Atypical teratoid/rhabdoid tumors (ATRTs) are fast-growing cancers of the central nervous system—the processing center of the body, which includes the brain and spinal cord—that are commonly seen in babies and toddlers.

These tumors are extremely rare. Only 58 people are diagnosed with atypical teratoid/rhabdoid tumors in the United States each year, most of them children.

Because the tumors are very fast-growing and typically don’t respond well to treatment, the outcome is poor for those diagnosed with atypical teratoid/rhabdoid tumors.

"ATRT is a rare, but devastating tumor,” says Smilow Cancer Hospital hematologist and oncologist Asher Marks, MD. “Despite its rarity, there is a tight-knit community of physicians, scientists, and advocates committed to finding a cure. Recent advances in supportive care and novel therapeutics continue to lead the fight against these tumors that affect the youngest and most vulnerable.”

Atypical teratoid/rhabdoid tumors are rare tumors that grow very quickly within the brain and/or spinal cord. They are found most frequently in children ages 3 and younger.

These tumors commonly arise when a child has a genetic mutation within one of two tumor-suppressor genes—SMARCB1 or SMARCA4. In healthy individuals, these genes produce a protein that helps the body to limit the growth of cancerous cells. However, in an individual with a SMARCB1 or SMARCA4 mutation, cancer cells may multiply uncontrollably, leading to the formation of atypical teratoid/rhabdoid tumors.

About half of the time, atypical teratoid/rhabdoid tumors are found in the following locations in the brain:

• Cerebellum, a region that helps to control balance and movement. A tumor within the cerebellum may cause motor problems, balance difficulties, or other symptoms.
• Brain stem, a region that helps control many of the muscles and nerves involved in seeing, hearing, walking, and talking. An atypical teratoid/rhabdoid tumor in the brain stem may cause walking difficulties or vision problems.

Atypical teratoid/rhabdoid tumors can arise when a child has a genetic mutation within one of two tumor-suppressor genes—SMARCB1 or SMARCA4. In healthy individuals, these genes produce a protein that helps the body to limit the growth of cancerous cells. However, in an individual with a SMARCB1 or SMARCA4 mutation, cancer cells may multiply uncontrollably, leading to the formation of atypical teratoid/rhabdoid tumors.

SMARCB1 and SMARCA4 genetic mutations may be inherited from parents, or they may arise on their own. Because the condition is so rare, doctors aren’t sure what may cause these tumor-suppressor genes to mutate spontaneously in instances when the mutation isn’t inherited.

Babies and children who have atypical teratoid/rhabdoid tumors may experience symptoms such as:

• Morning headaches
• Nausea
• Vomiting
• Sleeping more than usual
• Appearing lethargic
• Becoming less active than normal
• Difficulty walking
• Loss of balance/coordination problems
• Muscle weakness
• Enlarged head size
• Head tilt
• Paralysis on one side of the body
• Double vision
• Facial muscle weakness

A doctor who suspects an atypical teratoid/rhabdoid tumor will first obtain a child’s personal and family medical history from their parents. They will ask about any known genetic mutations that run in the family, especially SMARCB1 or SMARCA4.

During a physical exam, doctors will look for signs of atypical teratoid/rhabdoid tumors, such as an enlarged head, a head tilt, or facial muscle weakness, which may cause one corner of the mouth to droop. They will also perform a neurological exam to see if the child’s brain, spinal cord, and nerves are functioning normally. The doctor will also perform tests to determine I if there are balance problems, difficulty walking, muscle weakness, or paralysis on one half of the body.

To diagnose atypical teratoid/rhabdoid tumors, doctors rely on one or more of these tests:

• MRI, an imaging test of the brain and spinal cord, to look for the presence of a tumor.
• Spinal tap, during which doctors use a needle to remove spinal fluid from the spinal column to check for the presence of cancer cells.
• Genetic testing, which will detect the presence of genetic mutations to the SMARCB1 or SMARCA4 genes.
  
• Biopsy, to confirm the presence of atypical teratoid/rhabdoid tumor cells in a tumor. To perform the biopsy, doctors must remove a small section of the skull, then use a needle to remove cells from the affected region. If cancer is confirmed, the doctor may surgically remove as much of the tumor as is possible during the biopsy procedure.

The following treatment options are available for individuals with atypical teratoid/rhabdoid tumors, including:

• Surgery. Doctors will remove as much of the tumor as possible—often during the biopsy. The location and size of the tumor, as well as whether or not it has spread to other parts of the body, are factors that determine if a significant portion of the tumor can be removed surgically.
• Chemotherapy. Traditional chemotherapy is not an ideal treatment for atypical teratoid/rhabdoid tumors, because most medications don’t cross what’s called the “blood-brain barrier.” However, high-dose chemotherapy using a combination of drugs may be effective after surgery.
• High-dose chemotherapy plus stem-cell transplant. Because high doses of powerful chemotherapy medications may harm the blood-forming cells in the bone marrow, a stem-cell transplant may help the body resume its ability to replenish the blood supply effectively while fighting the tumor. Doctors may offer stem-cell transplants to younger patients who aren’t ideal candidates for radiation therapy.
• Radiation therapy. After surgery with or without chemotherapy, doctors may use radiation therapy on the brain and spinal cord to try to kill any remaining cancer cells. This therapy is usually not given to children younger than age 3, because radiation to the brain can harm a baby or young child’s growth and development.

Other treatments, such as targeted therapy or immunotherapy, may be available to children who enroll in clinical trials.

Children who are diagnosed with atypical teratoid/rhabdoid tumors generally have a poor prognosis. Around 50% survive 1 year after diagnosis, and roughly 30% survive 5 years or longer after diagnosis.

“Despite the aggressive nature of ATRT, the combined resources found in Yale New Haven Children’s Hospital’s (YNHCH) Blood and Bone Marrow Transplantation program, cutting edge radiation oncology department, and access to cutting-edge therapeutics allows the Pediatric Neuro-Oncology team at YNHCH to treat ATRT with expertise and compassion,” says Dr. Marks.