Glioblastoma Multiforme

Glioblastoma multiformes (GBMs) are high-grade gliomas that arise from the brain’s supportive tissue, known as glial cells. These are aggressive tumors that rapidly infiltrate adjacent healthy brain tissue and, as a result, are difficult to treat.

The majority of GBMs occur in the cerebral hemispheres, which control higher functions like speech, movement, thought, and sensation. They can also develop in the part of the brain that identifies sensations such as temperature, pain, and touch, and the region of the brain that controls balance and motor function.

These tumors are usually diagnosed between the ages of 5 and 9, and occur in boys and girls equally. GBMs occur with increased frequency in children with certain genetic syndromes, including neurofibromatosis 1, Li-Fraumeni syndrome, hereditary nonpolyposis colon cancer, and tuberous sclerosis. Most GBMs, however, have no known cause.

Brain tumors can cause a variety of symptoms in children based primarily on the location of the tumor, its size, and whether it has spread. Keep in mind that the symptoms of a brain tumor may resemble other more common conditions or medical problems. It is important to consult your child's physician for a diagnosis.

Most glioblastoma multiforme (GBM) symptoms result from increased pressure within the head. Other symptoms relate to the tumor’s specific location, rate of growth, and associated inflammation. Symptoms can develop slowly over time or begin very suddenly. The most common symptoms include:

• Headache and lethargy
• Seizures
• Compression of surrounding brain structures

There are certain hereditary conditions that are linked to these tumors. GBMs can occur with increased frequency in families with conditions including Li-Fraumeni syndrome, hereditary nonpolyposis colon cancer, tuberous sclerosis, and neurofibromatosis type 1.

The first step in treating your child is forming an accurate and complete diagnosis. In the case of glioblastoma multiforme (GBM), this is primarily done with a combination of imaging and biopsy. Your child’s physician may order a number of different tests including:

• Physical exam and complete medical history
• Computerized tomography scan (also called a CT or CAT scan)
• Magnetic resonance imaging (MRI)
• Magnetic resonance spectroscopy (MRS)
• Lumbar puncture (spinal tap)
• Positron emission tomography (or PET) scan
• Biopsy or tissue sample

There may be other diagnostic tests that your doctor will discuss with you depending on your child's individual situation. After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child's condition. Then we will meet with you and your family to discuss the results and outline the best possible treatment options. All patients undergoing resection of brain tumors in our program are also invited to participate in our ongoing research studies that allow genetic profiling of each child’s tumor. These studies may potentially guide personalized (precision) medicine.

Your child's physician will determine a specific course of treatment based on several factors, including your child's age, overall health and medical history, the type, location, and size of the tumor, and the extent of the disease. Treatments for GBMs may include neurosurgery, radiation, and chemotherapy.

Neurosurgery

The first treatment is usually surgery to remove as much of the tumor as possible, ideally using advanced techniques to maximize tumor removal, such as intraoperative MRI, in which surgeons can visualize the tumor as they operate. Complete resection, or surgical removal, of the entire tumor is ideal when possible, though most high-grade gliomas cannot be completely removed because they tend to infiltrate into adjacent healthy tissues. In general, the more completely the tumor can be removed, the greater the chances for survival.

Radiation

High-energy waves from a specialized machine damage or shrink tumors. Your child also may receive precisely targeted and dosed radiation to kill cancer cells left behind after surgery. This is important to control the local growth of tumors and helps increase survival in high-grade gliomas.

Chemotherapy

Chemotherapy refers to drugs that interfere with the cancer cells' ability to grow or reproduce. To date, no chemotherapy regimen has been demonstrated to increase survival rates in children with GBM, though chemotherapy before surgery may help shrink the tumor, making it possible to remove. A variety of chemotherapy regimens have been tested in the treatment of newly diagnosed high-grade gliomas, and some have produced responses but none have improved survival. Studies in adults have suggested that certain drugs can produce modest responses in high-grade gliomas, but they have less effect in children. High-intensity chemotherapy in conjunction with stem cell transplants also does not seem to improve chances of survival.

Unfortunately, the prognosis for GBM remains very poor. In general, more complete surgical removal of the tumor, when possible, results in greater chance of survival. Your child’s doctor will discuss treatment options with you, including experimental clinical trials and supportive care.

For children with relapsed GBMs, we offer access to the latest clinical trials and experimental therapies. Current trials include novel medications, as well as new methods for the delivery of more traditional agents.

Our Pediatric Advanced Care Team (PACT) is available to provide supportive treatments intended to optimize your child’s quality of life, as well as promote comfort and healing for children with life-threatening illnesses. In addition, PACT can provide psychosocial support and help arrange end-of-life care, when necessary.

Children successfully treated for a GBM should visit a survivorship clinic yearly to manage disease complications, screen for recurrence, and manage late treatment side effects. A typical follow-up visit is likely to include a physical exam, laboratory testing, and imaging scans.

Through our Stop & Shop Family Pediatric Neuro-Oncology Outcomes Clinic, children are able to meet with their neurosurgeon, radiation oncologist, pediatric neuro-oncologist, and neurologists at the same follow-up visit. Our multidisciplinary approach and depth of expertise will give your child on-site access to endocrinologists, neuro-psychologists, and alternative/complementary therapy specialists. School liaison and psychosocial personnel from the pediatric brain tumor team are also available. In addition, children needing rehabilitation may meet with speech, physical, and occupational therapists during and after their visit.

Children with GBMs are treated Dana-Farber/Boston Children's Cancer and Blood Disorders Center through our Glioma Program, one of the world's largest treatment programs focused on this kind of cancer. Our glioma specialists have extensive expertise in treating all types of gliomas, including GBMs. Our patients receive multidisciplinary care from neuro-oncologists, neurosurgeons, neurologists, and pediatric subspecialists.

Clinical trials, or research studies evaluating new treatment approaches, are a major offering at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Clinical trials are very important for children with hard-to-treat or relapsed conditions.

Clinical trials for GBMs

For many children with brain tumors or other rare or hard-to-treat conditions, clinical trials provide new options. It’s possible that your child will be eligible to participate in one of our brain tumor clinical trials. In addition to launching our own clinical trials, we also offer trials available through collaborative groups such as the Children's Oncology Group (COG) and the Pacific Pediatric Neuro-Oncology Consortium (PNOC). If your child has a progressive or recurrent tumor, she may be eligible for a number of experimental therapies available through these groups or from one of our independent clinical investigators.

Clinical and basic scientists at Dana-Farber/Boston Children’s are conducting numerous research studies to help clinicians better understand and treat malignant gliomas. Through the consortia of researchers to which we belong, a number of novel therapies are available for children with both newly diagnosed and current brain tumors. Participation in any clinical trial is completely voluntary. We will take care to fully explain all elements of the treatment plan prior to the start of the trial, and you may remove your child from the medical study at any time.