Brainstem Glioma

What is a brainstem glioma?

Tumors that arise out of the brainstem are generally called brainstem glioma and are part of the group of tumors known as astrocytoma. Brainstem gliomas can be grade 1, 2, 3, or 4 tumors. Grade 2 astrocytomas in the brainstem frequently grows much faster than grade 2 tumors in the rest of the brain, and will rapidly transform into a higher grade tumor. Grade 3 and grade 4 astrocytomas grow very fast, particularly in the brainstem. The reason for the very rapid growth of these tumors in this particular area of the brain is still unknown. Because many brainstem tumors are not biopsied, a diagnosis is made based on the MRI appearance of the lesion. The majority of tumors that arise from the brainstem region, other than proven grade 1 tumors, are considered highly malignant brain tumors.

Boys and girls are equally affected, and the most common age group is between 5 and 10 years of age. Neurological symptoms are usually rapid in onset, over days or weeks. Typical symptoms of a brainstem glioma can include abnormalities in eye movement, weakness of one side of the face, numbness or weakness of the extremities, difficulty with balance, headaches, and possibly nausea. An MRI scan can identify the specific area in the brainstem that the tumor arises from and often is all that is needed to diagnose a brainstem glioma. In some cases, the lesion is not typical for most brainstem gliomas and a neurosurgeon will discuss the option for surgery to remove a tumor, or at a minimum a biopsy. In recent years, biopsies of lesions in the brainstem are done much more frequently to both confirm the diagnosis, and to obtain tumor tissue for molecular analysis that may someday aid in decisions about treatment options.

What is the outcome?

Unfortunately, the majority of brainstem gliomas are rapidly growing grade 3 or grade 4 astrocytoma, and even the grade 2 tumors grow rapidly. Because the tumor grows directly in the brainstem, in an area called the pons, surgery to remove the tumor is not possible. This area of the brain controls many vital functions necessary for survival, including control of breathing, heart rate, and blood pressure. At the same time, if the tumor continues to grow, those functions can be affected directly by the tumor itself. This is why treatment is started as quickly as possible. If the treatment does not control tumor growth, the symptoms described above will eventually develop. In many cases, initial treatment will control the tumor growth, oftentimes for many months. Unfortunately, these tumors tend to grow back in less than one year. Treatment at that time less effective than the initial treatment, and may not control tumor growth, or control tumor growth for only a few months.

How serious is it?

Unfortunately, in the majority of cases, treatment cannot cure this disease. Because of this fact, many clinical research trials are done for children with this disease to try to find more effective therapies.

What are the treatment options?

The most effective and most common initial treatment is radiation therapy. This typically is done over a 6-week period. In some cases, physicians may add various forms of chemotherapy either during and/or after the radiation. If chemotherapy is given, it will be continued for as long as it works to control tumor growth. Treatment for tumor re-growth is typically chemotherapy, either using standard agents or experimental drugs. Most children and their parents in the United States are offered the option of participation in a clinical research study, both for newly diagnosed brainstem glioma and for brainstem glioma that grows despite initial therapy. The majority of clinical research studies include new experimental drugs.

However, for grade 1 brainstem gliomas, surgery alone is often curative. If surgery cannot be done to remove most of the visible tumor, treatment with radiation therapy is very effective treatment.

What clinical trials are testing new treatments for brainstem glioma?

Clinical trials for brainstem glioma are often sponsored by the Children’s Oncology Group. These groups include many institutions in the United States, and offer the potential of new and hopefully better treatment. Current clinical trials include drugs that may increase the effect of radiation (called “radiosensitizers”), or new drugs that may work independently to kill or slow the growth of tumor cells. Experimental drugs may be given during the time of radiation, after radiation, or at the time of tumor regrowth. Drugs are chosen based upon the expected known biology of the tumor, often targeting key metabolic pathways that are abnormal in tumor cells. The Pacific Pediatric Neuro-Oncology Consortium is currently developing a trial for recurrent diffuse intrinsic pontine glioma that will link the molecular profile of a patient's tumor to treatments aimed at the specific aberrations found in that tumor. The trial is scheduled to open in 2013. 

Click here for a list of trials for pediatric brain tumors currently offered at UCSF. Or contact Dennis Aguilling at (415) 476-9387 for additional information.

What research is being done on brainstem glioma?

At UCSF there are a number of research projects to study brainstem glioma. These include studies of tumor cell biology and the testing of various new drugs on tumors grown in cultures. In addition, efforts are ongoing to create what is called a “model” system in rodents, trying to mimic the tumor seen in humans. Having a reliable tumor model, where the tumor is growing in the brainstem of these rodents, allows researchers to test new agents or combinations of agents prior to using those agents in children. This is very important in order to try to be certain that a drug has at least a chance of working, and rejecting drugs that are not likely to work.

Of particular importance to the UCSF research group is a new research project to obtain tumor tissue from pediatric brain tumor patients, in order to more fully characterize the metabolic features of these tumors, to study the genetics of the lesions, and to discover through this research new targets that may slow or stop tumor cell growth. For many prior decades, a diagnosis of a brainstem glioma was made using MRI scans only, without obtaining a biopsy. Because of this fact, there is very little known about these tumors on a biologic basis. With new tools to fully study the DNA and RNA of tumors available, the possibility now exists to rapidly discover new pathways and targets, and ultimately, new drugs to treat the disease.

A clinical trial will open at UCSF, along with many other institutions across the country, to biopsy tumors in children when they are first diagnosed, and to use this tumor tissue to specifically choose various chemotherapy treatments tailored to the biology of that child’s tumor. Taking tumor tissue through a small biopsy procedure has been shown to be safe in the majority of cases, and can yield enough tissue to inform clinical researchers about the specific metabolic pathways that are abnormal in the tumor. Further research, including tissue culture work, animal model systems, and clinical trials are ongoing at a rapid pace using new technology and new experimental agents. It is this kind and extent of research that will be critical to eventually find effective treatments.