Astrocytoma

What Causes Astrocytoma?

The 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 expected 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 tumor, 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

In rare cases, astrocytomas appear to be associated with certain genetic disorders, including:

• Neurofibromatosis type 1
• Turcot syndrome
• Li Fraumeni syndrome
• Ollier’s disease

Is Astrocytoma Hereditary?

Most astrocytomas do not appear to be linked to inherited traits. Instead, researchers believe that most gene changes that cause tumors come from external environmental factors or changes within cells that occur randomly and with no external trigger.

However, the specific genetic syndromes sometimes associated with astrocytomas run in families. These syndromes are inherited in an autosomal dominant pattern. This means that children may develop the condition if they inherit even one copy of the mutated gene from either parent. If a parent carries the disorder-causing mutation, they will have a 50 percent chance of having an affected child with each pregnancy.

How Is Astrocytoma Detected?

Grade I and Grade II astrocytomas can be challenging to detect early because their symptoms may be too subtle to notice in the early stages of their growth.

Because Grade III and Grade IV astrocytomas tend to grow rapidly, symptoms often come on suddenly. When symptoms do present, they may vary depending on the location of the tumor and its growth rate. Some symptoms, such as headaches or nausea, are likely caused by pressure created as the tumor presses on surrounding brain tissue. Neurological symptoms, such as vision problems or weakness, may result from the specific areas of the brain affected by the tumor’s growth.

Some common warning signs of aggressive astrocytomas include:

• Headaches, especially when the patient has no history of headaches or the pattern or severity of headaches changes
• Nausea or vomiting that doesn’t have another apparent cause
• Problems with balance
• Blurred vision, double vision, or loss of peripheral vision
• Loss of strength on one side of the body
• Seizures

How Is Astrocytoma Diagnosed?

Doctors may take several different diagnostic steps when they suspect that a patient may have an astrocytoma.

• 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, if any.
• Imaging. Imaging technologies are non-invasive ways to look at brain tissue and possibly detect a tumor’s presence. They may also be used to judge the tumor’s size, location, and growth. 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 used 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 tumor 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 Astrocytoma Treated?

Treatment of an astrocytoma can vary depending on the tumor’s grade. Surgery to completely remove a Grade I tumor that has not infiltrated surrounding tissue is often successful. Surgery to remove higher-grade tumors is typically the first step, but growth into healthy brain tissue usually makes it impossible to remove all the cancer cells. Because of this, follow-up treatments with radiation and/or chemotherapy are generally necessary.

Some extremely slow-growing tumors may require only observation and no immediate treatment.

Grade IV astrocytoma is generally not curable, and treatments aim to control the tumor’s growth for as long as possible.

Surgery

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, when a tumor is located in an especially sensitive area or has infiltrated a critical part of the brain, the surgeon may not be able to remove all of the tumor, and other subsequent treatment options may be necessary.

Even when surgery is not successful in removing the entire tumor, partial removal may help to ease some symptoms.

Radiation Therapy

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 damage to healthy cells. Radiation therapy is often used when the tumor can’t be entirely removed with surgery or when the tumor is in a location that is not safely accessible.

Side effects of radiation therapy may include headaches, memory loss, fatigue, and scalp reactions.

Chemotherapy

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. Chemotherapy can effectively treat some tumors, but its success rate is not high in treating most brain tumors. One obstacle is the body’s blood-brain barrier, a border of cells that protects the brain by blocking the transmission of many substances from the circulatory system into the vulnerable brain tissue. The blood-brain barrier may prevent chemotherapy drugs from reaching the tumor.

Other Therapies

Some other therapies may help to slow the growth of aggressive astrocytomas.

• Tumor treating fields (TTF) use electric fields administered through electrodes on the scalp. The electric fields can interfere with the cancer cells’ ability to reproduce.  
• Targeted drug therapies use medications to attack vulnerabilities unique to the tumor cells, leaving healthy cells alone.

How Does Astrocytoma Progress?

The prognosis for a person with an astrocytoma depends on the tumor’s aggressiveness. Some low-grade astrocytomas may respond well to treatment, and a full recovery may be possible. However, more aggressive tumors are challenging to treat, and their growth is difficult to control.

Because of the rapid growth rate of Grade IV astrocytomas, the long-term outlook for people with this type of tumor is generally poor. Many people with this type of cancer do not survive for more than a year after diagnosis.

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
• Successful surgery to remove the tumor

How Is Astrocytoma Prevented?

There is no clear way to prevent an astrocytoma 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.

Astrocytoma 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 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 astrocytomas 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:

• People with brain tumors often experience depression or anxiety.
• Personality changes resembling bipolar disorder are sometimes an indication of a brain tumor.

Astrocytoma 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 glioblastomas 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 so that drug treatments can more effectively be delivered 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 that may detect tumors at earlier stages or monitor treatment effects on existing tumors more closely.

Astrocytoma Research

Title: Tadalafil to Overcome Immunosuppression During Chemoradiotherapy for IDH-wildtype Grade III-IV Astrocytoma

Stage: Recruiting

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: Repeated Super-selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Relapsed GBM and AA

Stage: Recruiting

Principal investigator: John Boockvar, MD

Lenox Hill Brain Tumor Center

New York, NY

The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in a median overall survival duration of only 9-12 months for GBM and 3-4 years for AA. Initial therapy consists of either surgical resection, external beam radiation, or both. All patients experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality of life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood-brain barrier (BBB). The investigators have shown in a previous phase I trial that a single Super-selective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM. Therefore, this phase I/II clinical research trial is an extension of that trial in that the investigators seek to test the hypothesis that repeated dosing of intraarterial Bevacizumab is safe and effective in the treatment of recurrent malignant glioma. By achieving the aims of this study, the investigators will also determine if IV therapy with Bevacizumab should be combined with repeated selected intraarterial Bevacizumab to improve progression-free and overall survival. The investigators expect that this project will provide important information regarding the utility of repeated SIACI Bevacizumab therapy for malignant glioma and may alter the way these drugs are delivered to patients in the near future.

Title: Trial of C134 in Patients With Recurrent GBM (C134-HSV-1)

Stage: Recruiting

Principal investigator: James Markert, MD

The University of Alabama at Birmingham

Birmingham, AL

The purpose of this project is to obtain safety information in small groups of individuals scheduled to receive escalating doses of C134, a cancer-killing virus (HSV-1) that has been genetically engineered to replicate and kill glioma tumor cells safely. Safety will be assessed at each dose level before proceeding to the next dose level. A unique statistical technique called the Continual Reassessment Method (CRM) will be used to determine when higher doses of virus can be administered. Other objectives of the study include characterization of the activity of C134 after injection into the tumor and of the local and systemic immune responses to C134. Patients will also be followed with MRI scans for potential clinical response to C134. The clinical strategy takes advantage of the virus’s ability to infect and kill tumor cells while making new viruses within the tumors cells; a critical enhancement of this effect is accomplished by the induction of an anti-tumor immune response; both effects are produced by the IRS-1 gene that was placed into the virus by genetic engineering. An additional important component of the research is systematic assessments of the quality of life on treated patients.