Brain Tumors

October 29, 2013

Disclaimer:

The information provided in this review is intended for general informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition. Feel free to share this information page with them.

Cancer Localization:

Brain, Eye.

Biology:

A brain tumor is an abnormal growth of cells in the brain or the eye. It can be a primary tumor which originates in the brain, or a secondary tumor which spreads to the brain from somewhere else in the body. Brain tumors can arise from different cell types in the brain, including neurons, which send signals throughout the brain, and glial cells, which support and protect the neurons.

Characteristics:

Brain tumors are the second most common type of cancer in children, after leukemias. Most pediatric brain tumors are diagnosed from the ages 1 to 9. The cause of brain tumors is unknown, although genetic and environmental factors are believed to contribute to their development.

Main Types of Brain Cancer:

There are many different types of brain tumors, which can be broadly categorized by cell type, location, and tumor name.

Cell types: Brain tumors are named based on the tye of cells they originate from. For example, tumors can develop from cells like astrocytes (support cells), ependymal cells (cells that line the spaces in the brain), or neurons.
Location: Brain tumors can develop in different parts of the brain. For example, the cerebrum, brainstem, cerebellum and the optic nerve.
Tumor name: Tumor names often reflect the origin of the tumor’s behavior. For example, gliomas (glial cells) and meningiomas (the meninges). Other common terms include blastomas, where tumors originate from developing cells, carcinomas from epithelial tissues and sarcomas from connective tissue.

A tumor’s name may combine its cell type, location, or both. Some common types of pediatric brain tumors include:

Brainstem Glioma: A glioma located in the brainstem
Medulloblastoma: The most common type of brain tumor in children, typically starting in the brainstem
Optic Glioma: A glioma that affects the optic nerve, potentially impacting vision
Cerebral Astrocytoma: A tumor arising from astrocytes located in the cerebrum
Atypical Teratoid/Rhabdoid Tumors (ATRT): Rare and aggressive tumors primarily found in the cerebellum or brainstem.

Note: Understanding the specific type of brain tumor helps guide treatment and prognosis.

Common Mutations in Brain Cancer:

Histone Gene Mutations: Histone genes help with organizing and packaging DNA in our cells. Mutations in the H3F3A gene are commonly found in pediatric glioblastomas. By disrupting histone function, the DNA is improperly packed inside cells and changes happen to which genes are turned off and on. This disruption can lead to the growth of tumors.
TP53 Mutations: TP53 is a critical “tumor suppressor” gene, responsible for regulating cell growth and responding to DNA damage, and it is frequently mutated in pediatric gliomas. The TP53 gene is mutated in 35-60% of malignant gliomas.
BRAF Mutations: Mutations in the BRAF gene, including gene fusions and a “V600E” mutation, are found in various pediatric brain tumors.
FGFR1 Mutations: Mutations that lead to overactivation of the FGFR1 gene promotes uncontrolled cell division and growth. Activating mutations in the FGFR1 gene have an incidence of 6% in pediatric gliomas.

Childhood Brain Cancer Noticeable Symptoms:

Note: Symptoms of brain cancer in children can vary depending on the tumor’s location, size, and type. The unique biology of the tumor can also influence the symptoms.

In infants, growing brain tumors can put pressure on nearby areas of the brain, which can lead to symptoms like headaches and nausea. In older children, the increased intracranial pressure can also lead to changes in vision, balance problems, difficulty speaking, and/or seizures. A fuller soft spot on the skull is sometimes seen in babies.

Childhood Cancer Diagnostic Methods

CT scans (computed tomography), MRI (magnetic resonance imaging), biopsy, lumbar puncture.

The diagnostic process often starts with a thorough neurological exam which assess the child’s reflexes, vision, muscle strength, and coordination, to check for any irregular functions of the nervous system.
After the neurological workup one can typically expect imaging, which provides detailed images of the child’s brain, which aids in identifying tumors and determining their size, type, and specific location.
If imaging identifies a tumor, a biopsy (removing a small amount of the tumor to be examined under a microscope) is taken from the child to determine whether a tumor is benign or malignant, and to inform what kind of treatment is needed.
A Lumbar puncture may also be performed after a biopsy, to determine if the cancer has spread outside of the brain.

These common diagnostic steps altogether help provide a detailed picture of the child’s cancer and can guide the treatment stages.

Childhood Cancer Treatment:

Surgery, radiation therapy, chemotherapy, immunotherapy, biopsy, and laser interstitial thermal therapy.

Surgery

Surgical removal is the most important step of treating pediatric brain tumors. Complete surgical resection of a tumor is associated with better survival outcomes. In pediatric brain cancer patients, a recent study found that total resection of tumors was associated with a 1- and 2-year survival rate of 69% and 74%, respectively, compared to 56% and 67% for patients with subtotal resection of tumors.
A tumor’s location can significantly impact the feasibility of total surgical removal. New technology has been developed that equips surgeons with novel minimally invasive ways to approach and remove pediatric brain tumors.

It’s important to note that a complete removal of the tumor is sometimes not possible because of the tumor location and concerns about damaging the surrounding normal brain tissue. The expertise of the neurosurgeons is critical in this context.

Radiation therapy

Radiation therapy is frequently used after surgery, especially if complete tumor resection is not possible.
External beam radiation therapy, conformal beam radiation and proton therapy precisely target brain tumor cells while minimizing exposure of healthy brain cells to radiation.

Note: The importance of precision in radiation delivery for pediatric brain cancers cannot be overstated, as children’s brains are still developing at these young ages, and improperly targeted radiation can interfere with healthy growth and cause long-term neurological deficits.

Newer technologies like stereotactic radiosurgery (SRS) allows for more precise targeting of tumors, delivering high-dose radiation to tumor sites while minimizing exposure to adjacent healthy brain cells.

Chemotherapy

The role of chemotherapy in pediatric brain tumor treatment is dependent on the tumor type and grade. For low-grade gliomas, complete surgical resection of a tumor is preferred over chemotherapy and is often curative on its own.
Greater extent of surgical tumor removal has been shown to improve overall survival rates and delay time to malignant cancer transformations in low-grade gliomas.
In high-grade gliomas and other aggressive tumors where complete surgical removal is challenging, chemotherapy is an important therapeutic option. Research into more targeted chemotherapies that minimize damage to healthy brain cells is ongoing.

Immunotherapy

Note: Immunotherapy is an emerging treatment option for pediatric brain tumors, with promising results but in need of further research.

While there is potential for immunotherapy, it is not yet a standard treatment and primarily is available through clinical trials. Immunotherapy may be used in combination with surgery, chemotherapy, and/or radiation in these clinical trials.
Pembrolizumab and nivolumab are being studied in pediatric brain cancer patients with medulloblastomas and Some early evidence of tumor regression has been observed.
Recent advances in neuroimaging have identified new molecular targets for immunotherapy, however drugs for these new targets have not yet been designed.
CAR-T cell therapy has been successful in some pediatric cancers, and its potential for pediatric brain tumors is being investigated.

Biopsy

A biopsy can be critical for confirming a tumor’s type and guiding treatment plans, especially if diagnosis is unclear or the tumor is in a location difficult to access surgically. A biopsy is not always necessary.
A biopsy can reveal key details about the tumor’s genetic makeup, which will be increasingly important for immunotherapies and other targeted therapies.

Note: It is important to be cautious with brain biopsies in infants because of their developing brains.

Laser Interstitial Thermal Therapy (LITT)

LITT is an emerging minimally invasive treatment option for pediatric brain cancer patients with deep brain tumors, particularly low-grade gliomas. When surgery is difficult, LITT can use directed heat to shrink the tumor mass. LITT is a popular option when conventional surgical removal poses high risks or has been attempted unsuccessfully.
A 2019-2022 study involving six pediatric brain tumor patients suggest that LITT can significantly reduce tumor size, with lasting effects. In this study, LITT was associated with a low incidence of unforeseen complications, and neurological function was largely maintained post-treatment.

Late Effects of the Treatment:

While treatments for pediatric brain tumors have significantly improved survival rates, they have the potential to cause lasting side effects. Long-term unwanted effects can vary based on the treatment used, the child’s age, and the tumor’s location. Prior to treatment, your child may undergo neuropsychological testing.

Follow-up, Late Effects:

Routine follow-up imaging, including MRI and CT scans, is recommended for up to 10 years post-treatment to monitor for tumor recurrence. Imaging surveillance can identify tumor recurrence before the onset of patient clinical symptoms. Hearing and vision testing may also be monitored to look out for late unwanted effects of cancer treatment.

The Main Goals Include:

Preserve the patient’s life.

Additional Treatment Options (examples):

Metformin:

Primarily used for diabetes management, metformin alters cell metabolism and suppresses brain tumor cell growth. Metformin is not FDA-approved for brain tumor treatment; however, studies have shown it is safe to use and tolerable in pediatric brian cancer patients. Metformin is often used off-label by physicians to potentially reduce the growth of pediatric brain tumors. Further clinical trials are needed to better understand effects.

Dexamethasone:

A steroid used to reduce inflammation, dexamethasone may help reduce swelling in the healthy tissue surrounding brain tumors. This could help alleviate headaches, nausea, and other symptoms caused by increased pressure in the brain.
Dexamethasone is clinically used to help manage symptoms during radiation therapy, or as a supplement to surgery pre- and/or post-operation.

Anticonvulsants:

Anti-seizure drugs levetiracetam and/or valproate may be used to manage epilepsy in pediatric brain tumor patients. Seizures are a relatively common side effect in pediatric brain cancer patients, especially in gliomas or other tumors located in seizure-prone areas of the brain.
Anticonvulsants may be used for seizure prevention and/or seizure management.

Review of Options Currently in Clinical Trials:

ReSPECT-PBC (Pediatric Brain Cancer) Clinical Trial – Plus Therapeutics is developing the Rhenium (186Re)0 Obisbemeda radiotherapeutic for the treatment of rare, fast-growing pediatric brain and spinal cord. Patients with ependymomas and high-grade gliomas are eligible, note however that they must have a poor prognosis. The ReSPECT-PCB U.S. Phase 1 clinical trial began in 2025 and recruitment is active and ongoing, for patients with documented disease progression. Please see the link for more details: https://www.respect-trials.com/pediatric-brain-cancer/
NCI-COG pediatric MATCH (National Cancer Institute – Children’s Oncology Group) Clinical Trial – Offered at about 200 children’s oncology group sites, the NCI-COG MATCH trial is testing the use of precision medicine for childhood solid tumors, including brain tumors. If your child is not responding to treatment, this trial would assign the child to an experimental treatment based on the genetic changes found in their tumors rather than by the type of cancer or the cancer site. Please see the link for more details: https://www.cancer.gov/research/infrastructure/clinical-trials/nci-supported/pediatric-match