Treatment of Brain Metastases

Brain metastases occur when cancer cells spread to the brain from a primary tumor located elsewhere in the body. The management of brain metastases is a complex process that involves a multidisciplinary approach.

Treatment decisions are often individualized based on factors such as the number and size of metastases, the location of the primary tumor, the patient's overall health, and the presence of symptoms. In this article we’ll discuss the different methods of treatment used in the management of brain metastases.

There are multiple, ever-evolving treatment strategies for brain metastases. These therapies may be used alone, or in combination with each other as needed on a case by case basis: 

Surgical removal of the metastatic tumors is often considered for a single or a few metastases that are accessible and not too close to critical brain structures. This can help alleviate symptoms and improve overall survival.

• Whole Brain Radiation Therapy (WBRT): This involves delivering radiation to the entire brain and is often used when there are multiple metastases or when metastases are scattered throughout the brain.
• Stereotactic Radiosurgery (SRS): While not technically surgery, SRS is a highly focused form of radiation therapy that delivers a precise, high dose of radiation to a specific target in the brain. It is often used for smaller metastases or for cases where surgery is not feasible.

• Chemotherapy: Traditional chemotherapy has limited efficacy in treating brain metastases due to the blood-brain barrier. However, some drugs may have the ability to penetrate the barrier, and intrathecal chemotherapy (direct injection into the cerebrospinal fluid) can be considered in certain cases.
• Targeted Therapies: These drugs are designed to specifically target molecular abnormalities present in cancer cells. Some targeted therapies may have activity against brain metastases.
• Immunotherapy: Checkpoint Inhibitors are immunotherapy drugs that block certain proteins involved in suppressing the immune system. These medications have shown promise in the treatment of brain metastases in some cases. The effectiveness may depend on the type of cancer and the characteristics of the metastases.

• Symptom Management: Depending on the symptoms caused by brain metastases, supportive care measures such as corticosteroids, anticonvulsants, and pain management may be employed to improve the patient's quality of life.
• Counseling and Psychosocial Support: Dealing with brain metastases can be emotionally challenging, and patients may benefit from counseling and support groups.

Participation in clinical trials may be an option for some patients, offering access to experimental treatments that could potentially be more effective than standard therapies. More information about clinical trial participation can be found here.

The choice of treatment depends on a thorough assessment by a multidisciplinary team, which may include neurosurgeons, radiation oncologists, medical oncologists, and other specialists.

The goal is often to balance the control of the metastases with minimizing damage to healthy brain tissue and maintaining the patient's quality of life.

It's important for patients to have open and informed discussions with their healthcare team to make decisions that align with their individual circumstances and preferences.

Surgery for brain metastases is considered in several scenarios, and the decision is typically made based on the specific characteristics of the metastases, the patient's overall health, and the goals of treatment. Here are some situations in which surgery for brain metastases may be considered:

Surgery is often considered when there is a single brain metastasis or a limited number of metastases that are accessible and not too close to critical brain structures. Removing these tumors can help control symptoms and improve overall survival.

If the metastases are located in areas of the brain where surgery can be safely performed without causing significant neurological deficits, surgical resection may be a viable option.

The size of the metastases matters. Larger tumors may be more challenging to completely remove without causing excessive damage to surrounding healthy brain tissue. However, in some cases, even larger tumors may be surgically addressed if the benefits outweigh the potential risks.

Surgery may be recommended when brain metastases are causing significant symptoms such as seizures, neurological deficits, or increased intracranial pressure. Removing the tumor can alleviate these symptoms and improve the patient's quality of life.

The type of cancer and its responsiveness to treatment play a role in the decision-making process. Some types of tumors may be more amenable to surgical resection, while others may require a different approach such as radiation therapy or systemic therapies.

The patient's overall health and ability to tolerate surgery are crucial factors. If a patient is in good general health and the surgical risks are deemed acceptable, surgery may be a suitable option.

The number and distribution of metastases in the brain influence the treatment approach. In some cases, surgery may be combined with other treatments such as radiation therapy, especially if there are multiple metastases.

Surgery for brain metastases, like any surgical procedure, comes with potential risks and complications. The specific risks can vary depending on factors such as the location and size of the metastases, the patient's overall health, and the surgical approach used.

It's important for patients to have a thorough discussion with their healthcare team to understand the potential risks and benefits of the surgery. Here are some common risks associated with surgery for brain metastases:

• Stroke
• Bleeding
• Death
• Infection
• Seizures
• Cerebrospinal Fluid Leak
• Reaction to Anesthesia

The decision to proceed with surgery is carefully weighed against the potential benefits, and the healthcare team works to minimize risks through careful planning and execution of the procedure.

Additionally, the risks and benefits are discussed with the patient, and informed consent is obtained before surgery. Patients are closely monitored during and after surgery, and any unexpected complications are addressed promptly.

Radiation therapy is a common treatment modality for brain metastases, and its mechanism of action involves disrupting the DNA of cancer cells, ultimately leading to cellular demise. 

The goal of radiation therapy is to selectively target and eliminate cancer cells while minimizing damage to surrounding healthy brain tissue.

There are different types of radiation therapy, but they all share the fundamental principle of disrupting the ability of cancer cells to divide and grow.

Whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) are two distinct approaches to the use of radiation therapy for treating brain metastases. Each has its unique characteristics and is applied based on specific clinical scenarios.

• WBRT is designed to treat multiple or widespread brain metastases throughout the entire brain.
• WBRT is typically delivered in fractions over a course of several days or weeks.
• This fractionation helps spare normal brain tissue from excessive radiation exposure and allows for recovery between treatments.
• The goal is to target both visible and microscopic metastatic lesions throughout the brain.

• SRS is a highly precise form of radiation therapy.
• SRS relies on a highly accurate targeting system to focus radiation beams directly on the metastatic lesion while sparing surrounding healthy brain tissue.
• This precision allows for a higher dose per treatment session.
• Despite the name, it is not a surgical procedure but rather a non-invasive radiation treatment.
• SRS can be delivered in a single session (single fraction) or in a few fractions, depending on the characteristics of the metastases and the overall treatment plan.

Some of the side effects of radiotherapy can include fatigue, hair loss, skin reactions, nausea & vomiting, and cognitive changes.

It's important for patients undergoing radiotherapy for brain metastases to discuss potential side effects with their healthcare team before starting treatment.

Additionally, supportive care measures and medications may be prescribed to manage specific symptoms and improve the overall quality of life during and after treatment.

Regular follow-up appointments and imaging studies are typically scheduled to monitor the treatment's effectiveness and detect any potential complications early on.

• Tyrosine Kinase Inhibitors (TKIs): Targeted therapies, especially TKIs, have shown promise in treating brain metastases.
• HER2-Targeted Therapies: In breast cancer, targeted therapies such as trastuzumab and lapatinib have been effective.

• Immune Checkpoint Inhibitors: These drugs enhance the immune system's ability to recognize and attack cancer cells.
• Combination Therapies: Studies are exploring combinations of immunotherapy with other treatment modalities, including radiation and chemotherapy, to enhance efficacy.

• Osmotic Blood-Brain Barrier Disruption (BBBD): Osmotic disruption is a technique that temporarily opens the blood-brain barrier, allowing for increased drug delivery to brain tumors.
• Nanoparticle Drug Delivery: Nanoparticle-based drug delivery systems are designed to improve the transport of drugs across the blood-brain barrier, increasing their concentration at the tumor site while minimizing systemic side effects.
• Intranasal Delivery: Some researchers are exploring intranasal delivery routes to bypass the blood-brain barrier and deliver drugs directly to the brain.

• Molecular Profiling: Identifying specific genetic mutations allows for targeted therapies tailored to the individual patient.
• Liquid Biopsy: Liquid biopsy, analyzing circulating tumor DNA in blood, is emerging as a non-invasive method for monitoring treatment response and detecting genetic alterations in brain metastases.

It's important to note that the treatment strategy for brain metastases is made through a collaborative effort involving a multidisciplinary team of healthcare professionals, including neurosurgeons, radiation oncologists, and medical oncologists.

The team considers various factors to develop a treatment plan that is tailored to the individual patient's circumstances. Additionally, one's preferences and values are important considerations in the decision-making process.

• Surgery forms the backbone of treatment of brain metastases. It is considered especially in circumstances such as few and surgically accessible brain metastases.
• Radiotherapy has a role in the management of surgically inaccessible tumors and multiple brain metastases. Radiotherapy is usually delivered as whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)
• Medical management currently has a limited role in the management of brain metastases. However, research is ongoing to make systemic therapies more effective.

• American Association of Neurological Surgeons (AANS): Metastatic Brain Tumors
• National Cancer Institute (NCI): Brain Tumors
• National Brain Tumor Society: Signs & Symptoms
• CancerCare: Brain Cancer