Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas

doi:10.1016/S0360-3016(02)04356-0

International Journal of Radiation OncologyBiologyPhysics

Volume 55, Issue 4, 15 March 2003, Pages 1000-1005

https://doi.org/10.1016/S0360-3016(02)04356-0 Get rights and content

Abstract

Purpose:

To compare tumor control rates after surgical resection or stereotactic radiosurgery for patients with small- to medium-size intracranial meningiomas.

Methods and materials:

Between 1990 and 1997, 198 adult meningioma patients treated at our center underwent either surgical resection (n = 136) or radiosurgery (n = 62) as primary management for benign meningiomas <35 mm in average diameter. Tumor recurrence or progression rates were calculated by the Kaplan-Meier method according to an independent radiographic review. The mean follow-up was 64 months.

Results:

The tumor resections were Simpson Grade 1 in 57 (42%), Grade 2 in 57 (42%), and Grade 3–4 in 22 (16%). The mean margin and maximal radiation dose at radiosurgery was 17.7 Gy and 34.9 Gy, respectively. Tumor recurrence/progression was more frequent in the surgical resection group (12%) than in the radiosurgical group (2%; p = 0.04). No statistically significant difference was detected in the 3- and 7-year actuarial progression-free survival (PFS) rate between patients with Simpson Grade 1 resections (100% and 96%, respectively) and patients who underwent radiosurgery (100% and 95%, respectively; p = 0.94). Radiosurgery provided a higher PFS rate compared with patients with Simpson Grade 2 (3- and 7-year PFS rate, 91% and 82%, respectively; p <0.05) and Grade 3–4 (3- and 7-year PFS rate, 68% and 34%, respectively; p <0.001) resections. Subsequent tumor treatments were more common after surgical resection (15% vs. 3%, p = 0.02). Complications occurred in 10% of patients after radiosurgery compared with 22% of patients after surgical resection (p = 0.06).

Conclusion:

The PFS rate after radiosurgery was equivalent to that after resection of a Simpson Grade 1 tumor and was superior to Grade 2 and 3-4 resections in our study. If long-term follow-up confirms the high tumor control rate and low morbidity of radiosurgery, this technique will likely become the preferred treatment for most patients with small- to moderate-size meningiomas without symptomatic mass effect.

Introduction

Meningiomas represent approximately 15% of adult intracranial neoplasms. Surgical resection is the preferred treatment whenever total removal can be accomplished with acceptable morbidity (1). Large series on meningioma surgery have found gross total resection possible for 38–80% of patients, depending primarily on tumor location 2, 3, 4, 5, 6, 7. However, the intimate relationship between some meningiomas and critical neurovascular structures makes complete resection impossible with acceptable risk 8, 9. Still, even when gross total resection has been achieved, tumor recurrence rates at 5 and 10 years have been reported to be 4–14% and 18–25%, respectively 2, 3, 4, 5, 6, 7.

Recently, stereotactic radiosurgery has been performed for an increasing number of patients with small- to moderate-size meningiomas as an alternative to surgical excision 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21. In this study, we compared the tumor control rates for adult patients undergoing either surgical resection or radiosurgery as primary management for benign meningiomas <35 mm in average diameter.

Section snippets

Patient population

All patients who underwent surgical resection of an intracranial meningioma between January 1990 and December 1997 were identified from the pathology files. Patient information regarding presenting symptoms, neurologic condition, tumor size and location, extent of surgical resection, tumor histologic type, and postoperative follow-up was retrospectively reviewed. Information on patients who underwent radiosurgery during the same interval was retrieved from a prospectively maintained computer

Tumor control and additional treatment

Tumor recurrence/progression was more frequent in the surgical resection group (11%) than in the radiosurgical group (2%; p <0.05; Fig. 1). Tumor progression by Simpson grade was Grade 1 in 1 (2%) of 57, Grade 2 in 7 (12%) of 57, and Grade 3–4 in 7 (58%) of 12. No statistically significant difference was detected in the 3- and 7-year actuarial PFS rate between patients with Simpson Grade 1 resections (100% and 96%, respectively) and those who underwent radiosurgery (100% and 95%, respectively;

Discussion

Simpson (1), in 1957, published his landmark paper documenting the direct correlation between the degree of meningioma resection and later tumor recurrence. In this report, he identified five grades of meningioma removal. A Grade 1 resection is the complete removal of all macroscopic tumor with excision of its dural attachments and any abnormal bone. Grade 2 is macroscopically complete tumor removal with coagulation of its dural attachments. Grade 3 is macroscopically complete removal of the

Conclusion

The results of this study demonstrated that the PFS rate after radiosurgery was equivalent to that of a Simpson Grade 1 resection for patients with small- to moderate-size meningiomas and provided superior tumor control for patients with either a Grade 2 or Grade 3–4 resection. Continued diligent follow-up of a large number of patients is required to assess completely the role that radiosurgery should play in the treatment of patients with intracranial meningiomas.

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We did a retrospective study of all the THM patients treated at our institute between May 1987 and June 2022. The demographic data, signs and symptoms, surgical notes, postoperative details, and radiotherapy were gathered retrospectively. Survival analysis was done with Kaplan-Meier tests along with predictors of the extent of resection as well as recurrence.
A total of 39 patients qualified to be included in the study, with 10 male patients (male:female 1:2.9) and an average age of 50.8 years. The average follow-up duration was 75.9 months. Simpson's grade 2 excision was achieved in 19 (48.7%) patients, followed by Simpson's grade 3 excision in 17 patients (43.6%). Progression-free survival in subtotal resection was 60 months, and 100 months in gross total resection. Statistically, the extent of the resection was determined by the involvement of sinuses/torcula and the number of quadrants involved around torcula. A total of 16 patients received radiosurgery for the residual or small reccurrence of the lesion. Follow-up revealed reccurrence in 5 cases.
Torcular meningiomas are relatively uncommon, described in few reports, and represent a therapeutic dilemma. Though some experts recommend complete removal of tumor and reconstruction of the sinus, others suggest maximum safe resection, followed by radiosurgery. The present study reflects reasonable control of the residual lesion with radiosurgery after maximum safe resection.
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We analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors’ affiliated institution.
96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression. Patients were treated to the gross tumor alone without margin or coverage of the dural tail to a median dose of 15 Gy. Median follow up was 7.4 years (inter-quartile range 4.8–11.3). Local control, marginal control, regional control, and progression-free survival were analyzed.
Local control at 5 and 10 years was 97 % and 95 %. PFS at 5 and 10 years was 94 % and 90 % with no failures reported after 6 years. Definitive and postoperative local control were similar at 5 (95 % [82–99 %] vs. 100 %) and 10 years (92 % [82–99 %] vs. 100 %). Patients treated with postoperative SRS did not have an increased marginal failure rate (p = 0.83) and only 2/39 (5 %) experienced recurrence elsewhere in the cavity.
Stereotactic radiosurgery targeting the gross tumor alone provides excellent local control and progression free survival in patients treated definitively and postoperatively. As in the definitive setting, patients treated postoperatively can be treated to gross tumor alone without need for additional margin or dural tail coverage.
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Evaluar el resultado del tratamiento con radiocirugía estereotáctica (RC) mediante acelerador lineal (LINAC) en meningiomas de ángulo pontocerebeloso (APC).
Analizamos 80 pacientes diagnosticados de meningiomas de APC entre los años 2001-2014, tratados mediante RC. El 81,9% (n = 68) fueron mujeres, con una media de edad de 59,1 años (32-79). La RC se aplicó como tratamiento primario en el 83,7% (n = 67), y en el 16,3% (n = 13) como adyuvante a la cirugía. El tratamiento con RC se lleva a cabo en un acelerador lineal (Varian 600, 6 MeV) con micromultiláminas M3 (BrainLab) y marco estereotáxico. El volumen tumoral medio fue de 3,14 cm³ (0,34-10,36 cm³) y la dosis de cobertura media fue de 14 Gy (12-16 Gy). Se realiza un análisis descriptivo retrospectivo, un análisis de supervivencia método Kaplan-Meier y se contrasta la relación entre las variables del estudio mediante análisis univariados.
Tras un periodo de seguimiento medio de 86,9 meses (12-184), la tasa de control tumoral fue del 92,8% (n = 77). Se comprobó una reducción global del volumen tumoral al final del estudio del 32,8%, con un volumen medio final de 2,11 cm³ (0-10,35 cm³). La tasa de supervivencia libre de progresión fue del 98% al año, del 95% a los 5 años y del 83,3% a los 10 y 12 años. El mayor volumen tumoral previo al tratamiento (p = 0,047) se relacionó con la progresión. Se produjo la mejoría clínica en el 26,5% (n = 21) de los casos y el deterioro en el 16,2% (n = 13); el empeoramiento se relaciona con la dosis de radiación que recibe el troncoencéfalo (p = 0,02). Respecto a las complicaciones, el 8,7% (n = 7) sufrieron deterioro de la audición, el 5% (n = 4) radionecrosis y el 3,7% (n = 3) neuropatía del V par craneal. La dosis máxima alcanzada (p = 0,037) y el tamaño tumoral inicial (p = 0,033) se relacionan con la progresión de la hipoacusia, y el desarrollo de radionecrosis, con la dosis máxima alcanzada (p = 0,037).
El tratamiento con RC mediante LINAC en meningiomas de ángulo pontocerebeloso es eficaz a largo plazo, obteniendo las mejores tasas de control tumoral en aquellos pacientes con lesiones de menor tamaño.
To evaluate the efficacy of treatment with linear accelerator-based stereotactic radiosurgery (LINAC) in cerebellopontine angle meningiomas.
We analyzed 80 patients diagnosed with cerebellopontine angle meningiomas between 2001 and 2014, treated with stereotactic radiosurgery (SRS), of whom 81.9% (n = 68) were women, with an average age of 59.1 years (32-79). SRS was applied as primary treatment in 83.7% (n = 67) and in 16.3% (n = 13) as an adjuvant treatment to surgery. SRS treatment was provided using LINAC (Varian 600, 6 MeV) with M3 micromultilamines (brainLab) and stereotactic frame. The average tumor volume was 3.12 cm³ (0.34-10.36 cm³) and the coverage dose was 14 Gy (12-16 Gy). We performed a retrospective descriptive analysis and survival analysis was performed with the Kaplan-Meier method and multivariate analysis to determine those factors predictive of tumor progression or clinical improvement.
After an average follow-up period of 86.9 months (12-184), the tumor control rate was 92.8% (n = 77). At the end of the study, there was an overall reduction in tumor volume of 32.8%, with an average final volume of 2.11 cm³ (0-10.35 cm³). The progression-free survival rate at 5, 10 and 12 years was 98%, 95% and 83.3% respectively. The higher tumor volume (P = .047) was associated with progression. There was clinical improvement in 26.5% (n = 21) of cases and clinical worsening in 16.2% (n = 13). Worsening is related to the radiation dose received by the brainstem (P = .02). Complications were 8.7% (7 cases) of hearing loss, 5% (4 cases) of brain radionecrosis, and 3.7% (3 cases) of cranial nerve V neuropathy. Hearing loss was related to initial tumor size (P = .033) and maximum dose (P = .037). The occurrence of radionecrosis with the maximum dose (P = .037).
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Innovative treatments for meningiomas
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Multi-recurrent high-grade meningiomas remain an unmet medical need in neuro-oncology when iterative surgeries and radiation therapy sessions fail to control tumor growth. Nevertheless, the last 10 years have been marked by multiple advances in the comprehension of meningioma tumorigenesis via the discovery of new driver mutations, the identification of activated intracellular signaling pathways, and DNA methylation analyses, providing multiple potential therapeutic targets. Today, Anti-VEGF and mTOR inhibitors are the most used and probably the most active drugs in aggressive meningiomas. Peptide radioactive radiation therapy aims to target SSTR2A receptors, which are strongly expressed in meningiomas, but have an insufficient effect in most aggressive meningiomas, requiring the development of new techniques to increase the dose applied to the tumor. Based on the multiple potential intracellular targets, multiple targeted therapy clinical trials targeting Pi3K-Akt-mTOR and MAP kinase pathways as well as cell cycle and particularly, cyclin D4-6 are ongoing. Recently discovered driver mutations, SMO, Akt, and PI3KCA, offer new targets but are mostly observed in benign meningiomas, limiting their clinical relevance mainly to rare aggressive skull base meningiomas. Therefore, NF2 mutation remains the most frequent mutation and main challenging target in high-grade meningioma. Recently, inhibitors of focal adhesion kinase (FAK), which is involved in tumor cell adhesion, were tested in a phase 2 clinical trial with interesting but insufficient activity. The Hippo pathway was demonstrated to interact with NF2/Merlin and could be a promising target in NF2-mutated meningiomas with ongoing multiple preclinical studies and a phase 1 clinical trial. Recent advances in immune landscape comprehension led to the proposal of the use of immunotherapy in meningiomas. Except in rare cases of MSH2/6 mutation or high tumor mass burden, the activity of PD-1 inhibitors remains limited; however, its combination with various radiation therapy modalities is particularly promising. On the whole, therapeutic management of high-grade meningiomas is still challenging even with multiple promising therapeutic targets and innovations.
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Clinical investigation: brainStereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas

Abstract

Purpose:

Methods and materials:

Results:

Conclusion:

Introduction

Section snippets

Patient population

Tumor control and additional treatment

Discussion

Conclusion

Int J Radiat Oncol Biol Phys

Mayo Clin Proc

Int J Radiat Oncol Biol Phys

Lancet

The recurrence of intracranial meningiomas after surgical treatment

J Neurol Neurosurg Psychiatry

The recurrence rate of intracranial meningiomas after surgical treatment

J Neurosurg

Radiation therapy in the treatment of partially resected meningiomas

Neurosurgery

Recurrence of cranial base meningiomas

Neurosurgery

MeningiomaAn analysis of recurrence and progression following neurosurgical resection

J Neurosurg

Infiltration of the carotid artery by cavernous sinus meningioma

J Neurosurg

Evidence of meningioma infiltration into cranial nervesClinical implications for cavernous sinus meningiomas

J Neurosurg

Treatment of cranial base meningiomas with linear accelerator radiosurgery

Neurosurgery

Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery

Neurosurgery

Results of linear accelerator-based radiosurgery for intracranial meningiomas

Neurosurgery

Judicious resection and/or radiosurgery for parasagittal meningiomasOutcomes from a multicenter review

Neurosurgery

Long-term outcomes after meningioma radiosurgeryPhysician and patient perspectives

J Neurosurg

Clinical investigation: brain
Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas