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Bruce E. Pollock, Scott L. Stafford, Michael J. Link, Yolanda I. Garces and Robert L. Foote

Object

Stereotactic radiosurgery (SRS) is an important treatment option for patients with cavernous sinus meningiomas (CSM). To analyze factors associated with local tumor control and complications after single-fraction SRS, the authors reviewed cases involving patients treated with Gamma Knife SRS between 1990 and 2008.

Methods

Excluded were patients with WHO Grade II or III tumors, radiation-induced tumors, multiple meningiomas, neurofibromatosis Type 2, and prior or concurrent radiotherapy. Five patients were lost to follow-up and 3 patients refused research authorization. The remaining 115 patients (29 men, 86 women) had either histologically confirmed WHO Grade I (n = 46, 40%) or presumed (n = 69, 60%) CSM. The median treatment volume was 9.3 cm3 (range 1.3–42.2 cm3). The median margin dose was 16 Gy (range 12–20 Gy). The median follow-up after SRS was 89 months (range 12–251 months). Thirty-nine patients (34%) had 10 or more years of follow-up after SRS.

Results

Six patients (5%) had tumor progression (in field, n = 3; marginal, n = 3) at a median of 74 months (range 42–145 months) after SRS. The local tumor control rate was 99% at 5 years and 93% at 10 years after SRS. No analyzed factor was associated with local control after SRS. Fourteen patients (12%) had permanent complications at a median onset of 23 months (range 2–146 months) including trigeminal dysfunction (n = 9), diplopia (n = 2), ischemic stroke (n = 2), and hypopituitarism (n = 1). The 2-year, 5-year, and 10-year rates of complications were 7%, 10%, and 15%, respectively. Multivariate analysis found larger treatment volume (HR 1.1, 95% CI 1.02–1.2, p = 0.01) to be associated with complications after SRS. The complication rate for patients with a treatment volume of 9.3 cm3 or less was 3% (2 of 58 cases) compared with 21% (12 of 57 cases) for patients with a treatment volume greater than 9.4 cm3.

Conclusions

Single-fraction SRS at the radiation doses used in this series provided durable tumor control for patients with benign CSM. Larger tumor volume remains the primary factor associated with complications after single-fraction SRS of benign CSM despite advancements in SRS technique.

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Bruce E. Pollock, Loi K. Phuong, Deborah A. Gorman, Robert L. Foote and Scott L. Stafford

Object. Each year a greater number of patients with trigeminal neuralgia (TN) undergo radiosurgery, including a large number of patients who are candidates for microvascular decompression (MVD).

Methods. The case characteristics and outcomes of 117 consecutive patients who underwent radiosurgery were retrieved from a prospectively maintained database. The mean patient age was 67.8 years; and the majority (58%) of patients had undergone surgery previously. The dependent variable for all analyses of facial pain was complete pain relief without medication (excellent outcome). Median follow-up duration was 26 months (range 1–48 months). The actuarial rate of achieving and maintaining an excellent outcome was 57% and 55% at 1 and 3 years, respectively, after radiosurgery. A greater percentage of patients who had not previously undergone surgery achieved and maintained excellent outcomes (67% at 1 and 3 years) than that of patients who had undergone prior surgery (51% and 47% at 1 and 3 years, respectively; relative risk [RR] = 1.77, 95% confidence interval [CI] 1.01–3.13, p = 0.04). New persistent trigeminal dysfunction was noted in 43 patients (37%). Tolerable numbness or paresthesias occurred in 29 patients (25%), whereas bothersome dysesthesias developed in 14 patients (12%). Only a radiation dose of 90 Gy correlated with new trigeminal deficits or dysesthesias (RR = 3.10, 95% CI 1.64–5.81, p < 0.001). Excellent outcomes in patients with new trigeminal dysfunction were achieved and maintained at rates of 76% and 74% at 1 and 3 years, respectively, after radiosurgery, compared with respective rates of 46% and 42% in patients who did not experience postradiosurgery trigeminal dysfunction (RR = 4.53, 95% CI 2.03–9.95, p < 0.01).

Conclusions. Radiosurgical treatment provides complete pain relief for the majority of patients with idiopathic TN. There is a strong correlation between the development of new facial sensory loss and achievement and maintenance of pain relief after this procedure. Because the long-term results of radiosurgery still remain unknown, MVD should continue to be the primary operation for medically fit patients with TN.

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Bruce E. Pollock, Todd B. Nippoldt, Scott L. Stafford, Robert L. Foote and Charles F. Abboud

Object. The goal of this study was to determine factors associated with endocrine normalization after radiosurgery is performed in patients with hormone-producing pituitary adenomas.

Methods. Between 1990 and 1999, 43 patients with hormone-producing pituitary adenomas underwent radiosurgery: 26 patients with growth hormone (GH)—producing tumors, nine with adrenocorticotrophic hormone—producing tumors, seven with tumors that produced prolactin (PRL) alone, and one with a tumor that secreted both GH and PRL. The median patient age was 42 years. Thirty-seven patients (86%) had undergone surgery earlier and in 30 (70%) there was tumor extension into the cavernous sinus. The product-limit method was used to calculate endocrine normalization while patients were not receiving any hormone-suppressive medication. The median follow-up period after radio-surgery was 36 months (range 12–108 months).

In 20 patients (47%) there was normalization of hormone secretion at a median of 14 months (range 2–44 months) after radiosurgery; no correlation was found between tumor type and cure. Actuarial cure rates were 20, 32, and 61% at 1, 2, and 4 years posttreatment. Multivariate analysis demonstrated that the absence of hormone-suppressive medications at the time of radiosurgery (relative risk 8.9, 95% confidence interval [CI] 1.2–68.7, p = 0.04) and maximum radiation doses greater than 40 Gy (relative risk 3.9, 95% CI 1.3–11.7, p = 0.02) correlated with an endocrine cure. A new anterior pituitary deficiency developed in seven patients (16%), temporal lobe necrosis was identified in two patients, an asymptomatic internal carotid artery stenosis was detected in two patients, and unilateral blindness occurred in one patient.

Conclusions. Radiosurgery provides an endocrine cure for many patients with persistent or recurrent hormone-producing pituitary adenomas. Further study is needed to determine whether pituitary hormone—suppressive medications have a radioprotective effect.

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Letter to the Editor

Radiosurgery and skull base meningiomas

Dueng-Yuan Hueng and Da-Tong Ju

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Bruce E. Pollock, Curtis B. Storlie, Michael J. Link, Scott L. Stafford, Yolanda I. Garces and Robert L. Foote

OBJECTIVE

Successful stereotactic radiosurgery (SRS) for the treatment of arteriovenous malformations (AVMs) results in nidus obliteration without new neurological deficits related to either intracranial hemorrhage (ICH) or radiation-induced complications (RICs). In this study the authors compared 5 AVM grading scales (Spetzler-Martin grading scale, radiosurgery-based AVM score [RBAS], Heidelberg score, Virginia Radiosurgery AVM Scale [VRAS], and proton radiosurgery AVM scale [PRAS]) at predicting outcomes after SRS.

METHODS

The study group consisted of 381 patients with sporadic AVMs who underwent Gamma Knife SRS between January 1990 and December 2009; none of the patients underwent prior radiation therapy. The primary end point was AVM obliteration without a decline in modified Rankin Scale (mRS) score (excellent outcome). Comparison of the area under the receiver operating characteristic curve (AUC) and accuracy was performed between the AVM grading scales and the best linear regression model (generalized linear model, elastic net [GLMnet]).

RESULTS

The median radiological follow-up after initial SRS was 77 months; the median clinical follow-up was 93 months. AVM obliteration was documented in 297 patients (78.0%). Obliteration was 59% at 4 years and 85% at 8 years. Fifty-five patients (14.4%) had a decline in mRS score secondary to RICs (n = 29, 7.6%) or ICH (n = 26, 6.8%). The mRS score declined by 10% at 4 years and 15% at 8 years. Overall, 274 patients (71.9%) had excellent outcomes. There was no difference between the AUC for the GLMnet (0.69 [95% CI 0.64–0.75]), RBAS (0.68 [95% CI 0.62–0.74]), or PRAS (0.69 [95% CI 0.62–0.74]). Pairwise comparison for accuracy showed no difference between the GLMnet and the RBAS (p = 0.08) or PRAS (p = 0.16), but it did show a significant difference between the GLMnet and the Spetzler-Martin grading system (p < 0.001), Heidelberg score (p < 0.001), and the VRAS (p < 0.001). The RBAS and the PRAS were more accurate when compared with the Spetzler-Martin grading scale (p = 0.03 and p = 0.01), Heidelberg score (p = 0.02 and p = 0.02), and VRAS (p = 0.03 and p = 0.02).

CONCLUSIONS

SRS provides AVM obliteration without functional decline in the majority of treated patients. AVM grading scales having continuous scores (RBAS and PRAS) outperformed integer-based grading systems in the prediction of AVM obliteration without mRS score decline after SRS.

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Bruce E. Pollock, Yolanda I. Garces, Scott L. Stafford, Robert L. Foote, Paula J. Schomberg and Michael J. Link

Object. The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at the Mayo Clinic during the past 10 years.

Methods. Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months.

The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long—repetition time MR imaging performed a median of 8 months (range 5–16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02).

Conclusions. It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.

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Jonathan A. Friedman, Bruce E. Pollock, Douglas A. Nichols, Deborah A. Gorman, Robert L. Foote and Scott L. Stafford

Object. Most dural arteriovenous fistulas (DAVFs) of the transverse and sigmoid sinuses do not have angiographically demonstrated features associated with intracranial hemorrhage and, therefore, may be treated nonsurgically. The authors report their experience using a staged combination of radiosurgery and transarterial embolization for treating DAVFs involving the transverse and sigmoid sinuses.

Methods. Between 1991 and 1998, 25 patients with DAVFs of the transverse and/or sigmoid sinuses were treated using stereotactic radiosurgery; 22 of these patients also underwent transarterial embolization. Two patients were lost to follow-up review. Clinical data, angiographic findings, and follow-up records for the remaining 23 patients were collected prospectively. The mean duration of clinical follow up after radiosurgery was 50 months (range 20–99 months).

The 18 women and five men included in this series had a mean age of 57 years (range 33–79 years). Twenty-two (96%) of 23 patients presented with pulsatile tinnitus as the primary symptom; two patients had experienced an earlier intracerebral hemorrhage (ICH). Cognard classifications of the DAVFs included the following: I in 12 patients (52%), IIa in seven patients (30%), and III in four patients (17%). After treatment, symptoms resolved (20 patients) or improved significantly (two patients) in 96% of patients. One patient was clinically unchanged. No patient sustained an ICH or irradiation-related complication during the follow-up period. Seventeen patients underwent follow-up angiographic studies at a mean of 21 months after radiosurgery (range 11–38 months). Total or near-total obliteration (> 90%) was seen in 11 patients (65%), and more than a 50% reduction in six patients (35%). Two patients experienced recurrent tinnitus and underwent repeated radiosurgery and embolization at 21 and 38 months, respectively, after the first procedure.

Conclusions. A staged combination of radiosurgery and transarterial embolization provides excellent symptom relief and a good angiographically verified cure rate for patients harboring low-risk DAVFs of the transverse and sigmoid sinuses. This combined approach is a safe and effective treatment strategy for patients without angiographically determined risk factors for hemorrhage and for elderly patients with significant comorbidities.

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Bruce E. Pollock, Robert L. Foote, Scott L. Stafford, Michael J. Link, Deborah A. Gorman and Paula J. Schomberg

Object. Gamma knife radiosurgery (GKS) is being increasing performed in the management of patients with medically unresponsive trigeminal neuralgia. The authors report the results of repeated GKS in patients with recurrent facial pain after their initial procedure.

Methods. Between April 1997 and December 1999, 100 patients with idiopathic trigeminal neuralgia underwent GKS at the authors' center. To date, 26 patients have required additional surgery because GKS provided no significant pain relief (15 patients) or because they had recurrent facial pain (11 patients). Ten of these patients underwent repeated GKS at a median of 13 months (range 4–27 months). All patients undergoing repeated GKS had a significant reduction in their facial pain after the first procedure (eight were pain free); no patient developed facial numbness or paresthesias. Initially, nine of 10 patients became pain free 1 to 4 weeks following repeated GKS. At a median follow up of 15 months (range 3–32 months), eight patients remained pain free and required no medication. All eight patients with persistent pain relief developed minor neurological dysfunction after repeated GKS (six patients had facial numbness and two had paresthesias).

Conclusions. Repeated GKS can be associated with a high rate of pain relief for patients with trigeminal neuralgia who experienced a significant reduction in their facial pain after the first operation. However, every patient with sustained pain relief after the second operation also developed some degree of trigeminal dysfunction. These findings of improved pain relief for patients who develop facial numbness after GKS for trigeminal neuralgia support the experimental data currently available.

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Jonathan M. Bledsoe, Michael J. Link, Scott L. Stafford, Paul J. Park and Bruce E. Pollock

Object

Stereotactic radiosurgery (SRS) has proven to be a safe and effective treatment for many patients with intracranial meningiomas. Nevertheless, the morbidity associated with radiosurgery of larger meningiomas is poorly understood.

Methods

The authors performed a retrospective review of 116 patients who underwent SRS for meningiomas (WHO Grade I) > 10 cm3 between 1990 and 2007, with a minimum follow-up of 12 months. Patients with atypical or malignant meningiomas and those who received prior radiotherapy were excluded. The average tumor volume was 17.5 cm3 (range 10.1–48.6 cm3); the average tumor margin dose was 15.1 Gy (range 12–18 Gy); and the mean follow-up duration was 70.1 months (range 12–199 months).

Results

Tumor control was 99% at 3 years and 92% at 7 years after radiosurgery. Thirty complications after radiosurgery were noted in 27 patients (23%), including 7 cases of seizures, 6 cases of hemiparesis, 5 cases of trigeminal injury, 4 cases of headaches, 3 cases of diplopia, 2 cases each of cerebral infarction and ataxia, and 1 case of hearing loss. Patients with supratentorial tumors experienced a higher complication rate compared with patients with skull base tumors (44% compared with 18%) (hazard ratio 2.9, 95% CI 1.3–6.7, p = 0.01).

Conclusions

The morbidity associated with SRS for patients with benign meningiomas > 10 cm3 is greater for supratentorial tumors compared with skull base tumors. Whereas radiosurgery is relatively safe for patients with large-volume skull base meningiomas, resection should remain the primary disease management for the majority of patients with large-volume supratentorial meningiomas.

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Hideyuki Kano, Douglas Kondziolka, David Mathieu, Scott L. Stafford, Thomas J. Flannery, Ajay Niranjan, Bruce E. Pollock, Anthony M. Kaufmann, John C. Flickinger and L. Dade Lunsford

Object

The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH).

Methods

Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26–83 years). The median duration of pain before GKS was 10 years (range 1.3–40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy.

Results

Favorable pain relief (Barrow Neurological Institute Grades I–IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS.

Conclusions

Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.