Neurosurgery Blog

Neurosurgery 69:284–293, 2011 DOI: 10.1227/NEU.0b013e31821bc44e

Nonfunctioning pituitary adenomas recur after microsurgery. Gamma Knife radiosurgery (GKRS) has been used to treat recurrent adenomas.

OBJECTIVE: To evaluate the long-term rates of tumor control and development of hypopituitarism in patients with nonfunctioning pituitary adenomas after GKRS.

METHODS: Forty-eight patients with a nonfunctioning pituitary adenoma treated between 1991 and 2004 at the University of Virginia were studied. All patients had more than 4 years of clinical and imaging follow-up.

RESULTS: All patients underwent follow-up imaging and endocrine evaluations, with a duration ranging from 50 to 215 months (median, 80.5 months) and 57 to 201 months (median, 95 months), respectively. New hormone deficiency after GKRS occurred in 19 of 48 patients (39%). Corticotropin/cortisol deficiency developed in 8% of patients, thyroid hormone deficiency in 20.8%, gonadotropin deficiency in 4.2%, growth hormone/insulin-like growth factor 1 in 16.7%, and diabetes insipidus in 2%. Panhypopituitarism including diabetes insipidus developed in 1 patient. Overall, control of tumor volume was 83%. Tumor volume decreased in 36 patients (75%), increased in 8 patients (17%), and was unchanged in 4 patients (8%). Tumor volumes greater than 5 mL at the time of GKRS were associated with a significantly greater rate of growth (P = .003) compared with an adenoma with a volume of 5 mL or less.

CONCLUSION: GKRS resulted in a high and durable rate of tumor control in patients with a nonfunctioning pituitary adenoma. A higher preoperative tumor volume was associated with an increased rate of tumor growth.

J Neurosurg 114:1399–1409, 2011. DOI: 10.3171/2010.11.JNS101193

Although numerous studies have analyzed the role of stereotactic radiosurgery for intracranial meningiomas, few studies have assessed outcomes of posterior fossa meningiomas after stereotactic radiosurgery. In this study, the authors evaluate the outcomes of posterior fossa meningiomas treated with Gamma Knife surgery (GKS). The authors also assess factors predictive of new postoperative neurological deficits and tumor progression.

Methods. A retrospective review was performed of a prospectively compiled database documenting the outcomes of 152 patients with posterior fossa meningiomas treated at the University of Virginia from 1990 to 2006. All patients had a minimum follow-up of 24 months. There were 30 males and 122 females, with a median age of 58 years (range 12–82 years). Seventy-five patients were treated with radiosurgery initially, and 77 patients were treated with GKS after resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression.

Results. Patients had meningiomas centered over the tentorium (35 patients, 23%), cerebellopontine angle (43 patients, 28%), petroclival region (28 patients, 18%), petrous region (6 patients, 4%), and clivus (40 patients, 26%). The median follow-up was 7 years (range 2–16 years). The mean preradiosurgical tumor volume was 5.7 cm3 (range 0.3–33 cm3), and mean postradiosurgical tumor volume was 4.9 cm3 (range 0.1–33 cm3). At last follow-up, 55 patients (36%) displayed no change in tumor volume, 78 (51%) displayed a decrease in volume, and 19 (13%) displayed an increase in volume. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 3, 5, and 10 years to be 98%, 96%, and 78%, respectively. In Cox multivariable analysis, pre-GKS covariates associated with tumor progression included age greater than 65 years (hazard ratio [HR] 3.24, 95% CI 1.12–9.37; p = 0.03) and a low dose to the tumor margin (HR 0.76, 95% CI 0.60–0.97; p = 0.03), and post-GKS covariates included shunt-dependent hydrocephalus (HR 25.0, 95% CI 3.72–100.0; p = 0.001). At last clinical follow-up, 139 patients (91%) demonstrated no change or improvement in their neurological condition, and 13 patients showed symptom deterioration (9%). In multivariate analysis, the only factors predictive of new or worsening symptoms were clival or petrous location (OR 4.0, 95% CI 1.1–13.7; p = 0.03).

Conclusions. Gamma Knife surgery offers an acceptable rate of tumor control for posterior fossa meningiomas and accomplishes this with a low incidence of neurological deficits. In patients selected for GKS, tumor progression is associated with age greater than 65 years and decreasing dose to the tumor margin. Clival- or petrous-based locations are predictive of an increased risk of new or worsening neurological deficit following GKS.

J Neurosurg 114:801–807, 2011.DOI: 10.3171/2010.8.JNS10674

Stereotactic radiosurgery (SRS) is an important management option for patients with small- and medium- sized vestibular schwannomas. To assess the potential role of SRS in larger tumors, the authors reviewed their recent experience.

Methods. Between 1994 and 2008, 65 patients with vestibular schwannomas between 3 and 4 cm in one extracanalicular maximum diameter (median tumor volume 9 ml) underwent Gamma Knife surgery. Seventeen patients (26%) had previously undergone resection.

Results. The median follow-up duration was 36 months (range 1–146 months). At the first planned imaging follow-up at 6 months, 5 tumors (8%) were slightly expanded, 53 (82%) were stable in size, and 7 (11%) were smaller. Two patients (3%) underwent resection within 6 months due to progressive symptoms. Two years later, with 63 tumors overall after the 2 post-SRS resections, 16 tumors (25%) had a volume reduction of more than 50%, 22 (35%) tumors had a volume reduction of 10–50%, 18 (29%) were stable in volume (volume change < 10%), and 7 (11%) had larger volumes (5 of the 7 patients underwent resection and 1 of the 7 underwent repeat SRS). Eighteen (82%) of 22 patients with serviceable hearing before SRS still had serviceable hearing after SRS more than 2 years later. Three patients (5%) developed symptomatic hydrocephalus and underwent placement of a ventriculoperitoneal shunt. In 4 patients (6%) trigeminal sensory dysfunction developed, and in 1 patient (2%) mild facial weakness (House-Brackmann Grade II) developed after SRS. In univariate analysis, patients who had a previous resection (p = 0.010), those with a tumor volume exceeding 10 ml (p = 0.05), and those with Koos Grade 4 tumors (p = 0.02) had less likelihood of tumor control after SRS.

Conclusions. Although microsurgical resection remains the primary management choice in patients with low comorbidities, most vestibular schwannomas with a maximum diameter less than 4 cm and without significant mass effect can be managed satisfactorily with Gamma Knife radiosurgery.

Neurosurgery 67:611-616, 2010 DOI: 10.1227/01.NEU.0000378026.23116.E6

Cavernous hemangioma in the cavernous sinus (CS) is a rare vascular tumor. Direct microsurgical approach usually results in massive hemorrhage. Radiosurgery has emerged as a treatment alternative to microsurgery.

OBJECTIVE: To further investigate the role of Gamma Knife surgery (GKS) in treating CS hemangiomas.

METHODS: This was a retrospective analysis of 7 patients with CS hemangiomas treated by GKS between 1993 and 2008. Data from 84 CS meningiomas treated during the same period were also analyzed for comparison. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Data on clinical and imaging changes after radiosurgery were analyzed.

RESULTS: Six months after GKS, magnetic resonance imaging revealed an average of 72% tumor volume reduction (range, 56%-83%). After 1 year, tumor volume decreased 80% (range, 69%-90%) compared with the pre-GKS volume. Three patients had > 5 years of follow- up, which showed the tumor volume further decreased by 90% of the original size. The average tumor volume reduction was 82%. In contrast, tumor volume reduction of the 84 cavernous sinus meningiomas after GKS was only 29% (P < .001 by Mann-Whitney U test). Before treatment, 6 patients had various degrees of ophthalmoplegia. After GKS, 5 improved markedly within 6 months. Two patients who suffered from poor vision improved after radiosurgery.

CONCLUSION: GKS is an effective and safe treatment modality for CS hemangiomas with long-term treatment effect. Considering the high risks involved in microsurgery, GKS may serve as the primary treatment choice for CS hemangiomas.

Neurosurgery 67:55-64, 2010 DOI: 10.1227/01.NEU.0000370204.68711.AC

The causes of failure after an initial Gamma procedure were studied, along with imaging and clinical outcomes, in a series of 140 patients with cerebral arteriovenous malformations (AVMs) treated with repeat Gamma Knife surgery (GKS).

METHODS: Causes of initial treatment failure included inaccurate nidus definition in 14 patients, failure to fill part of the nidus as a result of hemodynamic factors in 16, recanalization of embolized AVM compartments in 6, and suboptimal dose (< 20 Gy) in 23. Nineteen patients had repeat GKS for subtotal obliteration of AVMs. In 62 patients, the AVM failed to obliterate despite correct target definition and adequate dose. At the time of retreatment, the nidus volume ranged from 0.1 to 6.9 cm3 (mean, 1.4 cm3), and the mean prescription dose was 20.3 Gy.

RESULTS: Repeat GKS yielded a total angiographic obliteration in 77 patients (55%) and subtotal obliteration in 9 (6.4%). In 38 patients (27.1%), the AVMs remained patent, and in 16 patients (11.4%), no flow voids were observed on magnetic resonance imaging. Clinically, 126 patients improved or remained stable, and 14 experienced deterioration (8 resulting from a rebleed, 2 caused by persistent arteriovenous shunting, and 4 related to radiationinduced changes).

CONCLUSION: By using repeat GKS, we achieved a 55% angiographic cure rate. Although radiation-induced changes as visualized on magnetic resonance imaging occurred in 48 patients (39%), only 4 patients (3.6%) developed permanent neurological deficits. These findings may be useful in deciding the management of AVMs in whom total obliteration after initial GKS was not achieved.

J Neurosurg 113:23–29, 2010. DOI: 10.3171/2010.1.JNS081626

A retrospective study was conducted to reassess the benefit and safety of stereotactic radiosurgery (SRS) in patients with solitary cerebral cavernous malformations (CCMs) that bleed repeatedly and are poor candidates for surgical removal.

Methods. Between 1988 and 2005 at the University of Pittsburgh, the authors performed SRS in 103 evaluable patients (57 males and 46 females) with solitary symptomatic CCMs. The mean patient age was 39.3 years. Ninetyeight percent of these patients had experienced 2 or more hemorrhages associated with new neurological deficits. Seventeen patients (16.5%) had undergone attempted resection before radiosurgery. Ninety-three CCMs were located in deep brain structures and 10 were in subcortical lobar areas of functional brain importance. The median malformation volume was 1.31 ml, and the median tumor margin dose was 16 Gy.

Results. The follow-up ranged from 2 to 20 years. The annual hemorrhage rate—that is, a new neurological deficit associated with imaging evidence of a new hemorrhage—before SRS was 32.5%. After SRS 22 hemorrhages were observed within 2 years (10.8% annual hemorrhage rate) and 4 hemorrhages were observed after 2 years (1.06% annual hemorrhage rate). The risk of hemorrhage from a CCM was significantly reduced after radiosurgery (p < 0.0001). Overall, new neurological deficits due to adverse radiation effects following SRS developed in 14 patients (13.5%), with most occurring early in our experience. Modifications in technique (treatment volume within the T2- weighted MR imaging–defined margin, use of MR imaging, and dose reduction for CCM in critical brainstem locations) further reduced risks after SRS.

Conclusions. Data in this study provide further evidence that SRS is a relatively safe procedure that reduces the rebleeding rate for CCMs located in high-surgical-risk areas of the brain.

Neurosurgery 66:688-695, 2010. DOI: 10.1227/01.NEU.0000367554.96981.26

OBJECTIVE: To determine the limiting dose to the optic apparatus in single-fraction irradiation in patients with craniopharyngioma treated with gamma knife radiosurgery (GKRS).

METHODS: One hundred patients with 109 craniopharyngiomas treated with GKRS were evaluated with a median follow-up period of 68 months. Tumor volume varied from 0.1 to 36.0 (median, 3.3) cm3. Marginal doses varied from 10 to 18 (median, 11.4) Gy. Maximum dose to any part of the optic apparatus varied from 2 to 18 (median, 10) Gy.

RESULTS: The actuarial 5- and 10-year overall rates of survival of tumor progression after GKRS were 93% and 88%, respectively. Similarly, the actuarial 5- and 10-year progressionfree survival rates were 62% and 52%, respectively. Among 94 patients in whom visual function was evaluable after GKRS, only 3 patients developed radiation-induced optic neuropathy, indicating an overall Kaplan-Meier radiation-induced optic neuropathy rate of 5%. Of these patients, 2 received 15 Gy or greater to the optic apparatus. Another patient who received 8 Gy or less had undergone previous fractionated radiation therapy with a biologically effective dose of 60 Gy.

CONCLUSION: The optic apparatus seems to be more tolerant of irradiation than previously thought. Careful dose planning is essential, particularly in patients who underwent prior external beam radiation therapy.

J Neurosurg 111:359–364, 2009

Trigeminal neuralgia (TN) is a disorder of the trigeminal nerve that results in intense episodic pain. Primary treatment with Gamma Knife surgery (GKS) is well established; however, a significant number of patients experience recurrence of TN over time. Repeat GKS can be performed, but the retreatment dose has not been well established. In this study, the authors present their institutional retreatment results and compare them with other series.

Methods
Between December 2003 and January 2006, 28 patients were treated at Tufts Medical Center with repeat GKS for recurrence of TN. All patients had been initially treated with GKS at this institution, and only those with significant pain improvement were offered retreatment. The maximum dose was prescribed using a single isocenter; the 4-mm collimator was used. The initial median GKS dose was 80 Gy, the median retreatment dose was 45 Gy, and the median cumulative dose was 125 Gy. The median time between GKS procedures was 18.1 months. Facial pain outcomes were defined using the Marseille scale. Excellent outcome was defined as no pain (with or without medications), and good outcome was defined as > 50% pain relief. Toxicity was categorized as none, mild, or bothersome. The median clinical follow-up after the second GKS was 19.7 months. Our clinical outcomes were compared with 8 previously reported retreatment series (including 1 abstract), both for rate of pain control and for rate of complications.

Results
Outcomes after the second GKS were excellent in 29% (8 patients), good in 32% (9), and poor in 39% (11). Four patients (14%) experienced no improvement after repeat GKS. Eight patients (29%) experienced new trigeminal nerve dysfunction, including numbness (11%), paresthesia (14%), dysesthesia (4%), taste alteration (11%), and bite weakness (4%). None of these were bothersome. No patient developed corneal numbness. Univariate analysis failed to reveal any significant predictors of pain control or complications.

Seven published peer-reviewed retreatment series and the authors’ data (total 215 patients) were analyzed. There was a cumulative dose-response relationship for both pain control (p = 0.04) and new trigeminal dysfunction (p = 0.08). Successful pain control was strongly correlated with development of new dysfunction (p = 0.02). A cumulative dose > 130 Gy was more likely to result in successful (> 50%) pain control, but was also more likely (> 20%) to result in development of new dysfunction.

Conclusions
Successful retreatment of patients in whom the initial GKS treatment fails is feasible. Patients who respond initially may be at a higher risk of retreatment-related complications. There appears to be a dose-response relationship for both pain control and development of new side effects. It is important to counsel and treat patients individually based on this dose-response relationship.