebral metastases is whole brain external beam radiotherapy (WBRT).
• The role of radiation therapy in treatment of intracerebral metastases include:

• Control the growth of the tumor(s)
• Control neurological symptoms, such as headaches or seizures

• Whole brain radiation therapy (WBRT) is a type of external beam radiation therapy. Indications for WBRT include:

Indication	Explanation
Multiple brain metastases	More than 3 metastatic brain tumors or in people with poor performance status
Single brain metastasis that cannot be removed by surgery	Brain tumors are in an inaccesible area or if the affected area would be damaged by surgery
Post surgical removal of a single brain metastasis	To destroy remnant cancer cells post surgery and reduce the chance of recurrence

• One major concern with the use of whole brain radiotherapy is the risk of neurocognitive deficits, particularly short-term memory loss.

Chemotherapy

• Chemotherapy is the use of cytotoxic drugs that circulate throughout the body and destroy cancer cells.
• Chemotherapy may help shrink brain metastases and improve symptoms.
• Due to the failure of most drugs to cross the intact blood–brain barrier (BBB), the role of chemotherapy in the treatment of intracerebral metastases has been viewed critically. Chemotherapy drugs are generally large (> 150 kDa), ionized, hydrophilic, and often protein-bound and therefore, ill-suited to penetrate the tight-junctions, electrochemical barrier, astrocyte foot-processes, and highly regulated transmembrane transport proteins of the central nervous system’s endothelial vasculature.
• However, the effects of the blood-brain barrier may be over-estimated. First, there is evidence that the blood-brain barrier of intracerebral metastases is disrupted, as evidenced by the presence of peritumoral edema and the accumulation of contrast media during computed tomography or magnetic resonance assessments. Second, there is evidence of intracranial tumor response, even to drugs that in healthy systems have little central nervous system penetration.
• The response rates of intracerebral metastases to platinum-based agents (cisplatin) in seven clinical trials of treatment-naive non-small cell lung cancer patients were similar to those achieved extra-cranially, ranging from 30 to 50%. However, the median survival time remained only 5–8 months in most cases. However, three trials using temozolomide achieved a response rate of only 0–10%, suggesting that the selection of chemotherapy drugs should be based mainly on their established anti-tumor activity to extracranial sites, and not on considerations of blood-brain barrier penetrance.
• Responsiveness of brain metastases to chemotherapy depends on how sensitive the primary cancer is to chemotherapy drugs (chemosensitivity). For example, chemotherapy may be used to treat lung cancer, breast cancer, or melanoma that has spread to the brain.
• The chemotherapy drugs used depend on the type of primary tumor. The drugs, dose, and schedule will vary for each individual.

Gallery

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  _{Hippocampal sparing whole brain radiotherapy plan showing treatment of the whole brain to 30 Gy while sparing the hippocampi from high doses of radiation which is receiving less than 10 Gy mean dose. Furthermore, it is also possible to dose escalate the gross disease simultaneously (courtesy of Wolfgang Tomé, Ph.D.).}

References

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