What Are the Symptoms of ATRT? 6 Treatment Options

ATRT is a rare type of brain tumor that is highly malignant and mostly affects children. It grows quickly and primarily affects the brain and spinal cord (central nervous system).

Rhabdoid tumors contain many large cells. There are three types of rhabdoid tumors grouped together by locations in which they originate:

• ATRT: Occurs in the brain and spinal cord
• Malignant renal rhabdoid tumor: Occurs in the kidney (renal)
• Extra renal rhabdoid tumor: Occurs elsewhere in the body such as in the liver, lungs, and skin

ATRT may be classified as follows:

• Localized: Occurring in only one location in the brain
• Metastatic: Has spread to other parts of the brain or spinal cord
• Multifocal: Tumors form in more than one place at the same time (may occur in a child who has a genetic mutation)

Most ATRT cases are linked to genetic defects on chromosome 22. Changes in tumor suppressor genes SMARCB1 (located on chromosome 22) may be linked to ATRT (also known as INI1, SNF5, and BAF47 genes).

ATRT is caused by a defect in another tumor suppressor gene called SMARCA4 in less than 5% of cases. This type of gene produces a protein that aids in cell growth control. When the gene fails to function, the protein is not produced, and tumor growth is uncontrolled.

This defect, however, occurs only in cancer; the defect of this gene may be inherited. As a result, it is necessary to consult a doctor for genetic testing.

• ATRT affects about 1%-2% percent of all children with brain tumors.
• Infants and young children younger than 3 years of age are typically affected. 
• ATRT has been found in some older children and young adults in rare cases.
• Men have a slightly higher tumor incidence than women (in a 3:2 ratio).
• People of all ethnicities may be affected.

Rhabdoid tumors can be associated with a rhabdoid tumor predisposition syndrome, which means that some children are predisposed to developing this tumor. The majority of children with rhabdoid tumors have a gene loss or mutation. Because this tumor occurs in young children or infants, some researchers believe it develops from the germ cell stage or the stem cell stage.

In most cases, the child may have a defective gene, and genetic testing may be useful in diagnosing the brain tumor. If a patient has already shown signs of ATRT, imaging can help determine the diagnosis. Depending on the signs and symptoms, one or a combination of the following tests may be recommended:

• Computerized tomography (CT) scan
• Magnetic resonance imaging (MRI) of the brain and spine
• Blood tests
• Echocardiogram (heart scan)
• Biopsy or resection (removal) of the tumor
• Bone scan
• SMARCB1 and SMARCA4 gene testing, which is a laboratory test in which a blood or tissue sample is examined for changes in SMARCB1 and SMARCA4 genes.
• Lumbar puncture, in which a small sample of cerebrospinal fluid is extracted from the spine using a small needle. The sample is then analyzed to see if there are any tumor cells in the fluid surrounding the central nervous system.
• Ultrasound of the abdomen to ensure that all other organs are healthy and that no other tumors are present.

The most common way to confirm a diagnosis is to rely on MRI results, which are then confirmed by histopathology (brain biopsy/resection). Many clinical conditions can have symptoms that are similar to one another. To arrive at a definitive diagnosis, additional tests may be performed to rule out other clinical conditions.

Treatment ATRT is determined by the patient’s age and size and location of the tumor. These tumors are aggressive, and most patients receive a combination of treatment options:

1. Surgery

• Surgery is the first line of treatment for this condition.
• A diversionary procedure for cerebrospinal fluid is usually recommended.
• The majority of children undergo a craniotomy, with the tumor resected as far as it can safely be done.
• In about 50% of patients, total or near total resection of the tumor is possible. Gross total resection is possible in 64% of patients under age 3 and in 78% of children over age 3.
• Within 3 months of surgery, 81% of patients under age 3 develop a recurrence of the disease, and recurrence is mostly local in more than 70% of patients.

2. Chemotherapy

• Powerful drugs are used to kill cancer cells and slow their growth, usually administered after surgery.
• Chemotherapy is administered orally or by injection directly into the bloodstream.
• Most children with ATRT receive chemotherapy at some point during their clinical course, particularly those under age 2, to postpone radiation therapy.
• Recurrent or progressive ATRT in children who are 3 years old or younger appears to be resistant to chemotherapy as compared to in older children.

3. Radiation therapy

• In radiation therapy, X-rays or other high-energy radiation are used to kill cancer cells, while preventing them from further division and growth.
• Because most children diagnosed with ATRT are under 2 years of age, radiotherapy is not initially offered due to toxicity of radiation to developing brains.
• Currently, the goal is to keep the child on chemotherapy until they are at least 2-3 years old, at which point radiation effects will be less severe.

4. High-dose chemotherapy with stem cell transplant

• High doses of chemotherapy are administered to destroy cancer cells. Healthy cells are destroyed as well, including blood-forming cells. Stem cell transplantation is used to replace the blood-forming cells. 
• Stem cells (immature blood cells) are extracted from the patient's or donor's blood or bone marrow and frozen and stored.
• After the patient has finished chemotherapy, the stored stem cells are thawed and infused back into the patient. These reinfused stem cells develop into (and restore) blood cells in the body.

5. Targeted therapy

• Children with ATRT are eligible for ongoing clinical trials that involve targeted therapy, which is a type of cancer treatment in which drugs or other substances are used to specifically attack cancer cells.
• Targeted therapies are less likely to harm healthy cells than chemotherapy or radiation therapy.
• The use of targeted therapy in the treatment of recurrent ATRT is still being researched.

6. Supportive care

• Supportive care is an important part of ATRT treatment for children, with the goal being to keep the child as comfortable and symptom-free as possible.
• Supportive care includes treatment of infections, pain relief, and medication to reduce side effects such as sickness.
• In many areas, children with cancer are routinely referred to the local children's hospice team for help with symptom management while undergoing active treatment.

Participating in a clinical trial may be the best treatment option for some patients. Clinical trials are a component of cancer research. Clinical trials are conducted to determine whether new cancer treatments are safe and effective or if they are better than the standard treatment.

The prognosis for children with ATRT is bleak. Infants and children under age 3 (at the time of ATRT diagnosis) have a high mortality rate. Children aged 3 and older have a higher survival rate (70%). Patients with ATRT have a median survival period of less than 2 years. Children with metastatic tumors and large tumors have the worst outcomes. 

ATRT is resistant to many drugs which is one reason why prognosis is dismal. The discovery and characterization of the rhabdoid tumor predisposition gene on chromosome 22q may allow for the development of more focused, effective therapeutic agents, potentially increasing survival time. 

Currently, there is no known cure for ATRT. However, there have recently been dramatic advancements in treatment, and there is growing optimism that these new treatments will soon result in significantly higher survival rates.