# Meningioma: Observation, Surgery, and Adjuvant Radiation

## Overview

Meningiomas are the most common primary intracranial tumors, originating from meningothelial cells, also known as arachnoid cap cells. They account for approximately 37% of all primary central nervous system (CNS) tumors. The majority of meningiomas are benign, classified as World Health Organization (WHO) grade 1, comprising about 80% of cases. However, atypical (grade 2, around 18%) and anaplastic (grade 3, about 2%) subtypes carry a significantly higher risk of recurrence and mortality. Management strategies for meningiomas vary widely, ranging from observation to surgical resection and adjuvant radiation therapy. The choice of treatment depends on factors such as tumor grade, location, extent of surgical resection, and individual patient characteristics.

## Epidemiology and Risk Factors

The incidence of meningiomas increases with age, peaking in the sixth and seventh decades of life. There is a notable female predominance in grade 1 meningiomas, with a female-to-male ratio of approximately 2 to 3 to 1. Established risk factors include prior cranial irradiation, which is the strongest known risk factor, and neurofibromatosis type 2, which is associated with bilateral meningiomas. Hormonal influences also play a role, as evidenced by the expression of progesterone receptors in many meningiomas. Common anatomical locations for these tumors include the convexity of the brain, which is the most frequent site, as well as parasagittal and falcine regions, the sphenoid wing, posterior fossa, olfactory groove, tuberculum sellae, and cerebellopontine angle.

## WHO Grading System (2021)

### Grade 1 (Benign)

Grade 1 meningiomas constitute about 80% of cases and include nine histologic subtypes such as meningothelial, fibrous, transitional, and psammomatous variants. These tumors exhibit a low mitotic rate, defined as fewer than 4 mitoses per 10 high-power fields (HPF), and do not invade the brain parenchyma. After gross total resection (GTR), the five-year recurrence rate ranges from 5 to 10%.

### Grade 2 (Atypical)

Grade 2 meningiomas are defined by the presence of any one of three criteria: 4 to 19 mitoses per 10 HPF, evidence of brain invasion, or at least three of five histologic features including sheeting, spontaneous necrosis, prominent nucleoli, high cellularity, and small cell morphology. The clear cell and chordoid subtypes are automatically classified as grade 2. Following GTR, these tumors have a five-year recurrence rate of 30 to 40%.

### Grade 3 (Anaplastic/Malignant)

Grade 3 meningiomas are characterized by 20 or more mitoses per 10 HPF or overt malignant cytology resembling carcinoma, melanoma, or sarcoma. Papillary and rhabdoid subtypes are automatically assigned to grade 3. After GTR, the five-year recurrence rate is between 50 and 80%, and median survival ranges from 2 to 5 years despite aggressive treatment.

### Molecular Updates (2021)

Recent molecular insights have refined grading criteria. The presence of a TERT promoter mutation or homozygous deletion of CDKN2A/B upgrades any meningioma to grade 3 regardless of histologic features. Emerging molecular classifications, such as DNA methylation profiling, may provide superior prediction of recurrence risk compared to histologic grading alone.

## Observation

Observation is an appropriate management strategy for small, asymptomatic, incidentally discovered grade 1 meningiomas. Natural history studies indicate that growing tumors typically enlarge at a rate of 2 to 4 millimeters per year, although many remain stable for extended periods. Serial magnetic resonance imaging (MRI) surveillance is recommended every six months for the first two years, followed by annual imaging if the tumor remains stable. Intervention is generally triggered by symptomatic growth, significant radiographic progression, or tumor proximity to critical structures such as the optic apparatus or brainstem. Observation is more commonly employed in elderly patients or those with significant comorbidities.

## Surgery

### Simpson Grading System

The extent of surgical resection is classified by the Simpson grading system, which correlates with recurrence risk. Grade I resection involves complete removal of the tumor including the dural attachment and any abnormal bone, associated with a 1 to 9% ten-year recurrence rate. Grade II entails complete tumor removal with coagulation (cautery) of the dural attachment, resulting in a 19% recurrence rate. Grade III involves complete removal without resection or coagulation of the dural attachment, with a 29% recurrence rate. Grade IV corresponds to subtotal resection, which carries a 44% recurrence risk, while grade V is limited to decompression or biopsy only.

### Surgical Considerations

Gross total resection is the goal for tumors that are accessible, as it provides the best long-term control for grade 1 meningiomas. Tumor location significantly influences resectability; convexity meningiomas are most amenable to GTR, whereas skull base tumors, such as those in the cavernous sinus or petroclival region, often require subtotal resection to preserve cranial nerve function. Preoperative embolization may be employed to reduce intraoperative bleeding in highly vascular tumors. The risk of recurrence depends on both the Simpson grade of resection and the WHO tumor grade.

## Radiation Therapy

### Indications

For grade 1 meningiomas, adjuvant radiation therapy (RT) is considered after subtotal resection, although this remains controversial with some clinicians opting for observation. Definitive RT is used for unresectable tumors, and salvage RT is reserved for recurrences. In grade 2 meningiomas, adjuvant RT is recommended following subtotal resection, while its use after gross total resection is debated, with some centers favoring close surveillance. For grade 3 meningiomas, adjuvant RT is recommended regardless of the extent of resection. Recurrent meningiomas may be managed with re-resection, radiation, or a combination of both.

### Fractionated Radiation Therapy

Dose prescriptions for fractionated RT vary by tumor grade. Grade 1 tumors typically receive 50 to 54 Gy delivered in 25 to 30 fractions at 1.8 to 2.0 Gy per fraction. Grade 2 tumors are treated with 54 to 60 Gy in 30 to 33 fractions, while grade 3 tumors receive 59.4 to 60 Gy in 33 fractions, with some advocating doses up to 66 Gy.

| WHO Grade | Fractionated RT Dose | SRS Dose (single fx) | 5-yr Recurrence After GTR | Adjuvant RT Indication |
|---|---|---|---|---|
| Grade 1 | 50–54 Gy / 25–30 fx | 12–16 Gy | 5–10% | STR or unresectable; controversial after GTR |
| Grade 2 | 54–60 Gy / 30–33 fx | 14–18 Gy | 30–40% | Recommended after STR; debated after GTR |
| Grade 3 | 59.4–66 Gy / 33 fx | Not preferred (fractionated) | 50–80% | Recommended regardless of resection extent |

Target delineation begins with the gross tumor volume (GTV), defined as the residual or recurrent enhancing tumor visible on T1 post-contrast MRI, including the dural tail if it is thickened. The clinical target volume (CTV) encompasses the GTV plus a margin of 5 to 10 millimeters for grade 1 tumors and 10 to 20 millimeters for grades 2 and 3, respecting anatomical barriers. The dural tail is generally included in the CTV for grade 1 tumors, although this remains somewhat controversial, and is always included for higher-grade tumors. The planning target volume (PTV) adds an additional 2 to 5 millimeter margin depending on immobilization and image-guided radiation therapy (IGRT) techniques.

Outcomes for grade 1 meningiomas treated with subtotal resection plus RT show a ten-year local control rate of 85 to 95%, comparable to gross total resection alone. Retrospective series suggest improved progression-free survival with adjuvant RT after GTR in grade 2 tumors, although randomized data are lacking. For grade 3 meningiomas, surgery combined with adjuvant RT achieves five-year local control rates of 50 to 70%, but prognosis remains poor.

### Stereotactic Radiosurgery (SRS)

Single-fraction stereotactic radiosurgery is an effective alternative for small meningiomas, typically those less than 3 centimeters or 10 cubic centimeters in volume. The typical marginal dose for grade 1 tumors ranges from 12 to 16 Gy, with higher doses used for grade 2 and 3 tumors. Ten-year local control rates for grade 1 meningiomas treated with SRS are approximately 90 to 95%. SRS is preferred for skull base meningiomas where surgical morbidity is high, such as those in the cavernous sinus, petroclival region, and cerebellopontine angle. Cavernous sinus meningiomas treated with SRS achieve 95 to 97% ten-year control with a low risk of cranial neuropathy, reported at 3 to 5%. SRS is contraindicated when the tumor compresses the optic apparatus unless a fractionated approach is used to respect optic nerve dose constraints.

### Optic Apparatus Considerations

For single-fraction SRS, the maximum dose (Dmax) to the optic nerve and chiasm must be strictly limited to less than 8 to 10 Gy. In fractionated radiation therapy, the optic nerve and chiasm dose should remain below 54 to 55 Gy. When the tumor abuts the optic apparatus, fractionated SRS delivered over 3 to 5 fractions or conventional fractionated RT is preferred over single-fraction SRS to minimize the risk of optic neuropathy. A typical fractionated SRS regimen in this context is 25 Gy delivered in 5 fractions.

<image>A sagittal and axial MRI showing a large parasagittal meningioma with broad dural attachment and dural tail sign. Contours show the GTV (enhancing tumor mass in red), dural tail (orange), CTV (blue, including GTV and dural tail with margin), and PTV (green). Key anatomic landmarks including the sagittal sinus and motor cortex are labeled. A second panel shows a small cavernous sinus meningioma on axial MRI with SRS isodose lines (12 Gy marginal dose), demonstrating the steep dose gradient sparing the adjacent optic nerve and temporal lobe.</image>

<image>A treatment decision algorithm for meningioma management based on WHO grade and extent of resection. For grade 1: GTR leads to observation (MRI surveillance); STR leads to observation vs. adjuvant RT (50-54 Gy) based on growth risk and location. For grade 2: GTR leads to observation vs. adjuvant RT (54-60 Gy) -- debated; STR leads to adjuvant RT recommended. For grade 3: any resection leads to adjuvant RT (60 Gy) recommended. Small unresectable lesions at any grade may be treated with SRS. Molecular markers (TERT, CDKN2A/B) are flagged as modifying risk assessment.</image>

## Key Clinical Pearls

Not all meningiomas require immediate treatment; many small, asymptomatic grade 1 tumors are best managed with observation and serial imaging, particularly in elderly patients. For cavernous sinus meningiomas, stereotactic radiosurgery is often the primary treatment modality because surgical morbidity in this region is substantial, and SRS provides excellent long-term control with minimal risk of cranial neuropathy. The role of adjuvant radiation therapy after gross total resection for grade 2 meningiomas remains one of the most debated issues in neuro-oncology. The ongoing NRG BN003 randomized trial aims to clarify this question, but until results are available, institutional practices vary between observation with close surveillance and adjuvant radiation. It is essential to test grade 2 meningiomas for TERT promoter mutations and CDKN2A/B deletions, as the presence of these molecular markers upgrades the tumor to grade 3 and mandates adjuvant radiation therapy. The dural tail seen on MRI does not always represent tumor tissue; it may reflect reactive dural thickening. Nevertheless, it is generally included in the clinical target volume because microscopic tumor infiltration of the dural tail occurs in approximately 60% of cases. Radiation-induced meningiomas, which arise after prior cranial radiation therapy, tend to be higher grade and multifocal, making management more complex and often requiring repeat surgery and/or radiation with careful attention to cumulative dose constraints.

## References
- Goldbrunner R et al. "EANO guidelines for the diagnosis and treatment of meningiomas." *Lancet Oncol*. 2016;17(9):e383-e391.
- Rogers L et al. "Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO review." *J Neurosurg*. 2015;122(1):4-23.
- Simpson D. "The recurrence of intracranial meningiomas after surgical treatment." *J Neurol Neurosurg Psychiatry*. 1957;20(1):22-39.
- Pollock BE et al. "Stereotactic radiosurgery for cavernous sinus meningiomas." *J Neurosurg*. 2003;99(2):234-239.
- WHO Classification of Tumours Editorial Board. *Central Nervous System Tumours*. 5th ed. Lyon: IARC Press; 2021.