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|Classification and external resources|
|Classification and external resources|
Around 75% are diagnosed in children and young adults under the age of twenty, but have been known to affect older adults as well. Brainstem gliomas start in the brain or spinal cord tissue and typically spread throughout the nervous system. Brainstem gliomas are often primary brain tumors, and rarely metastasize, or spread, to affect another part of the body.
The cause is still unknown. Researchers have not found any direct genetic link. Children irradiated for tinea capitis have been found to have an increased risk for other central nervous system tumors, such as meningiomas, gliomas, and nerve sheath tumors, but not necessarily tumors of the brain stem.
Common symptoms include, but are not necessarily limited to:
Symptoms can develop slowly and subtly and may go unnoticed for months. In other cases, the symptoms may arise abruptly. A sudden onset of symptoms tends to occur with more rapidly growing, high-grade tumors.
Neuroimaging, such as MRI, is the main diagnostic tool for brain stem gliomas. In very rare cases, surgery and biopsy are performed.
Unlike most brain tumors, brainstem glioma is not often treated with neurosurgery due to complications in vital parts of the brain. More often, it is treated with chemotherapy and/or radiation therapy (though past use of radiation therapy has yielded mixed results.)
There are several new clinical trials in process. One such trial is dendritic cell immunotherapy which uses the patient’s tumor cells and white blood cells to produce a chemotherapy that directly attacks the tumor.
However, these treatments do produce side effects; most often including nausea, the breakdown of the immune system, and fatigue. Hair loss can occur from both chemotherapy and radiation, but usually grows back after chemotherapy has ceased. Steroids such as Decadron may be required to treat swelling in the brain. Decadron can lead to weight gain and infection. Patients may also experience seizures, which need to be treated to avoid complications. For some patients there is a chance of a neurological break down, this can include, but is not limited to, confusion and memory loss.
Brainstem glioma is an aggressive and dangerous cancer. Without treatment, the life expectancy is typically a few months from the time of diagnosis. With appropriate treatment, 37% survive more than one year, 20% survive 2 years. and 13% survive 3 years.
A Diffuse Intrinsic Pontine Glioma (DIPG) is a tumour located in the pons (middle) of the brain stem. The brain stem is the bottom most portion of the brain, connecting the cerebrum with the spinal cord. The majority of brain stem tumours occur in the pons (middle brain stem), are diffusely infiltrating (they grow amidst the nerves), and therefore are not able to be surgically removed. Glioma is a general name for any tumour that arises from the supportive tissue called glia, which help keep the neurons ("thinking cells") in place and functioning well. The brain stem contains all of the "wires" converging from the brain to the spinal cord as well as important structures involved in eye movements, face and throat muscle control and sensation.
DIPG has a 0 percent survival rate. The median overall survival of children diagnosed with DIPG is approximately 9 months. The 1 and 2 year survival rates are approximately 30% and less than 10%, respectively. These statistics make it one of the most devastating paediatric malignancies. Although 75- 85% of patients show some improvement in their symptoms after radiation therapy, DIPGs almost always begin to grow again (called recurrence, relapse, or progression). Clinical trials have reported that the median time between radiation therapy treatment and progression is 5-8.8 months. Patients whose tumours begin to grow again may be eligible for Pilot, Phase I, or Phase II clinical trials. These clinical trials use experimental drugs or other experimental therapeutic approaches to try to slow or stop the growth of the tumour. Unfortunately, clinical trials have not shown any significant benefit from these experimental therapies so far. However, researchers are always working to develop new potential therapies for DIPGs. By participating in clinical trials, patients and families can help researchers learn more about DIPG and perhaps help future patients. Unfortunately, DIPGs that progress usually grow quickly and affect important parts of the brain. Clinical trials have reported that the median time from tumour progression to death is usually very short, between 1 and 4.5 months. During this time, doctors focus on controlling symptoms and helping children to feel as comfortable as possible.
The standard treatment for DIPG is 6 weeks of radiation which often dramatically improves symptoms. Unfortunately, problems usually recur after 6 to 9 months, and progress rapidly. Neurosurgery: Surgery to attempt tumor removal is usually not possible or advisable for DIPG. By their very nature, these tumours invade diffusely throughout the brain stem, growing between normal nerve cells. Aggressive surgery would cause severe damage to neural structures vital for arm and leg movement, eye movement, swallowing, breathing, and even consciousness.
Surgery with less than total removal can be performed for many focal brain stem gliomas. Such surgery often results in quality long-term survival, without administering chemotherapy or radiotherapy immediately after surgery, even when a child has residual tumour. Surgery is particularly useful for tumours that grow out (exophytic) from the brain stem.
Focal brain stem tumours that arise at the top back of the midbrain (tectal gliomas) should be managed conservatively, without surgical removal. Nevertheless, shunt placement or ventriculostomy for hydrocephalus (see below) is frequently necessary. These tumours have been described to be stable for many years or decades without any intervention other than shunting.
Radiotherapy: Conventional radiotherapy, limited to the involved area of tumor, is the mainstay of treatment for DIPG. A total radiation dosage ranging from 5400 to 6000 cGy, administered in daily fractions of 150 to 200 cGy over 6 weeks, is standard. Hyperfractionated (twice-daily) radiotherapy was used previously to deliver higher irradiation dosages, but such did not lead to improved survival. Radiosurgery (e.g., gamma knife, Cyberknife) has no role in the treatment of DIPG.
Chemotherapy and other drug therapies: The role of chemotherapy in DIPG remains unclear. Studies to date with chemotherapy have shown little improvement in survival, although efforts (see below) through the Children's Oncology Group (COG), Paediatric Brain Tumour Consortium (PBTC), and others are underway to explore further the use of chemotherapy and other drugs. Drugs utilized to increase the effect of radiotherapy (radiosensitizers) have thus far shown no added benefit, but promising new agents are under investigation. Immunotherapy with beta-interferon and other drugs to modify biologic response have shown disappointing results. Intensive or high-dose chemotherapy with autologous bone marrow transplant or peripheral blood stem cell rescue has not demonstrated any effectiveness in brain stem gliomas and is not recommended. Future clinical trials may incorporate medicines to interfere with cellular pathways (signal transfer inhibitors) or other approaches that alter the tumor or its environment. Donaldson SS, Laningham F, Fisher PG. Advances toward an understanding of brain stem gliomas. J Clin Oncol 24:1266-1272, 2006.</ref>
Without research into brainstem tumours no cure can be found. Currently funding is the major issue that is limiting brain and brainstem research. 
Getting into the brain: approaches to enhance brain drug delivery A major difficulty in treating brain tumors is overcoming the blood-brain barrier. This is no less true with diffuse intrinsic pontine gliomas.
Unlike other areas of the body where substances can pass freely from the blood into the tissue because there are some space between the cells lining the blood vessels, in the brain movement of substances is significantly limited. This barrier between the blood and the brain is formed by the lining cells of the vessels as well as projections from nearby astrocytes. These two types of cells are knitted together by proteins to form what is called ‘tight junctions’. The entire structure is called the Blood Brain Barrier (BBB). The result is that chemicals, toxins, bacterial and other substances are often kept from getting into the brain. Thus, it serves a daily protective function preventing substances to get to the brain. However with disease such as brain tumors the BBB also can prevent diagnostic and therapeutic agents from reaching their target in the central nervous system. Researchers and clinicians have developed ways to try to overcome the blood brain barrier. Here are some examples: