What is a GBM ?

Glioblastoma multiforme is a high grade, or malignant glioma, a tumour of the glial (supportive) tissue of the brain. Glioblastoma multiforme and anaplastic astrocytoma, account for approximately 10 percent of paediatric central nervous system tumours.

These tumours arise primarily in the cerebral hemispheres (65 percent). Approximately 20 percent can occur in the area of the thalamus and hypothalamus or the diencephalon (responsible for identification of sensation, such as temperature, pain and touch, regulation of appetite/weight and body temperature, as well as connecting the brainstem to the cortex). Another 15 percent can occur in the region of the cerebellum and brain stem known as the posterior fossa. The median age at diagnosis is 9 to 10 years old, and these tumours occur with equal frequency in boys and girls.

As you read further below, you will find general information about glioblastoma multiforme.

What causes a glioblastoma multiforme?

Most high-grade gliomas occur sporadically or without identifiable cause. They do however, occur with increased frequency in families with Li-Fraumeni syndrome, hereditary nonpolyposis colon cancer and tuberous sclerosis. They have also been associated with exposure to vinyl chloride and to high doses of radiation therapy to the brain.

What are the symptoms of a glioblastoma multiforme?

Glioblastoma multiforme of the cerebral hemispheres and the diencephalon, so called supratentorial glioblastoma multiforme, produce non-specific symptoms as a result of increased pressure within the head, as well as more localizing symptoms as a function of their specific location, rate of growth and associated inflammation.

The duration of symptoms is variable from a slow, insidious onset to more abrupt presentations. The following are the most common symptoms of glioblastoma multiforme, however each child may experience symptoms differently. Common symptoms may include:

  • headache and lethargy
  • symptoms of increased pressure within the brain. These symptoms include:
  • headache (generally upon awakening in the morning)
  • seizures – can occur with supratentorial high-grade gliomas but do so less commonly than do low-grade lesions
  • compression of surrounding brain structures – depending on the location of the tumour, increased pressure can cause:
  • weakness and other motor dysfunction
  • neuroendocrine abnormalities
  • changes in behaviour or thought processes

How are glioblastoma multiformes classified?

The symptoms of a brain tumour may resemble other conditions or medical problems. Always consult your child’s physician for a diagnosis.

Gliomas are heterogeneous tumours that are classified according to their most aggressive appearing elements. The World Health Organization classification scheme includes 4 grades of glioma. Glioblastoma multiforme is a grade IV tumour. It is characterized as being of astrocytic origin but having increased numbers of cells (hypercellularity), abnormal cells and nuclei (cytologic and nuclear atypia), increased proliferation of cells (mitoses), increased cell death (necrosis) and increased growth of blood vessels (vascular endothelial proliferation). Glioblastoma multiformes are aggressive tumours that infiltrate adjacent normal brain tissue.

How is a glioblastoma multiforme diagnosed?

Diagnostic procedures for glioblastoma multiforme may include:

  • physical examination.
  • computerized tomography scan (also called a CT or CAT scan) – a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body. CT scans are more detailed than general x-rays.
  • A CT scan can assess the density of tumour tissue, compared to normal brain tissue, as well as establish the mass effect (the effect of an additional space occupying mass within the closed cavity of the skull on the normal brain). Glioblastoma multiforme most often appear as irregularly shaped masses. When intravenous dyes are injected, these tumours avidly absorb dye and therefore are referred to as enhancing lesions.
  • magnetic resonance imaging (MRI) – a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body. MRI provides greater anatomical detail than CT scan and can better distinguish between tumour, tumour-related swelling and normal tissue. MRI can distinguish between haemorrhage and tumour cyst.
  • magnetic resonance spectroscopy (MRS) – a test done along with MRI at specialized facilities that can detect the presence of particular organic compounds produced by the body’s metabolism within sample tissue that can identify tissue as normal or tumour, and may be able to distinguish between glial tumours and tumours of neuronal origin.
  • biopsy – a tissue sample from the tumour will be obtained either through a needle or by direct excision during a surgical procedure performed by a surgeon to confirm the diagnosis.

Specific treatment for a glioblastoma multiforme will be determined by your child’s physician based on:

  • your child’s age, overall health, and medical history
  • type, location, and size of the tumour
  • extent of the disease
  • your child’s tolerance for specific medications, procedures, or therapies
  • how your child’s doctors expects the disease to progress
  • your opinion or preference

What are the treatments for a glioblastoma multiforme?

The primary modes of therapy for newly diagnosed glioblastoma multiforme includes maximal surgical removal, when possible, followed by radiation therapy. To date, no chemotherapy regimen has been demonstrated to increase survival in paediatric high-grade gliomas. As with all paediatric cancers, care should be delivered at specialized centres where multidisciplinary teams can provide not only expert diagnostics and experienced medical, surgical and radiation oncologists, but also psychosocial support, neuro-psychological testing and specialized school plans, all delivered in a child- and family-sensitive and friendly environment.

Treatment may include (alone or in combination):

surgery – surgery has multiple roles in the management of glioblastoma multiforme, including treatment of increased intracranial pressure, biopsy and tumour removal. For operable tumours, the extent of surgical removal is clearly related to prognosis. Most high-grade gliomas cannot be completely removed because of the infiltrating fingers of tumour which characterize their growth. However, multiple studies have demonstrated that maximal removal results in greater survival. tumours of the cerebral hemispheres are in general more easily removed than those of the midline, diencephalic structures. Near complete resection of glioblastoma multiforme in combination with radiation therapy has been reported to produce a 5-year survival rate as high as 25 percent, whereas incompletely removed tumours were associated with a less than 5 percent 5-year survival. The infiltrating nature of these tumours makes removal difficult. Technological advances such as the intra-operative MRI, where surgeons can visualize the tumour as they operate with MRI scans, can enhance efforts at resection of difficult tumours and thereby improve survival.

radiation therapy – has been shown to increase survival in high-grade gliomas. Most recurrences of high-grade gliomas occur locally and thus a number of additional radiotherapy modalities are being evaluated to increase the local dose of radiation. Brachytherapy involves the instillation of radioactive material directly into the tumour. This allows for much greater doses to be delivered to the tumour. This has yet to be shown to offer a survival advantage and has been associated with increased toxicity. Additionally, radiosurgery to deliver additional radiation to residual tumour masses has been in trial and as yet is without clear survival benefit. Other techniques to increase dose have similarly been unable to enhance survival over conventional radiotherapy. Radiation therapy uses high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumours.

chemotherapy – a drug treatment that works by interfering with the cancer cell’s ability to grow or reproduce. Different groups of chemotherapy drugs work in different ways to fight cancer cells and shrink tumours. Often, a combination of chemotherapy drugs is used to fight a specific cancer. Certain chemotherapy drugs may be given in a specific order depending on the type of cancer it is being used to treat.

While chemotherapy can be quite effective in treating certain cancers, the agents do not differentiate normal healthy cells from cancer cells. Because of this, there can be many adverse side effects during treatment. Being able to anticipate these side effects can help the care team, parents, and child prepare, and, in some cases, prevent these symptoms from occurring, if possible.A variety of chemotherapeutic regimens have been evaluated in the treatment of newly diagnosed high-grade gliomas. While studies in adults have suggested that procarbazine, vincristine and CCNU (PVC) produce modest responses in grade III gliomas, this has not been demonstrated for paediatric cases or for grade IV tumours. Several other regimens have also produced responses, but none has improved survival. Increased doses of chemotherapy in the setting of autologous bone marrow transplant have also not produced notable advantage.

Chemotherapy is systemic treatment, meaning it is introduced to the bloodstream and travels throughout the body to kill cancer cells. Chemotherapy can be given:

  • as a pill to swallow
  • as an injection into the muscle or fat tissue
  • intravenously (directly to the bloodstream; also called IV)
  • intrathecally – chemotherapy given directly into the spinal column with a needle

Side effects in the treatment of glioblastoma multiforme can arise from surgery, radiation and chemotherapy. Surgical morbidity, especially the production of neurologic deficits, is minimized when procedures are performed in specialized centres where experienced neurosurgeons, working in the most technologically advanced settings, can provide the most extensive resections while preserving normal brain tissue.

How are side effects managed?

Radiation therapy often produces inflammation, which can temporarily exacerbate symptoms and dysfunction. To control this inflammation steroids are sometimes necessary.

Some of the chemotherapy agents are associated with fatigue, diarrhoea, constipation and headache. These side effects can be effectively managed under most circumstances with standard medical approaches.

Many specialized brain tumour treatment centres have now added staff who are expert in complementary or alternative medicine. These treatments, including acupuncture/acupressure, therapeutic touch, massage, herbs and dietary recommendations, can also help to control pain and side effects of therapy.

What is the expected outcome after treatment for glioblastoma multiforme?

The prognosis for glioblastoma multiformes remains poor. The best reported survival rates for radically removed tumours treated with adjuvant radiation therapy approaches 25 percent at 5 years. This is a minority of patients, however, and most fall into the incompletely removed category with 5-year survival rates of less than 5 percent. The more complete removal of hemispheric tumours may be associated with greater survival.

Source: Boston Children’s Hospital, USA.