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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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Desheng Xu, Dong Liu, Zhiyuan Zhang, Yipei Zhang, Yanhe Li, Xiaomin Liu, Qiang Jia, Ligao Zheng and Guoxiang Song

Object

The authors evaluated the results they obtained using Gamma Knife surgery (GKS) in patients with orbital tumors.

Methods

This is a retrospective clinical evaluation of 202 patients with orbital tumors who were treated with GKS between September 1995 and October 2008. The series included 84 men and 118 women with a mean age of 39.5 ± 14.6 years (range 5–85 years). The diagnoses were determined based on pathological analyses in 113 patients and presumed based on characteristic clinical and imaging findings in 89 patients. There were 84 meningiomas, 38 epithelial tumors of the lacrimal gland, 23 schwannomas, 18 malignant choroidal melanomas, 12 optic nerve gliomas, 11 orbital metastases, 10 pseudotumors of the orbit, 3 retinoblastomas, and 3 cases of fibromatosis. The median target volume was 5.4 cm3 (range 0.04–35.6 cm3). The tumor margin dose ranged from 10 to 40 Gy.

Results

At a median follow-up period of 34.5 ± 14.7 months (range 12–114 months), tumor shrinkage was observed in 118 patients (58.4%) and stable tumor size in 71 patients (35.1%). Regularly scheduled neuroimaging studies demonstrated evidence of tumor progression in only 13 patients (6.4%): 9 of these patients underwent repeated GKS and 4 received surgical treatment. Visual acuity was preserved in 129 patients. Seventy-two patients experienced some degree of improvement in vision. Severe deterioration of visual acuity was found in 18 of 147 patients who had useful vision before treatment. Nineteen patients (9.4%) experienced transient conjunctival edema; no other serious acute side effect was observed.

Conclusions

Gamma Knife surgery provides an effective management strategy in patients with orbital tumors; it achieves excellent preservation of neurological function and is associated with few treatment-related complications.

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Dong Liu, Desheng Xu, Zhiyuan Zhang, Yipei Zhang, Yanhe Li, Xiaomin Liu, Qiang Jia, Ligao Zheng and Guoxiang Song

Object

The goal of this study was to assess the long-term results of Gamma Knife surgery (GKS) in patients harboring an optic nerve sheath meningioma (ONSM).

Methods

Thirty patients harboring an ONSM were treated with GKS between 1998 and 2003. Gamma Knife surgery was performed as the sole treatment option in 21 of these patients and resection had been performed previously in 9 patients. The mean volume of the tumor at the time of GKS was 3.6 cm3 (range 1.4–9.7 cm3), and the mean prescription peripheral dose was 13.3 Gy (range 10–17 Gy). The mean number of isocenters used to treat these lesions was 8 (range 5–14 isocenters).

Results

At a median follow-up of 56 months, visual acuity improved in 11 patients, remained stable in 13 patients (including 4 patients who were completely blind before GKS), and deteriorated in 6 patients. Follow-up images were available in all patients and showed tumor regression in 20 patients and stable tumor in 8 patients. Persistent imaging evidence of progression was only present in 2 patients. With the exception of reversible conjunctival edema in 4 cases, no other serious acute side effect was observed.

Conclusions

Gamma Knife surgery provides long-term tumor control for ONSM. The results of this study add substantial evidence that GKS may definitely become a standard treatment approach in selected cases of ONSM.

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Qiang Jia, Yanhe Li, Desheng Xu, Zhenjiang Li, Zhiyuan Zhang, Yipei Zhang, Dong Liu, Xiaomin Liu, Peiyu Pu and Chunsheng Kang

Object

The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT).

Methods

First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses.

Results

The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged.

Conclusions

Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

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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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Jason P. Sheehan, Shota Tanaka, Michael J. Link, Bruce E. Pollock, Douglas Kondziolka, David Mathieu, Christopher Duma, A. Byron Young, Anthony M. Kaufmann, Heyoung McBride, Peter A. Weisskopf, Zhiyuan Xu, Hideyuki Kano, Huai-che Yang and L. Dade Lunsford

Object

Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors of this study examine the outcomes after radiosurgery in a large, multicenter patient population.

Methods

Under the auspices of the North American Gamma Knife Consortium, 8 Gamma Knife surgery centers that treat glomus tumors combined their outcome data retrospectively. One hundred thirty-four patient procedures were included in the study (134 procedures in 132 patients, with each procedure being analyzed separately). Prior resection was performed in 51 patients, and prior fractionated external beam radiotherapy was performed in 6 patients. The patients' median age at the time of radiosurgery was 59 years. Forty percent had pulsatile tinnitus at the time of radiosurgery. The median dose to the tumor margin was 15 Gy. The median duration of follow-up was 50.5 months (range 5–220 months).

Results

Overall tumor control was achieved in 93% of patients at last follow-up; actuarial tumor control was 88% at 5 years postradiosurgery. Absence of trigeminal nerve dysfunction at the time of radiosurgery (p = 0.001) and higher number of isocenters (p = 0.005) were statistically associated with tumor progression–free tumor survival. Patients demonstrating new or progressive cranial nerve deficits were also likely to demonstrate tumor progression (p = 0.002). Pulsatile tinnitus improved in 49% of patients who reported it at presentation. New or progressive cranial nerve deficits were noted in 15% of patients; improvement in preexisting cranial nerve deficits was observed in 11% of patients. No patient died as a result of tumor progression.

Conclusions

Gamma Knife surgery was a well-tolerated management strategy that provided a high rate of long-term glomus tumor control. Symptomatic tinnitus improved in almost one-half of the patients. Overall neurological status and cranial nerve function were preserved or improved in the vast majority of patients after radiosurgery.

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Yanhe Li, Desheng Xu, Zhiyuan Zhang, Yipei Zhang, Dong Liu, Xiaomin Liu, Guokai Wang and Yiguang Lin

Object

The goal of this study was to assess neuroimaging and clinical outcomes in patients harboring brainstem metastases that were treated with the Leksell Gamma Knife.

Methods

Twenty-eight patients with brainstem metastases (32 lesions: 8 midbrain, 21 pontine, and 3 medullary) were consecutively treated with GKS. The primary cancer diagnoses in this group included 22 cases of lung cancer, 5 cases of breast cancer, and 1 case of rectal cancer. The median age of the patients was 61 years (range 45–83 years). The median treated lesion volume was 0.78 cm3 (range 0.03–5.6 cm3), and the median GKS margin dose was 16 Gy (range 12–20 Gy). Overall survival in these patients was calculated using the Kaplan-Meier method.

Results

The median survival time was 9 months after GKS (range 2–32 months). Survival was 39.3% at 1 year and 10.7% at 2 years. The tumor control rate in the series was 90.6% (29 of 32 lesions). Development of peritumoral edema occurred in 1 patient after GKS; 4 months after GKS, the edema disappeared.

Conclusions

Gamma Knife surgery using a median margin dose of 16 Gy is a safe and effective local therapy for patients with brainstem metastases.

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David Weintraub, Chun-Po Yen, Zhiyuan Xu, Jesse Savage, Brian Williams and Jason Sheehan

Object

While some low-grade pediatric gliomas may be cured with resection, many patients harbor tumors that cannot be completely resected safely, are difficult to access via an open surgical approach, or recur. Gamma Knife surgery may be beneficial in the treatment of these tumors.

Methods

The authors reviewed a consecutive series of 24 pediatric patients treated at the authors' institution between 1989 and 2011. All patients harbored tumors that were either surgically inaccessible or had evidence of residual or recurrent growth after resection. Progression-free survival was evaluated and correlated with clinical variables. Additional outcomes evaluated were clinical outcome, imaging response, and overall survival.

Results

Between 1989 and 2011, 13 male and 11 female patients (median age 11 years, range 4–18 years) with gliomas were treated. Tumor pathology was pilocytic astrocytoma (WHO Grade I) in 15 patients (63%), WHO Grade II in 4 (17%), and WHO Grade III in 1 (4%). The tumor pathology was not confirmed in 4 patients (17%). The mean tumor volume at the time of treatment was 2.4 cm3. Lesions were treated with a median maximum dose of 36 Gy, median of 3 isocenters, and median marginal dose of 15 Gy.

The median duration of imaging follow-up was 74 months, and the median duration of clinical follow-up was 144 months. The tumors responded with a median decrease in volume of 71%. At last follow up, a decrease in tumor size of at least 50% was demonstrated in 18 patients (75%) and complete tumor resolution was achieved in 5 (21%). Progression-free survival at last follow-up was achieved in 20 patients (83%). Progression was documented in 4 patients (17%), with 3 patients requiring repeat resection and 1 patient dying. The initial tumor volume was significantly greater in patients with disease progression (mean volume 4.25 vs 2.0 cm3, p < 0.001). Age, tumor pathology, tumor location, previous radiation, Karnofsky Performance Scale score, symptom duration, and target dosage did not differ significantly between the 2 groups.

Conclusions

Gamma Knife surgery can provide good clinical control of residual or recurrent gliomas in pediatric patients. Worse outcomes in the present series were associated with larger tumor volumes at the time of treatment.

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David Schlesinger, Zhiyuan Xu, Frances Taylor, Chun-Po Yen and Jason Sheehan

Object

The Extend system for the Gamma Knife Perfexion makes possible multifractional Gamma Knife treatments. The Extend system consists of a vacuum-monitored immobilization frame and a positioning measurement system used to determine the location of the patient's head within the frame at the time of simulation imaging and before each treatment fraction. The measurement system consists of a repositioning check tool (RCT), which attaches to the Extend frame, and associated digital measuring gauges. The purpose of this study is to evaluate the performance of the Extend system for patient repositioning before each treatment session (fraction) and patient immobilization between (interfraction) and during (intrafraction) each session in the first 10 patients (36 fractional treatments) treated at the University of Virginia.

Methods

The RCT was used to acquire a set of reference measurements for each patient position at the time of CT simulation. Repositioning measurements were acquired before each fraction, and the patient position was adjusted until the residual radial difference from the reference position measurements was less than 1 mm. After treatment, patient position measurements were acquired, and the difference between those measurements and the ones obtained for patient position before the fraction was calculated as a measure of immobilization capability.

Analysis of patient setup and immobilization performance included calculation of the group mean, standard deviation (SD), and distribution of systematic (components affecting all fractions) and random (per fraction) uncertainty components.

Results

Across all patients and fractions, the mean radial setup difference from the reference measurements was 0.64 mm, with an SD of 0.24 mm. The distribution of systematic uncertainty (Σ) was 0.17 mm, and the distribution of random uncertainty (σ) was 0.16 mm. The root mean square (RMS) differences for each plate of the RCT were as follows: right = 0.35 mm; left = 0.41 mm; superior = 0.28 mm; and anterior = 0.20 mm.

The mean intrafractional positional difference across all treatments was 0.47 mm, with an SD of 0.30 mm. The distribution of systematic uncertainty was 0.18 mm, and the distribution of random uncertainty was 0.22 mm. The RMS differences for each plate of the RCT were 0.24 mm for the right plate, 0.22 mm for the left plate, 0.24 mm for the superior plate, and 0.34 mm for the anterior plate. Data from 1 fraction were excluded from the analysis because the vacuum-monitoring interlock detected patient motion, which in turn required repositioning in the middle of the fraction.

Conclusions

The Extend system can be used to reposition and immobilize patients in a radiosurgical setting. However, care should be taken to acquire measurements that can implicitly account for rotations of the patient's head. Further work is required to determine the sensitivity of the vacuum interlock to detect patient motion.

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Xiaomin Liu, Qi Yu, Zhiyuan Zhang, Yipei Zhang, Yanhe Li, Dong Liu, Qiang Jia, Ligao Zheng and Desheng Xu

Object

The goal of this study was to evaluate the efficacy and safety of same-day stereotactic aspiration and Gamma knife surgery (GKS) for cystic intracranial tumors.

Methods

Between 1996 and 2007, 77 patients harboring cystic intracranial tumors underwent a same-day procedure of MRI-guided cyst aspiration followed by GKS. The diagnoses were metastatic tumor in 43 patients, glial tumor in 12 patients, vestibular schwannoma in 10 patients, craniopharyngioma in 9 patients, and hemangioblastoma in 3 patients.

Results

An improvement in symptoms was achieved in 68 patients (88.3%) immediately after cyst aspiration. The mean tumor volume in this group of patients was 25.1 cm3 before aspiration and 11.1 cm3 afterward. Hemorrhage during the course of aspiration was encountered in 1 patient. Transient nausea after cyst aspiration developed in 3 patients. There was no treatment-related hematoma, seizure, neurological deficit, or infection. The median follow-up period was 16 months (range 6–108 months). Tumor control was achieved in 50 (80.6%) of 62 patients who participated in follow-up for at least 6 months.

Conclusions

The same-day stereotactic aspiration and GKS procedure was safe in patients with cystic brain tumors. Prompt symptom relief was obtained after cyst aspiration. The decrease in tumor volume following aspiration made GKS more effective because a higher prescription dose could be administered with a lower possibility of radiation-induced side effects.