Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5 years of clinical practice

Osama S. Abdelaziz; Alaa Kandil; Shaaban El-Assaal; Amro Abdelaziz; Yosry Rostom; Yaser Rashed

doi:10.1007/s10143-010-0288-z

Neurosurgical Review

January 2011, Volume 34, Issue 1, pp 87–99 | Cite as

Linear accelerator-based stereotactic radiosurgery of intracranial meningiomas: results of the first 5 years of clinical practice

Authors
Authors and affiliations

Osama S. AbdelazizEmail author
Alaa Kandil
Shaaban El-Assaal
Amro Abdelaziz
Yosry Rostom
Yaser Rashed

Original Article

First Online: 09 October 2010

Received: 01 January 2010

Revised: 22 March 2010

Accepted: 27 May 2010

Abstract

Meningiomas are mostly benign but some are atypical or malignant. Surgical resection is curative when complete removal of benign meningiomas is contemplated. Incompletely excised and recurrent tumors are frequently treated with fractionated radiation therapy or stereotactic radiosurgery. The purpose of this study is to evaluate the short-term radiological and functional outcomes of a single center using linear accelerator (Linac) stereotactic radiosurgery for the treatment of intracranial meningiomas. Twenty-nine patients (12 males and 17 females) with 30 meningiomas, in different brain locations (skull base and non-skull base meningiomas), were treated with Linac-based stereotactic radiosurgery. The mean tumor volume was 6.3 cm³, and the mean tumor marginal and maximum doses were 10.9 and 15 Gy, respectively. The median prescribed isodose line was 80%. The patients were followed-up for a minimum of 3 years. Regarding radiological outcome, nine (30%) meningiomas demonstrated evident volume reduction, 19 (63.3%) meningiomas remained unchanged, and two (6.7%) meningiomas increased in size after radiosurgery. The local tumor control rates for skull base meningiomas and non-skull base meningiomas after radiosurgery were 90.9% and 100%, respectively. Regarding functional outcomes, 64% of patients presenting with cranial neuropathies showed improvement of their cranial nerve functions and 29% of patients remained unchanged. One patient had temporary trigeminal neuropathy. Although radiosurgery for meningiomas is generally effective and quite safe in achieving high control rates with minimum morbidity over short- and intermediate-term periods of follow-up, tumor progression might occur in a delayed manner after initial apparent control for few years. We recommend continued follow-up for longer periods to better assess the long-term outcomes.

Keywords

Linear accelerator Meningiomas Radiosurgery Stereotaxy

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Notes

Comments

Ahmed Farhoud, Alexandria, Egypt

Radiosurgery is currently considered a good and safe treatment option in small meningiomas causing minor or no symptoms and in case of subtotal resection of large meningiomas. In this study, the authors present their experience with 29 patients with meningioma treated with Linac-based radiosurgery at the Neurosurgery Department of Alexandria University. The main disadvantage of their study is the small number of patients compared to similar studies that have been already published, but knowing the difficulties confronting the establishment of this sophisticated technique in a third world country, I find it worthwhile to present their preliminary experience and I admire their courage and persistence.

The authors have clearly shown that the results of Linac-based SRS are comparable to those of Gamma knife. Linear accelerators still have the advantage of being cheaper and easier to install.

Despite the promising results of stereotactic radiosurgery, there are still some limitations and uncertainties with this modality. The small size of the tumor needed for a good response, the lack of histological verification in some cases and the increasing reports about the delayed complications occurring years after treatment are some of the disadvantages of this modality. However, no one can argue that radiosurgery is a major addition to the treatment options of skull base meningioma

Jean Régis, Marc Leveque, Pierre Hugues Roche, Marseille, France

We consider radical microsurgical removal as the reference for treatment of intracranial meningiomas (20). In all the situations where this goal seems achievable there is little room for radiosurgery. When the complete resection of a meningioma appears unachievable safely due to its topography and close relationship to critical structures, radiosurgery may be considered upfront or as a combined treatment after a first stage of subtotal removal. Analysis of the modern literature indicates that radical microsurgical resection of skull base meningioma is achieved in 50–60% of cases, with permanent morbidity reaching 20%, and a mortality rate of 5–15% (2, 3) and with a recurrence of 10% at 10 years after surgery (8). Additionally, considering that 90 to 95% of diagnosed meningiomas are benign (WHO grade I), the preservation of quality of life together with the control of tumor growth should be the major goals of the treatment of this selected group of meningiomas.

In this perspective, stereotactic radiosurgery has become an effective alternative to microsurgery. Meningiomas are usually sharply delineated, encapsulated, and rarely infiltrate the brain tissue. Their clear identification by CT and MRI allows precise definition of target volumes and steep radiation falloff with sparing of adjacent normal tissue. Additionally, there are radiobiological arguments to consider that meningioma tissue responds better to single session and high-dose radiation therapy than low-dose fractionated regimen.

In the natural course of skull base meningiomas, spontaneous recovery and fluctuations of symptoms like cranial nerve deficits can be expected without any treatment. Thus, clinical improvement may be mistakenly attributed to radiosurgery without adequate long-term follow-up. Additionally, Meningiomas are frequently very slow-growing tumors. Thus, long-term follow-up is also needed for evaluation of tumor response considering the slow growth of a large amount of meningiomas. We consider that a serious evaluation of any neurosurgical approach of meningiomas requires large populations (minimum 100 patients in our summary of the modern literature) and a minimum follow-up of 5 years ideally 10 years. When patients with shorter follow-up are kept in the study population results must be presented as actuarial rates at 5 and 10 years. Recent papers fulfilling these criterions are summarized in Fig. 1. Although the 5-year tumor control rate is uniformly beyond 90% for WHO grade I meningiomas, the results are less favorable for aggressive meningiomas. Kondziolka et al. (13) indicated a tumor control of 50 and 17% for grades II and III meningiomas, respectively. In these cases, particularly in grade III meningiomas, an aggressive management strategy combining extensive microsurgery with fractionated radiation therapy should be considered. Malignant and atypical meningiomas are clearly more likely to fail to respond to radiosurgery (13). This is the reason why in Fig. 1 the actuarial rates are depicting only WHO 1 class tumor behavior.

In this respect, the paper from Abdelaziz et al. is providing us with no new valuable data.

In this study, the authors present their experience with only 29 patients with meningioma treated with Linac-based radiosurgery at the Neurosurgery department Alexandria University. However, knowing the difficulties confronting the establishment of this sophisticated technique in a third world country, the merit of this paper is to demonstrate the feasibility of radiosurgery even with limitated resources and with acceptable results. Of course, methodological limitations of their paper are not allowing the authors to compare their results to those of the main series of the literature. The main limitation of their study is the very small number of patients compared to similar studies that have been already published.

Most series indicate excellent results on tumor control comprised between 86.7% to 100% (5–7, 10, 13–15, 19). Respective distribution of stabilization and regression of tumor size after GKS is diversely estimated. Huge variations in the length of follow-up may also explain this heterogeneous data. Moreover, Zachenhoffer showed that patients could be “late responders” with tumor starting to shrink beyond 4 years after GKS. Several studies have reviewed the factors associated with failure.

The toxicity from radiosurgery of meningiomas comes mostly from symptomatic edema or damage to cranial nerves. In the majority of cases, the morbidity is temporary and rarely disabling, however, permanent complications have been reported in 0.4 to 6.5% of cases (5–7, 10, 13–15, 19). Flickinger et al. (4) showed that in their hands, the risk of post-radiosurgery sequelae lowered in patients treated after 1991, which corresponded to the routine use of stereotactic MRI during treatment planning, and lowering of delivered doses. Symptomatic peritumoral imaging changes developed in 4% of the patients reported by Kondziolka et al. (13) at a mean of 8 months and in 9.3% of patients who were followed by sequential MRI in another study (1). In this later series, imaging changes developed at a mean of 7.8 months (range 2.8 to 48.9 months) and were sustained for 13.5 months. Mechanisms of these changes are unclear. They are attributable to vasogenic edema with a potential role played by vascular endothelial growth factor or radiation injury to the vasculature. Symptoms due to edema may be transient headaches, seizures, or other neurological deficits. Postradiation edema has been correlated with tumor location. Parasagittal (12), parafalcine and anterior fossa locations are at risk (9). In the study from Chang et al. (1), imaging changes were evident in 5.1% of skull base meningiomas and in 50% of hemispheric locations. Previous surgery, patients older than 60, mean TV >10 cm³, maximum radiosurgical dose greater than 30 Gy, tumor margin dose greater than 16 Gy are also linked to an increased risk of edema. Patients presenting with such conditions must be informed about the increased possibility of side effects.

First-line radiosurgery is recommended for cavernous sinus meningiomas enclosed in the cavernous sinus when they are small enough and far enough from the optic pathways (18). When the lesion is too big or too close to the optic pathway, a combined approach (resection of the portion out of the cavernous sinus) or conventional radiotherapy is advocated (16).

Petroclival meningiomas may be excellent indication for radiosurgery, especially when there are growing, inducing few clinical signs and are small enough as they can be treated with lower morbidity than microsurgery (17).

Parasagital meningiomas have been demonstrated to correlate with the highest rate of brain edema especially in patients previously operated or presenting with a neurological deficit at time of radiosurgery (11).

For meningioma management, tumor size, tumor growth, patient’s age and neurological condition are the key parameters to decide the therapeutic option. As a general rule, patients with large tumors associated with neurological deficit are candidates for a first intention microsurgical resection. Conversely, elderly patients with an incidentally discovered meningioma are preferentially treated conservatively with serial observation. Apart from these two typical situations, radiosurgery can be individually discussed as the first option treatment. Even in cases of size-compatible meningiomas, the neurovascular environment of the tumor is carefully checked on the radiological work-up before treatment, with special attention to the optic pathway and brain stem. Previous treatments (radiation therapy, microsurgery) and histological grading of the meningioma are also taken into consideration prior to radiosurgery.

Analysis of the main published recent series (5–7, 10, 13–15, 19) indicates that radiosurgery is the first modality without previous surgery in 50–70% of treated cases while is performed after microsurgery (residual or recurrent meningiomas) in the remaining cases. Topography of the target is ubiquitous but skull base locations are predominant. The two main goals of radiosurgery of meningiomas are long-term tumor control and functional preservation. Evaluation of these results may be nuanced in several aspects. For patients who are treated in first intention, a histological proof is not available. In several locations like cavernous sinus or jugular foramen it may be difficult to distinguish meningioma from schwannoma, plasma cell granuloma, hemangiomas, or paraganglioma. A series published in 2003, reported on the treatment of 219 imaged diagnosed meningiomas, with a mean follow-up of 29 months (4). Tumor progression after GKS was showed in seven cases, two of which turned out to be different tumors. We fully agree with their conclusion that biopsy should be proposed before treatment in cases of atypical imaging features and/or unusual clinical presentation. In cases of typical radiological features of meningiomas, the risk of misdiagnosis seems too low to justify biopsies.

Given the 87–98.5% and 84–93% 5- and 10-years actuarial control rate and the lack of radiation-induced morbidity in patients with benign meningiomas, we feel increasingly comfortable recommending this type of treatment for most patients with small meningiomas. We also believe that radiosurgery has become the clear treatment of choice for small meningiomas in high-risk locations, especially those in the cavernous sinus.

References

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10. Kollova A, Liscak R, Novotny JJ, Vladyka V, Simonova G, Janouskova L: Gamma Knife surgery for benign meningioma. J Neurosurg 107:325–336, 2007.

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12. Kondziolka D, Levy EI, Niranjan A, Flickinger JC, Lunsford LD: Long-term outcomes after meningioma radiosurgery: physician and patient perspectives. J Neurosurg 91:44–50, 1999.

13. Kondziolka D, Mathieu D, Lunsford LD, Martin JJ, Madhok R, Niranjan A, Flickinger JC: Radiosurgery as definitive management of intracranial meningiomas. Neurosurgery 62:53–58; discussion 58–60, 2008.

14. Kreil W, Luggin J, Fuchs I, Weigl V, Eustacchio S, Papaefthymiou G: Long term experience of gamma knife radiosurgery for benign skull base meningiomas. J Neurol Neurosurg Psychiatry 76:1425–1430, 2005.

15. Malik I, Rowe JG, Walton L, Radatz MWR, Kemeny A: The use of stereotactic radiosurgery in the management of meningiomas. Br J Neurosurg 19:13–20, 2005.

16. Metellus P, Regis J, Muracciole X, Fuentes S, Dufour H, Nanni I, Chinot O, Martin PM, Grisoli F: Evaluation of fractionated radiotherapy and gamma knife radiosurgery in cavernous sinus meningiomas: treatment strategy. Neurosurgery 57:873–886; discussion 873–886, 2005.

17. Roche PH, Pellet W, Fuentes S, Thomassin JM, Regis J: Gamma knife radiosurgical management of petroclival meningiomas results and indications. Acta Neurochir (Wien) 145:883–888; discussion 888, 2003.

18. Roche PH, Regis J, Dufour H, Fournier HD, Delsanti C, Pellet W, Grisoli F, Peragut JC: Gamma knife radiosurgery in the management of cavernous sinus meningiomas. J Neurosurg 93 Suppl 3:68–73, 2000.

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20. Simpson D: The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22–39, 1957.

Author/Year	Device	Nb	MS	Vol	Dose	Fu	ATC 5 years (%)	ATC 10 years (%)	Compl. (%)	Location
Malik 2004(15)	GKS	277	56	7.3	19.7	31	87	?	3	All
Friedman 2005(5)	Linac	210	39%	7	13	56	96	84	2.30	All
Kreil 2005(14)	GKS	237	49.5	6.5	12	95	99	97	0.40	SB
Hasegawa 2007(6)	GKS	115	57	13.8	13	60	94	92	4	CSM
Kollova 2007(10)	GKS	368	30	6.3	12,5	60	98	89	5.70	All
Iwai 2008(7)	GKS	108	57	8.1	12	86	93	83	6.50	SB
Kondziolka 2008 (13)	GKS	972	48	7.4	14	48	98	93	4.80	All
Santacrocce 2009 (19)	GKS	4585	43,8	4.8	14	60	94	88	6.60	All

Figure 1. Actuarial tumor control rate (ATC) at 5 and 10 years in the main series of the literature. Have been identified, based on a Pubmed search, all the papers of the literature published between 2005 and 2010 reporting actuarial tumor control rate at least at 5 years in more than 100 meningiomas treated by radiosurgery (5–7, 10, 13–15, 19). Only one Linac-based series is fulfilling these criteria. Nb population size. MS refer to the percentage of patients previously operated microsurgically. Vol tumor volume at time of radiosurgery. Dose marginal dose. FU mean follow-up in months. ATC 5 years Actuarial control rate at 5 years from radiosurgery. ATC 10 years Actuarial control rate at 10 years from radiosurgery. Compl. percentage of patient presenting with a permanent neurological complication of radiosurgery. Sb Skull base. CSM Cavernous sinus meningioma

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Authors and Affiliations

Osama S. Abdelaziz
- 1
Email author
Alaa Kandil
- 2
Shaaban El-Assaal
- 2
Amro Abdelaziz
- 2
Yosry Rostom
- 2
Yaser Rashed
- 3

1.Department of Neurosurgery, Faculty of MedicineAlexandria UniversityAlexandriaEgypt
2.Department of Radiation Oncology and Nuclear Medicine, Faculty of MedicineAlexandria UniversityAlexandriaEgypt
3.Department of Medical Physics, Faculty of MedicineMenofeya UniversityShibeen ElkoomEgypt