BRAIN TUMORS: TYPES, CAUSES, AND EMERGING TREATMENTS

Medically Reviewed by Dr. Sony Sherpa (MBBS)

Brain tumors are irregular growths in the brain or surrounding tissues. They are either benign (non-cancerous) or malignant (cancerous) and can affect people of all ages. This article briefly touches upon the different types and classifications of brain tumors, their causes, available treatments, and the latest emerging options. 

Types and Classifications of Brain Tumors

Brain tumors can be classified depending on their location, the type of cells involved, and whether they are primary or secondary tumors.

Primary vs. Secondary Tumors

Brain tumor classifications fall into either primary or secondary.

• Primary brain tumors initially develop in the brain or tissues within the cranium. These are more common than secondary tumors.
• Secondary tumors are metastatic cancers that have spread from tumors in other parts of the body to the brain. As with secondary tumors, brain tumors can also metastasize and spread to other parts of the body.

Benign and Malignant

Benign brain tumors are non-cancerous and grow gradually, whereas malignant tumors are cancerous and can grow and spread quickly. Malignant tumors are more harmful as they can infiltrate and damage tissues within reach and can also spread to other parts of the body.

More than 50% of all brain tumors are malignant at the time of diagnosis.^[1]

Common Types of Brain Tumors

Some of the most diagnosed types of brain tumors include:

• Gliomas are tumors originating in the glial cells, which support and shield the nerve cells in the brain. They can occur in almost any area of the brain.^[2] Glioblastomas are the most aggressive type of glioma. Other types include:
  • Astrocytomas are brain tumors that derive from astrocytes.
  • Ependymomas arise from the ependymal cells found in the brain’s ventricles.
  • Oligodendrogliomas originate from oligodendrocytes, which produce the protective covering of nerve cells.
• Meningiomas are tumors that form in the meninges, the protective gland-like layers covering the brain and spinal cord. They are usually benign and slow-growing^[3] but can lead to symptoms if they grow extensively enough to press on the brain. Common types can result in problems with movement, speech, and sight.^[4]
• Schwannomas are tumors that grow in the cells that are a part of the protective covering of the nerves (the myelin sheath). They are usually benign and can occur in different brain parts, including the nerves that control hearing and balance. Vestibular schwannomas (also called acoustic neuromas) are the most prevalent type, affecting the auditory nerve.^[5]
• Pituitary tumors originate and develop in the pituitary gland, which releases hormones that regulate many bodily functions. Most pituitary tumors are benign yet may cause hormonal imbalances, Cushing syndrome, hyperthyroidism, reproductive issues, and vision problems.^[6]
• Choroid plexus tumors develop in the cells that line the brain's ventricles and those that produce cerebrospinal fluid, which envelops the brain and spinal cord. They are more common in children^[7]. These often result in hydrocephalus if not treated promptly, leading to an increase in brain fluids and pressure.
• Pineal tumors materialize in the pineal gland, which secretes the hormone melatonin to regulate sleep^[8]. They can block cerebral spinal fluid flow, leading to increased intracranial pressure (hydrocephalus). They may also cause hormonal imbalances and sleep disturbances due to their location.
• Medulloblastoma tumors are the most common type of brain tumor in children before the age of ten^[9]. They develop in the cerebellum, which is responsible for balance and coordination, and can be malignant.
• Skull base tumors develop in the bones at the base of the skull^[10]. These can cause headaches, facial numbness, and difficulty swallowing, amongst other symptoms.
• Nerve tumors can develop in any of the nerves in the brain and can be benign or malignant. They lead to hearing loss, balance problems, and facial weakness.

Other types of brain tumors include:

• Brain lymphomas are a type of Hodgkin's Lymphoma that spreads from the lymphatic system to the brain.^[11]
• Germ cell brain tumors originate from cells that form eggs in ovaries or sperm in testicles during fetal development. These cells can become stuck in the brain^[12], leading to intracranial germ cell tumors.
• Embryonal tumors are rare and usually occur in children. Similar to germ cell brain tumors, these develop in the brain from embryonic cells that never fully developed in utero.^[13]

Grading System

Brain tumors are also categorized following their grade, which demonstrates how aggressive they are and how likely they are to grow and spread rapidly.^[14]

The grading system ranges from grade I (slow-growing) to grade IV (fast-growing).

• Grade I brain tumors: slow-growing and less likely to spread
• Grade II brain tumors: infiltrative and may recur
• Grade III brain tumors: malignant and can grow rapidly
• Grade IV brain tumors: aggressive with a high likelihood of recurrence

Grade I and II tumors are often thought of as low-grade tumors, which comprise cells that are more similar to normal cells.

The remaining grades III-IV are high-grade tumors. The high grade indicates fast-growing tumors with abnormal-looking cells that are more aggressive.

How Common are Brain Tumors?

Approximately 6 in every 100,000 people who receive a brain tumor diagnosis in the United States are living with a primary brain tumor, and around 80,000 new cases are diagnosed each year. A quarter of all cases are gliomas.

Brain tumors can occur in individuals of all ages, but they are more common in older adults.^[15]

What are the Common Brain Tumors in Children?

Brain tumors are the most frequently seen type of solid tumor in children^[16]. These include:

• Medulloblastoma
• Astrocytoma
• Choroid plexus papilloma
• Ependymoma
• Germ cell tumors
• Brainstem glioma
• Craniopharyngioma

Brain Tumor Survival Rate

The survival rate for brain tumors varies in accordance with the type, location, and stage of the tumor. According to the US National Brain Tumor Society, the 5-year overall survival rate for brain tumors is around 36%^[17]. This number varies significantly depending on the tumor type and other factors.

How Long Can You Live with a Benign Brain Tumor?

The survival rate for benign brain tumors is generally higher than that of malignant tumors. However, the prognosis depends on the type and site of the tumor. Some benign tumors may not require treatment and can be monitored over time, while others may require surgery or other treatments.

What Causes Brain Tumors?

The actual cause of brain tumors is unknown and frequently multi-factorial.

Researchers have pinpointed some risk factors that raise the likelihood of acquiring a brain tumor^[18]. These include:

• Radiation exposure, including from radiotherapy, CT scans, X-rays, and frequent flying^19]
• Family history of brain tumors
• Certain genetic conditions, such as Turner syndrome, tuberous sclerosis, and MEN1 (Multiple endocrine neoplasia type 1)^[20]
• Age (brain tumors are more prevalent in older adults)
• Gender (depending on the tumor type)

Does Chicken Pox Lower the Risk?

Interestingly, having chickenpox as a child may reduce the odds of contracting a brain tumor later in life. This is because the virus that causes chickenpox can also attack and kill cancer cells.

One study suggests that those with childhood chickenpox may have a reduced risk of glioma by as much as 21%.

Symptoms of Brain Tumors

The most common symptom of brain tumors is frequent headaches. They often resemble migraines or tension headaches.

Many other symptoms can present themselves depending on the tumor size, type, and site.

Front of the brain (Frontal Lobe: thinking, movement, personality)

• Changes in personality, behavior, or mental status (confusion, memory problems, mood swings)
• Weakness or numbness (especially on one side of the body)
• Speech difficulties (finding words, slurred speech)
• Seizures (may be a generalized seizure)

Middle of the brain (Temporal Lobe, Parietal Lobe: senses, language)

• Vision problems (blurry vision, loss of vision in specific areas)
• Seizures (may involve strange sensations or unusual behaviors)
• Speech/Language problems (difficulty understanding or producing words)

Back of the brain (Occipital Lobe: vision, Cerebellum: balance)

• Vision problems (the primary symptom)
• Difficulty with balance or coordination
• Headaches (may be worse at the back of the head)

The lower part of the brain (Brainstem: vital functions, connection to spinal cord)

• Nausea and vomiting (especially unexplained)
• Headaches
• Difficulty with balance and coordination
• Weakness or sensation loss in the extremities (can be on one side or both sides of the body)
• Speech difficulties
• Vision problems

Other Symptoms

• Difficulty concentrating
• Changes in appetite
• Fatigue
• Sleep disturbances

How Long Before Brain Tumor Symptoms Show?

The time it takes for symptoms to present can vary. Some tumors may cause symptoms within a few weeks, while others may not cause symptoms for months or even years.

Early vs. Late-Stage Symptoms

Early-stage symptoms of a brain tumor may be subtle and easily overlooked. As the tumor grows, symptoms may become more severe and noticeable. Pay attention to any changes in your body and seek medical attention if you experience any of the above symptoms.

What are the Red Flags of a Brain Tumor?

Some red flags that may indicate a brain tumor include:

• More severe or frequent headaches than usual
• Headaches that are worse in the morning or wake you up at night
• Headaches along with nausea, vomiting, vision problems, or other severe symptoms
• Seizures
• Changes in vision, speech, or hearing
• Weakness or sensation loss in the arms or legs
• Sudden shifts in mood or behavior

Brain Tumor Diagnosis

During the initial consultation, a medical professional will conduct a sweeping medical history, physical examination, and neurological evaluation to assess the function of the brain and nervous system. These initial steps are crucial for gathering essential information and identifying potential symptoms.

If you are experiencing symptoms that indicate a brain tumor, a practitioner will perform a series of tests to diagnose the tumor. These may include:

• Imaging tests (CT, PET, and MRI) to determine the tumor's location and size.
• Biopsy to ascertain crucial information about the type and grade of the tumor.
• Blood tests to assess general health and screen for specific tumor markers.
• Spinal tap (lumbar puncture) to analyze the cerebrospinal fluid for any abnormal cells or signs of infection.

Recently, advancements in technology and research have led to significant innovations in the diagnosis of brain tumors. Traditional methods like surgical biopsy, while effective, carry risks and may not always provide comprehensive insights into tumor biology. New, minimally invasive approaches are emerging, offering faster, more precise diagnostic options that can guide personalized treatment plans. These developments, including liquid biopsies, artificial intelligence (AI) applications, and novel therapeutic combinations, are set to revolutionize how clinicians detect, monitor, and manage brain tumors, ultimately improving patient outcomes.

Liquid Biopsy

A minimally invasive diagnostic technique, liquid biopsy detects tumor-related genetic and molecular markers from a simple blood sample or other bodily fluids. By identifying circulating tumor DNA (ctDNA), RNA, and proteins shed by tumor cells, liquid biopsies can offer valuable insights into tumor genetics and progression without requiring a traditional surgical biopsy. For brain tumors, liquid biopsy holds promise in improving early diagnosis, monitoring treatment response, and detecting tumor recurrence. Research is ongoing to refine this technique, with goals to enhance its sensitivity and specificity for identifying brain tumor markers in the bloodstream or cerebrospinal fluid, which are often in very low concentrations.^[21]

Artificial Intelligence (AI) and Predictive Modeling

AI and predictive modeling are transforming the diagnostic landscape for brain tumors. Advanced AI algorithms can analyze medical images, such as MRI and CT scans, to accurately identify tumor characteristics, predict tumor types, and assess disease progression with remarkable speed and accuracy. Predictive modeling using AI can also assist clinicians in treatment planning by forecasting patient outcomes and identifying the best treatment approaches based on the tumor’s molecular and genetic profile.^[22]

Treatment Options

Brain tumor treatments vary from tumor to tumor and according to the individual's overall health^[23]. Some standard treatment options include:

Surgery

Surgery is oftentimes the first type of treatment for brain tumors. The goal is to remove as much of the tumor as possible without damaging any surrounding healthy brain tissue.

Some typical surgical procedures for brain tumors include:

• Craniotomy involves removing a portion of the skull to provide access to the brain and remove the tumor.
• Endoscopy entails placing a tiny camera through a small incision. It is a minimally invasive procedure to view and remove the tumor.

Radiosurgery

Radiosurgery is a non-invasive procedure that utilizes high quantities of radiation to target and destroy the tumor. After the tumor is mapped out with imaging techniques, such as MRI assistance, a device is used to target the tumor with high-energy radiation.

Some common types of radiosurgery include:

• Linear accelerator radiosurgery uses a machine called a linear accelerator to deliver high-energy radiation to the tumor.^[24]
• Gamma Knife radiosurgery targets the tumor from several angles using numerous radiation beams.^[25]
• Proton radiosurgery uses proton beams to target and destroy the tumor^[26]. This type of radiosurgery may be safer because it offers less radiation exposure.

Chemotherapy

Targeted medications are used in chemotherapy to eradicate cancer cells. For brain tumors, it is often used in combination with other therapies.

Commonly deployed chemotherapy drugs used to treat brain tumors include^[27]:

• Temozolomide
• Carmustine
• Individual or combined use of chemo drugs, procarbazine, lomustine, and vincristine
• Methotrexate
• Cisplatin

Brachytherapy

Brachytherapy (internal radiation therapy) involves placing radioactive material directly into or near the tumor to destroy it. It is usually carried out daily to weekly for several weeks.

Symptom Management

A key component of the overall brain tumor treatment strategy is symptom management. To help alleviate symptoms, various treatments are available:

• Medications, such as mannitol and corticosteroids, are prescribed to reduce swelling around the tumor and provide relief from pain, seizures, and other symptoms.
• Shunts may be recommended to improve the flow of cerebrospinal fluid and alleviate symptoms caused by increased intracranial pressure.
• Palliative care, focused on bettering the quality of life, provides comprehensive support for individuals experiencing physical, emotional, and psychological challenges throughout their journey.^[28]

By effectively managing symptoms, individuals with brain tumors can experience increased comfort and a better overall quality of life. It is important to work closely with a neuro-oncologist to ensure an optimal individualized treatment approach that considers each individual's needs and concerns.

Recovery

The recovery process has several common components: physical therapy, speech therapy, and occupational therapy. Each of these can help to strengthen skills lost due to having the tumor or undergoing surgery.^[29]

Emerging Therapies

Researchers are relentlessly working on novel and innovative treatments for brain tumors.

For instance, targeted therapy aims to target specific molecular (through molecular profiling) or genetic alterations present in tumor cells that drive tumor growth. Gene therapy, on the other hand, modifies the genetic material within cells to correct or replace faulty genes that contribute to tumor growth. This therapy is also used to enhance tumor drug uptake, making it more susceptible to destruction.^[30]

Other emerging therapies include:

Oncolytic Viruses

Oncolytic virus therapy uses genetically engineered viruses to selectively infect and eradicate cancer cells while leaving healthy cells unharmed. These viruses replicate within tumor cells until they burst, releasing more viruses to target nearby cancer cells. Additionally, this therapy stimulates the immune system, helping it recognize and attack tumor tissues more effectively. Current research focuses on refining virus specificity to avoid affecting non-tumor cells, reducing any associated toxicity, and combining oncolytic viruses with other immunotherapies, such as immune checkpoint inhibitors, to create a synergistic treatment effect that could improve outcomes for brain tumor patients.^[31]

CAR-T Cell Therapy

Chimeric Antigen Receptor T-cell (CAR-T) therapy is an advanced immunotherapy that involves engineering a patient’s own T-cells to recognize and destroy cancer cells. For brain tumors, researchers modify T-cells to target specific antigens expressed on the tumor surface. CAR-T therapy has shown success in treating certain blood cancers, but applying it to brain tumors presents challenges, including the blood-brain barrier that limits immune cell access to the brain, as well as the tumor's immune-suppressive environment. Studies are now focused on overcoming these barriers by improving CAR-T cell persistence, optimizing the targeting of specific tumor antigens, and finding methods to support T-cell infiltration within brain tumors.^[32]

Immunotherapy

Immune checkpoint inhibitors are designed to block certain proteins, such as PD-1/PD-L1 and CTLA-4, which tumors exploit to evade the immune system. By inhibiting these checkpoints, these therapies re-enable the immune system to recognize and fight cancer cells. Though successful in treating various cancers like melanoma and lung cancer, applying checkpoint inhibitors to brain tumors has shown mixed results due to challenges such as the immune-suppressive microenvironment of brain tumors and the blood-brain barrier. Researchers are exploring combinations of checkpoint inhibitors with other therapies, such as radiation or oncolytic viruses, to enhance their efficacy against brain tumors.^[33]

Focused Ultrasound (FUS)

Focused ultrasound (FUS) is a non-invasive technology that directs high-frequency sound waves to specific areas within the brain, temporarily disrupting the blood-brain barrier. This disruption allows for enhanced delivery of drugs directly to the brain tumor site, which could significantly improve the effectiveness of chemotherapy, immunotherapy, or gene therapy. FUS is also being studied in combination with other treatments to increase their penetration and action in the brain, and current research is aimed at identifying the optimal frequency and duration of FUS application to maximize drug delivery while minimizing potential side effects.^[34]

Targeted Alpha Therapy (TAT)

Targeted alpha therapy (TAT) uses alpha-emitting isotopes that are highly effective at killing cells in a very localized area. These alpha particles deliver high-energy radiation directly to the cancer cells while sparing nearby healthy cells due to their limited travel range, potentially making TAT particularly suited for cancers with well-defined boundaries. TAT has shown promise in treating cancers like prostate cancer, and researchers are now investigating its application for brain tumors by identifying suitable carriers and delivery methods to ensure the alpha particles reach the tumor cells effectively without affecting surrounding brain tissues.^[35]

Burst Sine Wave Electroporation

This technique involves the application of electric pulses in a specific burst sine wave pattern, which temporarily increases the permeability of tumor cell membranes. By doing so, it enhances the uptake of anti-cancer drugs directly into tumor cells, making treatments like chemotherapy more effective against brain tumors. In animals, burst sine wave electroporation has been shown to have a positive effect in allowing drugs to pass through the restrictive blood-brain barrier, and research is ongoing to determine the best parameters for its use in enhancing treatment efficacy while minimizing damage to surrounding tissues.^[36]

Antidepressant (Vortioxetine)

Vortioxetine, an antidepressant typically used for major depressive disorder, has shown unexpected promise in preclinical studies for brain tumors. Its mechanism may involve targeting specific pathways associated with tumor growth and survival, particularly those that overlap with pathways affecting serotonin, a neurotransmitter linked to both mood and cellular signaling. This repurposing of vortioxetine could offer a novel, cost-effective approach for brain tumor treatment, though further clinical studies are needed to confirm its effectiveness and clarify its action against tumor cells.^[37]

Conclusion

Understanding brain tumors, their types, causes, and treatments is crucial. Advancements in targeted therapies, immunotherapy, and gene therapy offer hope for improved outcomes. Recovery from brain tumor treatment involves physical therapy, occupational therapy, and speech therapy. With early detection and a comprehensive treatment plan, hope for a brighter future exists.

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