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  • Author or Editor: Colin J. Przybylowski x
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Jason P. Sheehan, Cheng-Chia Lee, Zhiyuan Xu, Colin J. Przybylowski, Patrick D. Melmer and David Schlesinger

OBJECT

Stereotactic radiosurgery (SRS) has been shown to offer a high probability of tumor control for Grade I meningiomas. However, SRS can sometimes incite edema or exacerbate preexisting edema around the targeted meningioma. The current study evaluates the incidence, timing, and degree of edema around parasagittal or parafalcine meningiomas following SRS.

METHODS

A retrospective review was undertaken of a prospectively maintained database of patients treated with Gamma Knife radiosurgery at the University of Virginia Health System. All patients with WHO Grade I parafalcine or parasagittal meningiomas with at least 6 months of clinical follow-up were identified, resulting in 61 patients included in the study. The median radiographic follow-up was 28 months (range 6–158 months). Rates of new or worsening edema were quantitatively assessed using volumetric analysis; edema indices were computed as a function of time following radiosurgery. Statistical methods were used to identify favorable and unfavorable prognostic factors for new or worsening edema.

RESULTS

Progression-free survival at 2 and 5 years was 98% and 90%, respectively, according to Kaplan-Meier analysis. After SRS, new peritumoral edema occurred or preexisting edema worsened in 40% of treated meningiomas. The median time to onset of peak edema was 36 months post-SRS. Persistent and progressive edema was associated with 11 tumors, and resection was undertaken for these lesions. However, 20 patients showed initial edema progression followed by regression at a median of 18 months after radiosurgery (range 6–24 months). Initial tumor volume greater than 10 cm3, absence of prior resection, and higher margin dose were significantly (p < 0.05) associated with increased risk of new or progressive edema after SRS.

CONCLUSIONS

Stereotactic radiosurgery offers a high rate of tumor control in patients with parasagittal or parafalcine meningiomas. However, it can lead to worsening peritumoral edema in a minority of patients. Following radiosurgery, transient edema occurs earlier than persistent and progressive edema. Longitudinal follow-up of meningioma patients after SRS is required to detect and appropriately treat transient as well as progressive edema.

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Robert M. Starke, Colin J. Przybylowski, Mukherjee Sugoto, Francis Fezeu, Ahmed J. Awad, Dale Ding, James H. Nguyen and Jason P. Sheehan

OBJECT

Stereotactic radiosurgery (SRS) has become a common treatment modality for intracranial meningiomas. Skull base meningiomas greater than 8 cm3 in volume have been found to have worse outcomes following SRS. When symptomatic, patients with these tumors are often initially treated with resection. For tumors located in close proximity to eloquent structures or in patients unwilling or unable to undergo a resection, SRS may be an acceptable therapeutic approach. In this study, the authors review the SRS outcomes of skull base meningiomas greater than 8 cm3 in volume, which corresponds to a lesion with an approximate diameter of 2.5 cm.

METHODS

The authors reviewed the data in a prospectively compiled database documenting the outcomes of 469 patients with skull base meningiomas treated with single-session Gamma Knife radiosurgery (GKRS). Seventy-five patients had tumors greater than 8 cm3 in volume, which was defined as a large tumor. All patients had a minimum follow-up of 6 months, but patients were included if they had a complication at any time point. Thirty patients were treated with upfront GKRS, and 45 were treated following microsurgery. Patient and tumor characteristics were assessed to determine predictors of new or worsening neurological function and tumor progression following GKRS.

RESULTS

After a mean follow-up of 6.5 years (range 0.5–21 years), the tumor volume was unchanged in 37 patients (49%), decreased in 26 patients (35%), and increased in 12 patients (16%). Actuarial rates of progression-free survival at 3, 5, and 10 years were 90.3%, 88.6%, and 77.2%, respectively. Four patients had new or worsened edema following GKRS, but preexisting edema decreased in 3 patients. In Cox multivariable analysis, covariates associated with tumor progression were 1) presentation with any cranial nerve (CN) deficit from III to VI (hazard ratio [HR] 3.78, 95% CI 1.91–7.45; p < 0.001), history of radiotherapy (HR 12.06, 95% CI 2.04–71.27; p = 0.006), and tumor volume greater than 14 cm3 (HR 6.86, 95% CI 0.88–53.36; p = 0.066). In those patients with detailed clinical follow-up (n = 64), neurological function was unchanged in 37 patients (58%), improved in 16 patients (25%), and deteriorated in 11 patients (17%). In multivariate analysis, the factors predictive of new or worsening neurological function were history of surgery (OR 3.00, 95% CI 1.13–7.95; p = 0.027), presentation with any CN deficit from III to VI (OR 3.94, 95% CI 1.49–10.24; p = 0.007), and decreasing maximal dose (OR 0.76, 95% CI 0.63–0.93; p = 0.007). Tumor progression was present in 64% of patients with new or worsening neurological decline.

CONCLUSIONS

Stereotactic radiosurgery affords a reasonable rate of tumor control for large skull base meningiomas and does so with a low incidence of neurological deficits. Those with a tumor less than 14 cm3 in volume and without presenting CN deficit from III to VI were more likely to have effective tumor control.

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Mark Quigg, Chun-Po Yen, Micaela Chatman, Anders H. Quigg, Ian T. McNeill, Colin J. Przybylowski, Guofen Yan and Jason P. Sheehan

Object

Diabetes mellitus (DM) and hypertension may be associated with complications following fractionated radiotherapy. To date no studies have determined the risk of radiation toxicity in patients with DM or hypertension who have undergone Gamma Knife surgery (GKS) for brain arteriovenous malformations (AVMs). The goal of the present study was to determine associations between DM or hypertension and other factors in the development of radiotoxicity, as measured by radiation-induced changes (RICs) on MR images following radiosurgery for AVM.

Methods

Using univariate methods and multivariate logistic regression, the authors compared the RIC status in patients 18 years of age and older with these patients' history of, or medication use for, DM or hypertension; tobacco use; patient age and sex; AVM volume; Spetzler-Martin AVM severity scale (Grades I and II vs Grades III–V); AVM surgery, AVM embolization, or hemorrhage prior to radiosurgery; AVM location; number of draining veins; and radiosurgery margin dose.

Results

Radiation-induced changes occurred in 38% of 539 adults within a mean (± standard deviation) of 12 ± 10 months after radiosurgery, as observed during a median follow-up time of 55 months. Among patients in whom RICs occurred, 34% had headaches, neurological deficits, or new-onset seizures. Larger RICs were associated with worse symptoms. According to a univariate analysis, DM (3% of patients), larger AVM volume, worse Spetzler-Martin grade, lack of AVM surgery prior to radiosurgery, lack of hemorrhage prior to radiosurgery, and smaller margin dose of radiation had significant associations with the presence of RICs. Hypertension (20%), patient sex, tobacco use, number of draining veins, superficial or deep location of the lesion, and AVM embolization prior to radiosurgery had no association with the presence of RICs. According to a multivariate analysis, larger AVM volume, worse Spetzler-Martin grade, and no AVM surgery prior to radiosurgery predicted the occurrence of an RIC. Diabetes mellitus had borderline significance.

Conclusions

Vascular factors such as hypertension, patient sex, and tobacco use did not convey additional risks of radiotoxicity, but DM remained a possible cardiovascular risk factor in the development of RICs.

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Dale Ding, Mark Quigg, Robert M. Starke, Zhiyuan Xu, Chun-Po Yen, Colin J. Przybylowski, Blair K. Dodson and Jason P. Sheehan

OBJECT

The temporal lobe is particularly susceptible to epileptogenesis. However, the routine use of anticonvulsant therapy is not implemented in temporal lobe AVM patients without seizures at presentation. The goals of this case-control study were to determine the radiosurgical outcomes for temporal lobe AVMs and to define the effect of temporal lobe location on postradiosurgery AVM seizure outcomes.

METHODS

From a database of approximately 1400 patients, the authors generated a case cohort from patients with temporal lobe AVMs with at least 2 years follow-up or obliteration. A control cohort with similar baseline AVM characteristics was generated, blinded to outcome, from patients with non-temporal, cortical AVMs. They evaluated the rates and predictors of seizure freedom or decreased seizure frequency in patients with seizures or de novo seizures in those without seizures.

RESULTS

A total of 175 temporal lobe AVMs were identified based on the inclusion criteria. Seizure was the presenting symptom in 38% of patients. The median AVM volume was 3.3 cm3, and the Spetzler-Martin grade was III or higher in 39% of cases. The median radiosurgical prescription dose was 22 Gy. At a median clinical follow-up of 73 months, the rates of seizure control and de novo seizures were 62% and 2%, respectively. Prior embolization (p = 0.023) and lower radiosurgical dose (p = 0.027) were significant predictors of seizure control. Neither temporal lobe location (p = 0.187) nor obliteration (p = 0.522) affected seizure outcomes. The cumulative obliteration rate was 63%, which was significantly higher in patients without seizures at presentation (p = 0.046). The rates of symptomatic and permanent radiation-induced changes were 3% and 1%, respectively. The annual risk of postradiosurgery hemorrhage was 1.3%.

CONCLUSIONS

Radiosurgery is an effective treatment for temporal lobe AVMs. Furthermore, radiosurgery is protective against seizure progression in patients with temporal lobe AVM–associated seizures. Temporal lobe location does not affect radiosurgery-induced seizure control. The low risk of new-onset seizures in patients with temporal or extratemporal AVMs does not seem to warrant prophylactic use of anticonvulsants.

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Colin J. Przybylowski, Dale Ding, Robert M. Starke, Chun-Po Yen, Mark Quigg, Blair Dodson, Benjamin Z. Ball and Jason P. Sheehan

OBJECT

Epilepsy associated with arteriovenous malformations (AVMs) has an unclear course after stereotactic radiosurgery (SRS). Neither the risks of persistent seizures nor the requirement for postoperative antiepileptic drugs (AEDs) are well defined.

METHODS

The authors performed a retrospective review of all patients with AVMs who underwent SRS at the University of Virginia Health System from 1989 to 2012. Seizure status was categorized according to a modified Engel classification. The effects of demographic, AVM-related, and SRS treatment factors on seizure outcomes were evaluated with logistic regression analysis. Changes in AED status were evaluated using McNemar's test.

RESULTS

Of the AVM patients with pre- or post-SRS seizures, 73 with pre-SRS epilepsy had evaluable data for subsequent analysis. The median patient age was 37 years (range 5–69 years), and the median follow-up period was 65.6 months (range 12–221 months). Sixty-five patients (89%) achieved seizure remission (Engel Class IA or IB outcome). Patients presenting with simple partial or secondarily generalized seizures were more likely to achieve Engel Class I outcome (p = 0.045). Twenty-one (33%) of 63 patients tapered off of pre-SRS AEDs. The incidence of freedom from AED therapy increased significantly after SRS (p < 0.001, McNemar's test). Of the Engel Class IA patients who continued AED therapy, 54% had patent AVM nidi, whereas only 19% continued AED therapy with complete AVM obliteration (p = 0.05).

CONCLUSIONS

Stereotactic radiosurgery is an effective treatment for long-term AVM-related epilepsy. Seizure-free patients on continued AED therapy were more likely to have residual AVM nidi. Simple partial or secondarily generalized seizure type were associated with better seizure outcomes following SRS.