What is Gliomatosis Cerebri?
Gliomatosis cerebri is a type of cancer that affects the brain or spinal cord. It is a primary central nervous system (CNS) cancer, meaning that it begins in the CNS and does not migrate from somewhere else in the body.
The term gliomatosis cerebri refers to a pattern of tumor growth in the CNS rather than a specific type of tumor. The growth pattern typically consists of an indistinct spread of tumor cells that infiltrate at least three different brain lobes, often on both sides of the brain.
Gliomatosis cerebri affects a type of brain cell called a glial cell. Glial cells help support the brain’s nerve cells both physically and nutritionally, and some of them assist in healing when the brain is injured. Gliomatosis cerebri often involves a type of glial cell called an astrocyte, but it can also include other glial cell types.
Types of Gliomatosis Cerebri
Gliomatosis cerebri is classified as one of two types depending on its growth pattern:
- Type 1 exhibits widespread tumor cell growth with indistinct borders, with no tumors having a well-defined mass.
- Type 2 shows a widespread, indistinct pattern and includes a well-defined tumor mass.
Gliomatosis cerebri tumors are assigned grades describing their aggressiveness and other characteristics. The tumor grade will influence the disease’s prognosis and the appropriate course of treatment.
- Grade II. This type is relatively slow-growing compared to higher grades, but it is likely to recur after treatment. This grade commonly shows a gene mutation that affects an enzyme called isocitrate dehydrogenase (IDH). IDH mutations are thought to be a key trigger in many types of cancer.
- Grades III and IV. These grades grow quickly and aggressively, and they are challenging to treat.
Symptoms of Gliomatosis Cerebri
Slow-growing gliomatosis cerebri may produce only mild symptoms that can go unnoticed. The specific symptoms vary from case to case and depend on the part of the brain affected. Because the cancer’s growth pattern often doesn’t include large tumor masses that press on sensitive brain tissue, symptoms may be relatively slight despite the extensive spread of tumor cells.
Faster-growing Grade III and Grade IV cancers are more likely to produce severe symptoms that come on quickly.
Common symptoms of gliomatosis cerebri include:
- Memory loss
- Problems with concentration or thought processes
- Fatigue or sleepiness
- Behavior or mood changes
- Weakness or movement problems in a specific part of the body
What Causes Gliomatosis Cerebri?
The specific causes of gliomatosis cerebri remain unknown. The general root cause of a brain tumor is a mutation or damage in the genes that control the growth of affected cells. In a healthy cell, these genes prevent the cell from growing or reproducing too rapidly, and the genes can also determine the cell’s normal lifespan. In a tumor’s cells, the damage to the genes causes the cells to grow and reproduce rapidly, and the cells may live longer than usual. As this rapid growth and reproduction continue, the cells grow into an abnormal mass. In some cases, the tumor produces chemicals that stop the body’s immune system from fighting the cancer, and the tumor cells may also trigger an increase in blood supply to support their growth.
The specific cause of the gene damage that triggers a tumor’s formation is usually not identifiable. Some risk factors that may play a role include:
- Exposure to ultraviolet rays
- Exposure to ionizing radiation
- Exposure to some chemicals
- Chronic stress
- Poor diet
Is Gliomatosis Cerebri Hereditary?
Gliomatosis cerebri does not appear to be linked to inherited traits. Instead, researchers believe most gene changes that cause the tumors result from external environmental factors or changes within cells that occur randomly and with no external trigger.
How Is Gliomatosis Cerebri Detected?
Gliomatosis cerebri can be challenging to detect early because its symptoms may be too subtle to notice. Because Grade III and Grade IV cancers grow more rapidly, symptoms are more likely to come on suddenly. When symptoms do present, they may vary depending on the location of the tumor cells and their growth rate.
Some potential warning signs of gliomatosis cerebri include:
- Headaches, especially when the patient has no history of headaches or the pattern or severity of headaches changes
- Loss of strength in one part of the body
How Is Gliomatosis Cerebri Diagnosed?
Doctors may take several different diagnostic steps when suspecting a patient may have gliomatosis cerebri.
- Neurological exam. A basic neurological exam will test a patient’s reflexes, balance, coordination, strength, vision, and hearing. The results of this exam may prompt a doctor to look further for a tumor’s presence, and it may give a clue to the affected part of the brain.
- Imaging. Imaging technologies are non-invasive ways to look at brain tissue and possibly detect the presence of cancer. They may also be used to judge the cancer’s location and growth pattern. For example, magnetic resonance imaging (MRI) uses a strong magnetic field to produce images of the brain and central nervous system. Computerized tomography (CT) scan may also be employed to look for tumors.
- Biopsy. Doctors may require a biopsy, in which a sample of the tumor is removed and analyzed by a pathologist. The biopsy might be conducted with surgery or, if the cancer is in a particularly hard-to-reach area, using a needle guided by imaging technology. A pathologist’s examination of the tissue sample can help suggest the best treatment course.
How Is Gliomatosis Cerebri Treated?
Treatment of gliomatosis cerebri can vary from case to case. Surgery is typically the first treatment step for most types of brain tumors, but the widespread and ill-defined boundaries of gliomatosis cerebri often rule out surgery as an effective treatment option. Because of this, treatment with radiation and/or chemotherapy is generally necessary.
The most direct way to treat a brain tumor is to remove as much of it as possible with surgical intervention. Typically, the surgery involves opening the skull and removing the tumor while being careful not to damage the surrounding healthy tissue. However, complete removal of gliomatosis cerebri tumor cells is usually not possible. Instead, surgeons will try to remove as much of the cancer as possible while obtaining a tissue sample for biopsy. A biopsy will tell doctors precisely the type of cells involved and help guide subsequent treatment.
Radiation therapies involve using high-energy x-rays to target and kill tumor cells directly. The radiation is typically focused on the tumor to avoid damaging healthy cells. Side effects of radiation therapy may include headaches, memory loss, fatigue, and scalp reactions.
Radiation may be used to treat gliomatosis cerebri, but because the tumor cells are typically spread over a large area of the brain, the required radiation exposure is often relatively extensive, increasing the likelihood of severe side effects.
Chemotherapy uses chemicals that intentionally damage the body’s cells with the expectation that healthy cells can more easily recover from the damage than tumor cells can. The chemotherapy drug temozolomide is sometimes used to treat gliomatosis cerebri.
How Does Gliomatosis Cerebri Progress?
Because of the rapid growth and diffuse nature of gliomatosis cerebri, the long-term outlook for people with this type of tumor is generally poor. The tumors often recur after treatment, and in some cases, other types of tumors, including aggressive glioblastomas, can develop later.
About half of people with gliomatosis cerebri do not survive for more than a year after diagnosis. The three-year survival rate is 25%, and the five-year survival rate is about 19%. However, some factors can increase the possibility of a better outcome or a longer life expectancy. These factors include:
- Age at diagnosis. Younger people tend to have a better prognosis.
- Relatively low level of impairment at diagnosis using a measurement called the Karnofsky Performance Status Scale
- Prompt treatment with radiation and/or chemotherapy
How Is Gliomatosis Cerebri Prevented?
There is no clear way to prevent gliomatosis cerebri from occurring. Even the lifestyle changes that can decrease the risk of many other types of cancer, such as quitting smoking or maintaining a healthy weight, may not reduce the chance of developing a brain tumor.
The only widely accepted preventative measure for brain tumors is the avoidance of high doses of radiation to the head.
Gliomatosis Cerebri Caregiver Tips
Caring for someone with a brain tumor can be even more challenging than the already high demands of caring for someone with any other type of severe and progressive illness. Along with the physical changes that make other cancers and serious illnesses so physically and emotionally exhausting to deal with, brain tumors also often produce psychological and cognitive changes in the patient that can also threaten the caregiver’s well-being.
As you care for your loved one through the progressive stages of their illness, keep these tips in mind:
- Learn as much as possible about the potential effects of your loved one’s specific type of brain tumor. This will allow you to understand how the illness affects the sufferer’s behavior.
- Get help from your friends and family. Caring for a brain tumor patient is a huge task, and you shouldn’t try to do it alone.
- Take time whenever possible to step away from the patient and the illness and find time for yourself. Acknowledge that it is normal and acceptable to need occasional relief from caregiving burdens.
- Find a support group. It can be beneficial to learn that you are not alone and that other people understand what you are going through.
Many people with brain tumors also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with these tumors:
Gliomatosis Cerebri Brain Science
Researchers are currently working on projects to increase our understanding of brain tumors and improve patients’ prognoses. Research is ongoing in areas ranging from risk factor identification to early diagnosis and more effective treatment.
Some currently active areas of research include:
- Gene research. Scientists are working to understand who is at risk for developing gliomas and find ways to prevent the development of the tumors.
- Blood-brain barrier research. Scientists are also trying to find ways to temporarily and safely disrupt the blood-brain barrier to more effectively deliver drug treatments to the site of tumors.
- Targeted drugs and viral therapies. Research is ongoing into drugs and viral agents that can precisely and effectively attack cancer cells without damaging healthy cells.
- Imaging technologies. New imaging technologies are being developed to detect tumors at earlier stages or monitor treatment effects on existing tumors more closely.
Gliomatosis Cerebri Research
Title: Tadalafil to Overcome Immunosuppression During Chemoradiotherapy for IDH-wildtype Grade III-IV Astrocytoma
Principal investigator: Jiayi Huang, MD
Washington University School of Medicine
Saint Louis, MO
Increasing preclinical and clinical data have shown that myeloid-derived suppressor cells (MDSCs) may represent a significant driver of immunosuppression in glioblastoma (GBM, grade IV astrocytoma) and a potential mechanism of treatment resistance to chemoradiotherapy. Tadalafil, an FDA-approved drug with inexpensive cost and excellent safety profile, has been shown to effectively reduce MDSCs and restore T-cell activation in the peripheral blood and the tumor microenvironment. This study investigates the impact of targeting MDSCs in newly diagnosed IDH-wildtype grade III-IV astrocytoma by combining tadalafil with standard of care radiation therapy (RT) and temozolomide (TMZ).
Title: Testing the Addition of the Immune Therapy Drugs Tocilizumab and Atezolizumab to Radiation Therapy for Recurrent Glioblastoma
Principal investigator: Stephen J. Bagley
This phase II trial studies the best dose and effect of tocilizumab combined with atezolizumab and stereotactic radiation therapy in treating glioblastoma patients whose tumor has come back after initial treatment (recurrent). Tocilizumab is a monoclonal antibody that binds to receptors for a protein called interleukin-6 (IL-6), which is made by white blood cells and other cells in the body as well as certain types of cancer. This may help lower the body’s immune response and reduce inflammation. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body’s immune system attack the cancer and interfere with tumor cells’ ability to grow and spread. Fractionated stereotactic radiation therapy uses special equipment to precisely deliver multiple, smaller doses of radiation spread over several treatment sessions to the tumor. The goal of this study is to change a tumor that is unresponsive to cancer therapy into a more responsive one. Therapy with fractionated stereotactic radiotherapy in combination with tocilizumab may suppress the inhibitory effect of immune cells surrounding the tumor and consequently allow an immunotherapy treatment by atezolizumab to activate the immune response against the tumor. Combination therapy with tocilizumab, atezolizumab, and fractionated stereotactic radiation therapy may shrink or stabilize the cancer better than radiation therapy alone in patients with recurrent glioblastoma.
Title: PRO-GLIO: PROton Versus Photon Therapy in IDH-mutated Diffuse Grade II and III GLIOmas
Principal investigator: Petter Brandal, MD PhD
Oslo University Hospital
Proton therapy is a powerful tool enabling oncologists to spare normal tissue around the target for irradiation much better than what can be achieved with photon irradiation. The infiltrative nature of IDH-mutated grade II and III diffuse glioma, however, renders proton therapy a potential problem. A randomized controlled trial (RCT) is the only option when trying to ensure that chances of long-term survival are not impaired, seeking to reduce unwanted late treatment effects. Non-inferiority of proton therapy compared to photon irradiation is the primary endpoint of the RCT.
Hence, PRO-GLIO has two main objectives. First, PRO-GLIO will evaluate if proton therapy is safe in patients with IDH-mutated grade II and III diffuse glioma, showing that survival figures at two years from radiotherapy are not poorer in the proton arm than in the photon arm. Second, researchers want to find the actual number of patients in need of rehabilitation in both arms and evaluate if proton therapy conveys a higher QoL than photon irradiation at two years from radiotherapy.