When Lung Cancer Spreads to the Brain

What is Brain Metastasis?

Metastasis refers to the occurrence of a secondary cancer being found in a different location than the primary diagnosis. This happens when some of the cancer cells move from the original cancer site to another part of the body. The brain, which is part of the central nervous system (CNS), is a common site of metastasis for many cancer types. In fact, the majority of CNS tumors are metastasized from another primary cancer type. You may hear these brain metastases referred to in short as ‘brain mets.’ It is important to note that brain mets are not the same as brain cancer. The cancer cells in brain mets would match the primary cancer, not the site of metastasis.

Leptomeningeal Disease

Although ‘brain mets’ typically describes brain tumors that metastasize from another primary cancer, there can also be a disease in the fluid that surrounds the brain. This is another form of metastasis called leptomeningeal disease. 

Brain Cancer Cells in Lung Cancer

Lung cancer metastasis to the brain is common. A cohort study found that approximately 16% of lung cancer patients develop brain metastases within 5 years of diagnosis. The lifetime risk of developing brain mets after a lung cancer diagnosis is estimated to be ~50%. Many patients already have brain mets when they are initially diagnosed with lung cancer. The existence of brain mets upon initial diagnosis is indicative of Stage 4 (IV) cancer. This has a significant impact on lung cancer life expectancy.

Who is at Greatest Risk?

The lung cancer type, genetic mutations, and metastasis to other parts of the body, especially the lymph nodes, are risk factors for developing brain metastases from lung cancer.

There are two main types of lung cancer: 

• Small cell lung cancer (SCLC)
• Non-small cell lung cancer (NSCLC)

Although SCLC is the less common lung cancer type, it has a higher occurrence of cancer spreading to the brain than NSCLC. However, this may be due to the fact that SCLC is usually in the later (severe) stages by the time it is diagnosed. NSCLC is often diagnosed earlier in the progression of the disease, before brain metastasis has had the opportunity to likely occur.

Presence of genetic mutations helps to assess the risk of brain metastasis and guides treatment decisions. In patients with NSCLC, certain common mutations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, have higher incidence of brain mets than patients with NSCLC without these mutations.

How are Brain Mets Diagnosed?

Brain metastases apply pressure to the brain tissue, resulting in a variety of negative symptoms. However, sometimes they are discovered on scans prior to the patient noticing symptoms. Magnetic Resonance Imaging (MRI) with contrast is the preferred type of scan used for diagnosis. An MRI uses magnetic waves to create an image of the brain. Contrast is a dye that is injected into the patient’s arm prior to the scan. The purpose of the contrast is to make the brain image clearer and concise.

An MRI with contrast is usually performed when lung cancer is first diagnosed to check for brain mets, as well as metastasis to other areas of the body. Although there is no set guidelines for how often a patient should be screened, in advanced disease, it is typically performed at least annually. A Computed Tomography (CT) scan works similarly to an MRI, but instead it uses x-rays to generate an image of the brain. A CT scan with contrast would also provide doctors with the information they need for diagnosis if an MRI is not possible due to insurance or availability.

Leptomeningeal disease is diagnosed with a lumbar puncture. The fluid that surrounds your brain and the fluid in your spinal cord are connected. This is called cerebrospinal fluid.  A needle is inserted into the lumbar area to take a sample of the cerebrospinal fluid. This allows physicians to scan the fluid for cancer cells. Leptomeningeal disease is typically only seen in advanced stage lung cancer and has a poor prognosis.

What Symptoms are Common?

Since brain mets are found in the central nervous system, the associated symptoms may vary. They are often classified as either focal symptoms or global symptoms. Focal symptoms are more specific to the area of the brain that is most affected by the tumor. Common focal symptoms include:

• Stroke
• Blurry vision
• Loss of coordination
• Difficulty walking
• Limb weakness

Global symptoms are not specific to a particular part of the brain. Leptomeningeal disease is more often associated with non-specific complications since it affects the fluid surrounding the brain. Global symptoms include:

• Headaches
• Altered mental status
• Changes in personality
• Nausea and vomiting
• Seizures
• Confusion

Several of these symptoms can be treated with medications, such as anticonvulsants for seizures, memory loss medications, drugs to decrease nausea, and pain medications.

In some cases, brain mets may cause bleeding in the brain (hemorrhagic brain mets), which are higher risk and may require surgical intervention to remove.

Late Stage Disease

Complications in the later stages of the disease are significant and require a palliative care team to focus on comfort care for the patient. Symptoms include:

• Pain
• Decreased consciousness
• Significant confusion
• Partial or complete paralysis of affected nerves
• Difficulty breathing

What are the Treatment Options?

Treatment of brain mets often involves a combination approach. The presence of genetic mutations, stage at diagnosis, extent of metastases, and the patient’s symptom burden and physical health play an important role in treatment selection. It is becoming increasingly important to have genetic testing done before choosing a course of treatment. Several newer therapies target specific mutations and proteins. This can create a more individualized approach to care. Treatment options include:

• Focused radiation
• Whole brain radiation
• Proton therapy
• Systemic chemotherapy
• Targeted therapy
• Immunotherapy
• Surgery
• Palliative Care

Focused Radiation

If possible, this is one of the preferred treatments for brain mets originating from lung cancer. It is also referred to as stereotactic radiosurgery.  A machine is used to deliver radiation only to the portion of the brain where the tumor is located. This method minimizes the side effects of the treatment because tumor cells are targeted.

Radiation Necrosis

Radiation necrosis can occur when the normal cells that were near the tumor are affected and begin to die off. This tends to cause some inflammation and swelling in the surrounding tissue. Steroids can help swelling caused by radiation necrosis by decreasing the part of our immune system that is causing the inflammation. Bevacizumab, for example, is another medication commonly prescribed for radiation necrosis.

Whole Brain Radiation

Whole brain radiation therapy has a higher risk of side effects than focused radiation. This involves the administration of radiation over the entire brain. Risks of whole brain radiation include memory loss, nausea and vomiting, and possible seizures. These symptoms can be mitigated with medications, such as memantine for memory loss. The overall benefit versus risk should be weighed carefully.

Whole brain radiation is useful for patients who have multiple brain mets that cannot be effectively treated with focused radiation. It is also often used after tumors have been surgically removed to prevent the risk of brain metastasis recurrence. Patients with late stage brain mets or leptomeningeal disease may also undergo whole brain radiation therapy to improve complications associated with the tumor and improve quality of life.

Proton Therapy

Proton therapy works similarly to focused radiation. The advantage of proton therapy over traditional radiation is fewer side effects. Traditional radiation works using x-rays. Despite radiation being targeted to the tumor site, x-rays still need to exit the body, and will impact healthy tissue in the process. This is called the exit dose. Protons work differently than x-rays in that they can stop at the targeted tumor and do not have an exit dose. However, proton therapy is significantly more costly than traditional radiation therapy and may not be available to all patients.

Systemic Chemotherapy

Chemotherapy works primarily by treating the underlying cancer in the lung. This helps minimize the extension of cancer cells to the brain. Systemic chemotherapy has difficulty treating the brain metastases, due to our brains being protected by the blood-brain barrier. It is difficult for many chemotherapy drugs to penetrate into the brain.

Targeted Therapy

If certain genetic mutations are present, there may be targeted therapy options available. These medications are more suited to cross the blood-brain barrier compared to traditional systemic chemotherapy. For EGFR mutations, a drug class called tyrosine kinase inhibitors offers some pharmacologic options that are able to penetrate the blood-brain barrier and ultimately treat the tumor. ALK inhibitors are also highly effective for ALK-rearrangement positive brain metastases. Research is ongoing whether these targeted therapies should be used alone, or with radiation and other systemic treatments.

Immunotherapy

Like targeted therapies, immunotherapy options are also able to cross the blood-brain barrier more effectively than systemic chemotherapy. Typically, cancer cells make proteins that protect the cells from the body’s natural immune system. These medications prevent these cancer-protective proteins from working properly. This allows the patient’s body to recognize the cancer and use the immune system to fight the cancer on its own. Patients may be tested for certain immune system proteins, to determine if an immunotherapy medication option may be appropriate. Although these medications are new, they are improving outcomes in patients with lung cancer metastasis to the brain.

Pseudoprogression

After beginning immunotherapy treatment, brain metastases can appear to increase in size/shape or number. This is referred to as pseudoprogression. This is not due to the progression of the disease, but is rather part of how the drug works. This is thought to occur, in part, due to immune cells flooding to the area of the cancer and surrounding the tumor, making it appear larger. The tumor can be expected to decrease in size later on in treatment once the immune system has attacked the cancer. If new metastases appear, it is suspected that there already existed groups of cancerous cells that were just too small-scale to detect with imaging or that are now seen on a scan, surrounded by immune cells. It is important to distinguish this pseudoprogression from true progression, which would signal that the immunotherapy is ineffective.

Surgery

Surgical removal of the tumor, if possible, is often part of initial treatment. This could mean removing the whole tumor, or just a part of it. The location, number, and shape/size of the tumors determines if surgery is a viable option. In some instances, a partial tumor removal can help improve quality of life by decreasing symptoms. If the tumors are small and the patient is not experiencing symptoms, surgery may not be needed. Surgery is typically followed by radiation or medications to prevent recurrence.

Palliative Care

Palliative care refers to symptom management with the goal of increasing a patient’s quality of life. This type of care is often thought to be the same as end-of-life care, however, palliative care can be started at any time during disease progression. Appropriate symptom management improves patients’ lives and survival time.

Lung Cancer Life Expectancy with Brain Mets

Lung cancer is still the leading cause of cancer-related death. Once it has metastasized to the brain, the lung cancer life expectancy is typically less than one year. However, as our knowledge of the disease and its treatment options improve, so does the outlook on survival.  Advancements in diagnostic tools have led to earlier detection of lung cancer and brain metastases. Changes in surgical and radiation techniques are becoming more tumor-specific. Targeted therapy and immunotherapy also provide individualized treatment options and are becoming more widely used, leading to overall better survival.

The Graded Prognostic Assessment is a tool used to help estimate median survival time. This tool considers several factors. Cancer type, patient’s age, patient’s functional impairment, the presence of metastases outside the brain, number of brain metastases, and presence of gene mutations and immune system proteins, help to estimate a patient’s prognosis. It is important to remember, however, that this is just an estimate. Every individual’s cancer will respond differently. Advancements in genetic testing bring us closer to being able to tailor treatment plans to each individual patient most effectively.

Lung cancer with brain metastasis can be a scary diagnosis to receive. There are many resources and online communities available to help patients get the information they need and connect with others who may have received similar diagnoses.

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