Keywords

Meningiomas are the most frequent primary intracranial neoplasm, for which the treatment strategies range from observation to surgical resection and/or radiotherapy, depending on tumor size, location, histology, and growth pattern over time. Notably, stereotactic radiosurgery and conventionally fractionated radiotherapy are well-established techniques for the treatment of meningiomas with high local control rates and robust long-term follow-up data. Recent studies have applied the principles of SRS to fractionated stereotactic radiotherapy techniques, typically for patients with large tumors or those abutting critical OARs. Fractionation schemes are variable, though early data are promising. This chapter summarizes hypofractionated radiotherapy techniques, including SRS and FSRT, for meningiomas.

1 Pearls

  • Arise from arachnoid cap cells of the arachnoid villi and are the most frequent primary intracranial neoplasm, accounting for one-third of all primary brain tumors.

  • The average annual age-adjusted incidence is 7.86 per 100,000 people, with a median age at diagnosis of 65 years.

  • More frequently diagnosed in women; female:male ratio of 2–3:1.

  • Risk factors include exposure to ionizing radiation (therapeutic or incidental) and genetic conditions such as type 2 neurofibromatosis (NF2) and schwannomatosis.

  • The link between ionizing radiation exposure and risk for meningioma is well established from studies of therapeutic radiation, atomic bomb fallout, and historic use of cranial and scalp irradiation for tinea capitis.

  • The role of sex hormones is less clear, although more than 70% of meningiomas express PR and nearly 40% express ER and androgen receptor.

  • Meningiomas can arise from any location of the dura (see local anatomy below) and presenting symptoms depend largely on anatomic location, time course over which it developed, and presence of edema.

  • While generally slow growing and clinically asymptomatic, there is a higher association with seizure in convexity and parasagittal/falcine locations and those with peritumoral edema.

  • The WHO describes 3 grades (I–III) and 13 histologic subtypes (see Sect. 2).

  • Local anatomy:

    • Meninges: Comprised of three membranes that envelop the brain and spinal cord, including the outer dura mater (including an outer endosteal and an inner meningeal layer), the middle arachnoid mater, and the inner pia mater. The arachnoid and pia mater form the leptomeninges and CSF flows between the two.

      • The dura has four areas of infolding to form the falx cerebri (separating the cerebral hemispheres), the tentorium cerebelli (separating the occipital lobes from the cerebellum), the falx cerebelli (separating the cerebellar hemispheres), and the diaphragma sellae (covering the pituitary gland and sella turcica).

    • Meningiomas develop in various regions: parasagittal/falcine (25%), convexity (19%), sphenoid ridge (17%), suprasellar (9%), posterior fossa (8%), olfactory groove (8%), middle fossa/Meckel’s cave (4%), tentorial (3%), peri-torcular (3%), lateral ventricle (1–2%), foramen magnum (1–2%), and orbit/optic nerve sheath (1–2%) [1]. Of those in the parasagittal region, 49% occur in the anterior one-third of the falx cerebri.

  • Medical workup:

    • History: Assessment of performance status, potential risk factors (prior therapeutic radiation exposure, hormonal status), genetic predisposition syndromes (NF2, schwannomatosis), conditions that can also cause a dural-based lesion (sarcoidosis, hematologic and non-hematologic malignancy, infection/fungal/tuberculosis), and associated neurological symptoms (e.g., seizures, headaches, vision changes).

    • Physical examination: Thorough neurologic examination.

  • Imaging workup:

    • CT: Meningiomas are well-circumscribed, extra-axial masses that display strong, homogenous contrast enhancement, and are iso- or hyper-dense to normal brain parenchyma—which is often displaced adjacently. Approximately 20–30% of meningiomas harbor calcifications, while approximately 50% are associated with hyperostosis or osteolysis in the adjacent bone.

    • MRI: Meningiomas are typically iso- or hypo-intense to gray matter on T1-weighted images, and hyperintense to gray matter on FLAIR sequences, and may display associated peritumoral edema. More than 90% of meningiomas display strong, homogenous contrast enhancement and approximately two-thirds demonstrate an adjacent dural thickening or “dural tail.”

  • Management strategies include observation, surgical resection, and/or radiotherapy, depending on tumor size, location, histology, and growth pattern over time.

2 Staging, Grading, and Other Classifications

The WHO describes 3 grades (I–III) and 13 histologic subtypes of meningioma. The WHO grade is prognostic, with strong associations between grade, RFS, and OS (Table 5.1, [2]). Surgery is often an appropriate therapy for benign (WHO Grade I) meningiomas, with extent of resection based on the Simpson grade and correlating to the rate of tumor recurrence (Table 5.2, [3, 4]).

Fig. 5.1
figure 1figure 1

A 2.6 cc left frontal meningioma; GTV target delineation in red. (a) Simulation CT (left), post-contrast T1-weighted MRI (right). (b) Treatment plans with prescription IDL in green, effective normalization 90%. FSRT, 3 GyRBE protons × 13 fx (39 GyRBE total). Simulation CT axial (left) and coronal (right). IDL, isodose line

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Table 5.1 The 2016 WHO meningioma grading criteriaa
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Table 5.2 Simpson grade of resection and recurrence riska
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3 Patient Selection for SRS or FSRT

  • Factors influencing treatment recommendations include patient age, medical comorbidities, cranial nerve deficits, tumor size and/or growth rate, presenting symptoms, competing symptoms (i.e., contralateral hearing or vision loss), and proximity to critical organs at risk (OAR, such as brainstem, cochlea, optic apparatus, eloquent brain).

  • For single-fraction SRS, targets should generally be:

    • <3 cm.

    • Not directly abutting critical OARs.

    • >3–5 mm from the optic apparatus (optic chiasm, optic nerves) to achieve adequate dose falloff between the prescription dose and OAR tolerance (<8–10 Gy for single-fraction SRS).

  • For FSRT, tumors may be larger (>3–4 cm), in closer proximity to or involving OARs.

  • Case-by-case consideration of SRS for parasellar meningiomas (including cavernous sinus and medial sphenoid wing) given proximity to optic apparatus.

  • Optic nerve sheath and tuberculum sellae meningiomas are generally a contraindication for SRS in patients with preserved vision given that the lowest therapeutic dose (12–13 Gy) exceeds optic apparatus tolerance (8–10 Gy).

4 Treatment Planning Considerations (Table 5.3)

Table 5.3 Treatment planning considerations
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5 Commonly Used Dose/Fractionation Schemes (Table 5.4)

Table 5.4 Commonly used dose/fractionation schemes
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6 Normal Tissue Tolerances

Rates of radiation-induced optic neuropathy are very rare <8–10 Gy but reach >10% at single-SRS doses between 12 and 15 Gy [11, 12] (Table 5.5). In a study by Kano et al., patients with vestibular schwannomas treated with GammaKnife SRS had improved serviceable hearing preservation if they received a central cochlea dose <4.2 Gy [13].

Table 5.5 Relevant literature
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7 Patient Management Considerations

  • Premedication/prophylactic medication:

    • There is no standard premedication regimen.

    • Consideration of steroids, benzodiazepines, and/or anticonvulsants is dependent on severity and progression of symptoms or neurologic deficit(s), treatment volume/location and number of fractions, if known prior seizures, as well as patient age and/or medical comorbidities.

  • Acute toxicity: Side effects are tumor location dependent and include, but are not limited to, rare transient nausea, headache, alopecia, skin erythema, conjunctivitis, and fatigue.

  • Late toxicity: Transient complications (3%), permanent neurologic deficits (5–9%), radionecrosis, or delayed CN deficits (<6%) [16, 17].

8 Follow-Up

  • H&P every 6–12 months.

  • Yearly imaging (ideally MRI, CT with contrast if non-tolerant, or MRI contraindicated) for 4–5 years, then every 2 years.

  • For cavernous sinus or base of skull locations, monitor for hypopituitarism with regular serum analyses annually or as needed.

    • Recommend endocrinologist for long-term management and monitoring of endocrine dysfunction.

9 Relevant Literature

  • Stereotactic radiosurgery and conventionally fractionated radiotherapy are well-established techniques for meningiomas with high local control rates and extensive long-term follow-up data.

  • While FSRT is a promising treatment modality in patients with large tumors or those abutting critical OARs, more mature data are needed for robust evaluation of the long-term efficacy and toxicity profile for FSRT compared to SRS or conventionally fractionated radiotherapy (Table 5.6).

Table 5.6 Relevant literature
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