Glioblastoma (GBM)

Glioblastomas (also called GBM) are malignant Grade IV tumors, where a large portion of tumor cells are reproducing and dividing at any given time. They are nourished by an ample and abnormal tumor vessel blood supply. The tumor is predominantly made up of abnormal astrocytic cells, but also contain a mix of different cell types (including blood vessels) and areas of dead cells (necrosis). Glioblastomas are infiltrative and invade into nearby regions of the brain. They can also sometimes spread to the opposite side of the brain through connection fibers (corpus callosum). It is exceedingly rare for glioblastomas to spread outside of the brain.

Glioblastomas may arise de novo, meaning they begin as a Grade IV tumor with no evidence of a lower grade precursor. De novo tumors are the most common form of glioblastoma and tend to be more aggressive and tend to affect older patients. Alternatively, secondary glioblastomas may progress from a lower-grade astrocytic tumors (Grade II or Grade III) and evolve into Grade IV tumors over time. In general, these tumors tend to be slower growing initially, but can progressively become aggressive.

Glioblastomas are usually diagnosed as either IDH-wildtype or IDH-mutant (please see the Genetic Profile section below for more information). IDH-wildtype glioblastomas are more common, tend to be more aggressive, and have worse prognosis than IDH-mutant glioblastomas.

Location:

Glioblastomas are generally found in the cerebral hemispheres of the brain, but can be found anywhere in the brain. IDH mutant glioblastomas tend to arise preferentially in the frontal lobe

Symptoms:

Patients with glioblastomas develop symptoms rapidly due to mass effect from the tumor itself or from the fluid surrounding the tumor (edema) that causes further brain swelling. For example, common symptoms at diagnosis are related to the increased pressure in the brain (nausea, vomiting, and severe headaches which are typically worse in the morning). Patients can also present with neurological symptoms which are dependent on the tumor location (for example, weakness or sensory changes of face, arm or leg, balance difficulties and neurocognitive/memory issues). Other common presentation includes seizures.

Treatment:

Glioblastoma can be difficult to treat since some cells may respond well to certain therapies, while others may not be affected at all. Because of this, the treatment plan for glioblastoma may combine several approaches. 

The first step in treating glioblastoma is a surgical procedure to make a diagnosis, to relieve pressure on the brain, and to safely remove as much tumor as possible. Glioblastomas are diffuse and have finger-like tentacles that infiltrate the brain, which makes them very difficult to remove completely. This is particularly true when the tumors are growing near important regions of the brain that control functions such as language and movement/coordination.

Radiation and chemotherapy are used to slow down the growth of residual tumor after surgery and for tumors that cannot be removed with surgery. Tumor Treating Fields (TTFields) may be also be offered in combination with chemotherapy.

Standard of care treatment for newly diagnosed GBM depends on a variety of factors, including molecular biomarkers (MGMT status & IDH mutation) and age. Recurrent GBM is treated based on the patient’s response to initial treatments and assessment of disease progression.

Incidence:

Glioblastomas represent about 15% of all primary brain tumors. Glioblastomas are slightly more common in men than in women. IDH mutant glioblastomas account for approximately 10% of all glioblastomas.

Glioblastoma (GBM)