GLIOBLASTOMA

What are brain tumors?

Brain tumors are uncontrolled and abnormal cell growth in the brain or the spine (central nervous system or CNS), causing life-threatening complications, as well as damage to the brain. These may either be primary (one that starts in the brain) or secondary (one that starts in another part of the body and metastasizes to the brain). Primary tumors may be classified as glial tumors or gliomas (composed of glial cells) and non-glial tumors (developed on or in the structures of the brain, including nerves, blood vessels, and glands). About 80% of malignant brain tumors may be categorized as glioma. The highest-grade glioma or glioblastoma multiforme is one of the most lethal cancers in adults recording an annual incidence of 5.26 per 100,000 population and 17,000 new diagnoses per year. The incidence rate of glioblastomas is 1.58 times higher in men than in women in the United States. More than 80% of cases of malignant gliomas are glioblastomas and these are histologically characterized.


Classification

Glioblastomas are heterogeneous or pleomorphic because the cells in these tumors vary in size and shape and are derived different origins. This heterogeneous nature of glioblastomas poses a maximum hindrance in the development of an effective therapeutic approach with a uniform result. Radiation-induced glioblastomas have been observed after several years of therapeutic radiation indicated for another tumor or condition. Environmental exposure to vinyl chloride, pesticides, smoking, petroleum refining, and synthetic rubber manufacturing have been loosely associated with the development of gliomas. An increased risk of glioma development is seen in some specific genetic diseases, such as neurofibromatosis 1 and 2, tuberous sclerosis, Li-Fraumeni syndrome, retinoblastoma, and Turcot syndrome; however, less than 1% of glioma cases have been associated with a hereditary disease.

According to the new 2016 WHO Classification of Tumors of the Central Nervous System, glioblastomas are now mainly classified according to the status of isocitrate dehydrogenase (IDH) mutation: IDH-wildtype (~90%) or IDH-mutant (~10%).


Diagnosis and Treatment

The diagnosis of brain tumors primarily depends on imaging techniques that can accurately pinpoint the location of brain tumors such as magnetic resonance imaging (MRI) and computed tomography (CT or CAT scan). A scan of the brain is followed by a biopsy. Depending on the location of the tumor, the biopsy and removal of the tumor may be performed at the same time. If doctors cannot perform a biopsy, then they determine a treatment plan based on the brain scan results. The mainstay of glioblastoma treatment is surgery, followed by radiation and chemotherapy. Surgery aims at removing the tumor as much as possible without injuring the surrounding normal brain tissue that is necessary for normal neurological function. However, glioblastomas are surrounded by migrating, infiltrating tumor cells that invade surrounding tissues, thus making it practically impossible to ever remove the entire tumor. The doctors thus perform the surgery to reduce the amount of solid tumor tissue within the brain, remove those cells in the center of the tumor that may be resistant to radiation and/or chemotherapy, and reduce intracranial pressure, which may aid to prolong the lives of some patients and improve the quality of remaining life. After the wound from surgery has healed properly, radiation therapy and chemotherapy are utilized. Radiation therapy is repeated for a total of 10 to 30 cycles depending on the type of tumor.


The current standard of treatment for glioblastomas is chemotherapy with the drug temozolomide, which is administered every day during radiation therapy and then for six cycles after radiation during the maintenance phase. Tumor treating fields are another relatively new and different treatment modality that is introduced during the maintenance phase of radiation therapy. It creates alternating electrical fields, which prevents the growth and division of cancer cells. Lomustine (chemotherapy) and Bevacizumab (targeted therapy) are usually applied when the tumor progresses.


Written By: Souvik Datta, Ph.D., Lawrence D. Jones, Ph.D.