Metastases to Central Nervous System

When cancer spreads from other parts of the body to the brain or spinal cord, it creates metastases to the central nervous system. These tumors are far more common than cancers that start in the brain itself, and modern medicine now offers more treatment options than ever before.

Table of contents

• What Is Central Nervous System Metastasis?
• How Common Is This Condition?
• Which Cancers Spread to the Central Nervous System?
• How Cancer Spreads to the Central Nervous System
• Signs and Symptoms
• How Doctors Diagnose Central Nervous System Metastases
• Treatment Options
• Outlook and Survival

What Is Central Nervous System Metastasis?

Central nervous system metastasis is the spread and growth of cancer cells from their original tumor to form secondary tumors in parts of the central nervous system (CNS), which includes the brain and spinal cord^[1][2]. The original cancer is called the primary tumor, while the new tumors that develop in the brain or spinal cord are called metastases or secondary tumors^[2].

Central nervous system metastases can occur in different locations within the CNS. They may develop in the brain tissue itself (called parenchymal brain metastases), in the spinal cord (known as intramedullary spinal cord metastases), in the membranes covering the brain and spinal cord (called leptomeningeal metastases), or in the space around the spinal cord (the epidural space)^[1][2][4].

CNS metastasis, brain metastases, metastatic brain tumors, secondary brain tumors, brain metastasis, spinal metastases

How Common Is This Condition?

Metastases to the central nervous system are much more common than cancers that start in the brain. In fact, they are approximately ten times more common than primary brain tumors^[1]. Brain metastases alone represent the most common type of brain tumor in adults, being four times more common than primary brain tumors^[4].

Up to 30% of adults with cancer develop CNS metastases at some point during their illness^[1][2]. This number is expected to rise as treatments for cancer in other parts of the body continue to improve, allowing people to live longer. Better imaging techniques also help doctors detect metastases earlier than before^[1].

Although CNS metastases are traditionally associated with late-stage cancer, they can be diagnosed at any time during the course of the disease. In some cases, CNS metastases may even be the first sign that someone has cancer^[1]. About 5 to 10% of diagnosed CNS metastases come from unknown primary sources, meaning doctors cannot initially identify where the original cancer started^[2].

Which Cancers Spread to the Central Nervous System?

Any type of cancer can potentially spread to the central nervous system, but certain cancers are more likely to do so^[1][2]. The most common cancers that spread to the brain and spinal cord are:

• Lung cancer: This is the most common source, accounting for 40% to 50% of all brain metastases^[4]. Up to 50% of people with lung cancer may develop CNS metastases^[1].
• Breast cancer: Approximately 15% to 25% of brain metastases originate from breast cancer^[4]. About 10% to 15% of people with metastatic breast cancer develop brain metastases^[1].
• Melanoma (skin cancer): Although melanoma accounts for 5% to 20% of brain metastases, it has the highest tendency to spread to the brain among all cancers^[4]. About 50% of people who die from melanoma have brain involvement^[4].

For spinal metastases specifically, the most common sources are breast cancer, lung cancer, prostate cancer, thyroid cancer, and kidney cancer (also called renal cell cancer)^[1].

Less commonly, CNS metastases can develop from kidney cancer, colon cancer, and thyroid cancer, among others^[1].

How Cancer Spreads to the Central Nervous System

The process by which cancer spreads to the CNS is complex. It typically begins when tumor cells separate from the primary tumor and enter the bloodstream or lymph system (the body’s drainage system) through a process called intravasation^[2]. Once in the circulatory system, these cancer cells can travel to distant parts of the body, including the brain and spinal cord^[2].

The brain is normally protected by the blood-brain barrier, a special layer of cells that prevents harmful substances from entering brain tissue. Similarly, the blood-spinal barrier protects the spinal cord. CNS metastases occur when these protective barriers break down under abnormal conditions, allowing cancer cells to pass through^[4].

For cancer cells to successfully form metastases in the CNS, they must adapt to the new environment, which is very different from where the original tumor grew^[2]. Cancer cells undergo changes in their characteristics once they separate from the primary tumor, developing new abilities that help them survive in the brain or spinal cord^[2]. In particular, they need characteristics that allow them to disrupt the blood-brain barrier and establish themselves in brain tissue^[2].

Recent research shows that the spread of cancer cells from the primary tumor is not a simple step-by-step process. Instead, it involves multiple overlapping processes and routes^[2]. Cancer cells interact with surrounding tissues while also evolving to avoid detection by the immune system and adapting to survive various treatments^[2].

Signs and Symptoms

CNS metastasis usually indicates that cancer has reached stage 4, which carries a poor prognosis^[2]. At this stage, cancer typically causes numerous and varying symptoms depending on the type of underlying cancer and where the metastases are located^[2].

Many patients with CNS metastases experience neurological symptoms, although some people may not have any symptoms at all. The specific symptoms depend on the size and location of the tumors^[2]. For example, if a tumor is located near the front of the brain, it might cause sadness or memory problems. If it’s near the back of the brain, it might affect balance or vision^[1].

Common symptoms of CNS metastases include:

• Headaches, sometimes accompanied by nausea and vomiting^[1]
• Seizures^[1]
• Weakness on one side of the body^[1]
• Problems with thinking, short-term memory, or mood changes^[1]
• Difficulty producing or understanding speech^[1]
• Vision problems^[1]

As brain metastases progress, additional symptoms may develop, including problems with hearing, swallowing, or double vision. Drowsiness is the most common symptom in end-stage brain metastases^[1].

CNS metastases can also cause bleeding (hemorrhage) or blockage in the brain, leading to a buildup of fluid called hydrocephalus^[2]. While most symptoms develop slowly and worsen over time, in rare cases, brain metastases can cause a stroke, which produces sudden symptoms^[1].

How Doctors Diagnose Central Nervous System Metastases

When a patient with cancer develops new neurological symptoms, healthcare providers will perform several tests to diagnose CNS metastases. Diagnosis typically involves the following approaches:

Neurological Examination

A healthcare professional checks various aspects of brain and nervous system function, including thinking ability, speech, vision, hearing, balance, coordination, strength, sensation, and reflexes. Changes in these areas can point to the part of the brain affected by the tumor^[8].

Imaging Tests

Magnetic resonance imaging (MRI) is the main test used to show the location and size of brain metastases^[8]. During an MRI scan, a dye may be injected through a vein in the arm to help highlight the tumors. MRI uses magnets and radio waves to create detailed pictures of the brain without using radiation^[8].

Other imaging tests may include computed tomography (CT) scans, which use X-rays to create cross-sectional images of the body, and positron emission tomography (PET) scans, which can show how tissues and organs are functioning^[8].

Molecular Analysis

Modern approaches include molecular analysis of tumors. Doctors can now perform genomic sequencing on tissue removed from CNS metastases during surgery or biopsy to look for specific genetic changes^[1]. In some cases, doctors can analyze spinal fluid for cancer cells, a technique called a liquid biopsy^[1].

Biopsy

A healthcare professional may recommend a procedure to remove a sample of tissue for testing in a laboratory. This can be done with a needle or during surgery to remove a brain tumor^[8].

For patients with known cancer elsewhere in the body, doctors may consider doing a biopsy of the primary cancer site rather than performing a more invasive brain procedure, as this generally carries lower risk^[11].

Treatment Options

Treatment for CNS metastases has evolved significantly in recent years. The approach depends on multiple factors, including the patient’s life expectancy, performance status (how well they can carry out daily activities), the extent and number of metastases, and the type of primary cancer^[4]. Managing CNS metastases requires a cooperative approach involving neurosurgery, radiation oncology, medical oncology, and neurology^[1].

Medications to Control Symptoms

Before and during definitive treatment, doctors use medications to help control symptoms and make patients more comfortable:

Corticosteroids (such as dexamethasone) are high-dose medicines that decrease swelling in the brain caused by metastases^[8][11]. If a patient is experiencing symptoms like headaches, nausea, vomiting, or neurological deficits, doctors typically prescribe 4 to 6 mg of dexamethasone every 6 hours^[11]. While these medications are very effective at reducing brain swelling, they must be used carefully because they can affect blood sugar control, cause stomach bleeding, increase infection risk, and suppress the adrenal gland^[11].

Anticonvulsants are medications used to prevent or control seizures, which are very common in patients with brain metastases. Doctors often start anticonvulsant therapy for all brain metastasis patients, even if they haven’t had seizures^[11]. Commonly used medications include levetiracetam (500 to 1,000 mg twice daily) or phenytoin (100 mg three times daily)^[11].

Surgery

Surgery plays an important role in managing carefully selected cases of CNS metastases. It can provide accurate diagnosis, reduce pressure from the tumor mass, improve neurological symptoms, and may improve overall survival, all with relatively low risk^[4]. To benefit from surgery, a patient must have reasonable medical fitness and a disease process that can benefit from removing the tumor^[4].

Radiation Therapy

Radiation therapy is a key treatment for CNS metastases, and approaches have evolved significantly:

Stereotactic radiosurgery (SRS) delivers precise, high-dose radiation to specific tumors while minimizing exposure to surrounding healthy brain tissue. It has become increasingly popular for treating brain metastases^[1][4].

Whole-brain radiation therapy (WBRT) delivers radiation to the entire brain. Traditionally, this was the standard treatment approach, but it can contribute to cognitive problems over time, especially in patients who survive more than a year^[11]. Current efforts focus on limiting whole-brain radiation and instead treating only visible lesions with surgery or stereotactic radiosurgery, which may help preserve thinking and memory function^[11].

Targeted Therapies and Immunotherapy

For patients whose CNS metastases have specific genetic changes that can be targeted, a wide variety of treatment options are now available^[1]. Targeted therapies are drugs designed to attack cancer cells with specific genetic mutations. Many of these medications can be taken by mouth and can reach the brain, unlike older chemotherapy drugs^[1].

Immunotherapy helps the body’s immune system recognize and fight cancer cells. For some patients with CNS metastases, immunotherapy or targeted therapy may be tried instead of or before radiation therapy^[1].

Chemotherapy

Traditional chemotherapy is usually chosen based on the type of primary cancer and is applied for overall disease control. However, its effectiveness specifically for CNS metastases is unclear, as many chemotherapy drugs do not cross the blood-brain barrier well^[4].

Observation

In some cases, particularly when metastases are very small or patients are not experiencing symptoms, doctors may recommend careful monitoring without immediate treatment^[4].

Outlook and Survival

Thanks to technological advances in diagnosis and treatment, outcomes for patients with CNS metastases have improved, with better progression-free survival (the time before the cancer worsens), overall survival, and quality of life, particularly for certain types of cancer^[1].

Patient survival has continued to improve as new treatment strategies have been developed^[6]. Treatment can help ease symptoms, slow tumor growth, and extend life. However, even with successful treatment, metastases may return, which is why healthcare providers follow patients closely over time^[8].

The outlook for individual patients varies widely depending on several factors, including the type of primary cancer, the number and location of metastases, the patient’s overall health, and how well the cancer responds to treatment. These days, people are living longer after a CNS metastasis diagnosis than in the past^[12].

Managing CNS metastases requires not just medical treatment but also attention to quality of life. A multidisciplinary approach that includes supportive care throughout the course of disease can greatly benefit patients^[18]. This may involve managing symptoms, supporting emotional and mental health, and providing palliative care when needed to ease suffering and maximize quality of life^[18].