Malignant glioma is a fast-growing type of brain tumor that requires urgent and carefully planned treatment. The main goal of therapy is to slow disease progression, relieve symptoms, and maintain the best possible quality of life for as long as possible.

Why Treating Malignant Glioma is a Complex Challenge

Malignant gliomas are among the most aggressive brain tumors that can develop in adults. These tumors arise from glial cells, which are the supporting cells that normally protect and nourish nerve cells in the brain. When these glial cells begin to grow out of control, they form tumors that can quickly invade surrounding healthy brain tissue. Unlike many other cancers, malignant gliomas rarely spread outside the brain, but they grow rapidly within it, making them particularly difficult to treat.^[1][2]

Treatment for malignant glioma is highly individualized. The approach depends on several factors, including the tumor’s exact location in the brain, its size, how fast it is growing, and the patient’s overall health and age. Some patients may be candidates for aggressive treatment involving multiple therapies, while others may benefit from a more conservative approach focused on symptom management and quality of life.^[3]

Medical professionals recognize that malignant gliomas include several types of tumors, such as glioblastoma (the most aggressive form), anaplastic astrocytoma, and anaplastic oligodendroglioma. All of these are considered high-grade tumors, meaning they grow quickly and require immediate medical attention. The standard treatment combines surgery, radiation therapy, and chemotherapy, but researchers are continuously exploring new therapies in clinical trials to improve outcomes for patients facing this challenging disease.^[3][10]

Standard Treatment: The Foundation of Care

The cornerstone of malignant glioma treatment begins with surgery. The main goal of the operation is to remove as much of the tumor as possible without damaging vital brain structures. This is called a gross total resection. Surgeons use advanced imaging techniques during the operation to identify tumor boundaries and preserve normal brain tissue. Studies have shown that removing a larger portion of the tumor can lead to better outcomes and longer survival. However, because malignant gliomas often have microscopic extensions that spread into surrounding brain tissue, surgery alone cannot eliminate the disease entirely.^[9][13]

Following surgery, patients typically receive radiation therapy. This treatment uses high-energy beams to destroy any remaining tumor cells that could not be removed during surgery. The radiation is carefully directed at the area where the tumor was located, plus a surrounding margin of brain tissue, to target invisible tumor cells that may have spread. The standard approach is called involved-field radiotherapy, and the total dose is usually between 6,000 and 6,500 cGy, delivered over approximately six weeks. Radiation therapy has been proven to improve survival rates when given after surgery.^[13]

Chemotherapy is another critical component of standard treatment for malignant gliomas. The most commonly used chemotherapy drug is temozolomide, which is taken as a pill by mouth. Patients usually take temozolomide at the same time as they receive radiation therapy, and then continue taking it for several additional months afterward. This drug works by damaging the DNA inside tumor cells, which prevents them from dividing and growing. Research has shown that adding temozolomide to surgery and radiation can extend survival for many patients with malignant glioma, particularly those with glioblastoma.^[9][13]

Other chemotherapy options include nitrosourea drugs such as carmustine (also called BCNU) or a combination regimen known as PCV-3, which includes procarbazine, lomustine (CCNU), and vincristine. These medications may be used instead of or in addition to temozolomide, depending on the specific type of tumor and individual patient factors. Anaplastic oligodendrogliomas, for example, often respond particularly well to chemotherapy, especially when the tumor has certain genetic characteristics.^[13]

The duration of treatment varies by patient, but the typical course includes surgery followed by about six weeks of combined radiation and chemotherapy, then an additional six to twelve months of chemotherapy alone. During this time, patients undergo regular brain scans, usually every two to three months, to check for signs of tumor growth. Blood tests are also performed frequently to monitor for side effects of chemotherapy, particularly changes in blood cell counts that might increase the risk of infection or bleeding.^[9]

Some patients may receive additional treatments as part of standard care. Carmustine wafers, also known as Gliadel wafers, are small biodegradable discs that can be placed directly into the cavity left behind after tumor removal. These wafers slowly release chemotherapy directly into the surrounding brain tissue over several weeks, potentially extending survival by a few months. Another approved treatment option is tumor-treating fields, a device that delivers low-intensity electrical fields to the scalp. Patients wear this device for most of the day, and studies suggest it can modestly improve survival when combined with standard chemotherapy.^[18]

Innovative Therapies Being Tested in Clinical Trials

Because standard treatments for malignant glioma offer limited long-term control of the disease, researchers around the world are actively testing new approaches in clinical trials. These trials represent hope for better outcomes and are exploring therapies that work in fundamentally different ways than traditional chemotherapy and radiation.

One of the most promising areas of research involves targeted therapies that attack specific genetic mutations found in some malignant gliomas. Scientists have discovered that certain brain tumors have mutations in genes called IDH1 or IDH2. These mutations change how tumor cells process energy and grow. Several drugs called IDH inhibitors are now being tested in clinical trials. These medications are designed to block the abnormal protein produced by mutated IDH genes, potentially slowing tumor growth with fewer side effects than traditional chemotherapy. Early results from Phase I and Phase II trials have shown that IDH inhibitors can be well tolerated and may postpone the need for more aggressive treatments in some patients.^[20]

Another exciting avenue of research focuses on immunotherapy, which harnesses the body’s own immune system to fight cancer. Several different immunotherapy approaches are being studied for malignant gliomas. One strategy uses checkpoint inhibitors, drugs that remove the “brakes” on immune cells, allowing them to recognize and attack tumor cells more effectively. While checkpoint inhibitors have shown remarkable success in treating some other cancers, their effectiveness against brain tumors has been more limited so far, and trials continue to explore ways to make them work better in this disease.^[12]

Vaccine therapies represent another immunotherapy approach being tested in clinical trials. These experimental vaccines are designed to train the immune system to recognize specific proteins found on the surface of glioma cells. When the vaccine is given, it stimulates the patient’s immune cells to seek out and destroy tumor cells bearing those proteins. Some vaccine trials have shown promising preliminary results, with certain patients experiencing longer survival times, though much more research is needed to determine which patients might benefit most from this approach.

Oncolytic virus therapy is an innovative treatment strategy that uses genetically modified viruses to attack cancer cells. Researchers have engineered viruses, such as modified herpes simplex virus, that can infect and kill tumor cells while leaving healthy brain tissue unharmed. When the virus destroys a tumor cell, it releases new viral particles that can then infect nearby tumor cells, spreading the destruction throughout the tumor. Additionally, as the virus kills tumor cells, it releases tumor-specific proteins that can trigger an immune response, effectively creating a personalized vaccine effect. Clinical trials of oncolytic viruses are being conducted at specialized cancer centers, and early-phase studies are evaluating the safety and effectiveness of different viral constructs.^[14]

Researchers are also exploring treatments that target the tumor’s blood supply. Malignant gliomas often stimulate the growth of new blood vessels to feed their rapid expansion. Drugs called anti-angiogenic agents, such as bevacizumab, work by blocking the signals that tumors use to create new blood vessels. Bevacizumab is already approved for treating recurrent glioblastoma in many countries, and trials are investigating whether it works better when combined with other treatments or used at different stages of the disease.^[12]

Clinical trials are also examining combination therapies that use multiple treatment approaches together. For example, some trials are testing whether adding an IDH inhibitor to standard chemotherapy improves outcomes, or whether combining immunotherapy with radiation therapy makes the immune system more effective at recognizing tumor cells. Phase III trials, which compare new treatments directly against current standard care in large groups of patients, are critical for determining whether these innovative approaches truly offer better results.

Eligibility for clinical trials depends on many factors, including the specific type of tumor, whether it is newly diagnosed or has returned after previous treatment, the patient’s age and overall health, and the availability of trials at nearby treatment centers. Clinical trials are conducted at major cancer centers throughout the United States, Europe, and other regions around the world. Patients interested in participating should discuss options with their healthcare team, who can help identify appropriate trials and explain the potential benefits and risks.^[20]

Most common treatment methods

• Surgery
  • Gross total resection to remove as much tumor as possible
  • Surgical goal is maximum tumor removal while preserving brain function
  • Advanced imaging techniques used during surgery to identify tumor boundaries
  • Carmustine wafers may be placed in surgical cavity to deliver local chemotherapy
• Radiation therapy
  • Involved-field radiotherapy targeting tumor area and surrounding tissue
  • Standard dose of 6,000 to 6,500 cGy delivered over approximately six weeks
  • Stereotactic radiotherapy may be used in some cases for focused treatment
• Chemotherapy
  • Temozolomide taken orally during and after radiation therapy
  • Nitrosourea drugs including carmustine (BCNU)
  • PCV-3 regimen combining procarbazine, lomustine (CCNU), and vincristine
  • Treatment typically continues for six to twelve months after radiation
• Targeted therapy
  • IDH inhibitors targeting tumors with IDH1 or IDH2 mutations
  • Anti-angiogenic agents like bevacizumab that block tumor blood vessel growth
  • Drugs targeting specific molecular pathways involved in tumor growth
• Immunotherapy
  • Checkpoint inhibitors that activate immune system against tumor cells
  • Vaccine therapies designed to train immune system to recognize tumor proteins
  • Oncolytic virus therapy using modified viruses to destroy cancer cells
• Device-based therapy
  • Tumor-treating fields device delivering electrical fields to the scalp
  • Worn for most of the day to disrupt tumor cell division
  • Used in combination with chemotherapy for newly diagnosed glioblastoma