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Dong Liu, Desheng Xu, Zhiyuan Zhang, Yipei Zhang and Ligao Zheng

Object

The authors sought to assess the results of Gamma Knife surgery (GKS) in patients with vestibular schwannomas (VSs).

Methods

Seventy-four consecutive patients (33 men and 41 women) were evaluated by means of serial imaging studies, clinical examinations, and questionnaires. Nineteen patients had undergone resection of their VS. Facial nerve function was normal in 63 patients (85.1%) before GKS, and 63.5% of them had useful hearing. The prescription peripheral dose varied between 10 and 14 Gy (mean 12.27 ± 0.96 Gy); the corresponding central dose was 21 to 30 Gy (mean 24.9 ± 2.18 Gy). The mean volume of the tumor at GKS was 10.79 ± 5.52 ml (range 0.11–27.8 ml). A mean of eight isocenters (range 3–17) was used for treating these lesions.

At a median follow-up period of 68.3 months (range 30–122 months), tumor shrinkage was observed in 60 patients (81.1%), and the tumor size was stable in 11 (14.8%). Persistent neuroimaging demonstrated evidence of progression in only three patients (4.1%): two underwent repeated GKS after an interval of 18 months and one continues to be observed. Five patients experienced trigeminal dysfunction: in three the dysfunction was transient and in the other two the dysfunction persists. Three patients suffered facial palsy. Useful hearing was preserved in 34 patients. Thirteen patients experienced some degree of hearing improvement. Deterioration of hearing was found in 13 of 62 patients who had Class I or II hearing before treatment.

Conclusions

Gamma Knife surgery prevents tumor growth; it achieves excellent neurological function preservation and produces few treatment-related complications.

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Mohamed Elsharkawy, Zhiyuan Xu, David Schlesinger and Jason P. Sheehan

Object

Most intracranial schwannomas arise from cranial nerve (CN) VIII. Stereotactic radiosurgery is a mainstay of treatment for vestibular schwannomas. Intracranial schwannomas arising from other CNs are much less common. We evaluate the efficacy of Gamma Knife surgery on nonvestibular schwannomas including trigeminal, hypoglossal, abducent, facial, trochlear, oculomotor, glossopharyngeal, and jugular foramen tumors.

Methods

Thirty-six patients with nonvestibular schwannomas were treated at the University of Virginia Gamma Knife center from 1989 to 2008. The median patient age was 48 years (mean 45.6 years, range 10–72 years). Schwannomas arose from the following CNs: CN III (in 1 patient), CN IV (in 1), CN V (in 25), CN VI (in 2), CN VII (in 1), CN IX (in 1), and CN XII (in 3). In 2 patients, tumors arose from the jugular foramen. The median tumor volume was 2.9 cm3 (mean 3.3 cm3, range 0.07–8.8 cm3). The median margin dose was 13.5 Gy (range 9.3–20 Gy); the median maximum dose was 30 Gy (range 21.7–50.0 Gy).

Results

The mean and median follow-up times of 36 patients were 54 and 37 months, respectively (range 2–180 months). At the last radiological follow-up, the tumor size had decreased in 20 patients, remained stable in 9 patients, and increased in 7 patients. The 2-year actuarial progression-free survival was 91%. Higher maximum dose was statistically related to tumor control (p = 0.027).

Thirty-three patients had adequate clinical follow-up. Among them, 21 patients had improvement in their presenting symptoms, 8 patients were stable after treatment with no worsening of their presenting symptoms, 2 patients developed new symptoms, and 1 patient experienced symptom deterioration. Notably, 1 patient with neurofibromatosis Type 2 developed new symptoms that were unrelated to the tumor treated with Gamma Knife surgery.

Conclusions

Gamma Knife surgery is a reasonably effective treatment option for patients with nonvestibular schwannomas. Patients require careful follow-up for tumor progression and signs of neurological deterioration.

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Douglas Kondziolka

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Jason P. Sheehan, Gregory Patterson, David Schlesinger and Zhiyuan Xu

Object

Obsessive-compulsive disorder (OCD) is a challenging psychiatric condition associated with anxiety and ritualistic behaviors. Although medical management and psychiatric therapy are effective for many patients, severe and extreme cases may prove refractory to these approaches. The authors evaluated their experience with Gamma Knife (GK) capsulotomy in treating patients with severe OCD.

Methods

A retrospective review of an institutional review board–approved prospective clinical GK database was conducted for patients treated for severe OCD. All patients were evaluated preoperatively by at least one psychiatrist, and their condition was deemed refractory to pharmacological and psychiatric therapy.

Results

Five patients were identified. Gamma Knife surgery with the GK Perfexion unit was used to target the anterior limb of the internal capsule bilaterally. A single 4-mm isocenter was used; maximum radiation doses of 140–160 Gy were delivered. All 5 patients were preoperatively and postoperatively assessed for clinical response by using both subjective and objective metrics, including the Yale-Brown Obsessive Compulsive Scale (YBOCS); 4 of the 5 patients had postoperative radiological follow-up. The median clinical follow-up was 24 months (range 6–33 months). At the time of radiosurgery, all patients had YBOCS scores in the severe or extreme range (median 32, range 31–34). At the last follow-up, 4 (80%) of the 5 patients showed marked clinical improvement; in the remaining patient (20%), mild improvement was seen. The median YBOCS score was 13 (range 12–31) at the last follow-up. Neuroimaging studies at 6 months after GK treatment demonstrated a small area of enhancement corresponding to the site of the isocenter and some mild T2 signal changes in the internal capsule. No adverse clinical effects were noted from the radiosurgery.

Conclusions

For patients with severe OCD refractory to medications and psychiatric therapy, GK capsulotomy afforded clinical improvement. Further study of this approach seems warranted.

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Brian J. Williams, Zhiyuan Xu, David J. Salvetti, Ian T. McNeill, James Larner and Jason P. Sheehan

Object

Gamma Knife surgery (GKS) is a safe and effective treatment for patients with small to moderately sized vestibular schwannomas (VSs). Reports of stereotactic radiosurgery for large VSs have demonstrated worse tumor control and preservation of neurological function. The authors endeavored to assess the effect of size of VSs treated using GKS.

Methods

This study was a retrospective comparison of 24 patients with large VSs (> 3 cm in maximum diameter) treated with GKS compared with 49 small VSs (≤ 3 cm) matched for age, sex, radiosurgical margin and maximal doses, length of follow-up, and indication.

Results

Actuarial tumor progression-free survival (PFS) for the large VS cohort was 95.2% and 81.8% at 3 and 5 years, respectively, compared with 97% and 90% for small VSs (p = 0.009). Overall clinical outcome was better in small VSs compared with large VSs (p < 0.001). Patients with small VSs presenting with House-Brackmann Grade I (good facial function) had better neurological outcomes compared with patients with large VSs (p = 0.003). Treatment failure occurred in 6 patients with large VSs; 3 each were treated with resection or repeat GKS. Treatment failure did not occur in the small VS group. Two patients in the large VS group required ventriculoperitoneal shunt placement. Univariate analysis did not identify any predictors of treatment failure among the large VS cohort.

Conclusions

Patients with large VSs treated using GKS had shorter PFS and worse clinical outcomes compared with age-, sex-, and indication-matched patients with small VSs. Nevertheless, GKS has efficacy for some patients with large VSs and represents a reasonable treatment option for selected patients.

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Mohamed Samy Elhammady and Roberto C. Heros

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Dale Ding, Zhiyuan Xu, Ian T. McNeill, Chun-Po Yen and Jason P. Sheehan

Object

Parasagittal and parafalcine (PSPF) meningiomas represent the second most common location for intracranial meningiomas. Involvement of the superior sagittal sinus or deep draining veins may prevent gross-total resection of these tumors without significant morbidity. The authors review their results for treatment of PSPF meningiomas with radiosurgery.

Methods

The authors retrospectively reviewed the institutional review board–approved University of Virginia Gamma Knife database and identified 65 patients with 90 WHO Grade I parasagittal (59%) and parafalcine (41%) meningiomas who had a mean MRI follow-up of 56.6 months. The patients' mean age was 57 years, the median preradiosurgery Karnofsky Performance Status score was 80, and the median initial tumor and treatment volumes were 3 and 3.7 cm3, respectively. The median prescription dose was 15 Gy, isodose line was 40%, and the number of isocenters was 5. Kaplan-Meier analysis was used to determine progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to identify factors associated with PFS.

Results

The median overall PFS was 75.6 months. The actuarial tumor control rate was 85% at 3 years and 70% at 5 years. Parasagittal location, no prior resection, and younger age were found to be independent predictors of tumor PFS. For the 49 patients with clinical follow-up (mean 70.8 months), the median postradiosurgery Karnofsky Performance Status score was 90. Symptomatic postradiosurgery peritumoral edema was observed in 4 patients (8.2%); this group comprised 3 patients (6.1%) with temporary and 1 patient (2%) with permanent clinical sequelae. Two patients (4.1%) died of tumor progression.

Conclusions

Radiosurgery offers a minimally invasive treatment option for PSPF meningiomas, with a good tumor control rate and an acceptable complication rate comparable to most surgical series.

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Or Cohen-Inbar, Cheng-Chia Lee, Zhiyuan Xu, David Schlesinger and Jason P. Sheehan

OBJECT

The authors review outcomes following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs) and their correlation to postradiosurgery adverse radiation effects (AREs).

METHODS

From a prospective institutional review board–approved database, the authors identified patients with a minimum of 2 years of follow-up and thin-slice T2-weighted MRI sequences for volumetric analysis. A total of 105 AVM patients were included. The authors analyzed the incidence and quantitative changes in AREs as a function of time after GKRS. Statistical analysis was performed to identify factors related to ARE development and changes in the ARE index.

RESULTS

The median clinical follow-up was 53.8 months (range 24–212.4 months), and the median MRI follow-up was 36.8 months (range 24–212.4 months). 47.6% of patients had an AVM with a Spetzler-Martin grade ≥ III. The median administered margin and maximum doses were 22 and 40 Gy, respectively. The overall obliteration rate was 70.5%. Of patients who showed complete obliteration, 74.4% developed AREs within 4–6 months after GKRS. Late-onset AREs (i.e., > 12 months) correlated to a failure to obliterate the nidus. 58.1% of patients who developed appreciable AREs (defined as ARE index > 8) proceeded to have a complete nidus obliteration. Appreciable AREs were found to be influenced by AVM nidus volume > 3 ml, lobar location, number of draining veins and feeding arteries, prior embolization, and higher margin dose. On the other hand, a minimum ARE index > 8 predicted obliteration (p = 0.043).

CONCLUSIONS

ARE development after radiosurgery follows a temporal pattern peaking at 7–12 months after stereotactic radiosurgery. The ARE index serves as an important adjunct tool in patient follow-up and outcome prediction.

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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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Or Cohen-Inbar, Han-Hsun Shih, Zhiyuan Xu, David Schlesinger and Jason P. Sheehan

OBJECTIVE

Melanoma represents the third most common cause of CNS metastases. Immunotherapy has evolved as a treatment option for patients with Stage IV melanoma. Stereotactic radiosurgery (SRS) also elicits an immune response within the brain and may interact with immunotherapy. The authors report on a cohort of patients treated for brain metastases with immunotherapy and evaluate the effect of SRS timing on the intracranial response.

METHODS

All consecutively treated melanoma patients receiving ipilimumab and SRS for treatment of brain metastases at the University of Virginia between 2009 and 2014 were included in this retrospective analysis; data from 46 patients harboring 232 brain metastases were reviewed. The median duration of clinical follow-up was 7.9 months (range 3–42.6 months). The median age of the patients was 63 years (range 24.3–83.6 years). Thirty-two patients received SRS before or during ipilimumab cycles (Group A), whereas 14 patients received SRS after ipilimumab treatment (Group B). Radiographic and clinical responses were assessed at approximately 3-month intervals after SRS.

RESULTS

The 2 cohorts were comparable in pertinent baseline characteristics with the exception of SRS timing relative to ipilimumab. Local recurrence–free duration (LRFD) was significantly longer in Group A (median 19.6 months, range 1.1–34.7 months) than in Group B patients (median 3 months, range 0.4–20.4 months) (p = 0.002). Post-SRS perilesional edema was more significant in Group A.

CONCLUSIONS

The effect of SRS and ipilimumab on LRFD seems greater when SRS is performed before or during ipilimumab treatments. The timing of immunotherapy and SRS may affect LRFD and postradiosurgical edema. The interactions between immunotherapy and SRS warrant further investigation so as to optimize the therapeutic benefits and mitigate the risks associated with multimodality, targeted therapy.