Malignant meningiomas, known as Grade 3 or anaplastic meningiomas, are rare and aggressive tumors that form in the protective layers covering the brain and spinal cord. While most meningiomas are slow-growing and noncancerous, these high-grade tumors grow and spread quickly, requiring specialized treatment approaches that combine surgery, radiation, and sometimes experimental therapies tested in clinical trials.

Understanding Treatment Goals for Aggressive Meningiomas

When dealing with malignant meningiomas, the main goals of treatment focus on removing as much of the tumor as possible, preventing its return, and maintaining the patient’s quality of life. Unlike typical meningiomas that may simply be watched over time, malignant meningiomas demand immediate action because they grow rapidly and can invade nearby brain tissue or even spread to other organs in the body.^[1]

Treatment decisions depend heavily on where the tumor is located in the brain, how large it has grown, whether it can be completely removed through surgery, and the patient’s overall health condition. The tumor’s grade, determined by examining tissue under a microscope, also plays a crucial role in deciding the treatment path. Grade 3 meningiomas, also called anaplastic meningiomas, are the most severe form and include subtypes such as papillary and rhabdoid meningiomas.^[3]

Medical teams use established treatment protocols approved by professional medical societies, but they also recognize that many patients with these aggressive tumors need access to new therapies being studied in research settings. Clinical trials are testing innovative drugs and treatment combinations that might work better than current options. Understanding both standard approaches and emerging treatments helps patients and families make informed decisions about care.

Standard Treatment Approaches

The foundation of treating malignant meningiomas begins with surgery. The goal is to remove the entire tumor along with the membranes from which it originates. Complete removal decreases the risk of the tumor returning and can sometimes be curative, though this depends on the tumor’s location and whether it has attached to critical nerves or blood vessels.^[4]

During surgery, doctors perform a procedure called a craniotomy, which involves creating a window-like opening in the skull to access and remove the tumor. Surgeons work carefully to preserve healthy brain tissue and vital structures. The type and complexity of surgery varies greatly depending on where the tumor sits. Some locations, such as the base of the skull or areas near important blood vessels supplying the brain, present more challenging surgical conditions and require evaluation by skull base specialists.^[4]

After surgery, patients typically receive radiation therapy, especially for aggressive meningiomas. This treatment is commonly applied in newly diagnosed atypical and anaplastic meningiomas, particularly if complete surgical removal wasn’t possible.^[13] Radiotherapy uses high-energy beams to target any remaining tumor cells and reduce the chance of the cancer coming back.

For tumors that return after initial treatment, additional surgery may be performed, sometimes followed by radiosurgery. This technique delivers a focused, high dose of radiation to a small area. Research has shown that radiosurgery can provide favorable tumor control in patients whose meningiomas have recurred. In one study of fifteen patients with malignant meningiomas, four experienced recurrence, and two were treated with radiosurgery after secondary tumor removal while two others received radiosurgery alone. No further recurrences were reported during the follow-up period.^[6]

The duration of treatment varies by patient. Surgery is a one-time event, though some people need additional operations if the tumor returns. Radiation therapy is typically given over several weeks, with daily sessions scheduled from Monday through Friday. The exact length of the treatment course depends on the total dose needed and the specific radiation technique used.

Side effects from surgery can include temporary swelling of the brain, headaches, seizures, or problems related to the area of the brain that was operated on. Radiation therapy may cause fatigue, skin irritation at the treatment site, hair loss in the treated area, and sometimes long-term effects like memory problems or hormone changes if the radiation affects certain brain structures. In the study of fifteen patients who underwent surgery followed by radiotherapy, only two patients experienced postoperative complications.^[6]

Treatment in Clinical Trials

Because standard treatments don’t always prevent malignant meningiomas from returning, researchers are actively testing new medications in clinical trials. These studies offer hope for patients whose tumors are difficult to control with surgery and radiation alone.

One promising area of research involves medications that block the growth of new blood vessels that tumors need to survive. Angiogenesis is the process by which tumors create their own blood supply, and stopping this process can slow or shrink tumor growth. A medication called bevacizumab is a monoclonal antibody that targets a protein called VEGF, which tumors use to form new blood vessels. Small phase 2 trials have shown promising antitumor activity with this approach.^[13]

Another medication being studied is sunitinib, which belongs to a class of drugs called tyrosine kinase inhibitors. These drugs work by blocking specific enzymes that cancer cells need to grow and divide. Sunitinib has also shown encouraging results in phase 2 clinical trials for meningiomas, particularly those that have come back after initial treatment.^[13]

Clinical trials progress through different phases. Phase I trials test a new drug’s safety and determine the proper dose to use. These studies involve small numbers of patients and focus on identifying side effects. Phase II trials examine whether the drug actually works against the disease and continue to monitor safety. These studies enroll more patients, typically dozens to a few hundred. Phase III trials compare the new treatment to the current standard treatment to see if it works better. These are the largest trials, sometimes involving hundreds or thousands of patients.

Researchers are exploring how meningiomas grow at the molecular level, looking for specific changes in genes and proteins that drive tumor growth. By understanding these mechanisms, scientists can develop drugs that target these specific abnormalities. Some studies focus on molecular pathways that control cell division, while others look at how tumors interact with the immune system.

The scientific community continues to investigate new treatment approaches. Some studies examine whether combining different targeted therapies might work better than using them alone. Others look at whether adding these newer medications to radiation therapy improves outcomes. Preliminary results from various trials have reported improvements in clinical parameters, reduction of symptoms, and positive safety profiles, though more research is needed to confirm these findings.

One advantage of participating in clinical trials is gaining access to potentially effective treatments before they become widely available. However, participants must understand that experimental treatments may not work and could cause unexpected side effects. Clinical trials have strict protocols to protect patient safety and ensure that results are scientifically valid.

Most common treatment methods

• Surgical resection
  • Craniotomy procedure to remove the tumor through an opening in the skull
  • Goal is complete removal of tumor and originating membranes
  • Effectiveness depends on tumor location, size, and involvement of critical structures
  • May be repeated for recurrent tumors
• Radiation therapy
  • High-energy beams target remaining tumor cells after surgery
  • Commonly used for atypical and anaplastic meningiomas in adjuvant setting
  • Applied when complete surgical resection is not feasible
  • Radiosurgery provides focused, high-dose radiation for recurrent tumors
• Targeted drug therapy
  • Bevacizumab: monoclonal antibody targeting angiogenic signaling (VEGF)
  • Sunitinib: tyrosine kinase inhibitor blocking enzymes needed for tumor growth
  • Other tyrosine kinase inhibitors under investigation in phase 2 trials
  • Focus on blocking specific molecular pathways that drive tumor growth
• Observation with imaging
  • Regular monitoring with MRI scans to track tumor progression
  • May be appropriate for very small recurrent tumors in select cases
  • Not typically used for malignant meningiomas due to aggressive nature