ABSTRACTS JANUARY TO MARCH 2015

GAMMA KNIFE® RADIOSURGERY

1

CRANIOPHARYNGIOMA

Neuropathology.2015;35(1):50-5. Epub 2014/08/13 Malignant transformation of craniopharyngioma with detailed follow-up Wang, W., Chen, X. D., Bai, H. M., Liao, Q. L., Dai, X. J., Peng, D. Y. and Cao, H. X.,Department of Pathology, Guangzhou Liuhuaqiao Hospital, Guangzhou, China. A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature.

ESSENTIAL TREMOR

J Korean Neurosurg Soc.2015;57(3):192-6. Epub 2015/03/27 Outcome of gamma knife thalamotomy in patients with an intractable tremor Cho, K. R., Kim, H. R., Im, Y. S., Youn, J., Cho, J. W. and Lee, J. I.,Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Department of Neurosurgery, Konyang University Hospital, College of Medicine, Konyang University, Daejeon, Korea. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

OBJECTIVE: Tremor is a common movement disorder that interferes with daily living. Since the medication for tremor has some limitations, surgical intervention is needed in many patients. In certain patients who cannot undergo aggressive surgical intervention, Gamma Knife thalamotomy (GKT) is a safe and effective alternative. METHODS: From June 2012 to August 2013, 7 patients with an intractable tremor underwent GKT. Four of these 7 patients had medical comorbidities, and 3 patients refused to undergo traditional surgery. Each patient was evaluated with the modified Fahn-Tolosa-Marin tremor rating scale (TRS) along with analysis of handwriting samples. All of the patients underwent GKT with a maximal dose of 130 Gy to the left ventralis intermedius (VIM) nucleus of the thalamus. Follow-up brain MRI was performed after 3 to 8 months of GKT, and evaluation with the TRS was also performed. RESULTS: Six patients showed objective improvement in the TRS score. Excluding one patient who demonstrated tremor progression, there was 28.9% improvement in the TRS score. However, five patients showed subjective improvement in their symptoms. On comparing the TRS scores between follow-up periods of more and less than 4 months, the follow-up TRS score at more than 4 months of

2

GKT was significantly improved compared to that at less than 4 months of GKT. Follow-up MRI showed radiosurgical changes in 5 patients. CONCLUSION: GKT with a maximal dose of 130 Gy to the VIM is a safe procedure that can replace other surgical procedures.

Radiother Oncol.2015;Epub 2015/02/19 Gamma knife stereotactic radiosurgical thalamotomy for intractable tremor: A systematic review of the literature Campbell, A. M., Glover, J., Chiang, V. L., Gerrard, J. and Yu, J. B.,Yale School of Medicine, New Haven, United States. Yale School of Medicine, New Haven, United States; Cushing Memorial Medical Library, Yale School of Medicine, New Haven, United States. Yale School of Medicine, New Haven, United States; Department of Neurosurgery, Yale School of Medicine, New Haven, United States. Yale School of Medicine, New Haven, United States; Department of Therapeutic Radiology, Yale School of Medicine, New Haven, United States. Electronic address: james.b.yu@yale.edu. Tremor markedly reduces quality of life and causes a significant psychological burden for patients who are severely affected by this movement disorder. Pharmacologic and surgical treatments for tremor exist, but for patients who have failed medical therapy and are not surgical candidates, stereotactic radiosurgery is the only available treatment option. Of available stereotactic radiosurgical techniques for intractable tremor, the authors chose to evaluate the safety and efficacy of gamma knife stereotactic radiosurgical thalamotomy. In order to qualitatively synthesize available data a systematic review was conducted by searching MEDLINE (OvidSP 1946-January Week 1 2014) and Embase (OvidSP 1974-2014 January). The search strategy was not limited by study design or language of publication. All searches were conducted on January 7, 2014. Treatment efficacy, adverse outcomes, and patient deaths were reviewed and tabulated. Complications appeared months to years post procedure and most commonly consisted of mild contralateral numbness and transient hemiparesis. Rarely, more severe complications were reported, including dysphagia and death. Though no data from randomized controlled trials are available, our analysis of the literature indicates that unilateral gamma knife thalamotomy using doses from 130 to 150Gy appears safe and well tolerated.

OCD

Neuropsychopharmacology.2015;Epub 2015/02/04 Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients Batistuzzo, M. C., Hoexter, M. Q., Taub, A., Gentil, A. F., Cesar, R. C., Joaquim, M. A., D'Alcante, C. C., McLaughlin, N. C., Canteras, M. M., Shavitt, R. G., Savage, C. R., Greenberg, B. D., Noren, G., Miguel, E. C. and Lopes, A. C.,Department & Institute of Psychiatry, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. Department of Psychiatry and Behavioral Sciences, Butler Hospital and Brown Medical School, Providence, RI, USA. Institute of Neurological Radiosurgery-Hospital Santa Paula, Sao Paulo, Brazil. Center for Health Behavior Neuroscience, University of Kansas Medical Center, Kansas City, KS, USA. Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI, USA.

3

Gamma ventral capsulotomy (GVC) radiosurgery is intended to minimize side effects while maintaining the efficacy of traditional thermocoagulation techniques for the treatment of refractory obsessive-compulsive disorder (OCD). Neuropsychological outcomes are not clear based on previous studies and, therefore, we investigated the effects of GVC on cognitive and motor performance. A double-blind, randomized controlled trial (RCT) was conducted with 16 refractory OCD patients allocated to active treatment (n=8) and sham (n=8) groups. A comprehensive neuropsychological evaluation including intellectual functioning, attention, verbal and visuospatial learning and memory, visuospatial perception, inhibitory control, cognitive flexibility, and motor functioning was applied at baseline and one year after the procedure. Secondary analysis included all operated patients: eight from the active group, four from the sham group who were submitted to surgery after blind was broken, and five patients from a previous open pilot study (n=5), totaling 17 patients. In the RCT, visuospatial memory (VSM) performance significantly improved in the active group after GVC (p=0.008), and remained stable in the sham group. Considering all patients operated, there was no decline in cognitive or motor functioning after one year of follow-up. Our initial results after 1 year of follow-up suggests that GVC not only is a safe procedure in terms of neuropsychological functioning but in fact may actually improve certain neuropsychological domains, particularly VSM performance, in treatment refractory OCD patients. Neuropsychopharmacology advance online publication, 4 March 2015; doi:10.1038/npp.2015.33.

TRIGEMINAL NEURALGIA

J Neurosurg.2015;1-6. Epub 2015/03/31 A successful case of multiple stereotactic radiosurgeries for ipsilateral recurrent trigeminal neuralgia Daugherty, E., Bhavsar, S., Hahn, S. S., Bassano, D. and Hall, W.,Departments of 1 Radiation Oncology and.

Trigeminal neuralgia is a common pain syndrome primarily managed medically, although many patients require surgical or radiotherapeutic intervention. Stereotactic radiosurgery has become a preferred method of treatment given its high efficacy rates and relatively favorable toxicity profile. However, many patients have refractory pain even after repeat courses of stereotactic radiosurgery. Historically, 2 courses have been the limit in such patients. The authors present a case of multiply recurrent trigeminal neuralgia treated with a third course of radiosurgery in which the patient had successful pain control and no additional toxicity. Meticulous attention to the therapeutic technique allows the continued application of stereotactic radiosurgery in patients.

Neurosurgery.2015;Epub 2015/03/27 Decreased Probability of Initial Pain Cessation in Classic Trigeminal Neuralgia Treated With Gamma Knife Surgery in Case of Previous Microvascular Decompression: A Prospective Series of 45 Patients With >1 Year of Follow-up

Tuleasca, C., Carron, R., Resseguier, N., Donnet, A., Roussel, P., Gaudart, J., Levivier, M. and Regis, J.,*Functional and Stereotactic Neurosurgery Unit, Centre Hospitalier Universitaire La Timone Assistance Publique-Hopitaux de Marseille, Universite de la Mediterranee, INSERM U 751, Marseille, France; double daggerSignal Processing Laboratory (LTS 5), Swiss Federal Institute of Technology, Marseille, France; section signMedical Image Analysis Laboratory, Centre Hospitalier Universitaire Vaudois, Marseille, France; paragraph signCentre Hospitalier Universitaire Vaudois, Department of Clinical

4

Neurosciences, Neurosurgery Service and Gamma Knife Center, Lausanne, Switzerland; ||University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland; #Department of Public Health and Medical Information, Centre Hospitalier Universitaire La Timone Assistance Publique-Hopitaux de Marseille, UMR 912 (INSERM-IRD-Universite de la Mediterranee), Marseille, France; **Department of Neurology, Clinical Neuroscience Federation, Centre Hospitalier Universitaire La Timone Assistance Publique-Hopitaux de Marseille, Marseille, France.

BACKGROUND: Microvascular decompression (MVD) is the reference technique for pharmacoresistant trigeminal neuralgia (TN). OBJECTIVE: To establish whether the safety and efficacy of Gamma Knife surgery for recurrent TN are influenced by prior MVD. METHODS: Between July 1992 and November 2010, 54 of 737 patients (45 of 497 with >1 year of follow-up) had a history of MVD (approximately half also with previous ablative procedure) and were operated on with Gamma Knife surgery for TN in the Timone University Hospital. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range, 3.9-11.9 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range, 70-90 Gy) was delivered. RESULTS: The median follow-up time was 39.5 months (range, 14.1-144.6 months). Thirty-five patients (77.8%) were initially pain free in a median time of 14 days (range, 0-180 days), much lower compared with our global population of classic TN (P = .01). Their actuarial probabilities of remaining pain-free without medication at 3, 5, 7, and 10 years were 66.5%, 59.1%, 59.1%, and 44.3%. The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable until 12 years (median, 8 months). CONCLUSION: Patients with previous MVD showed a significantly lower probability of initial pain cessation compared with our global population with classic TN (P = .01). The toxicity was low (only 9.1% hypoesthesia); furthermore, no patient reported bothersome hypoesthesia. However, the probability of maintaining pain relief without medication was 44.3% at 10 years, similar to our global series of classic TN (P = .85). ABBREVIATIONS: BNI, Barrow Neurological InstituteCI, confidence intervalCTN, classic trigeminal neuralgiaGKS, Gamma Knife surgeryHR, hazard ratioMVD, microvascular decompressionTN, trigeminal neuralgia.

Stereotact Funct Neurosurg.2015;93(2):110-113. Epub 2015/02/28 Gamma Knife Stereotactic Radiosurgery for Trigeminal Neuralgia Caused by a Developmental Venous Anomaly Harrison, G., Lunsford, L. D. and Monaco Iii, E. A.,Department of Neurosurgery, New York University Langone Medical Center, New York, N.Y., USA. Background: Trigeminal neuralgia (TN) is mostly caused by vascular compression of the nerve's root entry zone due to an ectatic artery. Rarer causes include compression from tumors, vascular malformations or multiple sclerosis plaques. Developmental venous anomalies (DVAs) are benign, aberrantly appearing venous structures that drain normal cerebral tissue. DVAs are a rare etiology of TN. The management of TN caused by a DVA is controversial as disruption of the DVA can be catastrophic. Methods: We report a case of a young man with severe medically refractory TN related to a brachium pontis DVA who was successfully treated by gamma knife stereotactic radiosurgery (GKSR) to the trigeminal nerve. Results: Within 2 weeks of GKSR, the patient reported experiencing 60% pain relief; 5 years postoperatively, he remains completely pain free with some mild sensory loss in the V2 and V3 areas. Conclusions: GKSR has an established role in the management of TN. This is the first reported case of using GKSR to treat TN caused by a DVA. In the setting of a DVA, GKSR should be an initial consideration for TN therapy after medical failure because of the high surgical risk related to disrupting the DVA. (c) 2015 S. Karger AG, Basel.

5

GLIOMA

J Neurosurg.2015;1-9. Epub 2015/01/17 Role of adjuvant or salvage radiosurgery in the management of unresected residual or progressive glioblastoma multiforme in the pre-bevacizumab era Niranjan, A., Kano, H., Iyer, A., Kondziolka, D., Flickinger, J. C. and Lunsford, L. D.,Departments of 1 Neurological Surgery and. OBJECT After initial standard of care management of glioblastoma multiforme (GBM), relatively few proven options remain for patients with unresected progressive tumor. Numerous reports describe the value of radiosurgery, yet this modality appears to remain underutilized. The authors analyzed the outcomes of early adjuvant stereotactic radiosurgery (SRS) for unresected tumor or later salvage SRS for progressive GBM. Radiosurgery was performed as part of the multimodality management and was combined with other therapies. Patients continued to receive additional chemotherapy after SRS and prior to progression being documented. In this retrospective analysis, the authors evaluated factors that affected patient overall survival (OS) and progression-free survival. METHODS Between 1987 and 2008 the authors performed Gamma Knife SRS in 297 patients with histologically proven GBMs. All patients had received prior fractionated radiation therapy, and 66% had undergone one or more chemotherapy regimens. Ninety-six patients with deep-seated unresectable GBMs underwent biopsy only. Of those in whom excision had been possible, resection was considered to be gross total in 68 and subtotal in 133. The median patient age was 58 years (range 23-89 years) and the median tumor volume was 14 cm3 (range 0.26-84.2 cm3). The median prescription dose delivered to the imaging-defined tumor margin was 15 Gy (range 9-25 Gy). The median follow-up duration was 8.6 months (range 1.1-173 months). Cox regression models were used to analyze survival outcomes. Variables examined included age, residual versus recurrent tumor, prior chemotherapy, time to first recurrence, SRS dose, and gross tumor volume. RESULTS The median survival times after radiosurgery and after diagnosis were 9.03 and 18.1 months, respectively. The 1-year and 2-year OS after SRS were 37.9% and 16.7%, respectively. The 1-year and 2-year OS after diagnosis were 76.2% and 30.8%, respectively. Using multivariate analysis, factors associated with improved OS after diagnosis were younger age (< 60 years) at diagnosis (p < 0.0001), tumor volume < 14 cm3 (p < 0.001), use of prior chemotherapy (p = 0.001), and radiosurgery at the time of recurrence (p < 0.0001). Multivariate analysis showed that younger age (p < 0.0001) and smaller tumor volume (< 14 cm3) (p = 0.001) were significantly associated with increased OS after SRS. Adverse radiation effects were seen in 69 patients (23%). Fifty-eight patients (19.5%) underwent additional resection after SRS. The median survivals after diagnosis for recursive partitioning analysis Classes III, IV and V+VI were 31.6, 20.8, and 16.7 months, respectively. CONCLUSIONS In this analysis 30% of a heterogeneous cohort of GBM patients eligible for SRS had an OS of 2 years. Radiosurgery at the time of tumor progression was associated with a median survival of 21.8 months. The role of radiosurgery for GBMs remains controversial. The findings in this study support the need for a funded and appropriately designed clinical trial that will provide a higher level of evidence regarding the future role of SRS for glioblastoma patients in whom disease has progressed despite standard management.

J Neurooncol.2015;121(2):311-8. Epub 2014/12/10 Outcome of radiosurgery for recurrent malignant gliomas: assessment of treatment response using relative cerebral blood volume

6

Kim, H. R., Kim, S. H., Lee, J. I., Seol, H. J., Nam, D. H., Kim, S. T., Park, K., Kim, J. H. and Kong, D. S.,Department of Neurosurgery, Konyang University Hospital, Konyang University School of Medicine, Daejeon, Korea. Gamma knife radiosurgery (GKS) is efficacious for treating recurrent malignant gliomas as a salvage treatment. However, contrast enhancement alone on MR imaging remains difficult to determine the treatment response following GKS. The purpose of this study was to evaluate the radiosurgical effect for recurrent malignant gliomas and to clarify if relative cerebral blood volume (rCBV) derived from dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MR imaging could represent the treatment response. Between March 2006 and December 2008, 38 patients underwent GKS for recurrent malignant gliomas. Before and after GKS, DSC perfusion MR imaging datasets were retrospectively reprocessed and regions of interest were drawn around the contrast-enhancing region targeted with GKS. DSC-perfusion MR scans were assessed at a regular interval of two months. Following GKS for the recurrent lesions, MR images showed response (stable disease or partial response) in 26 of 38 patients (68.4 %) at post-GKS 2 months and 18 of 38 patients (47.3 %) at post-GKS 4 months. Initial mean rCBV value was 2.552 (0.586-6.178) at the pre-GKS MRI. In the response group, mean rCBV value was significantly decreased (P < 0.05) at the follow up of 2 and 4 months. However, in the treatment-failure group, mean rCBV value had no significant change. We suggest that GKS is an alternative treatment choice for the recurrent glioma. DSC-perfusion MR images are helpful to predict the treatment response after GKS.

J Clin Neurosci.2015;22(3):468-73. Epub 2015/01/18 Outcome of salvage treatment for recurrent glioblastoma Kim, H. R., Kim, K. H., Kong, D. S., Seol, H. J., Nam, D. H., Lim do, H. and Lee, J. I.,Department of Neurosurgery, Konyang University Hospital, Konyang University School of Medicine, Daejeon, Republic of Korea. Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea. Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea. Electronic address: jilee.lee@samsung.com. Most glioblastoma (GBM) cases recur within a year and almost all cases recur at some point. Standard treatment for recurrent GBM has not yet been established. We investigated the outcome of various salvage treatments for recurrent GBM. Retrospective analysis was undertaken in 144 patients who received salvage treatment at the time of first progression after maximum debulking surgery followed by concomitant chemoradiotherapy and adjuvant temozolomide (TMZ) chemotherapy. The median follow-up period was 18.2months. We grouped these patients into five groups according to the salvage modalities: Gamma Knife radiosurgery (GKS) group (n=29), TMZ group (n=31), GKS+TMZ group (n=28), reoperation group (n=38) and "other treatment" group (n=18). The median time to first progression from initial diagnosis was 8.8months. The median overall survival (OS) of the five different treatment groups; GKS, TMZ, GKS+TMZ, reoperation, and "other treatment", was 9.2, 5.6, 15.5, 13.2, and 8.0months, respectively. Median progression-free survival (PFS) was 3.6, 2.3, 6.0, 4.3, and 2.6months, respectively. Pairwise comparison of OS of the GKS+TMZ group with the other groups showed that the OS of the GKS+TMZ group was significantly better than all others except the reoperation group.

7

Statistically significant prolongation of PFS was observed in the GKS+TMZ group compared with the TMZ group and the "other treatment" group. GKS followed by TMZ salvage treatment was a good prognostic factor for both PFS and OS in multivariate analysis. Retrospectively, GKS+TMZ as a salvage treatment, tended to provide a superior survival benefit at the time of recurrence.

Acta Neurochir (Wien).2015;157(2):247-56. Epub 2014/12/17 Gamma Knife radiosurgery for low-grade tectal gliomas El-Shehaby, A. M., Reda, W. A., Abdel Karim, K. M., Emad Eldin, R. M. and Esene, I. N.,Gamma Knife Center Cairo, Cairo, Egypt, amrelshehaby@yahoo.com. BACKGROUND: Tectal gliomas are present in a critical location that makes their surgical treatment difficult. Stereotactic radiosurgery presents an attractive noninvasive treatment option. However, tectal gliomas are also commonly associated with aqueductal obstruction and consequently hydrocephalus. This necessitates some form of CSF diversion procedure before radiosurgery. The aim of the study was to assess the efficacy and safety of Gamma Knife radiosurgery for tectal gliomas. PATIENTS AND METHODS: Between October 2002 and May 2011, 11 patients with tectal gliomas were treated with Gamma Knife radiosurgery. Five patients had pilocytic astrocytomas and six nonpilocytic astrocytomas. Ten patients presented with hydrocephalus and underwent a CSF diversion procedure [7 V-P shunt and 3 endoscopic third ventriculostomy (ETV)]. The tumor volume ranged between 1.2-14.7 cc (median 4.5 cc). The prescription dose was 11-14 Gy (median 12 Gy). RESULTS: Patients were followed for a median of 40 months (13-114 months). Tumor control after radiosurgery was seen in all cases. In 6/11 cases, the tumors eventually disappeared after treatment. Peritumoral edema developed in 5/11 cases at an onset of 3-6 months after treatment. Transient tumor swelling was observed in four cases. Four patients developed cysts after treatment. One of these cases required aspiration and eventually disappeared, one became smaller spontaneously, and two remained stable. CONCLUSION: Gamma Knife radiosurgery is an effective and safe technique for treatment of tectal gliomas. Tumor shrinkage or disappearance after Gamma Knife radiosurgery may preclude the need for a shunt later on.

HEMANGIOBLASTOMA

J Neurosurg.2015;1-10. Epub 2015/03/31 Stereotactic radiosurgery for intracranial hemangioblastomas: a retrospective international outcome study Kano, H., Shuto, T., Iwai, Y., Sheehan, J., Yamamoto, M., McBride, H. L., Sato, M., Serizawa, T., Yomo, S., Moriki, A., Kohda, Y., Young, B., Suzuki, S., Kenai, H., Duma, C., Kikuchi, Y., Mathieu, D., Akabane, A., Nagano, O., Kondziolka, D. and Lunsford, L. D.,Departments of 1 Neurological Surgery, University of Pittsburgh, Pennsylvania;

OBJECT The purpose of this study was to evaluate the role of stereotactic radiosurgery (SRS) in the management of intracranial hemangioblastomas. METHODS Six participating centers of the North American Gamma Knife Consortium and 13 Japanese Gamma Knife centers identified 186 patients with 517 hemangioblastomas who underwent SRS. Eighty patients had 335 hemangioblastomas associated with von Hippel-Lindau disease (VHL) and 106 patients had 182 sporadic hemangioblastomas. The median target volume was 0.2 cm3 (median diameter 7 mm) in patients with VHL and 0.7 cm3 (median diameter 11 mm) in those with sporadic hemangioblastoma. The median margin dose was 18 Gy in VHL patients and 15 Gy in those with sporadic hemangioblastomas. RESULTS At a median of 5 years (range 0.5-18 years) after treatment, 20 patients had died of intracranial disease progression and 9 patients

8

had died of other causes. The overall survival after SRS was 94% at 3 years, 90% at 5 years, and 74% at 10 years. Factors associated with longer survival included younger age, absence of neurological symptoms, fewer tumors, and higher Karnofsky Performance Status. Thirty-three (41%) of the 80 patients with VHL developed new tumors and 17 (16%) of the106 patients with sporadic hemangioblastoma had recurrences of residual tumor from the original tumor. The 5-year rate of developing a new tumor was 43% for VHL patients, and the 5-year rate of developing a recurrence of residual tumor from the original tumor was 24% for sporadic hemangioblastoma patients. Factors associated with a reduced risk of developing a new tumor or recurrences of residual tumor from the original tumor included younger age, fewer tumors, and sporadic rather than VHL-associated hemangioblastomas. The local tumor control rate for treated tumors was 92% at 3 years, 89% at 5 years, and 79% at 10 years. Factors associated with an improved local tumor control rate included VHL-associated hemangioblastoma, solid tumor, smaller tumor volume, and higher margin dose. Thirteen patients (7%) developed adverse radiation effects (ARE) after SRS, and one of these patients died due to ARE. CONCLUSIONS When either sporadic or VHL-associated tumors were observed to grow on serial imaging studies, SRS provided tumor control in 79%-92% of tumors.

MENINGIOMA

J Clin Neurosci.2015;22(1):161-5. Epub 2014/12/03 Stereotactic radiosurgery of meningiomas following resection: Predictors of progression Przybylowski, C. J., Raper, D. M., Starke, R. M., Xu, Z., Liu, K. C. and Sheehan, J. P.,Department of Neurosurgery, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22903, USA. Department of Neurosurgery, University of Virginia Health System, 1215 Lee Street, Charlottesville, VA 22903, USA; Department of Radiation Oncology, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: jsheehan@virginia.edu. Residual or recurrent meningiomas after initial surgical resection are commonly treated with stereotactic radiosurgery (SRS), but progression of these tumors following radiosurgery is difficult to predict. We performed a retrospective review of 60 consecutive patients who underwent resection and subsequent Gamma Knife (Elekta AB, Stockholm, Sweden) radiosurgery for residual or recurrent meningiomas at our institution from 2001-2012. Patients were subdivided by Simpson resection grade and World Health Organization (WHO) grade. Cox multivariate regression and Kaplan-Meier analyses were performed to assess risk of tumor progression. There were 45 men (75%) and 15 women (25%) with a median age of 56.8years (range 26.5-82years). The median follow-up period was 34.9months (range 6-108.4months). Simpson grade 1-3 resection was achieved in 17 patients (28.3%) and grade 4 resection in 43 patients (71.7%). Thirty-four tumors (56.7%) were WHO grade 1, and 22 (36.7%) were WHO grade 2-3. Time from resection to SRS was significantly shorter in patients with Simpson grade 4 resection compared to grade 1-3 resection (p<0.01), but did not differ by WHO grade (p=0.17). Post-SRS complications occurred in five patients (8.3%). Overall, 19 patients (31.7%) experienced progression at a median of 15.3months (range 1.2-61.4months). Maximum tumor diameter >2.5cm at the time of SRS (p=0.02) and increasing WHO grade (p<0.01) were predictive of progression in multivariate analysis. Simpson resection grade did not affect progression-free survival (p=0.90). The mortality rate over the study period was 8.3%. SRS offers effective tumor control for residual or recurrent meningiomas following resection, especially for small benign tumors.

9

J Korean Neurosurg Soc.2015;57(2):77-81. Epub 2015/03/04 Change in plasma vascular endothelial growth factor after gamma knife radiosurgery for meningioma: a preliminary study Park, S. H., Hwang, J. H. and Hwang, S. K.,Department of Neurosurgery, Kyungpook National University Hospital, Daegu, Korea. OBJECTIVE: The purpose of this study was to investigate changes in the plasma level of vascular endothelial growth factor (VEGF) after Gamma Knife radiosurgery (GKRS) for the treatment of meningioma. METHODS: Fourteen patients with meningiomas had peripheral venous blood collected at the time of GKRS and at 1 week, 1 month, 3 month and 6 month visits. Plasma VEGF levels were measured using commercially available enzyme-linked immunosorbent assay. For controls, peripheral blood samples were obtained from 20 healthy volunteers. RESULTS: The mean plasma VEGF level (29.6 pg/mL) in patients with meningiomas before GKRS was significantly lower than that of the control group (62.4 pg/mL, p=0.019). At 1 week after GKRS, the mean plasma VEGF levels decreased to 23.4 pg/mL, and dropped to 13.9 pg/mL at 1 month, 14.8 pg/mL at 3 months, then increased to 27.7 pg/mL at 6 months. Two patients (14.3%) with peritumoral edema (PTE) showed a level of VEGF 6 months after GKRS higher than their preradiosurgical level. There was no significant association found in an analysis of correlation between PTE and tumor size, marginal dose, age, and sex. CONCLUSION: Our study is first in demonstrating changes of plasma VEGF after stereotactic radiosurgery (SRS) for meningioma. This study may provide a stimulus for more work related to whether measurement of plasma level has a correlation with tumor response after SRS for meningioma.

J Neurosurg.2015;122(3):536-42. Epub 2015/01/03 Gamma Knife radiosurgery for meningiomas in patients with neurofibromatosis Type 2 Liu, A., Kuhn, E. N., Lucas, J. T., Jr., Laxton, A. W., Tatter, S. B. and Chan, M. D.,Departments of 1 Neurosurgery and. OBJECT Neurofibromatosis Type 2 (NF2) is a rare autosomal dominant disorder predisposing patients to meningiomatosis. The role of stereotactic radiosurgery (SRS) is poorly defined in NF2, and although the procedure has excellent control rates in the non-NF2 population, its utility has been questioned because radiation has been hypothesized to predispose patients to malignant transformation of benign tumors. To the authors' knowledge, this is the first study to examine the use of SRS specifically for meningiomas in patients with NF2. METHODS The authors searched a tumor registry for all patients with NF2 who had undergone Gamma Knife radiosurgery (GKRS) for meningioma in the period from January 1, 1999, to September 19, 2013, at a single tertiary care cancer center. Medical records were retrospectively reviewed for patient and tumor characteristics and outcomes. Results Among the 12 patients who met the search criteria, 125 meningiomas were identified, 87 (70%) of which were symptomatic or progressive and thus treated with GKRS. The median age at the first GKRS was 31 years (interquartile range [IQR] 27-37 years). Five patients (42%) had multiple treatments with a median of 27 months (IQR 14-50 months) until the subsequent GKRS. The median follow-up in surviving patients was 43 months (IQR 34-110 months). The 5-year local tumor control and distant treatment failure rates were 92% and 77%, respectively. Toxicities occurred in 25% of the GKRS treatments, although the majority were Grade 1 or 2. At the last follow-up, 4 patients (33%) had died a neurological death at a median age of 39 years (IQR 37-46 years), and their cases accounted for 45% of all tumors, 55% of all treated tumors, and 58% of all GKRSs. Univariate analysis revealed several predictive variables for distant failure, including male sex (HR 0.28, 95% CI 0.086-0.92, p = 0.036), age at distant failure (HR 0.92, 95% CI 0.90-0.95, p < 0.0001),

10

and prior number of GKRS treatments (HR 1.2, 95% CI 1.1-1.4, p = 0.0049). Local failure, maximum size of the treated tumor, delivered tumor margin dose, and WHO grade were not significant. On multivariate analysis, age at distant failure (HR 0.91, 95% CI 0.88-0.95, p < 0.0001) and prior number of GKRSs (HR 1.3, 95% CI 1.1-1.5, p = 0.004) remained significant. No malignant transformation events among treated tumors were observed. CONCLUSIONS Radiosurgery represents a feasible modality with minimal toxicity for NF2-associated meningiomas. Increasing patient age was associated with a decreased rate of distant failure, whereas an increasing number of prior GKRS treatments predicted distant failure. Further studies are necessary to determine the long-term patterns of treatment failure in these patients.

METASTASES

HISTOLOGY

BREAST

Breast Cancer Res Treat.2015;149(3):743-9. Epub 2015/02/02 The use of stereotactic radiosurgery for brain metastases from breast cancer: Who benefits most? Cho, E., Rubinstein, L., Stevenson, P., Gooley, T., Philips, M., Halasz, L. M., Gensheimer, M. F., Linden, H. M., Rockhill, J. K. and Gadi, V. K.,Department of Medicine, University of Washington, Seattle, WA, USA. Brain metastases (BM) from primary breast cancer can arise despite use of systemic therapies that provide excellent extracranial disease control. Local modalities for treating BM include surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). We sought to determine the benefits of SRS for management of BM arising from different biologic breast cancer subtypes. We reviewed records of 131 patients who received SRS for breast cancer BM between 2001 and 2013. Survival was estimated by the Kaplan-Meier method. Effects of tumor biology, number and location of lesions, and number of SRS sessions on survival were evaluated by Cox proportional hazards regression. Of the 122 patients with subtypes available, 41 patients (31 %) were classified as estrogen receptor positive/HER2 negative (ER(+)HER2(-)); 30 patients (23 %), ER(+)HER2(+); 23 patients (18 %), ER(-)HER2(+); and 28 patients (21 %), ER(-)HER2(-) (or triple negative breast cancer, TNBC). Median age at first SRS was 50 years. Median overall survival for ER(+)HER2(-), ER(+)HER2(+), ER(-)HER2(+), and TNBC was 16, 26, 23, and 7 months, respectively (p < 0.001 for difference between groups). Patients with TNBC had the shortest time to retreatment with WBRT or SRS or death with hazard ratio of 3.12 (p < 0.001) compared to ER(+)HER2(-). In all subtypes other than TNBC, SRS can provide meaningful control of BM even in the setting of multiple lesions and may be worth repeating for new lesions that develop metachronously. For patients with TNBC, prognosis is guarded following SRS, and there is an urgent need to develop more effective treatment strategies.

LUNG

World Neurosurg.2015;Epub 2015/03/10 Perspective - Fighting Cancer on All Fronts: Stereotactic Radiosurgery and the Role for Aggressive Primary Treatment in Non-Small Cell Lung Cancer Patients with One Brain Metastasis Cohen-Inbar, O. and Sheehan, J. P.,Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA. Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA. Electronic address: jsheehan@virginia.edu.

11

J Neurosurg.2015;1-7. Epub 2015/02/07 Gamma Knife radiosurgery for the management of cerebral metastases from non-small cell lung cancer Bowden, G., Kano, H., Caparosa, E., Park, S. H., Niranjan, A., Flickinger, J. and Lunsford, L. D.,Departments of 1 Neurological Surgery and. OBJECT Non-small cell lung cancer (NSCLC) is the most frequent cancer that metastasizes to brain. Stereotactic radiosurgery (SRS) has become the management of choice for most patients with such metastatic tumors. Therefore, the authors endeavored to elucidate the survival and SRS outcomes for patients with NSCLC metastasis at their center. METHODS In this single-institution retrospective analysis, the authors reviewed their experience with NSCLC metastasis during a 10-year period from 2001 to 2010. Seven hundred twenty patients underwent Gamma Knife radiosurgery. A total of 1004 SRS procedures were performed, and 3143 tumors were treated. The NSCLC subtype was adenocarcinoma in 386 patients, squamous cell carcinoma in 111 patients, and large cell carcinoma in 34 patients. The median aggregate tumor volume was 4.5 cm3 (range 0.1-88 cm3). RESULTS The median survival time after diagnosis of brain metastasis from NSCLC was 12.6 months, and the median survival after SRS was 8.5 months. The 1-, 2-, and 5-year survival rates after SRS were 39%, 21%, and 10%, respectively. Postradiosurgery survival was decreased in patients treated with prior whole-brain radiation therapy compared with SRS alone (p = 0.003). Aggregate tumor volume was inversely related to survival after SRS (p < 0.001), and the histological subgroups demonstrated significant survival differences (p = 0.023). The overall local tumor control rate in the entire group was 92.8%. One hundred seventy-four patients (24%) underwent repeat SRS for new or resistant metastatic deposits. CONCLUSIONS Stereotactic radiosurgery is an effective means of providing local control for NSCLC metastases. Neurological function and survival benefit from serial patient monitoring and repeat SRS for new tumors.

World Neurosurg.2015;Epub 2015/02/11 Comparison between surgical resection and stereotactic radiosurgery in patients with a single brain metastasis from non-small cell lung cancer Bougie, E., Masson-Cote, L. and Mathieu, D.,Division of Neurosurgery, Department of Surgery, Universite de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada. Department of Radiation Oncology, Universite de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada. Division of Neurosurgery, Department of Surgery, Universite de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada. Electronic address: david.mathieu@usherbrooke.ca. BACKGROUD: The management of patients with single brain metastasis (BM) from non-small cell lung cancer (NSCLC) remains controversial. Surgical resection with adjuvant irradiation (SR) as well as stereotactic radiosurgery (SRS) are used in the treatment of such lesions. This study compared both modalities in terms of tumor control and survival. METHODS: 115 patients with single BM from NSCLC were treated with SR or SRS at our institution between 2004 and 2011. Median age was 61 years. 43 patients underwent resection and 72 had SRS. Most surgical patients had adjuvant irradiation. 63% of patients in the resection group and 56% in the SRS group had synchronous presentation of their BM and lung primary. Thoracic disease was managed with curative intent in 60% of SR patients compared to 50% of SRS patients. RESULTS: Median follow-up was 10.2 months. Local control was 72% in SR patients and

12

79% in the SRS group (p=0.992). Median survival for SR and SRS patients was 13.3 months and 7.8 months, respectively (p=0.047). Multivariate analyses revealed aggressive treatment of the primary NSCLC as an independent factor associated with prolonged survival in surgical patients. SRS patients with metachronous metastasis showed better prognosis. Metachronous presentation was associated with more aggressive management of the primary. CONCLUSIONS: In this study, patients with single BM undergoing resection had a survival advantage. However, as resection and SRS achieved comparable BM local control, SRS patients should benefit from an equally aggressive treatment of their primary NSCLC, since thoracic management was the most important survival predictor.

Pract Radiat Oncol.2015;5(1):e37-44. Epub 2014/11/22 Local recurrence and survival following stereotactic radiosurgery for brain metastases from small cell lung cancer Rava, P., Sioshansi, S., DiPetrillo, T., Cosgrove, R., Melhus, C., Wu, J., Mignano, J., Wazer, D. E. and Hepel, J. T.,Department of Radiation Oncology, UMass Medical Center, Worcester, Massachusetts. Electronicaddress: paul.rava@umassmemorial.org.Department of Radiation Oncology, UMass Medical Center, Worcester, Massachusetts.Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts; Department ofRadiation Oncology, Rhode Island Hospital, Providence, Massachusetts.Department of Neurosurgery, Brown University, Rhode Island Hospital, Providence, Rhode Island.Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts.Department of Neurosurgery, Tufts Medical Center, Boston, Massachusetts.PURPOSE: Stereotactic radiosurgery (SRS) represents a treatment option for patients with brainmetastases from small cell lung cancer (SCLC) following prior cranial radiation. Inferior local control hasbeen described. We reviewed our failure patterns following SRS treatment to evaluate this concern.METHODS AND MATERIALS: Individuals with SCLC who received SRS for brain metastases from 2004 to2011 were identified. Central nervous system (CNS) disease was detected and followed by gadolinium-enhanced, high-resolution magnetic resonance (MR) imaging. SRS dose was prescribed to the tumorperiphery. Local recurrence was defined by increasing lesion size or enhancement, MR-spectroscopy,and perfusion changes consistent with recurrent disease or pathologic confirmation. Any new enhancinglesion not identified on the SRS planning scan was considered a regional failure. Overall survival (OS) andCNS control were evaluated using the Kaplan-Meier method. Factors predicted to influence outcomewere tested by univariate log-rank analysis and Cox regression. RESULTS: Fifteen males and 25 females(median age of 61 years [range, 36-79]) of which 39 received prior brain irradiation were identified. Inall, 132 lesions (3.3 per patient) between 0.4 and 4.7 cm received a median dose of 16 Gy (12-22 Gy).Thirteen metastases (10%) ultimately recurred locally with 6- and 12-month control rates of 81% and69%, respectively. Only 1 of 110 metastases <2 cm recurred. Local failure was more likely for size >2 cm(P < .001) and dose <16 Gy (P < .001). The median OS was 6.5 months, and the time to regional CNSrecurrence was 5.2 months. For patients with single brain metastases, both OS (P = .037) and regionalCNS recurrence (P = .003) were improved. CNS control (P = .001), and survival (P = .057), were alsolonger for patients with controlled systemic disease. CONCLUSIONS: Local control following SRS for SCLCmetastases is achievable for lesions <2 cm. For metastases >2 cm, local failure is more common thanexpected. Patients with controlled systemic disease and limited CNS involvement would benefit mostfrom aggressive treatment.

13

MELANOMA

Cancer Med.2015;4(1):1-6. Epub 2014/08/29 Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery Tazi, K., Hathaway, A., Chiuzan, C. and Shirai, K.,Hematology/Oncology, Medical University of South Carolina, Charleston, South Carolina. Historically, melanoma with brain metastases has a poor prognosis. In this retrospective medical record review, we report the outcome of patients with stage IV melanoma with brain metastases treated with ipilimumab and brain stereotactic radiosurgery (SRS). All patients with metastatic melanoma treated with ipilimumab from June 2010 to September 2012 were identified and stratified by presence (A) or absence (B) of brain metastases at the time of ipilimumab administration. All patients with brain metastases received SRS. Overall survival (OS) was defined as time from the date of stage IV diagnosis and the time of ipilimumab administration to death or last follow-up. Survival curves were estimated using the Kaplan-Meier method, and Cox proportional hazards model was employed to compute the hazard ratios (HR). RESULTS: Five out of 10 patients in Cohort A and 10 out of 21 patients in Cohort B died as of last follow-up. In Cohort A, median number of lesions treated with SRS was 3. Median survivals from date of stage IV for Cohorts A and B were 29.3 and 33.1 months, respectively (HR = 0.93, P = 0.896). Median survival from cycle 1 ipilimumab was 16.5 and 24.5 months for Cohort A and B, respectively (HR = 1.05, P = 0.931). The 3-year survival rates from the date of cycle one of ipilimumab administration for Cohort A and B were 50% (95% CI: 27-93%) and 39% (95% CI: 19-81%), respectively. Eight of 10 patients in Cohort A maintained a good PS. Survival of patients with melanoma brain metastases treated with ipilimumab combined with SRS may be comparable to patients without brain metastases.

RENAL CELL

Am J Clin Oncol.2015;Epub 2015/03/03 Radiotherapy for Brain Metastases From Renal Cell Carcinoma in the Targeted Therapy Era: The University of Rochester Experience Bates, J. E., Youn, P., Peterson, C. R., 3rd, Usuki, K. Y., Walter, K. A., Okunieff, P. and Milano, M. T.,*School of Medicine and Dentistry Departments of daggerRadiation Oncology double daggerNeurosurgery, University of Rochester Medical Center, Rochester, NY section signDepartment of Radiation Oncology, University of Florida, Gainesville, FL. OBJECTIVES:: Radiotherapy remains the standard approach for brain metastases from renal cell carcinoma (RCC). Kinase inhibitors (KI) have become standard of care for metastatic RCC. They also increase the radiosensitivity of various tumor types in preclinical models. Data are lacking regarding the effect of KIs among RCC patients undergoing radiotherapy for brain metastases. We report our experience of radiotherapy for brain metastatic RCC in the era of targeted therapy and analyzed effects of concurrent KI therapy. METHODS:: We retrospectively analyzed 25 consecutive patients who received radiotherapy for brain metastases from RCC with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Kaplan-Meier rates of overall survival (OS) and brain progression-free survival (BPFS) were calculated and univariate analyses performed. RESULTS:: Lower diagnosis-specific graded prognostic assessment (DS-GPA) score and multiple intracranial metastases were associated with

14

decreased OS and BPFS on univariate analysis; DS-GPA is also a prognostic factor on multivariate analysis. There was no significant difference in OS or BPFS for SRS compared with WBRT or WBRT and SRS combined. The concurrent use of KI was not associated with any change in OS or BPFS. CONCLUSIONS:: This hypothesis-generating analysis suggests among patients with brain metastatic RCC treated with the most current therapies, those selected to undergo SRS did not experience significantly different survival or control outcomes than those selected to undergo WBRT. From our experience to date, limited in patient numbers, there seems to be neither harm nor benefit in using concurrent KI therapy during radiotherapy. Given that most patients progress systemically, we would recommend considering KI use during brain radiotherapy in these patients.

OTHER METASTATIC TUMOR TOPICS

LARGE

Technol Cancer Res Treat.2015;Epub 2015/01/31 Treatment of Large Brain Metastases With Stereotactic Radiosurgery Zimmerman, A. L., Murphy, E. S., Suh, J. H., Vogelbaum, M. A., Barnett, G. H., Angelov, L., Ahluwalia, M., Reddy, C. A. and Chao, S. T.,Case Western Reserve University School of Medicine, Cleveland, OH, USA. Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, OH, USA Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, OH, USA Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, OH, USA Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. Rose Ella Burkhardt Brain Tumor and Neuro-oncology Center, Cleveland Clinic, Cleveland, OH, USA Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA chaos@ccf.org. INTRODUCTION: We report our series of patients with large brain metastases, >3 cm in diameter, who received stereotactic radiosurgery (SRS) as a component of their treatment, focusing on survival and intracranial recurrence rates. MATERIAL AND METHODS: The brain tumor database was queried for patients treated with SRS for large brain metastases. Local recurrence (LR) and distant brain recurrence (DBR) rates were calculated using cumulative incidence analysis, and overall survival (OS) was calculated using Kaplan-Meier analysis. Patients were classified into 1 of the 4 groups based on treatment strategy: SRS alone, surgery plus SRS, SRS plus whole-brain radiation therapy (WBRT), and salvage SRS from more remote WBRT and/or surgery. RESULTS: A total of 153 patients with 164 lesions were evaluated. The SRS alone was the treatment approach in 62 lesions, surgery followed by SRS to the resection bed (S + SRS) in 33, SRS + WBRT in 19, and salvage SRS in 50. There was no statistically significant difference in OS between the 4 treatment groups (P = .06). Median survival was highest in patients receiving surgery + SRS (12.2 months) followed by SRS + WBRT (6.9 months), SRS alone (6.6 months), and salvage SRS (6.1 months). There was also no significant difference for LR rates between the groups at 12 months. No significant variables on univariate analysis were noted for LR. The 12-month DBR rates were highest in the S + SRS group (52%), followed by salvage SRS (31%), SRS alone (28%), and SRS + WBRT (13%; P = .03). CONCLUSION: There were no significant predictors for local control. Keeping in mind that patient numbers in the SRS + WBRT group are small, the addition of WBRT to SRS did not appear to significantly improve survival or local control, supporting the delayed use of WBRT for some patients to prevent

15

potential side effects provided regular imaging surveillance and salvage therapy are utilized. Prospective studies are needed to optimize SRS treatment regimens for patients with large brain metastases.

REPEAT RADIOSURGERY

J Neurooncol.2015;Epub 2015/02/18 Outcomes of gamma knife radiosurgery, bi-modality & tri-modality treatment regimens for patients with one or multiple brain metastases: the Columbia University Medical Center experience Wang, T. J., Saad, S., Qureshi, Y. H., Jani, A., Isaacson, S. R., Sisti, M. B., Bruce, J. N., McKhann, G. M., 2nd, Lesser, J., Cheng, S. K., Clifford Chao, K. S. and Lassman, A. B.,Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY, 10032, USA, tjw2117@cumc.columbia.edu. Optimal treatment of brain metastases (BMs) is debatable. However, surgery or gamma knife radiosurgery (GKRS) improves survival when combined with whole brain radiotherapy (WBRT) versus WBRT alone. We retrospectively reviewed an institutional database of patients treated with GKRS for BMs from 1998 to 2013 to explore effects of single or multi-modality therapies on survival. There were 528 patients with median age 62 years. Histologies included 257 lung, 102 breast, 62 melanoma, 40 renal cell, 29 gastrointestinal, and 38 other primary cancers. Treatments included: 206 GKRS alone, 111 GKRS plus WBRT, 109 GKRS plus neurosurgical resection (NSG), and 102 all three modalities. Median overall survival (mOS) was 16.6 months. mOS among patients with one versus multiple metastasis was 17.2 versus 16.0 months respectively (p = 0.825). For patients with one BM, mOS following GKRS alone, GKRS plus WBRT, GKRS plus NSG, and all three modalities was 9.0, 19.1, 25.5, and 25.0 months, respectively, and for patients with multiple BMs, mOS was 8.6, 20.4, 20.7, 24.5 months for the respective groups. Among all patients, multivariate analysis confirmed that tri-modality group had the longest survival (HR 0.467; 95 % CI 0.350-0.623; p < 0.001) compared to GKRS alone; however, this was not significantly different than bi-modality approaches. Uncontrolled primary extra-CNS disease, age and KPS were also independent predictors of survival. Patients treated with GKRS plus NSG, GKRS plus WBRT, or all three modalities had improved OS versus GKRS alone. In our analysis, resection and GKRS allowed avoidance of WBRT without shortening survival.

IMAGING

Neuroradiology.2015;Epub 2015/01/17 Which is the best advanced MR imaging protocol for predicting recurrent metastatic brain tumor following gamma-knife radiosurgery: focused on perfusion method Koh, M. J., Kim, H. S., Choi, C. G. and Kim, S. J.,Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 86 Asanbyeongwon-Gil, Songpa-Gu, Seoul, 138-736, South Korea. INTRODUCTION: High spatial resolution of dynamic contrast-enhanced (DCE) MR imaging allows characterization of heterogenous tumor microenvironment. Our purpose was to determine which is the best advanced MR imaging protocol, focused on additional MR perfusion method, for predicting recurrent metastatic brain tumor following gamma-knife radiosurgery (GKRS). METHODS: Seventy-two consecutive patients with post-GKRS metastatic brain tumor were enrolled. Two readers independently calculated the percentile histogram cutoffs for normalized cerebral blood volume (nCBV) from dynamic susceptibility contrast (DSC) imaging and initial area under the time signal-intensity curve (IAUC) from

16

DCE imaging, respectively. Area under the receiver operating characteristic curve (AUC) and interreader agreement were assessed. RESULTS: For differentiating tumor recurrence from therapy effect, adding DCE imaging to diffusion-weighted imaging (DWI) significantly improved AUC from 0.79 to 0.95 for reader 1 and from 0.80 to 0.96 for reader 2, respectively. There was no significant difference of AUC between the combination of DWI with DSC imaging and the combination of DWI with DCE imaging for both readers. With the combination of DWI and DCE imaging, the sensitivity and specificity were 86.7 and 88.1 % for reader 1 and 90.0 and 85.7 % for reader 2, respectively. The intraclass correlation coefficient (ICC) between readers was highest for calculation of the 90th percentile histogram cutoffs for IAUC (ICC, 0.87). CONCLUSION: Adding perfusion MR imaging to DWI significantly improves the prediction of recurrent metastatic tumor; however, the diagnostic performance is not affected by selection of either DSC or DCE MR perfusion method.

SURGERY PLUS SRS

Neurosurgery.2015; Epub 2015/01/20 Tumor Progression in Patients Receiving Adjuvant Whole-Brain Radiotherapy vs Localized Radiotherapy After Surgical Resection of Brain Metastases Hsieh, J., Elson, P., Otvos, B., Rose, J., Loftus, C., Rahmathulla, G., Angelov, L., Barnett, G., Weil, R. and Vogelbaum, M. A.,*Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio; double daggerQuantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio; section signDepartment of Neurosurgery, Neurological Institute, Cleveland Clinic, Cleveland, Ohio; paragraph signRose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, Ohio; ||Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. BACKGROUND:: Surgery followed by adjuvant radiotherapy is a well-established treatment paradigm for brain metastases. OBJECTIVE:: To examine the effect of postsurgical whole-brain radiotherapy (WBRT) or localized radiotherapy (LRT), including stereotactic radiosurgery and intraoperative radiotherapy, on the rate of recurrence both local and distal to the resection site in the treatment of brain metastases. METHODS:: We retrospectively identified patients who underwent surgery for brain metastasis at the Cleveland Clinic between 2004 and 2012. Institutional review board-approved chart review was conducted, and patients who had radiation before surgery, who had nonmetastatic lesions, or who lacked postadjuvant imaging were excluded. RESULTS:: The final analysis included 212 patients. One hundred fifty-six patients received WBRT, 37 received stereotactic radiosurgery only, and 19 received intraoperative radiotherapy. One hundred forty-six patients were deceased, of whom 60 (41%) died with no evidence of recurrence. Competing risks methodology was used to test the association between adjuvant modality and progression. Multivariable analysis revealed no significant difference in the rate of recurrence at the resection site (hazard ratio [HR] 1.46, P = .26) or of unresected, radiotherapy-treated lesions (HR 1.70, P = .41) for LRT vs WBRT. Patients treated with LRT had an increased hazard of the development of new lesions (HR 2.41, P < .001) and leptomeningeal disease (HR 2.45, P = .04). Median survival was 16.5 months and was not significantly different between groups. CONCLUSION:: LRT as adjuvant treatment to surgical resection of brain metastases is associated with an increased rate of development of new distant metastases and leptomeningeal disease compared with WBRT, but not with recurrence at the resection site or of unresected lesions treated with radiation. ABBREVIATIONS:: BM, brain metastasisIORT, intraoperative radiotherapyLMD, leptomeningeal diseaseLRT, localized radiotherapySRS, stereotactic radiosurgeryWBRT, whole-brain radiotherapy.

17

Neurosurgery.2015;Epub 2015/04/02

The Energy Index Does Not Affect Local Control of Brain Metastases Treated by Gamma Knife Stereotactic Radiosurgery

Jani, A., Rozenblat, T., Yaeh, A. M., Nanda, T., Saad, S., Qureshi, Y. H., Feng, W., Sisti, M. B., Bruce, J. N., McKhann, G. M., 2nd, Lesser, J., Lassman, A. B., Isaacson, S. R. and Wang, T. J.,double daggerDepartment of Radiation Oncology, section signDepartment of Neuropathology, paragraph signHerbert Irving Comprehensive Cancer, ||Department of Neurological Surgery, and #Department of Neurology, Columbia University Medical Center, New York, New York.

BACKGROUND: The energy index (EI) is a measure of dose homogeneity within a target volume calculated by the integral dose divided by the product of prescription dose and tumor volume. OBJECTIVE: To assess whether a higher EI is associated with greater local control for brain metastases (BMs) treated by Gamma Knife radiosurgery (GKRS). METHODS: We reviewed all patients treated with GKRS for BM at our institution between January 2009 and February 2014. Data on the prescription dose, prescription isodose line, minimum dose, mean dose, integral dose, tumor volume, and EI were collected. Tumor response was assessed by reviewing follow-up brain imaging studies and classified according to the Response Evaluation Criteria in Solid Tumors. Local control per lesion and dosimetric prognostic factors for local control were assessed by univariate and multivariate Cox proportional hazards regression analyses. RESULTS: Of 213 patients treated, 126 had follow-up imaging available with a median follow-up of 6 months. Three hundred seventy-three individual tumors were analyzed. Of these, 133 showed a complete response, 157 showed a partial response, 46 remained stable, and 37 developed local failure. Tumors with EI >/=1.6 mJ.mL.Gy showed a higher rate of complete response. Local control rates at 6, 11, and 17 months were 95.4%, 86.5%, and 81.5%, respectively. On univariate analysis, the following factors were associated with higher rates of local failure: prescription doses of 16 and 18 Gy compared with a prescription dose of 20 Gy. The following factors were associated with a greater rate of local control: maximum dose and mean dose. On multivariate analysis, the only statistically significant factor associated with a greater rate of local failure was prescription dose of 16 Gy compared with 20 Gy. CONCLUSION: GKRS for BM results in a high rate of local control with an 11-month rate of 86.5%. A higher EI was not significantly associated with a higher rate of local control on multivariate analysis. Prescription dose was found to be the only significant predictor of local control on multivariate analysis. ABBREVIATIONS: BM, brain metastasisCI, confidence intervalEI, energy indexGKRS, Gamma Knife radiosurgeryHR, hazard ratioIDL, isodose lineSRS, stereotactic radiosurgeryWBRT, whole-brain radiotherapy.

NEUROCYTOMA

J Huazhong Univ Sci Technolog Med Sci.2015;35(1):105-10. Epub 2015/02/13 Treatment strategies for huge central neurocytomas Department of Neurosurgery, Taipei Veterans General Hospital, 201 Shi-Pai Road, Section 2, Taipei 11217, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. This article elucidates the role of stereotactic radiosurgery for the management of central neurocytoma. This rare intraventricular tumor is usually benign and is best treated with surgical excision if the tumor is

18

large and symptomatic. However, some distinctive neuroimaging features are found in this tumor that help to identify the tumor based on detailed MRI and computed tomography examinations. The cumulative experience shows that single-session radiosurgery using Gamma Knife radiosurgery is an effective and safe alternative treatment of incidental central neurocytoma. After radiosurgery, a serial MRI examination performed every 6 months for long-term follow-up is necessary to monitor radiosurgical response of the tumor.

Neurosurg Clin N Am.2015;26(1):37-44. Epub 2014/11/30 The management of central neurocytoma: radiosurgery Monaco, E. A., 3rd, Niranjan, A. and Lunsford, L. D.,Department of Neurological Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Electronic address: monacoea2@upmc.edu. Department of Neurological Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Stereotactic radiosurgery (SRS) has evolved into a mainstay in the primary and adjuvant management of most intracranial tumors. Central neurocytomas are rare, usually benign, intraventricular tumors that can be challenging to completely resect and often recur. Adjuvant therapy has been suggested for residual or recurrent tumors, especially in the setting of atypical neurocytomas. The limited data available suggest that SRS is a highly effective treatment approach for primary and adjuvant therapy, with tumor control rates of 80% to 90%. Due to its highly conformal and selective nature, SRS avoids the inconvenience and delayed toxicity of conventional radiation therapy.

PITUITARY

World Neurosurg.2015;Epub 2015/02/24 Stereotactic Radiosurgery as the Initial Treatment for Patients with Nonfunctioning Pituitary Adenomas Hasegawa, T., Shintai, K., Kato, T. and Iizuka, H.,Department of Neurosurgery, Gamma Knife Center, Komaki City Hospital, Komaki, Japan. Electronic address: h-toshi@komakihp.gr.jp. Department of Neurosurgery, Gamma Knife Center, Komaki City Hospital, Komaki, Japan. OBJECTIVE: The aim of this study was to confirm the efficacy and safety of stereotactic radiosurgery as the initial treatment for patients with nonfunctioning pituitary adenomas (NFPAs), and to decide the optimum dose to achieve long-term tumor control as well as preservation of pituitary endocrine function. METHODS: The study was a single-center retrospective analysis of 16 patients with primary NFPAs treated using gamma knife surgery (GKS). Fifteen of 16 NFPAs were growing to the suprasellar region and slightly compressing or very close to the optic apparatus. Initial GKS was selected to avoid visual disturbance caused by further tumor growth that would require surgical resection under general anesthesia. The median tumor volume was 2.0 cm3, and the median tumor margin dose was 15 Gy. RESULTS: The median clinical follow-up period was 98 months. The last follow-up images demonstrated tumor regression in 15 patients, and stable tumor in 1. No patient developed tumor progression. One patient who had pituitary apoplexy before treatment required hormone replacements 2 years after GKS. The other patients did not experience pituitary insufficiency requiring hormone replacements during the clinical follow-up period. No patient developed cranial nerve injury or radiation-induced neoplasm. CONCLUSIONS: GKS was a safe and effective treatment option in patients with primary NFPAs, especially for patients with advanced age or comorbidity. Attention should be paid to late adverse radiation effects

19

such as hypopituitarism, optic neuropathy, and radiation-induced neoplasms. However, stereotactic radiosurgery with a conformal treatment plan sparing the normal pituitary gland will contribute to avoidance of such complications as well as achievement of long-term tumor control.

UVEAL MELANOMA

J Clin Ultrasound.2015;Epub 2015/02/24 Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery Venturini, M., Colantoni, C., Modorati, G., Di Nicola, M., Colucci, A., Agostini, G., Picozzi, P., De Cobelli, F., Parmiani, G., Mortini, P., Bandello, F. and Del Maschio, A.,Department of Radiology, San Raffaele Scientific Institute, Milan, Italy. PURPOSE: Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR. METHODS: Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test. RESULTS: The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p < 0.05, both comparisons). Compared with baseline data, the median flow quantitative parameters on CEUS were significantly changed as follows: the peak enhancement (in arbitrary units [au]) at baseline was 5 x 106 ; 6 months after GKR, it was 2 x 101 (p < 0.05), and 12 months after GKR, it was 4 x 101 (p < 0.05). The wash-in rate (in au) at baseline was 1 x 106 ; 6 months after GKR, it was 2.1 (p < 0.05), and 12 months after GKR, it was 9.3 (p < 0.05). The wash-in perfusion index (in au) at baseline was 2 x 107 ; 6 months after GKR, it was 7 x 101 (p < 0.05), and 12 months after GKR, it was 1 x 102 (p < 0.05). The area under the curve during the wash-in phase (in au) at baseline was 1 x 108 ; 12 months after GKR, it was reduced to 6 x 102 (p < 0.05). CONCLUSIONS: At 6 months after GKR, a reduction of tumor thickness, as detected on US, occurred in 6 of the 10 patients, whereas a reduction in all the quantitative parameters measured on CEUS occurred in all 10 patients. However, a larger population is needed to investigate whether CEUS could become the first-choice technique for monitoring the response of UM to GKR. (c) 2015 Wiley Periodicals, Inc. J Clin Ultrasound, 2015.

VASCULAR DISORDERS

J Clin Neurosci.2015;Epub 2015/04/05 Clinical outcome and complications of gamma knife radiosurgery for intracranial arteriovenous malformations Bir, S. C., Ambekar, S., Maiti, T. K. and Nanda, A.,Department of Neurosurgery, Louisiana State University Health, 1501 Kings Highway, Shreveport, LA 71130-3932, USA. Department of Neurosurgery, Louisiana State University Health, 1501 Kings Highway, Shreveport, LA 71130-3932, USA. Electronic address: ananda@lsuhsc.edu.

We sought to evaluate the outcome of intracranial arteriovenous malformation (AVM) treated with gamma knife radiosurgery (GKRS) (Elekta, Stockholm, Sweden) as a primary treatment as well as an

20

adjunct therapy. GKRS has emerged as an important treatment option for intracranial AVM. However, the long term outcome of GKRS on AVM is not well understood. We performed a retrospective review of 85 patients with AVM from 2000-2012 who received GKRS. Out of 85 patients, 13 had undergone prior embolization. The study population was monitored clinically and radiographically after GKRS treatment. Outcome following GKRS for intracranial AVM showed significant variations in nidus obliteration (obliteration in 67 [79%] patients and increase of nidus size on MRI in 18 [21%] patients). The median time to nidus obliteration was 31 months. Overall two (2.3%) patients had intracranial bleeding and the annual bleeding risk was 1.6% after GKRS. Predictive factors for obliteration of the nidus in patients with AVM were low AVM score, Spetzler-Martin grade I-III and female sex. Seventeen (20%) and one (1.17%) patients underwent repeat GKRS and resection, respectively, after initial GKRS, due to increased size of the nidus and GKRS related cyst formation. Thus, GKRS offers a high obliteration rate of AVM, low risk of intracranial bleeding and neurological morbidity, both as primary modality and as an adjunctive treatment. Therefore, GKRS is an effective treatment option for new patients with AVM as well as an adjuvant therapy in patients with recurrent AVM.

Acta Neurochir (Wien).2015; 157(2):293-8. Epub 2014/12/17 Pathological characteristics of cyst formation following gamma knife surgery for arteriovenous malformation Shuto, T., Yagishita, S. and Matsunaga, S.,Department of Neurosurgery, Yokohama Rosai Hospital, 3211 Kozukue-cho, Kouhoku-ku, Yokohama, Kanagawa, 222-0036, Japan, shuto@yokohamah.rofuku.go.jp. BACKGROUND: The pathological characteristics of cyst development after gamma knife surgery (GKS) for arteriovenous malformation (AVM) were analysed. METHOD: Sixteen male and 12 female patients aged 17-67 years (mean 31.3 years) were retrospectively identified among 868 patients who underwent GKS for AVM at our hospital. The pathological characteristics of the reddish nodular lesion and chronic encapsulated expanding haematoma associated with cyst following GKS for AVM were examined. RESULTS: Cyst was associated with chronic encapsulated expanding haematoma in 13, and with nodular lesion in 12 patients. The nidus volume at GKS was 0.1-36 ml (median 6.0 ml), and the prescription dose at the nidus margin was 18-25 Gy (median 20 Gy). Cyst formation was detected from 1.1 to 16 years (mean 7.3 years) after GKS. Seven of the 12 patients with nodular lesion underwent surgery. Ten of the 13 patients with expanding haematoma underwent surgical removal of expanding haematoma. Histological examination was possible in 17 cases. Dilated capillary vessels with wall damage such as hyalinisation and fibrinoid necrosis, marked protein exudation and haemorrhage were the most common findings. Brain parenchyma was observed among the dilated vessels in some cases. Structureless necrotic tissue was not evident. CONCLUSIONS: The present study suggests that enhanced nodular lesion on magnetic resonance imaging and chronic encapsulated expanding haematoma associated with cyst may have common aetiopathology caused by late radiation effects, mainly consisting of dilated capillary vessels with wall damage. Massive protein exudation from such damaged capillary vessels is important in cyst development.

J Neurosurg.2015; 1-7. Epub 2015/01/24 Seizure and anticonvulsant outcomes following stereotactic radiosurgery for intracranial arteriovenous malformations Przybylowski, C. J., Ding, D., Starke, R. M., Yen, C. P., Quigg, M., Dodson, B., Ball, B. Z. and Sheehan, J. P.,Departments of 1 Neurological Surgery.

21

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.

Acta Neurochir (Wien).2015;157(1):51-2. Epub 2014/11/14 Stereotactic radiosurgery for cavernous malformations: prejudice from ignorance Lee, S. H. and Lim, Y. J.,Department of Neurosurgery, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 130-702, Korea.

J Korean Neurosurg Soc.2015;57(2):127-30. Epub 2015/03/04 Paradoxical exacerbation of symptoms with obstruction of the venous outflow after gamma knife radiosurgery for treatment of a dural arteriovenous fistula of the cavernous sinus Ko, J. K., Cho, W. H., Lee, T. H. and Choi, C. H.,Department of Neurosurgery, Medical Research Institute, Pusan National University Hospital, Busan, Korea. Department of Diagnostic Radiology, Medical Research Institute, Pusan National University Hospital, Busan, Korea. A 59-year-old female presented with progressive right proptosis, chemosis and ocular pain. An imaging work-up including conventional catheter angiography showed a right-sided dural arteriovenous fistula of the cavernous sinus, which drained into the right superior petrosal sinus, right superior ophthalmic vein, and right inferior ophthalmic vein, and cortical venous reflux was seen via the right petrosal vein in the right posterior fossa. After failure of transvenous embolization, the patient underwent Gamma Knife radiosurgery (GKRS). At one month after GKRS, she developed increasing ocular pain and occipital headache. Repeat angiography showed partial obliteration of the fistula and loss of drainage via the superior and inferior ophthalmic veins with severe congestion, resulting in slow flow around the right cerebellar hemisphere. Prompt transarterial embolization relieved the patient's ocular symptoms and headache. We report on a case of paradoxical exacerbation of symptoms resulting from obstruction of the venous outflow after GKRS for treatment of a dural arteriovenous fistula of the cavernous sinus.

22

Turk Neurosurg.2015;25(1):100-10. Epub 2015/02/03 Combined treatment of brain avms by onyx embolization and gamma knife radiosurgery decreased hemorrhage risk despite low obliteration rate Huo, X., Li, Y., Wu, Z., Jiang, Y., Yang, H. and Zhao, Y.,Capital Medical University, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Department of Interventional Neuroradiology, Beijing, China. AIM: The effectiveness and risk of cerebral arteriovenous malformations (AVMs) treatment with Onyx embolization combined with Gamma Knife surgery (GKS) were rarely reported. In the present study, we analyzed the radiographic and clinical outcomes of combined Onyx embolization and GKS for cerebral AVMs. MATERIAL AND METHODS: A total of 86 patients' clinical outcomes were fully collected. Modalities and complications of the procedure were analyzed as well as the clinical and anatomic outcomes. Risk factors associated with hemorrhage were determined by multivariate analysis. RESULTS: The mean duration of radiological and clinical follow-up was 42 months (12.3-82.5 months) and 57.6 months (12.3-108.9 months), respectively. The total annual hemorrhage rate was 1.66% with 2.26% for ruptured AVMs and 1.08% for unruptured AVMs. The annual mortality rate was 0.4%. The total obliteration rate was 28.2% at follow-up. Clinical deterioration occurred in 4 patients (4.7%). Volume larger than 22 ml, diameter prior GKS larger than 3.5 cm and margin dose less than 16 Gy significantly increased the hemorrhage risk. CONCLUSION: The post-treatment hemorrhage could be predictable based on AVM's characteristics and treatment approaches. The annual hemorrhage rate was low for both ruptured and unruptured AVMs after combined treatment; however, the total obliteration rate was low. Long-term follow-up and larger population are needed for evaluating the clinical effect for this combined treatment.

Cerebrovasc Dis.2015; 39(1):53-62. Epub 2014/12/31 Effect of prior hemorrhage on intracranial arteriovenous malformation radiosurgery outcomes Ding, D., Yen, C. P., Starke, R. M., Xu, Z. and Sheehan, J. P.,University of Virginia, Department of Neurological Surgery, Charlottesville, Va., USA. BACKGROUND: Intracerebral hemorrhage is simultaneously the most frequent and most debilitating manifestation of intracranial arteriovenous malformations (AVM), but its impact on success and complications of radiosurgery has not been rigorously assessed. In this case-control study, we define the effect of prior hemorrhage on AVM radiosurgery outcomes. METHODS: From a prospective, institutional database of 1,400 AVM patients treated with Gamma Knife radiosurgery, unruptured and ruptured AVMs were matched in a 1:1 fashion, blinded to outcome, based on patient demographics, prior embolization (26.6% of each cohort), AVM size (mean volume of unruptured AVMs 3.7 cm(3) versus ruptured AVMs 3.5 cm(3), p = 0.195), Spetzler-Martin grade (Grade I 17.0%, Grade II 37.8%, Grade III 34.8%, Grade IV 10.4% for each cohort), and radiosurgical treatment parameters (mean prescription dose for unruptured AVMs 20.9 Gy versus ruptured AVMs 21.0 Gy, p = 0.837). There were 270 patients in each cohort. Matched statistical analyses were used to compare the baseline characteristics, obliteration rates, post-radiosurgery latency period hemorrhage risks, and incidences of radiation-induced changes (RIC) between the two cohorts. RESULTS: The actuarial obliteration rates of the two cohorts were similar (unruptured AVMs: 38, 58, and 76% at 3, 5, 10 years, respectively; ruptured AVMs: 40, 60, and 73% at 3, 5, 10 years, respectively; p = 0.592). However, for embolized AVMs, complete obliteration was more likely to be achieved in unruptured lesions (unruptured AVMs: 25, 32, and 54% at 3, 5, 10 years, respectively; ruptured AVMs: 18, 27, and 42% at 3, 5, 10 years, respectively; p = 0.038). Prior AVM rupture resulted in a higher annual risk of post-radiosurgery latency period hemorrhage (ruptured AVMs 2.3% versus unruptured AVMs 1.1%, p = 0.025) but a lower rate of cumulative and

23

symptomatic RIC (cumulative RIC: ruptured AVMs 30.4% versus unruptured AVMs 48.9%, p < 0.0001; symptomatic RIC: ruptured AVMs 7.0% versus unruptured AVMs 12.2%, p = 0.041, respectively). The rates of permanent RIC were similar between the unruptured (2.2%) and ruptured (1.9%) AVM cohorts (p = 0.761). The mean time interval to onset of RIC (unruptured AVMs 13.3 months versus ruptured AVMs 12.1 months, p = 0.783), and the mean duration of RIC (unruptured AVMs 22.0 months versus ruptured AVMs 21.7 months, p = 0.599) were not significantly different between the two cohorts. CONCLUSIONS: Prior AVM rupture significantly alters the risk of latency period hemorrhage and RIC following radiosurgery. These effects should be taken into consideration with the multidisciplinary management of AVM patients. Radiosurgery does not significantly alter the natural history of the hemorrhage risks of unruptured and ruptured AVMs unless obliteration is achieved. (c) 2014 S. Karger AG, Basel.

World Neurosurg.2015;Epub 2015/03/11 Cerebral Arteriovenous Malformations and Epilepsy, Part 1: Predictors of Seizure Presentation Ding, D., Starke, R. M., Quigg, M., Yen, C. P., Przybylowski, C. J., Dodson, B. K. and Sheehan, J. P.,University of Virginia, Department of Neurological Surgery, P.O. Box 800212, Charlottesville, VA 22908, United States. University of Virginia, Department of Neurology, P.O. Box 800394, Charlottesville, VA 22908, United States. University of Virginia, School of Medicine, P.O. Box 800793, Charlottesville, VA 22908, United States. University of Virginia, Department of Neurological Surgery, P.O. Box 800212, Charlottesville, VA 22908, United States. Electronic address: jps2f@virginia.edu. OBJECTIVE: Seizures are relatively common in patients harboring cerebral arteriovenous malformations (AVM). Since the pathogenesis of AVM-associated epilepsy is not well-defined, we aim to determine the factors associated with seizure presentation in AVM patients. METHODS: We evaluated our institutional AVM radiosurgery database, from 1989 to 2013, to select patients in whom pertinent clinical information at presentation and adequate clinical and radiologic follow-up was available. Baseline patient demographics and AVM angioarchitectural features were compared between patients with and without seizure presentation. In addition to standard descriptive statistics, logistic regression analyses were performed to identify predictors of seizure presentation. RESULTS: Of the 1,007 AVM patients included for analysis, 229 patients presented with seizures (22.7%). The incidence of seizure presentation was significantly higher in cortical than non-cortical AVMs (33.1% versus 6.6%, P<0.0001). Amongst the cortical locations, occipital AVMs had the lowest rate of seizure presentation (21.5%, P=0.0012), whereas the rates of seizure presentation in frontal (37.3%), temporal (37.7%), and parietal (34.0%) AVMs were similar. The lack of prior AVM hemorrhage (P<0.0001), larger nidus diameter (P<0.0001), and cortical location (P<0.0001) were independent predictors of seizure presentation in the multivariate analysis. The strongest independent predictors of seizure presentation were lack of prior AVM hemorrhage (OR 16.8) and cortical location (OR 4.2). CONCLUSIONS: Large, unruptured, cortical nidi are most prone to seizure presentation in patients referred for radiosurgery. Further investigations of the molecular biology, neuronal and glial physiology, and natural history of AVM-associated epilepsy appear warranted.

24

Acta Neurochir (Wien).2015; Epub 2015/03/10 Pathogenesis of radiosurgery-induced cyst formation in patients with cerebral arteriovenous malformations Ding, D.,Department of Neurosurgery, University of Virginia, P.O. Box 800212, Charlottesville, VA, 22908, USA, dmd7q@hscmail.mcc.virginia.edu.

Acta Neurochir (Wien).2015; 157(1):49-50. Epub 2014/10/25 Effect of stereotactic radiosurgery on the hemorrhage risk of cerebral cavernous malformations: fact or fiction? Ding, D.,Department of Neurosurgery, University of Virginia, P.O. Box 800212, Charlottesville, VA, 22908, USA, dmd7q@hscmail.mcc.virginia.edu.

Clin Neurol Neurosurg.2015; Epub 2015/02/11 Controversies in the management of brainstem cavernous malformations: Role of stereotactic radiosurgery Ding, D.,University of Virginia, Department of Neurosurgery, Charlottesville 22908, USA. Electronic address: dmd7q@hscmail.mcc.virginia.edu.

J Neurosurg Pediatr.2015;15(1):20-5. Epub 2014/11/02 Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain Dashti, S. R., Spalding, A., Kadner, R. J., Yao, T., Kumar, A., Sun, D. A. and LaRocca, R.,Norton Neuroscience Institute and. Radiation necrosis (RN) is a serious complication that can occur in up to 10% of brain radiotherapy cases, with the incidence dependent on both dose and brain location. Available medical treatment for RN includes steroids, vitamin E, pentoxifylline, and hyperbaric oxygen. In a significant number of patients, however, RN is medically refractory and the patients experience progressive neurological decline, disabling headaches, and decreased quality of life. Vascular endothelial growth factor (VEGF) is a known mediator of cerebral edema in RN. Recent reports have shown successful treatment of RN with intravenous bevacizumab, a monoclonal antibody for VEGF. Bevacizumab, however, is associated with significant systemic complications including sinus thrombosis, pulmonary embolus, gastrointestinal tract perforation, wound dehiscence, and severe hypertension. Using lower drug doses may decrease systemic exposure and reduce complication rates. By using an intraarterial route for drug administration following blood-brain barrier disruption (BBBD), the authors aim to lower the bevacizumab dose while increasing target delivery. In the present report, the authors present the cases of 2 pediatric patients with cerebral arteriovenous malformations, who presented with medically intractable RN following stereotactic radiosurgery. They received a single intraarterial infusion of 2.5 mg/kg bevacizumab after hyperosmotic BBBD. At mean follow-up duration of 8.5 months, the patients had significant and durable clinical and radiographic response. Both patients experienced resolution of their previously intractable headaches and reversal of cushingoid features as they were successfully weaned off steroids. One of the patients regained significant motor strength. There was an associated greater than 70% reduction in cerebral edema. Intraarterial administration of a single low dose of bevacizumab after BBBD was safe and resulted in durable clinical and radiographic improvements at concentrations well below those required for the typical systemic intravenous route. Advantages over the intravenous route may include higher concentration of drug delivery to the affected brain, decreased systemic toxicity, and a significantly lower cost.

25

Neurosurgery.2015; Epub 2015/01/31 Draining Vein Shielding in Intracranial Arteriovenous Malformations During Gamma-Knife: A New Way of Preventing Post Gamma-Knife Edema and Hemorrhage Bose, R., Agrawal, D., Singh, M., Kale, S. S., Gopishankar, N., Bisht, R. K. and Sharma, B. S.,Department of Neurosurgery and Gamma Knife, All India Institute of Medical Sciences, New Delhi, India. BACKGROUND:: Following gamma knife (GK) therapy for intracranial arteriovenous malformations (AVMs), obliteration of the nidus occurs over several years. During this period, complications like rebleeding have been attributed to early draining vein occlusion. OBJECTIVE:: To evaluate if shielding the draining vein(s) during GK therapy prevents early draining vein obliteration and complications following GK therapy. METHODS:: This was a nonrandomized case-control study over 5 years (January 2009-February 2014) and included patients with intracranial AVM who underwent GK therapy at our center. All patients who underwent draining vein shielding by the senior author (D.A.) were included in the test group, and patients who did not undergo draining vein shielding were put in the control group. Patients were followed up for at least 6 months (and every 6 months thereafter) clinically as well as radiologically with computed tomography head scans/magnetic resonance imaging brain scans to check for postradiosurgery imaging (PRI) changes. RESULTS:: One hundred eighty-five patients were included in this study, of which 96 were in the control group and 89 were in the test group. Both groups were well matched in demographics, comorbidities, adjuvant treatment, angioarchitecture, and radiation dosing. Because of shielding, the test group patients received significantly less radiation to the draining vein than the control group (P = .001). On follow-up, a significantly lower number of patients in the test group had new neurological deficits (P = .001), intracranial hemorrhage (P = .03), and PRI changes (P = .002). CONCLUSION:: Shielding of the draining vein is a potent new strategy in minimizing PRI and hemorrhage as well as clinical deterioration following GK therapy for intracranial AVMs. ABBREVIATIONS:: AVM, arteriovenous malformationDSA, digital subtraction angiographyDV, draining veinDVS, draining vein shieldingGK, gamma knifePRI, postradiosurgery imagingSD, standard deviationSM, Spetzler-Martin.

J Neurosurg.2015; 122(2):419-32. Epub 2014/11/26 A treatment paradigm for high-grade brain arteriovenous malformations: volume-staged radiosurgical downgrading followed by microsurgical resection Abla, A. A., Rutledge, W. C., Seymour, Z. A., Guo, D., Kim, H., Gupta, N., Sneed, P. K., Barani, I. J., Larson, D., McDermott, M. W. and Lawton, M. T.,Departments of 1 Neurological Surgery and. OBJECT The surgical treatment of many large arteriovenous malformations (AVMs) is associated with substantial risks, and many are considered inoperable. Furthermore, AVMs larger than 3 cm in diameter are not usually treated with conventional single-session radiosurgery encompassing the entire AVM volume. Volume-staged stereotactic radiosurgery (VS-SRS) is an option for large AVMs, but it has mixed results. The authors report on a series of patients with high-grade AVMs who underwent multiple VS-SRS sessions with resultant downgrading of the AVMs, followed by resection. METHODS A cohort of patients was retrieved from a single-institution AVM patient registry consisting of prospectively collected data. VS-SRS was performed as a planned intentional treatment. Surgery was considered as salvage therapy in select patients. RESULTS Sixteen AVMs underwent VS-SRS followed by surgery. Four AVMs presented with rupture. The mean patient age was 25.3 years (range 13-54 years). The average initial Spetzler-Martin grade before any treatment was 4, while the average supplemented Spetzler-Martin grade (Spetzler-Martin plus Lawton-Young) was 7.1. The average AVM size in maximum

26

dimension was 5.9 cm (range 3.3-10 cm). All AVMs were supratentorial in location and all except one were in eloquent areas of the brain, with 7 involving primary motor cortex. The mean number of VS-SRS sessions was 2.7 (range 2-5 sessions). The mean interval between first VS-SRS session and resection was 5.7 years. There were 4 hemorrhages that occurred after VS-SRS. The average Spetzler-Martin grade was reduced to 2.5 (downgrade, -1.5) and the average supplemented Spetzler-Martin grade was reduced to 5.6 (downgrade, -1.5). The maximum AVM size was reduced to an average of 3.0 cm (downsize = -2.9 cm). The mean modified Rankin Scale (mRS) scores were 1.2, 2.3, and 2.2 before VS-SRS, before surgery, and at last follow-up, respectively (mean follow-up, 6.9 years). Fifteen AVMs were cured after surgery. Ten patients had good outcomes at last follow-up (7 with mRS Score 0 or 1, and 3 with mRS Score 2). There were 2 deaths (both mRS Score 1 before treatment) and 4 patients with mRS Score 3 outcome (from mRS Scores 0, 1, and 2 [n = 2]). CONCLUSIONS Volume-staged SRS can downgrade AVMs, transforming high-grade AVMs (initially considered inoperable) into operable AVMs with acceptable surgical risks. This treatment paradigm offers an alternative to conservative observation for young patients with unruptured AVMs and long life expectancy, where the risk of hemorrhage is substantial. Difficult AVMs were cured in 15 patients. Surgical morbidity associated with downgraded AVMs is reduced to that of postradiosurgical/preoperative supplemented Spetzler-Martin grades, not their initial AVM grades.

VESTIBULAR SCHWANNOMA

J Clin Neurosci.2015;Epub 2015/04/05 Extreme volume expansion of a vestibular schwannoma due to intratumoral hemorrhage after gamma knife radiosurgery Miki, S., Ishikawa, E., Yamamoto, T., Akutsu, H., Matsuda, M., Sakamoto, N. and Matsumura, A.,Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 2-1-1 Tennodai, Tsukuba, Ibaraki 305-8576, Japan. Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 2-1-1 Tennodai, Tsukuba, Ibaraki 305-8576, Japan. Electronic address: e-ishikawa@md.tsukuba.ac.jp. A 48-year-old man with right hemi-facial palsy and cerebellar ataxia was referred to our hospital. Three years and 10months earlier he had undergone gamma knife radiosurgery (GKRS) at the referring hospital for an 18mm right vestibular schwannoma. Slight tumor enlargement had been observed on MRI performed at the referring hospital 3years after the GKRS. On close follow-up after another 6months an MRI showed an obvious enlargement of the tumor. An MRI on admission revealed an iso-intense mass lesion measuring 36mm in maximum diameter at the right cerebellopontine angle. A two stage surgery was conducted using a retrosigmoid approach because bleeding from the tumor wall was difficult to control intraoperatively during the first operation. At the second operation, the majority of the tumor capsule had converted to necrotic tissue. A large hematoma cavity was present inside the tumor capsule which explained the rapid increase in size over a short period of time. Near total removal was achieved. Histopathological examination revealed massive intratumoral hemorrhage within a typical vestibular schwannoma with no malignancy. The complication of intratumoral hemorrhage is very rare and the utility of stereotactic radiation surgery/therapy, including GKRS, for vestibular schwannoma is well known. However, we must emphasize that careful follow-up is still required, even after several years.

27

Laryngoscope.2015;Epub 2015/02/14 What is the risk of malignant transformation of vestibular schwannoma following radiosurgery? Nicolli, E. A. and Ruckenstein, M.,Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Neurosurgery.2015;Epub 2015/02/24 Hearing Preservation up to 3 Years After Gamma Knife Radiosurgery for Gardner-Robertson Class I Patients With Vestibular Schwannomas Mousavi, S. H., Kano, H., Faraji, A. H., Gande, A., Flickinger, J. C., Niranjan, A., Monaco, E. and Lunsford, L. D.,*Departments of Neurological Surgery and section signRadiation Oncology, University of PittsburghMedical Center, Pittsburgh, Pennsylvania; double daggerUniversity of Pittsburgh School of Medicine,Pittsburgh, Pennsylvania.BACKGROUND: Vestibular schwannoma patients with Gardner-Robertson (GR) class I hearing seek tomaintain high-level hearing whenever possible. OBJECTIVE:: To evaluate hearing outcomes at 2 to 3years in GR class I patients who underwent Gamma Knife radiosurgery (GKRS). METHODS:: Sixty-eightpatients with GR class I hearing were identified between 2006 and 2009. Twenty-five patients had nosubjective hearing loss (group A) and 43 patients reported subjective hearing loss (group B) beforeGKRS. The median tumor volume (1 cm) and tumor margin dose (12.5 Gy) were the same in bothgroups. RESULTS:: Serviceable hearing retention rates (GR grade I or II) were 100% for group Acompared with 81% at 1 year, 60% at 2 years, and 57% at 3 years after GKRS for group B patients. GroupA patients had significantly higher rates of hearing preservation in either GR class I (P < .001) or GR classII (P < .001). Patients with a pure tone average (PTA) <15 dB before GKRS had significantly higher rates ofpreservation of GR class I or II hearing. CONCLUSION:: At 2 to 3 years after GKRS, patients withoutsubjective hearing loss or a PTA <15 dB had higher rates of grade I or II hearing preservation.Modification of the GR hearing classification into 2 groups of grade I hearing (group A, those with nosubjective hearing loss and a PTA <15 dB; and group B, those with subjective hearing loss and a PTA >15dB) may be useful to help predict hearing preservation rates at 2 to 3 years after GKRS. ABBREVIATIONS:CI, confidence intervalGKRS, Gamma Knife radiosurgeryGR, Gardner-RobertsonHR, hazard ratioPTA,pure tone averageSDS, speech discrimination score.

Auris Nasus Larynx.2015;Epub 2015/02/11 Cervical vestibular-evoked myogenic potential in vestibular schwannoma after gamma-knife surgery Lee, Y. F., Lee, C. C., Wang, M. C., Liu, K. D., Wu, H. M., Guo, W. Y., Shiao, A. S., Pan, D. H., Chung, W. Y. and Hsu, S. P.,Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Radiology, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: doc3379b@gmail.com. OBJECTIVE: Gamma-knife radiosurgery (GKS) for vestibular schwannomas (VSs) has become popular during the last two decades, and a promising tumor control rate has been reported. Therefore, the evaluation and preservation of auditory-vestibular nerve function after GKS have become more and more important in these patients with long-term survival. We have traditionally used pure-tone

28

audiometry (PTA) for evaluation of auditory nerve function, and the caloric test for superior vestibular nerve function. Vestibular-evoked myogenic potential (VEMP) has recently emerged from various neurophysiological examinations for assessment of the integrity of the inferior vestibular nerve function. This novel tool has been established to represent a sacculo-collic reflex. By using these three tools, the auditory-vestibular nerve function of VS patients can be evaluated and monitored before and after GKS. METHODS: Fourteen patients with unilateral VS that underwent GKS were prospectively recruited. All of them received a battery of auditory-vestibular function tests including PTA, caloric, and cVEMP tests before and after GKS at each time point (1, 6, and 12 months). Our data also included the tumor volumes and their relationship with the PTA, caloric, and cVEMP test results. RESULTS: The PTA, caloric, and cVEMP tests showed abnormal results before GKS in 85.7%, 78.6% and 78.6% of our VS patients, respectively. The PTA, caloric, and cVEMP results did not show strong correlations between each other. However, there was a tendency that when the tumor grew larger, the auditory-vestibular function deficits became more severe. The PTA and cVEMP test results remained stable during the 1-year follow-up after GKS. However, the caloric test showed transient deterioration at the 6th month follow-up, which then recovered by the 1-year follow-up. CONCLUSION: The combination of these three tests can help us diagnose VS and assess the change in auditory-vestibular nerve function during the post-GKS follow-up period. The results of these three tests were independent for smaller tumors, but all tests may show abnormal findings with larger tumors. Although the study is still ongoing, the preliminary data showed that GKS treatment would not affect the auditory-vestibular nerve function within a 1-year follow-up period.

J Neurosurg.2015;1-10. Epub 2015/01/03 Long-term quality of life in patients with vestibular schwannoma: an international multicenter cross-sectional study comparing microsurgery, stereotactic radiosurgery, observation, and nontumor controls Carlson, M. L., Tveiten, O. V., Driscoll, C. L., Goplen, F. K., Neff, B. A., Pollock, B. E., Tombers, N. M., Castner, M. L., Finnkirk, M. K., Myrseth, E., Pedersen, P. H., Lund-Johansen, M. and Link, M. J.,Departments of 1 Otolaryngology-Head and Neck Surgery and. OBJECT The optimal treatment for sporadic vestibular schwannoma (VS) is highly controversial. To date, the majority of studies comparing treatment modalities have focused on a narrow scope of technical outcomes including facial function, hearing status, and tumor control. Very few publications have investigated health-related quality of life (HRQOL) differences between individual treatment groups, and none have used a disease-specific HRQOL instrument. METHODS All patients with sporadic small- to medium-sized VSs who underwent primary microsurgery, stereotactic radiosurgery (SRS), or observation between 1998 and 2008 were identified. Subjects were surveyed via postal questionnaire using the 36-Item Short Form Health Survey (SF-36), the 10-item Patient-Reported Outcomes Measurement Information System short form (PROMIS-10), the Glasgow Benefit Inventory (GBI), and the Penn Acoustic Neuroma Quality-of-Life (PANQOL) scale. Additionally, a pool of general population adults was surveyed, providing a nontumor control group for comparison. RESULTS A total of 642 respondents were analyzed. The overall response rate for patients with VS was 79%, and the mean time interval between treatment and survey was 7.7 years. Using multivariate regression, there were no statistically significant differences between management groups with respect to the PROMIS-10 physical or mental health dimensions, the SF-36 Physical or Mental Component Summary scores, or the PANQOL general, anxiety, hearing, or energy subdomains. Patients who underwent SRS or observation reported a better total PANQOL score and higher PANQOL facial, balance, and pain subdomain scores than the microsurgical

29

cohort (p < 0.02). The differences in scores between the nontumor control group and patients with VS were greater than differences observed between individual treatment groups for the majority of measures. CONCLUSIONS The differences in HRQOL outcomes following SRS, observation, and microsurgery for VS are small. Notably, the diagnosis of VS rather than treatment strategy most significantly impacts quality of life. Understanding that a large number of VSs do not grow following discovery, and that intervention does not confer a long-term HRQOL advantage, small- and medium-sized VS should be initially observed, while intervention should be reserved for patients with unequivocal tumor growth or intractable symptoms that are amenable to treatment. Future studies assessing HRQOL in VS patients should prioritize use of validated disease-specific measures, such as the PANQOL, given the significant limitations of generic instruments in distinguishing between treatment groups and tumor versus nontumor subjects.

Laryngoscope.2015; Epub 2015/02/14 What is the risk of malignant transformation of vestibular schwannoma following radiosurgery? Nicolli, E. A. and Ruckenstein, M.,Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.

Neurosurgery.2015;Epub 2015/02/24 Hearing Preservation up to 3 Years After Gamma Knife Radiosurgery for Gardner-Robertson Class I Patients With Vestibular Schwannomas Mousavi, S. H., Kano, H., Faraji, A. H., Gande, A., Flickinger, J. C., Niranjan, A., Monaco, E. and Lunsford, L. D.,*Departments of Neurological Surgery and section signRadiation Oncology, University of PittsburghMedical Center, Pittsburgh, Pennsylvania; double daggerUniversity of Pittsburgh School of Medicine,Pittsburgh, Pennsylvania.BACKGROUND:: Vestibular schwannoma patients with Gardner-Robertson (GR) class I hearing seek tomaintain high-level hearing whenever possible. OBJECTIVE:: To evaluate hearing outcomes at 2 to 3years in GR class I patients who underwent Gamma Knife radiosurgery (GKRS). METHODS:: Sixty-eightpatients with GR class I hearing were identified between 2006 and 2009. Twenty-five patients had nosubjective hearing loss (group A) and 43 patients reported subjective hearing loss (group B) beforeGKRS. The median tumor volume (1 cm) and tumor margin dose (12.5 Gy) were the same in bothgroups. RESULTS:: Serviceable hearing retention rates (GR grade I or II) were 100% for group Acompared with 81% at 1 year, 60% at 2 years, and 57% at 3 years after GKRS for group B patients. GroupA patients had significantly higher rates of hearing preservation in either GR class I (P < .001) or GR classII (P < .001). Patients with a pure tone average (PTA) <15 dB before GKRS had significantly higher rates ofpreservation of GR class I or II hearing. CONCLUSION:: At 2 to 3 years after GKRS, patients withoutsubjective hearing loss or a PTA <15 dB had higher rates of grade I or II hearing preservation.Modification of the GR hearing classification into 2 groups of grade I hearing (group A, those with nosubjective hearing loss and a PTA <15 dB; and group B, those with subjective hearing loss and a PTA >15dB) may be useful to help predict hearing preservation rates at 2 to 3 years after GKRS.ABBREVIATIONS:: CI, confidence intervalGKRS, Gamma Knife radiosurgeryGR, Gardner-RobertsonHR,hazard ratioPTA, pure tone averageSDS, speech discrimination score.

30

Auris Nasus Larynx.2015; Epub 2015/02/11 Cervical vestibular-evoked myogenic potential in vestibular schwannoma after gamma-knife surgery Lee, Y. F., Lee, C. C., Wang, M. C., Liu, K. D., Wu, H. M., Guo, W. Y., Shiao, A. S., Pan, D. H., Chung, W. Y. and Hsu, S. P.,Department of Otolaryngology, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Radiology, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: doc3379b@gmail.com. OBJECTIVE: Gamma-knife radiosurgery (GKS) for vestibular schwannomas (VSs) has become popular during the last two decades, and a promising tumor control rate has been reported. Therefore, the evaluation and preservation of auditory-vestibular nerve function after GKS have become more and more important in these patients with long-term survival. We have traditionally used pure-tone audiometry (PTA) for evaluation of auditory nerve function, and the caloric test for superior vestibular nerve function. Vestibular-evoked myogenic potential (VEMP) has recently emerged from various neurophysiological examinations for assessment of the integrity of the inferior vestibular nerve function. This novel tool has been established to represent a sacculo-collic reflex. By using these three tools, the auditory-vestibular nerve function of VS patients can be evaluated and monitored before and after GKS. METHODS: Fourteen patients with unilateral VS that underwent GKS were prospectively recruited. All of them received a battery of auditory-vestibular function tests including PTA, caloric, and cVEMP tests before and after GKS at each time point (1, 6, and 12 months). Our data also included the tumor volumes and their relationship with the PTA, caloric, and cVEMP test results. RESULTS: The PTA, caloric, and cVEMP tests showed abnormal results before GKS in 85.7%, 78.6% and 78.6% of our VS patients, respectively. The PTA, caloric, and cVEMP results did not show strong correlations between each other. However, there was a tendency that when the tumor grew larger, the auditory-vestibular function deficits became more severe. The PTA and cVEMP test results remained stable during the 1-year follow-up after GKS. However, the caloric test showed transient deterioration at the 6th month follow-up, which then recovered by the 1-year follow-up. CONCLUSION: The combination of these three tests can help us diagnose VS and assess the change in auditory-vestibular nerve function during the post-GKS follow-up period. The results of these three tests were independent for smaller tumors, but all tests may show abnormal findings with larger tumors. Although the study is still ongoing, the preliminary data showed that GKS treatment would not affect the auditory-vestibular nerve function within a 1-year follow-up period.

J Neurosurg.2015;1-10. Epub 2015/01/03 Long-term quality of life in patients with vestibular schwannoma: an international multicenter cross-sectional study comparing microsurgery, stereotactic radiosurgery, observation, and nontumor controls Carlson, M. L., Tveiten, O. V., Driscoll, C. L., Goplen, F. K., Neff, B. A., Pollock, B. E., Tombers, N. M., Castner, M. L., Finnkirk, M. K., Myrseth, E., Pedersen, P. H., Lund-Johansen, M. and Link, M. J.,Departments of 1 Otolaryngology-Head and Neck Surgery and. OBJECT The optimal treatment for sporadic vestibular schwannoma (VS) is highly controversial. To date, the majority of studies comparing treatment modalities have focused on a narrow scope of technical

31

outcomes including facial function, hearing status, and tumor control. Very few publications have investigated health-related quality of life (HRQOL) differences between individual treatment groups, and none have used a disease-specific HRQOL instrument. METHODS All patients with sporadic small- to medium-sized VSs who underwent primary microsurgery, stereotactic radiosurgery (SRS), or observation between 1998 and 2008 were identified. Subjects were surveyed via postal questionnaire using the 36-Item Short Form Health Survey (SF-36), the 10-item Patient-Reported Outcomes Measurement Information System short form (PROMIS-10), the Glasgow Benefit Inventory (GBI), and the Penn Acoustic Neuroma Quality-of-Life (PANQOL) scale. Additionally, a pool of general population adults was surveyed, providing a nontumor control group for comparison. RESULTS A total of 642 respondents were analyzed. The overall response rate for patients with VS was 79%, and the mean time interval between treatment and survey was 7.7 years. Using multivariate regression, there were no statistically significant differences between management groups with respect to the PROMIS-10 physical or mental health dimensions, the SF-36 Physical or Mental Component Summary scores, or the PANQOL general, anxiety, hearing, or energy subdomains. Patients who underwent SRS or observation reported a better total PANQOL score and higher PANQOL facial, balance, and pain subdomain scores than the microsurgical cohort (p < 0.02). The differences in scores between the nontumor control group and patients with VS were greater than differences observed between individual treatment groups for the majority of measures. CONCLUSIONS The differences in HRQOL outcomes following SRS, observation, and microsurgery for VS are small. Notably, the diagnosis of VS rather than treatment strategy most significantly impacts quality of life. Understanding that a large number of VSs do not grow following discovery, and that intervention does not confer a long-term HRQOL advantage, small- and medium-sized VS should be initially observed, while intervention should be reserved for patients with unequivocal tumor growth or intractable symptoms that are amenable to treatment. Future studies assessing HRQOL in VS patients should prioritize use of validated disease-specific measures, such as the PANQOL, given the significant limitations of generic instruments in distinguishing between treatment groups and tumor versus nontumor subjects.