Atypical teratoid rhabdoid tumor (ATRT)

Atypical teratoid rhabdoid tumor (ATRT) is a very rare, fast growing cancer that starts in the brain or spinal cord. It's a cancerous type of brain tumor. Cancerous tumors also are called malignant tumors.

The World Health Organization (WHO) classifies ATRT as a grade 4 tumor, which means it's aggressive and tends to grow and spread quickly. ATRT is grouped into three molecular types: ATRT-TYR, ATRT-SHH and ATRT-MYC.

ATRT happens mainly in very young children, usually under age 3. But it also can occur in older kids, teenagers and, very rarely, adults.

ATRT can form in different parts of the central nervous system. Common areas include the cerebellum and the brain stem. The cerebellum helps with balance. The brain stem controls breathing and heart rate. ATRT also can occur in the spinal cord.

Treatment usually includes surgery to take out as much of the tumor as is safely possible. Then medicine called chemotherapy is used. Depending on age and whether the tumor has spread, radiation therapy may be added.

Outcomes vary by age, stage and treatment plan. Survival tends to be better for children age 3 or older when the tumor has not spread and when aggressive therapy is possible. Survival is lower for babies and when there is spread at diagnosis.

Types

Researchers have found that ATRT is not a single disease. There are three main molecular ATRT types based on gene activity: ATRT-TYR, ATRT-SHH and ATRT-MYC.

• ATRT-TYR usually affects babies younger than 1 year of age. It tends to form in the back of the brain and may spread through the spinal fluid.
• ATRT-SHH tends to occur in toddlers around 2 years old. It can occur in the upper or lower part of the brain. It shows activity in a cell signaling pathway called the sonic hedgehog (SHH) pathway. The signals in this pathway control how brain cells grow and develop.
• ATRT-MYC is more common in older preschoolers and school-age children but sometimes happens in adults. It tends to form in the upper part of the brain and may grow more quickly than the other types. Median age at diagnosis is about 27 months, with many diagnoses made at age 3 or older.

These types of ATRT help researchers study which treatments work best for each type. In the future, this information may help guide care and improve survival.

Symptoms of atypical teratoid rhabdoid tumor (ATRT) depend on the tumor's size and where it forms in the brain or spinal cord. Because ATRT grows quickly, symptoms often appear suddenly and worsen over days or weeks.

Common signs of ATRT include:

• Headaches that are often worse in the morning.
• Nausea or vomiting.
• Trouble with balance, walking or coordination.
• Changes in behavior or activity level.
• Unusual sleepiness or irritability.
• Seizures.
• Weakness or loss of movement in part of the body.

When ATRT affects the spinal cord, it can cause back pain, weakness in the legs, or changes in bladder or bowel function.

Symptoms in babies

In babies, symptoms can be harder to see. Parents may notice rapid head growth or a bulging soft spot on top of the head. Babies may become unusually sleepy or fussy or not have much appetite. Vomiting, poor head control, or sudden eye or limb movements also can occur.

Because babies cannot describe pain or headaches, physical signs such as increased head size, slowed development or changes in alertness are important clues.

Symptoms in children

In older infants and young children, ATRT often causes changes in mood or coordination. A child may become clumsier, lose balance, or have new trouble walking or using one side of the body. Headaches, nausea and vomiting also are common.

Some children have vision changes, facial weakness or crossed eyes if the tumor presses on the nerves that control eye or face muscles. Others may develop seizures or loss of appetite.

Can ATRT be detected early?

ATRT is difficult to detect early because it grows fast and symptoms often resemble common childhood illnesses. There is no routine screening test for ATRT. Most tumors are found after children show signs of the condition and have imaging such as MRI.

Families with a known SMARCB1 or SMARCA4 gene change may have regular checkups or imaging as part of genetic counseling or surveillance plans.

When to seek care

Because ATRT grows quickly, contact your child's care team as soon as symptoms appear or change. Seek medical attention right away if a child has symptoms such as persistent headaches, vomiting, or trouble with balance, walking or coordination.

Reach out if a baby's head size increases faster than expected or the soft spot bulges. Other warning signs include new seizures, sleepiness that is not typical and weakness on one side of the body.

These symptoms can have many causes, but sudden or worsening changes need prompt exam. If ATRT or another serious condition is suspected, imaging such as an MRI can help find the cause and guide next steps.

ATRT is one of many types of pediatric brain tumors. It develops when certain genes that control how cells grow and divide stop working. When these control signals break down, cells in the brain or spinal cord can grow out of control and form a tumor.

The genes most often affected are SMARCB1 and SMARCA4. They help cells make a protein that keeps growth in check. When one of these genes is missing or damaged, the protein is not made correctly. Then cells divide too fast and become cancerous.

Most ATRTs are linked to changes in genes that control how cells grow. In most tumors, the SMARCB1 gene, also called INI1, stops working. A smaller number affect the SMARCA4 gene. Some people are born with a change in one of these genes in all their cells. This raises the chance of rhabdoid tumors and is called rhabdoid tumor predisposition syndrome.

Most of these gene changes happen by chance after birth and are not passed down from parents. But in some people, the change is inherited and present in every cell of the body. That inherited form increases the risk of ATRT and other rhabdoid tumors.

Experts do not know why these gene changes occur in most people with ATRT. The tumors are not caused by injury, diet or environmental factors. Nothing a parent did or did not do causes the tumor to form.

ATRT can affect anyone, but it happens most often in very young children. Most tumors occur before age 3. ATRT is rare in older children and extremely rare in adults.

The condition affects all genders in similar numbers. There is no known link to lifestyle, environment or family habits.

Some people are born with a change in one of two genes called SMARCB1 and SMARCA4. The change can increase the risk of developing ATRT or a related tumor. This increased risk is called rhabdoid tumor predisposition syndrome.

ATRT in adults

Adult cases are extremely rare and make up only a small fraction of all ATRT diagnoses. When ATRT appears in adults, it often develops in the upper part of the brain and causes headache, seizures or weakness. Treatment follows the same general approach as in children, with surgery, chemotherapy and radiation.

ATRT can cause serious complications because it grows quickly and can spread through the fluid that surrounds the brain and spinal cord. This spread, called metastasis, makes treatment more complex and can lower survival rates.

The tumor itself can increase pressure inside the skull, leading to headaches, vomiting or changes in alertness. If it blocks the typical flow of cerebrospinal fluid, hydrocephalus can occur and may require surgery to relieve pressure. Hydrocephalus is a buildup of fluid in the brain.

Treatment for ATRT also can lead to complications. Surgery, chemotherapy and radiation can affect thinking, growth or hormone function, especially in very young children. These side effects may appear months or years after treatment ends.

Even after successful treatment, ATRT can come back. This is called recurrence. It often happens within the first few years after diagnosis, so regular follow-up imaging is important.

Because the brains and bodies of very young children are still developing, treatment-related late effects, such as changes in learning, growth or hormone levels, may appear years later.

There is no known way to prevent ATRT. Most tumors happen without any warning or family history.

Because ATRT is linked to changes in the SMARCB1 or SMARCA4 genes, some families may choose genetic counseling. This can help identify whether a child or relative carries a gene change that increases the chance of developing a rhabdoid tumor.

If a gene change is found, regular checkups and imaging may help detect any tumors early. These steps cannot prevent ATRT but can allow care teams to start treatment sooner.

ATRT is not caused by injury, diet or environmental exposures. Nothing a parent did or did not do causes this tumor to form.

Researchers continue to study the genetic and molecular causes of ATRT to better understand how to prevent it in the future.

ATRT is diagnosed using exams, imaging and lab tests that look for changes in the tumor's cells and genes. Because this tumor grows quickly, getting an accurate diagnosis early is important.

Diagnosis usually begins with a medical history and physical exam. The care team reviews symptoms, medical history and family history. A neurological examination checks vision, hearing, balance, coordination, reflexes and strength to see how the brain and spinal cord are working.

Tests and procedures may include:

• Brain MRI. MRI uses magnets and radio waves to make detailed pictures of the tumor's size, shape and location. An MRI may be done on the brain or the spine. An MRI with contrast helps show how the tumor interacts with nearby tissue.
• Brain CT. CT may be used if MRI is not available or to check for bone changes.
• Biopsy. A small sample of tumor tissue is removed with a needle biopsy or during surgery. Pathologists study the cells under a microscope to confirm ATRT. They also run molecular tests and determine the tumor grade. ATRT is always grade 4, which means it grows quickly and is considered aggressive. Grading happens in the lab as part of tissue analysis, not through a separate test.
• Lumbar puncture. This test is done after diagnosis to help stage the tumor. During the test, a needle is used to take a sample of cerebrospinal fluid between the bones of the spine. These bones are called vertebrae. The fluid is then studied in a lab to see whether the tumor has spread through the cerebrospinal fluid.
• Surgical resection. For many children, surgery is the first step instead of doing a separate needle biopsy. Imaging can strongly suggest ATRT, and when the tumor’s size and location make surgery possible, the team may go straight to removing the tumor. The tissue taken out during surgery is then studied in the lab to confirm ATRT. It also goes through molecular testing, which looks for changes in the tumor’s genes that help guide care.

Because imaging test results for ATRT can look like those of other brain tumors, healthcare professionals often use pathology to make a clear diagnosis. Pathology means studying a small sample of the tumor under a microscope and running special tests to look at the tumor's cells and their features. These tests show whether ATRT is present and help the care team understand how the tumor behaves.

Once ATRT is confirmed, the care team stages the tumor and discusses treatment options.

Treatment for ATRT usually includes several steps. The plan depends on the child's age, tumor location and whether the cancer has spread. Because ATRT grows quickly, treatment often starts soon after diagnosis.

Children with ATRT are often treated at specialty centers with experience in pediatric brain tumors. Care teams often include experts in neurosurgery, oncology, radiation therapy, rehabilitation and genetics.

Surgery or other procedures

Brain tumor surgery is usually the first step in treating ATRT. The goal is to take out as much tumor as safely possible without harming nearby brain tissue.

Most children have a craniotomy for tumor removal. Complete removal may not always be possible if the tumor is near vital areas that control breathing, movement or vision.

MRI after surgery

After surgery, imaging is used to see how much of the tumor remains. Usually, this is an MRI. If there is fluid buildup on the brain, also called hydrocephalus, a temporary or permanent brain shunt may be placed to drain extra fluid. A shunt is a small tube that helps move fluid from the brain to another part of the body where it can be absorbed.

Even with surgery, most children need more treatments to destroy remaining tumor cells and reduce the risk of the cancer coming back, also called recurrence.

Medicines

Most children with ATRT receive chemotherapy after surgery. Chemotherapy uses strong medicines to kill cancer cells or stop them from growing. These medicines travel through the bloodstream to reach cells that surgery cannot take out.

Many treatment plans use several medicines together in cycles. Common medicines include cisplatin, cyclophosphamide, etoposide and vincristine. High-dose chemotherapy followed by a stem cell rescue may be used for some children, especially infants, to delay or reduce the need for radiation.

Some children also may receive medicines directly into the fluid around the brain and spinal cord. This is called intrathecal chemotherapy. It helps target any tumor cells that have spread through that fluid.

Chemotherapy can cause side effects such as tiredness, nausea and low blood counts. Care teams monitor children closely and adjust doses as needed to protect healthy cells.

Therapies

Therapies for ATRT often include radiation and other treatments that help manage symptoms or side effects. The type and timing of therapy depend on the child's age and whether the cancer has spread.

Radiation therapy uses high-energy beams to destroy tumor cells. Older children and teens may receive radiation to the tumor site or, if the cancer has spread, to the brain and spinal cord. Because radiation can affect the developing brain, care teams may delay or avoid it in babies and toddlers.

Most treatment centers use proton beam therapy, which can focus radiation more precisely on the tumor and limit exposure to nearby healthy tissue. This can help reduce long-term effects on thinking, learning and growth. Proton therapy is available only at specialized centers. It may be recommended when precise targeting can reduce long-term side effects.

Rehabilitation therapy may help children recover strength, balance and coordination after surgery or radiation. Physical, occupational and speech therapy can support recovery and improve daily functioning.

Children often receive supportive therapies during and after treatment. These may include nutritional support, hearing checks, hormone testing or cognitive evaluations to monitor for late effects. Emotional and social support also are key parts of care.

Potential future treatments

Researchers are studying new medicines that target the genes and cell pathways involved in ATRT. These treatments may help when standard therapies stop working or cannot be used.

One example is tazemetostat. It is a targeted medicine that blocks a protein called EZH2. This protein helps tumor cells grow. By turning off this protein, tazemetostat may slow or stop tumor growth in cancers that have changes in the SMARCB1 gene.

Tazemetostat is still being studied in clinical trials for children and adults with ATRT and other rare tumors. It is not yet a standard treatment but may become an option in the future as research continues.

Other studies are testing new chemotherapy combinations, immune-based treatments and drugs that target the genetic drivers of ATRT.

Researchers also are testing immunotherapy, such as checkpoint inhibitors and chimeric antigen receptor (CAR-T) cell therapy, and virus-based treatments in clinical trials. These approaches are experimental and available only through studies.

There are no alternative medicines proved to treat or cure ATRT. Families who want to try natural or home remedies should talk with their care teams before starting these treatments. Some products and supplements can interfere with cancer medicines or cause side effects.

Complementary and integrative therapies may help children and families cope with treatment and recovery. These approaches work best when used with, not instead of, medical care. They can reduce stress, improve mood and support overall well-being.

Examples include:

• Music or art therapy to help children express feelings or lessen anxiety.
• Relaxation or breathing exercises to improve sleep and ease tension.
• Massage or gentle movement therapy for comfort and relaxation, if approved by the care team.
• Nutritional support to help maintain energy and strength during treatment. Nutrition support means working with a dietitian to plan meals or use special drinks or feeding formulas that meet a child's needs when eating is difficult.

Families should always tell the care team about any vitamins, herbs or supplements they plan to use. These therapies are safest and most helpful when part of an integrative care plan that supports both physical and emotional health.

Integrative care programs, such as art or music therapy and family counseling, are offered at many children's cancer centers to support emotional and physical healing.

While there are no home treatments for ATRT, families can take steps at home to support recovery and well-being during and after treatment. These steps work best when combined with the care team's plan.

• Healthy routines can help children regain strength. Offer small, nutritious meals and snacks to keep up energy. Encourage rest and gentle activity as advised by the care team. Make sure to take medicines as directed. Follow all care instructions at home.
• Emotional support also is important. Children may feel scared or frustrated during treatment. Reading, art and music can provide comfort and help with coping. Parents and caregivers also may benefit from counseling or support groups.
• Follow-up care helps track recovery and detect any new issues early. Regular appointments, imaging and lab tests are important even after treatment ends.

Contact the care team with any new symptoms, side effects or emotional concerns. Early communication helps manage concerns quickly and keeps treatment on track.

Many hospitals offer survivorship programs, rehabilitation or counseling to help families adjust after treatment and to support long-term recovery.

An ATRT diagnosis affects the whole family. Treatment can be stressful, and it's common to feel anxious, sad or overwhelmed. Support from the care team and from others who understand can make a difference.

• Stay connected with your care team. Ask the care team all of your questions. And write down questions for the care team between visits. Understanding the plan and what to expect can help families feel more in control.
• Seek emotional and practical support. Many cancer centers have child life specialists, social workers and counselors who can help with emotional needs, daily stress or financial concerns. Support groups, both online and in person, can connect families with others facing similar experiences.
• Take care of yourself. Parents and caregivers need rest, healthy food and breaks to manage stress. Accepting help from friends, family or community resources can make long treatment periods easier.
• Use supportive programs. Activities such as art, music or relaxation therapy can help children cope with hospital stays and treatment routines. Many hospitals offer these services through integrative medicine or child life programs.

Living with ATRT may feel difficult, but support, communication and connection can help you find strength and hope throughout treatment and recovery.

See your child's doctor or other healthcare professional if your child has any symptoms that worry you. If ATRT is suspected, ask for a referral to an experienced specialist in pediatric brain tumors.

Consider taking a family member or friend along to the appointment to help remember all the information provided.

Here's some information to help you and your child get ready for the appointment.

What you can do

Before your child's appointment, make a list of:

• Symptoms, including any that do not seem related to the reason for the appointment.
• Any medicines that your child is taking. Include vitamins, herbs and medicines you buy without a prescription and their dosages.
• Key personal information, including any major stresses or recent changes in your child's life.
• Questions to ask your child's healthcare team to make the most of your time.

For ATRT, some basic questions to ask include:

• Where is the brain tumor located? How large is it?
• How aggressive is the brain tumor?
• Is the brain tumor cancerous?
• Will my child need additional tests?
• What are the treatment options?
• What are the benefits and risks of each treatment?
• Can any treatments cure my child's brain tumor?
• Is there one treatment you feel is best for my child?
• Should my child see other specialists? What will that cost, and will my insurance cover it?
• Are there brochures or other printed material that I can have? What websites do you recommend?

Don't hesitate to ask other questions you have.

What to expect from your doctor

Be prepared to answer some questions about your child's medical history and symptoms. These might include:

• When did your child first begin experiencing symptoms?
• Do the symptoms happen all the time or do they come and go?
• How severe are the symptoms?
• What, if anything, seems to make your child's symptoms better?
• What, if anything, appears to worsen the symptoms?

Survival rate means the percentage of people who are alive a certain amount of time after diagnosis, usually five years.

Survival varies by age and tumor stage. The five-year relative survival rate for ATRT is about 48% for children up to age 14, 42% for teenagers and young adults ages 15 to 39, and 25% for adults age 40 and older.

Average survival times reported in studies range from 12 to 24 months, though many children live longer with aggressive treatment and participation in ongoing research trials.

Returning cancer, also called recurrence, is common, especially within the first 2 to 3 years after diagnosis. The chance of the tumor coming back depends on age, tumor spread and how completely the tumor could be removed.

Children who respond well to their first treatments and finish therapy have the best chance of long-term survival. Regular follow-up imaging helps find any regrowth of tumors early.

Prognosis

Prognosis means the expected outcome or course of a disease. It helps describe how likely it is that treatment will control or remove the tumor and what factors may affect long-term health.

ATRT is an aggressive form of brain cancer, but outcomes have improved as treatments advance. Prognosis depends on many factors, including age, tumor size, tumor spread and how much of the tumor can be safely taken out.

Children age 3 or older who have surgery followed by intensive chemotherapy and radiation tend to have better outcomes. Babies and toddlers often face a harder course because treatment must be adjusted to protect their developing brains. Radiation is generally not used on babies and children younger than age 3.

Prognosis also is influenced by whether the cancer has spread through the brain or spinal fluid. Tumors that are found only in one place have a higher chance of long-term control than do tumors that have already spread.

Genetic factors also may affect outcomes. Tumors with SMARCB1 changes can behave differently from those with SMARCA4 changes. Ongoing research continues to study these differences.

Survival is highest for children age 3 or older when the tumor can be fully removed and treated with intensive chemotherapy and radiation.