The most common primary brain tumor is undergoing a revolution in how it is diagnosed and treated.
Imagine being told you have a brain tumor, and then learning it's one of the most common types—a meningioma. For approximately 39,000 Americans who receive this diagnosis each year, the journey begins with understanding this complex condition 2 .
Meningiomas arise from the meninges, the protective layers surrounding the brain and spinal cord. While approximately 80% of these tumors are benign, their location can still cause serious health issues, including seizures, vision problems, and cognitive challenges 2 6 .
Recent breakthroughs in molecular profiling and targeted therapies are transforming how we classify and treat meningiomas, offering new hope to patients with recurrent or aggressive forms.
Meningiomas represent about 41.7% of all central nervous system tumors, making them the most frequently diagnosed primary brain tumors in adults 6 . They affect about 10.15 out of every 100,000 people, with incidence rates rising with age and peaking in people in their 70s and 80s 6 .
These tumors originate from arachnoid cap cells in the meninges and can develop anywhere these protective coverings exist 8 . They're categorized into three grades based on their growth potential and likelihood of recurrence:
of all CNS tumors are meningiomas
Americans diagnosed annually
| WHO Grade | Classification | Prevalence | Recurrence Rate | Key Characteristics |
|---|---|---|---|---|
| Grade 1 | Benign | 75-80% | 7-25% | Slow-growing, excellent prognosis with complete resection |
| Grade 2 | Atypical | 20-25% | 29-52% | Intermediate growth, higher recurrence risk |
| Grade 3 | Malignant | 1-6% | 50-94% | Aggressive, invades brain tissue, may metastasize |
The 2021 WHO Classification of Central Nervous System Tumors marked a pivotal shift by incorporating molecular criteria alongside traditional histology for the first time 1 6 . This recognizes that how a tumor looks under the microscope doesn't always predict its behavior.
The cIMPACT-NOW consortium has further refined these standards, proposing that meningiomas with chromosomal arm 1p deletion in combination with 22q deletion and/or NF2 mutations should be classified as CNS WHO grade 2, even if they appear grade 1 under microscopy 1 .
A multi-institutional team led by researchers at Mayo Clinic examined over 1,200 meningioma samples from patients across Canada, Germany, and the United States 3 . Their goal was to determine whether TERT expression levels—even without full TERT mutations—could predict tumor behavior.
The researchers analyzed tumor specimens for:
The findings, published in Lancet Oncology, revealed that nearly one-third of meningiomas without TERT mutations showed high TERT expression 3 . These patients experienced significantly earlier tumor regrowth compared to those without TERT expression, though their outcomes were better than patients with full TERT mutations.
Most notably, researchers discovered that TERT-positive tumors behaved as if they were one grade worse than their official diagnosis. A grade 1 tumor with TERT expression acted more like a grade 2 tumor, and a grade 2 tumor with TERT expression behaved like a grade 3 tumor 3 .
"This makes TERT a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease," said Dr. Gelareh Zadeh, the study's senior author 3 .
| Tumor Grade | TERT Status | Observed Behavior | Clinical Implications |
|---|---|---|---|
| Grade 1 | High Expression | Similar to Grade 2 | May require closer monitoring, consider earlier intervention |
| Grade 2 | High Expression | Similar to Grade 3 | Likely benefits from more aggressive treatment |
| Grade 3 | High Expression | Highly aggressive | Maximum therapeutic intervention warranted |
While surgery and radiation remain cornerstone treatments, several innovative approaches are showing promise for recurrent or aggressive meningiomas.
Somatostatin receptor type 2 (SSTR2) is expressed in 80-95% of meningiomas, making it an ideal therapeutic target 5 6 .
The LUMEN-1 trial (EORTC-2334-BTG), activated in March 2025, is the first prospective randomized trial investigating [¹⁷⁷Lu]Lu-DOTATATE in recurrent meningioma 5 .
This approach uses a radioactive compound that binds specifically to SSTR2, delivering targeted radiation to tumor cells while sparing healthy tissue. Early studies have shown disease control rates of 57-63% in refractory meningiomas 5 6 .
Early disease control rate: ~60%Several targeted agents are under investigation for meningiomas with specific molecular profiles:
Researchers at the University of Plymouth recently identified a protein called ANXA3 that drives growth in certain meningioma cells 7 . In laboratory experiments, blocking ANXA3 slowed or completely stopped tumor cell growth, particularly in meningiomas resulting from NF2 mutations 7 .
"This research brings hope — not just for treatment, but for better outcomes and quality of life," said Dr. Karen Noble of Brain Tumour Research 7 .
Inhibition shows promise in NF2-mutated meningiomas
| Reagent | Function | Application in Meningioma Research |
|---|---|---|
| [¹⁷⁷Lu]Lu-DOTATATE | SSTR2-targeting radiopharmaceutical | Delivers targeted radiation to meningioma cells in PRRT 5 |
| [⁶⁸Ga]Ga-DOTATATE | SSTR2-targeting PET tracer | Visualizes meningiomas and identifies candidates for PRRT 6 |
| Anti-ANXA3 agents | Inhibits ANXA3 protein function | Blocks growth driver in NF2-mutated meningiomas 7 |
| FAK Inhibitors | Blocks focal adhesion kinase | Targets NF2-deficient meningiomas 4 8 |
| CDK Inhibitors | Inhibits cell cycle progression | Slows tumor growth in aggressive meningiomas 4 |
Despite these promising developments, significant challenges remain. Validated biomarkers for treatment response are still lacking, and resistance mechanisms in aggressive meningiomas are not fully understood 8 . The blood-brain barrier also continues to pose obstacles for drug delivery, though techniques like convection-enhanced delivery are being explored to overcome this limitation 8 .
Future progress will require large-scale, biomarker-driven clinical trials to confirm the efficacy of emerging treatments and establish optimal combination regimens 8 . The integration of molecular profiling into standard diagnosis will continue to refine our ability to match patients with the most effective therapies.
Establishing reliable biomarkers for treatment response and resistance mechanisms.
Large-scale trials to confirm efficacy of emerging targeted therapies.
Developing methods to overcome the blood-brain barrier for better drug penetration.
Exploring synergistic effects of multiple treatment approaches.
The landscape of meningioma care is undergoing a remarkable transformation, moving from a one-size-fits-all approach to personalized, precision medicine. As research continues to unravel the molecular complexities of these common brain tumors, patients stand to benefit from more accurate prognoses and increasingly effective, targeted treatments.
"The work being done by our Centre of Excellence at Plymouth is world-leading," noted Dr. Karen Noble, "and now is the time to build on this momentum" 7 . With ongoing advances in molecular profiling and innovative therapies, the future for meningioma patients looks increasingly hopeful.