Diffuse Midline Glioma
Diffuse midline glioma refers to astrocytomas that have certain characteristics and are located along the midline of the brain and body.
The majority of these tumors are found in the brainstem (which controls many critical functions like breathing, swallowing, and heart rate), but can also be found in other midline structures like the thalamus and spinal cord. Diffuse midline glioma primarily affect children, but can occasionally be found in adults as well.
Diffuse midline gliomas tumors are extremely aggressive, and are classified as grade IV tumors. As the name suggests, the tumor cells tend to spread out and invade neighboring tissue. Often, diffuse midline gliomas will have grown throughout the brainstem.
Another key characteristic of diffuse midline gliomas is the presence of specific mutations in the H3F3A gene; these tumors are described as “H3 K27M-mutant.” With advances in DNA sequencing and our understanding of tumor genetics, these tumors are increasingly biopsied and analyzed for genetic markers. In fact, diffuse midline glioma is a new classification group recognizing that tumors with these mutations are similar, and thus may respond similarly to certain treatment options. Brainstem tumors that were previously termed as diffuse intrinsic pontine glioma (DIPG) are included in this new group, along with tumors in the thalamus or spinal cord that have similar growth patterns and mutations.
Because diffuse midline glioma grows quickly, symptoms can develop rapidly, over the course of days or weeks. These tumors can impact normal brainstem function, leading to common symptoms that include the following:
- Abnormalities in eye movement
- Weakness of one side of the face
- Numbness or weakness of the extremities
- Difficulty with balance
- Headaches
- Nausea
Diffuse midline gliomas usually occur in children, but can occasionally be found in adults. Brainstem tumors, which comprise the majority of diffuse midline glioma, account for 11% of primary brain tumors in children and adolescents.1
For most patients, the cause of diffuse midline glioma is unknown. However, there are a few rare, genetic conditions that may increase a patient’s chance of developing diffuse midline glioma, which includes brainstem glioma. For example, patients with neurofibromatosis type 1 (NF1) are more likely to develop brainstem gliomas, among other tumors.2
Diffuse midline gliomas are grade IV and grow rapidly, which can begin impacting critical brainstem functions. In many cases, surgery to remove the tumor may not be possible, depending on the spread of the tumor. This because the brainstem 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 must be started as quickly as possible to control tumor growth.
The most effective and most common initial treatment is radiation therapy. This is typically 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.
Chemotherapy is typically used to treat tumor re-growth, 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 diffuse midline glioma and for diffuse midline glioma that grows despite initial therapy. The majority of clinical research studies include new experimental drugs. In addition, there are new techniques of infusing drugs directly into the tumor (convection-enhanced delivery; CED) that are being studied at UCSF.
Diffuse midline glioma is a serious condition that will be treated by a multidisciplinary team consisting of neurosurgeons, oncologists, and radiation oncologists. The primary goal of treatment is to prolong survival for patients, by slowing the growth of the tumor.
If the treatment does not control tumor growth, the tumor may begin impacting critical body functions like breathing and heart rate. In many cases, initial treatment can control tumor growth, often for many months. Unfortunately, these tumors tend to grow back in less than one year. Treatment at that time is less effective than the initial treatment, and may not control tumor growth; tumor growth may be controlled for only a few months.
In most cases, treatment unfortunately cannot cure this disease. Because of this, many ongoing clinical research trials are searching for more effective therapies for children with diffuse midline gliomas.
- Ostrom, Q.T., et al., CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol, 2017. 19(suppl_5): p. v1-v88.
- Campian, J. and D.H. Gutmann, CNS Tumors in Neurofibromatosis. J Clin Oncol, 2017. 35(21): p. 2378-2385.
This content was reviewed by UCSF pediatric neurosurgeon, Nalin Gupta MD, PhD.
