Paediatric Astrocytoma

Overall definition of Astrocytoma

Astrocytomas belong to the glioma types of cancer1. They are the most common type of brain and spinal cord tumour in children. Children may develop an astrocytoma at any age and both boys and girls are likely to be affected. An astrocyte is a large, starshaped cell that holds nerve cells in place and helps them develop and work the way they should by bringing them food and oxygen, for example. They also provide a protective effect to prevent diseases and infections.

In children, astrocytoma is usually located at the base of the brain. It is typically low grade, meaning that it develops slowly. However, there is a possibility that it will develop into a faster-growing tumor2

Most brain tumours result from gene or chromosomal mutations. However, researchers are uncertain about the cause of these mutations. Some chemicals may play a role in it, but research is still ongoing.

Symptoms and Diagnosis

The symptoms of astrocytomas are not very specific and can often evoke other pathologies found in children. They include nausea and vomiting, balance and walking problems, morning headaches, slowness of speech, and vision or hearing problems. Some of these symptoms may appear several months before a worsening of the general condition and are variable in their appearance because they depend on the location of the tumour3 .

In order to diagnose astrocytoma, the first step is taking the history of the patient's symptoms, followed by a basic neurological examination including balance and vision tests3 Following this examination, if general practitioners suspect a brain tumour, they prescribe a second battery of tests, mainly imaging. There are usually two choices, cranial tomography using X-rays or magnetic resonance imaging (MRI). These two techniques can confirm the presence of an abnormal mass in the brain4 . In order to confirm the nature of the tumour, a biopsy is necessary and consists of a sample of the tumour that is analysed in a pathology laboratory5

6-9

Treatments and prognosis

Prognosis is determined by the symptoms, age and general health status of the child, as well as by the severity of the condition. Staging is the process used to determine the spread and severity of cancer in children. However, there is no standard staging system for childhood astrocytomas. Rather, the treatment is based on whether the tumour is low-grade or high-grade. Also, if the tumour was recently diagnosed or it is a recurrence. The stage of the tumour describes how abnormal the cancer cells look under the microscope and how fast the tumour is likely to grow and spread.

Low-grade astrocytomas grow slowly and rarely spread to other parts of the brain and spinal cord or to other parts of the body. However, it should be watched closely because it may develop into a faster-growing tumour. On the contrary high-grade astrocytomas grow and spread quickly.

Childhood astrocytomas do not ordinarily spread to other areas of the body, but sometimes, keep growing or return after treatment. Progressive childhood astrocytoma is a type of cancer that continues to grow, spread and get worse. Progression of the disease may indicate a refractory (unresponsive) cancer to treatment. A recurrent childhood astrocytoma is a cancer that has recurred after being treated. The cancer might reappear in the same place as the first tumour or in other parts of the body. High-grade astrocytomas often recur within three years, either at the site where the cancer first formed or elsewhere in the CNS.

Astrocytoma management involves one or several of the options below:

Observation is monitoring a patient's condition closely without treatment until signs or symptoms appear or change. It may be used if the patient has no symptoms, such as patients with low-grade cancer, or if the tumour is small and discovered at the same time as another health problem. It is also important to follow the surgical removal of tumours until signs or symptoms appear or change.

Surgery is used for diagnosis and treatment purposes. After surgery, Magnetic Resonance Imaging (MRI) is performed to determine if any cancer cells remain. If any cancer cells are found, further treatment depends on either the location, grade and age of the child. Once all cancer cells are removed, and visible at the time of surgery, some patients may undergo chemotherapy or radiation therapy after surgery to kill the remaining cancer cells. Treatment given after surgery to lower the risk of cancer recurring is called adjuvant therapy.

Radiation: uses high-energy x-rays or other types of radiation to kill cancer cells or prevent them from growing. An external machine delivers radiation to the affected areas of the body. Some ways of delivering radiation therapy help to prevent the radiation from damaging nearby healthy tissue. Radiation therapy can affect growth and development, especially in young children. For children under 3 years old, chemotherapy can be used instead to delay or reduce the need for radiation therapy.

Chemotherapy: uses drugs to stop the growth of cancer cells, either by killing them or by stopping their division. When chemotherapy is administered orally or injected through veins or muscles, the drugs pass into the bloodstream and are delivered to cancer cells throughout the body (systemic chemotherapy). When chemotherapy is administered into the spinal fluid, an organ or a cavity such as the abdomen, the drugs primarily affect cancer cells in these areas (regional chemotherapy). The administered chemotherapy depends on the type of tumour and where the tumour has formed in the brain or spinal cord. Systemic combination chemotherapy is used to treat children with astrocytoma, and high-dose chemotherapy may be used to treat children with newly diagnosed high-grade astrocytoma.

Other options may include: high-dose chemotherapy followed by a stem cell transplant, targeted therapy, corticosteroids, antiseizure medicine, ventriculoperitoneal (VP) shunt, Supportive care Antibiotics, and hormones.

Cancer treatments are aggressive and associated with many harmful side effects. Usually, they start after the beginning of the treatment and can last for months or years after the end of the therapy. Short-term side effects are directly linked to the therapy used and the underlying toxicity while late effects mechanisms (vision issues, endocrine dysregulation, blood vessel problems…) are still not totally understood10 .

Ongoing research

Actually, research on astrocytoma and more generally children's brain tumours is focused on different lines of sight. The first axis is mostly on the actual treatment and its effects on the normal cognitive development of children's brains. The global concern about long-term effects, especially on still-developing brain environments (neurons and supportive cells), emerged only a few years ago after an observation was made on children with cognitive impairment after being treated by both chemotherapy and radiotherapy for acute leukaemia. This kind of impairment is commonly called “chemobrain” and lasts for years, drastically affecting patients in their daily life11

The second research field is on innovative therapies leading to new targets or processes to reduce the tumour. A promising path emerging is the field of immunotherapy, a kind of biotherapy. Immunotherapy is based on the enhancement of the immune system specifically by targeting cancer cell markers allowing to improve T cell efficacy12 .

Besides these two research axes, there is still an underlying process of improvement in the global knowledge and understanding of the mechanisms involved in tumour formation and resistance to chemotherapy.