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Cossu et al. Mini-invasive Surg 2020;4:60 I http://dx.doi.org/10.20517/2574-1225.2020.52 Page 11 of 15

RS can be considered as first line treatment for small symptomatic CS meningiomas if they present a safe
distance from the optic pathway [38-43] . For large meningiomas, a single fraction RS may be problematic
as the risk of damaging healthy tissues is high and a complication rate of 21% vs. 3% was reported for
[44]
3
meningiomas larger than 10 cm vs. smaller lesions respectively . Furthermore, the distance between the
optic apparatus and the tumor should be carefully considered before choosing the primary treatment: a
distance of at least 5 mm between the meningioma and the optic nerve is considered safe [45,46] . Thus, when
the meningioma is large or too close to the optic pathways, a combined approach with a surgical partial
decompression followed by adjuvant radiation therapy should be preferred.

Whether RS should be routinely performed in the months after surgery or only in cases of postoperative
tumor progression is still a matter of debate. Considering the natural history of meningiomas, we know
that they have a slow tendency to grow but about one fourth of all the meningiomas, in particular those
[47]
calcified, do not seem to grow . In common practice, the irradiation is generally performed 3-6 months
after surgery, while, for minimal residual tumors, radiation is performed when a growth is visible on
follow-up images. This waiting time should help in the recovery of cranial nerves and pituitary gland
surgical manipulation . For atypical meningiomas or meningiomas showing an aggressive behavior with a
[32]
[32]
higher growth rate, radiotherapy should be performed in a shorter period of time . Beside the histological
grade, the previous treatments performed should also be taken into account before planning the treatment.
The inclusion of the dural tail in the TV is matter of debate, and, when an irregular shape is present, the
dose distribution should be accurately checked [48-50] .

For radiosurgical treatments, the dose recommended is between 12 and 15 Gy, which allows a good
compromise between tumor growth control and local neurotoxicity. The risk of damaging the optic
apparatus exists when the dose (to nerve) received is more than 8 Gy. The oculomotor nerve in the
cavernous sinus tolerates doses greater than 20 Gy while the trigeminal nerve is at risk with doses beyond
19 Gy. However, in common practice, the lateral wall of the cavernous sinus, the pituitary gland, and stalk,
the hypothalamus and brainstem should not receive more than 15 Gy.

[51]
In their review of the outcomes of large radiosurgical series, Fariselli et al. showed progression free
survival at 5 and 10 years of 80%-100% and 73%-98%, respectively, and a radiological volume reduction
was observed in 29-69% of cases. No mortality was described as secondary to radiation therapy, while
the reported morbidity included new neurologic symptoms or symptoms of neurotoxicity (optic
neuropathy, pituitary dysfunction, diplopia, and radiation-induced edema), which ranged from 6% to
27.5% [52-55] . A meta-analysis comparing primary RS vs. surgery followed by adjuvant RS showed a lesser
[55]
[56]
rate of neurological morbidity in the primary RS group (27.5% vs. 59.6%) . Kano et al. reported that
improvement in cranial nerve palsies was less likely to occur in patients who had undergone previous
surgery when compared to those treated with radiosurgery alone (14% vs. 39%). One explanation may
be that operated patients had permanently damaged cranial nerves as a result of the surgery. It is well
described that about 75% of recurrences occur outside the treatment field and this reflects the paramount
[57]
importance that needs to be placed on the contouring phase of the treatment .

For recurrent meningiomas, data on the efficacy of repeated RS are limited. Mifepristone and bevacizumab
have been described as promising agents for recurrent tumors, but these results still need to be validated
in larger studies. Nonetheless, these drugs, which target tumor receptors, highlight the importance of
obtaining a histological diagnosis and genomic profiling before their introduction to select effective
targeted therapies [58,59] .

CONCLUSION
The management of CS meningiomas depends on the size and extension of the tumor and on the clinical
manifestations of the patient. The treatment decision varies among a simple annual clinico-radiological