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Daily bibliographic review of the Neurosurgery Department. La Fe University Hospital. Valencia, Spain

Cystic Vestibular Schwannomas Respond Best to Radiosurgery

Neurosurgery 81:490–497, 2017

Vestibular schwannomas (VS) have a well-documented response to Gamma Knife R  (Elekta AB, Stockholm, Sweden) Stereotactic radiosurgery (SRS). However, there are limited data available regarding the volumetric response of cystic tumors.

OBJECTIVE: This report correlates the radiographic appearance of VS before radiosurgery with the delayed volumetric response.

METHODS: This study reviewed our SRS experience with 219 VS patients between 2003 and 2013. Patients were treatment naïve and had a significant extracanalicular tumor volume. Magnetic resonance imaging at the time of SRS identified 42 contrast-enhancing macrocystic tumors, 45 contrast-enhancing microcystic tumors, and 132 homogeneously enhancing tumors with no intratumoral cyst formation. The median follow-up was 49.1 months. The median tumor volume was 2.6 cm3 (0.70-16.1 cm3) and the median dose was 12.5 Gy (11-13 Gy).

RESULTS: The actuarial tumor control rate was 99.4% at 2 years and 96.4% at 5 years. A volumetric reduction of >20% occurred in 85.4% of macrocystic tumors, 76.1% of microcystic tumors, and 62.8% of homogeneously enhancing VS. The median volume decrease per year for macrocystic, microcystic, and homogenous tumors was 17.2%, 7.5%, and 7.9% per year respectively (P < .001). A 2:1 blinded volumetric case match showed a significant size reduction in macrocystic tumors compared to noncystic tumors (P = .007). Serviceable hearing was maintained in 61.5% of patients that had Gardner-Robertson grade I-II hearing before treatment. Surgical resection or repeat radiosurgery was performed in 8 patients (3.6%) who had sustained tumor progression.

CONCLUSION: SRS provided VS tumor control in >95% of patients, regardless of radiographic characteristics. Tumor volume regression was most evident in patients with cystic tumors.

Trigeminal nerve contrast enhancement after radiosurgery

J Neurosurg 127:219–225, 2017

Contrast enhancement of the retrogasserian trigeminal nerve on MRI scans frequently develops after radiosurgical ablation for the management of medically refractory trigeminal neuralgia (TN). The authors sought to evaluate the clinical significance of this imaging finding in patients who underwent a second radiosurgical procedure for recurrent TN.

METHODS During a 22-year period, 360 patients underwent Gamma Knife stereotactic radiosurgery (SRS) as their first surgical procedure for TN at the authors’ center. The authors retrospectively analyzed the data from 59 patients (mean age 72 years, range 33–89 years) who underwent repeat SRS for recurrent pain at a median of 30 months (range 6–146 months) after the first SRS. The isocenter was 4 mm, and the median maximum doses for the first and second procedures were 80 Gy and 70 Gy, respectively. A neuroradiologist and a neurosurgeon blinded to the treated side evaluated the presence of nerve contrast enhancement on MRI series at the time of the repeat procedure. The authors correlated the presence of this imaging change with clinical outcomes. Pain outcomes and development of trigeminal sensory dysfunction were evaluated with the Barrow Neurological Institute (BNI) Pain Scale and BNI Numbness Scale, respectively. The mean length of follow-up after the second SRS was 58 months (95% CI 49–68 months).

RESULTS At the time of the repeat SRS, contrast enhancement of the trigeminal nerve on MRI scans was observed in 31 patients (53%). Five years after the SRS, patients with this enhancement had lower actuarial rates of complete pain relief after the repeat SRS (27% [95% CI 7%–47%]) than patients without the enhancement (76% [95% CI 58%–94%]) (p < 0.001). At the 5-year follow-up, patients with the contrast enhancement also had a higher risk for trigeminal sensory loss after repeat SRS (75% [95% CI 59%–91%]) than patients without contrast enhancement (26% [95% CI 10%–42%]) (p = 0.001). Dysesthetic pain after repeat SRS was observed for 8 patients with and for 2 patients without contrast enhancement.

CONCLUSIONS Trigeminal nerve contrast enhancement on MRI scans observed at the time of a repeat SRS for TN was associated with less satisfactory pain control and more frequently detected facial sensory loss. Residual contrast enhancement at the time of a repeat SRS may warrant consideration of dose reduction or further separation of the radiosurgical targets.

Comparing Preoperative With Postoperative Stereotactic Radiosurgery for Resectable Brain Metastases: A Multi-institutional Analysis

Motor function after stereotactic radiosurgery for brain metastases in the region of the motor cortex

Neurosurgery 79:279–285, 2016

Stereotactic radiosurgery (SRS) is an increasingly common modality used with surgery for resectable brain metastases (BM).

OBJECTIVE: To present a multi-institutional retrospective comparison of outcomes and toxicities of preoperative SRS (Pre-SRS) and postoperative SRS (Post-SRS).

METHODS: We reviewed the records of patients who underwent resection of BM and either Pre-SRS or Post-SRS alone between 2005 and 2013 at 2 institutions. Pre-SRS used a dose-reduction strategy based on tumor size, with planned resection within 48 hours. Cumulative incidence with competing risks was used to determine estimated rates.

RESULTS: A total of 180 patients underwent surgical resection for 189 BM: 66 (36.7%) underwent Pre-SRS and 114 (63.3%) underwent Post-SRS. Baseline patient characteristics were balanced except for higher rates of performance status 0 (62.1% vs 28.9%, P , .001) and primary breast cancer (27.2% vs 10.5%, P = .010) for Pre-SRS. Pre-SRS had lower median planning target volume margin (0 mm vs 2 mm) and peripheral dose (14.5 Gy vs 18 Gy), but similar gross tumor volume (8.3 mL vs 9.2 mL, P = .85). The median imaging follow-up period was 24.6 months for alive patients. Multivariable analyses revealed no difference between groups for overall survival (P = .1), local recurrence (P = .24), and distant brain recurrence (P = .75). Post-SRS was associated with significantly higher rates of leptomeningeal disease (2 years: 16.6% vs 3.2%, P = .010) and symptomatic radiation necrosis (2 years: 16.4% vs 4.9%, P = .010).

CONCLUSION: Pre-SRS and Post-SRS for resected BM provide similarly favorable rates of local recurrence, distant brain recurrence, and overall survival, but with significantly lower rates of symptomatic radiation necrosis and leptomeningeal disease in the Pre-SRS cohort. A prospective clinical trial comparing these treatment approaches is warranted.

Comparing Preoperative With Postoperative Stereotactic Radiosurgery for Resectable Brain Metastases

Motor function after stereotactic radiosurgery for brain metastases in the region of the motor cortex

Neurosurgery 79:279–285, 2016

Stereotactic radiosurgery (SRS) is an increasingly common modality used with surgery for resectable brain metastases (BM).

OBJECTIVE: To present a multi-institutional retrospective comparison of outcomes and toxicities of preoperative SRS (Pre-SRS) and postoperative SRS (Post-SRS).

METHODS: We reviewed the records of patients who underwent resection of BM and either Pre-SRS or Post-SRS alone between 2005 and 2013 at 2 institutions. Pre-SRS used a dose-reduction strategy based on tumor size, with planned resection within 48 hours. Cumulative incidence with competing risks was used to determine estimated rates.

RESULTS: A total of 180 patients underwent surgical resection for 189 BM: 66 (36.7%) underwent Pre-SRS and 114 (63.3%) underwent Post-SRS. Baseline patient characteristics were balanced except for higher rates of performance status 0 (62.1% vs 28.9%, P < .001) and primary breast cancer (27.2% vs 10.5%, P = .010) for Pre-SRS. Pre-SRS had lower median planning target volume margin (0 mm vs 2 mm) and peripheral dose (14.5 Gy vs 18 Gy), but similar gross tumor volume (8.3 mL vs 9.2 mL, P = .85). The median imaging follow-up period was 24.6 months for alive patients. Multivariable analyses revealed no difference between groups for overall survival (P = .1), local recurrence (P = .24), and distant brain recurrence (P = .75). Post-SRS was associated with significantly higher rates of leptomeningeal disease (2 years: 16.6% vs 3.2%, P = .010) and symptomatic radiation necrosis (2 years: 16.4% vs 4.9%, P = .010).

CONCLUSION: Pre-SRS and Post-SRS for resected BM provide similarly favorable rates of local recurrence, distant brain recurrence, and overall survival, but with significantly lower rates of symptomatic radiation necrosis and leptomeningeal disease in the Pre-SRS cohort. A prospective clinical trial comparing these treatment approaches is warranted.

Control of vestibular schwannomas treated with Gamma Knife

vestibular-schwannoma

J Neurosurg 124:1619–1626, 2016

The authors of this study sought to assess tumor control and complication rates in a large cohort of patients who underwent Gamma Knife radiosurgery (GKRS) for vestibular schwannoma (VS) and to identify predictors of tumor control. Methods The records of 420 patients treated with GKRS for VS with a median marginal dose of 11 Gy were retrospectively analyzed. Patients with neurofibromatosis Type 2 or who had undergone treatment for VS previously were excluded. The authors assessed tumor control and complication rates with chart review and used the Cox proportional hazards model to identify predictors of tumor control. Preservation of serviceable hearing, defined as Gardner-Robertson Class I–II, was evaluated in a subgroup of 71 patients with serviceable hearing at baseline and with available followup audiograms.

Results The median VS tumor volume was 1.4 cm3, and the median length of follow-up was 5.1 years. Actuarial 5- and 10-year tumor control rates were 91.3% and 84.8%, respectively. Only tumor volume was a statistically significant predictor of tumor control rate. The tumor control rate decreased from 94.1% for tumors smaller than 0.5 cm3 to 80.7% for tumors larger than 6 cm3. Thirteen patients (3.1%) had new or increased permanent trigeminal nerve neuropathy, 4 (1.0%) had new or increased permanent facial weakness, and 5 (1.2%) exhibited new or increased hydrocephalus requiring a shunting procedure. Actuarial 3-year and 5-year hearing preservation rates were 65% and 42%, respectively.

Conclusions The 5-year actuarial tumor control rate of 91.3% in this cohort of patients with VS compared slightly unfavorably with the rates reported in other large studies, but the complication and hearing preservation rates in this study were similar to those reported previously. Various factors may contribute to the observed differences in reported outcomes. These factors include variations in treatment indication and in the definition of treatment failure, as well as a lack of standardization of terminology and of evaluation of complications. Last, differences in dosimetric variables may also be an explanatory factor.

Stereotactic Radiosurgery for Arteriovenous Malformations: The Effect of Treatment Period on Patient Outcomes

AVM

Neurosurgery 78:499–509, 2016

Stereotactic radiosurgery (SRS) has been performed on patients with cerebral arteriovenous malformations (AVMs) for over 40 years.

OBJECTIVE: To evaluate the impact of treatment period on obliteration, intracranial hemorrhage (ICH), and radiation-induced complications (RICs).

METHODS: Retrospective comparison of 381 AVM patients having SRS during a 20-year period (group 1, January 1990 through March 1997, n = 160; group 2, April 1997 through December 2009, n = 221). The median radiological and clinical follow-up after initial SRS was 77 months and 93 months, respectively.

RESULTS: Obliteration was 59.1% at 4 years and 85.1% at 8 years. Obliteration was more common in patients with hemispheric or cerebellar AVMs (P = .001), smaller prescription isodose volume (PIV) (P < .001), and group 1 patients (P < .001). The ICH rate was 7.7% at 4 years and 10.6% at 8 years. ICH was more common in older patients (P = .02), patients with deep AVM (P = .01), and larger PIV (P < .001). There was no difference in the ICH rate between the treatment groups (P = .18). The rate of permanent RICs was 4.4% at 4 years and 8.6% at 8 years. RICs were more common with larger PIVs (P < .001) and group 1 patients (P = .02). There was no difference in the number of patients having obliteration without new deficits between the 2 treatment periods (68.8% vs 73.3%, P = .33).

CONCLUSION: Advances in SRS procedures over the past 20 years have resulted in a lower risk of RIC, but fewer patients had AVM obliteration. Increasing the prescription dose for patients with medium- and large-volume AVMs by using current conformal dose-planning techniques may improve the obliteration rate while maintaining a low risk of RICs.

Safety and Efficacy of Gamma Knife Radiosurgery for the Management of Koos Grade 4 Vestibular Schwannomas

Safety and Efficacy of Gamma Knife Radiosurgery for the Management of Koos Grade 4 Vestibular Schwannomas

Neurosurgery 78:521–530, 2016

Gamma Knife radiosurgery (GKRS) is commonly used in treating small vestibular schwannomas; however, its use for larger vestibular schwannomas is still controversial.

OBJECTIVE: To assess the long-term safety and efficacy of treating eligible Koos grade 4 vestibular schwannomas with GKRS.

METHODS: We conducted a single-center, retrospective evaluation of patient undergoing GKRS for Koos grade 4 vestibular schwannomas. We evaluated clinical, imaging, and treatment characteristics and assessed treatment outcome. Inclusion criteria were tumor size of ≥4 cm3 and follow-up of at least 6 months. Patients with neurofibromatosis type 2 were excluded. Primary outcomes measured were tumor control rate, hearing and facial function preservation rate, and complications. All possible factors were analyzed to assess clinical significance.

RESULTS: Sixty-eight patients met inclusion criteria. Median follow-up was 47 months (range, 6-125 months). Baseline hearing was serviceable in 60%. Median tumor volume at radiosurgery was 7.4 cm3 (range, 4-19 cm3). The median marginal dose used was 12 Gy at the 50% isodose line. Actuarial tumor control rates were 95% and 92% at 2 and 10 years, respectively. Actuarial serviceable hearing preservation rates were 89% and 49% at 2 and 5 years, respectively. Facial nerve preservation was 100%. Clinical complications included balance disturbance (11%), facial pain (10%), facial numbness (5%), and tinnitus (10%). Most complications were mild and transient. Hydrocephalus occurred in 3 patients, requiring ventriculoperitoneal shunt insertion. Larger tumor size was significantly associated with persisting symptoms post-treatment.

CONCLUSION: Patients with Koos grade 4 vestibular schwannomas and minimal symptoms can be treated safely and effectively with GKRS.

Microrecording and stereotactic biopsy of brain tumors

Microrecording and image-guided stereotactic biopsy of deep-seated brain tumors

J Neurosurg 123:978–988, 2015

Image-guided stereotactic brain tumor biopsy cannot easily obtain samples of small deep-seated tumor or selectively sample the most viable region of malignant tumor. Image-guided stereotactic biopsy in combination with depth microrecording was evaluated to solve such problems.

Methods Operative records, MRI findings, and pathological specimens were evaluated in 12 patients with small deep-seated brain tumor, in which image-guided stereotactic biopsy was performed with the aid of depth microrecording. The tumors were located in the caudate nucleus (1 patient), thalamus (7 patients), midbrain (2 patients), and cortex (2 patients). Surgery was performed with a frameless stereotactic system in 3 patients and with a frame-based stereotactic system in 9 patients. Microrecording was performed to study the electrical activities along the trajectory in the deep brain structures and the tumor. The correlations were studied between the electrophysiological, MRI, and pathological findings. Thirty-two patients with surface or large brain tumor were also studied, in whom image-guided stereotactic biopsy without microrecording was performed.

Results The diagnostic yield in the group with microrecording was 100% (low-grade glioma 4, high-grade glioma 4, diffuse large B-cell lymphoma 3, and germinoma 1), which was comparable to 93.8% in the group without microrecording. The postoperative complication rate was as low as that of the conventional image-guided method without using microelectrode recording, and the mortality rate was 0%, although the target lesions were small and deep-seated in all cases. Depth microrecording revealed disappearance of neural activity in the tumor regardless of the tumor type. Neural activity began to decrease from 6.3 ± 4.5 mm (mean ± SD) above the point of complete disappearance along the trajectory. Burst discharges were observed in 6 of the 12 cases, from 3 ± 1.4 mm above the point of decrease of neural activity. Injury discharges were often found at 0.5–1 mm along the trajectory between the area of decreased and disappeared neural activity. Close correlations between electrophysiological, MRI, and histological findings could be found in some cases.

Conclusions Image-guided stereotactic biopsy performed using depth microrecording was safe, it provided accurate positional information in real time, and it could distinguish the tumor from brain structures during surgery. Moreover, this technique has potential for studying the epileptogenicity of the brain tumor.

Treatment Outcomes of Unruptured Arteriovenous Malformations With a Subgroup Analysis of ARUBA Eligible Patients

AVM

Neurosurgery 76:563–570, 2015

The design and conclusions of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial are controversial, and its structure limits analysis of patients who could potentially benefit from treatment.

OBJECTIVE: To analyze the results of a consecutive series of patients with unruptured brain arteriovenous malformations (BAVMs), including a subgroup analysis of ARUBAeligible patients.

METHODS: One hundred five patients with unruptured BAVMs were treated over an 8-year period. From this series, 90 adult patients and a subgroup of 61 patients determined to be ARUBA eligible were retrospectively reviewed. A subgroup analysis for Spetzler-Martin grades I/II, III, and IV/V was performed. The modified Rankin Scale was used to assess functional outcome.

RESULTS: Persistent deficits, modified Rankin Scale score deterioration, and impaired functional outcome occurred less frequently in ARUBA-eligible grade I/II patients compared with grade III to V patients combined (P = .04, P = .04, P = .03, respectively). Twenty-two of 39 patients (56%) unruptured grade I and II BAVMs were treated with surgery without and with preoperative embolization, and all had a modified Rankin Scale score of 0 to 1 at the last follow-up. All patients treated with surgery without and with preoperative embolization had radiographic cure at the last follow-up.

CONCLUSION: The results of ARUBA-eligible and unruptured grade I/II patients overall show that excellent outcomes can be obtained in this subgroup of patients, especially with surgical management. Functional outcomes for ARUBA-eligible patients were similar to those of patients who were randomized to medical management in ARUBA. On the basis of these data, in appropriately selected patients, we recommend treatment for low-grade BAVMs.

Frameless robotic stereotactic biopsies: a consecutive series of 100 cases

Frameless robotic stereotactic biopsies- a consecutive series of 100 cases

J Neurosurg 122:342–352, 2015

Stereotactic biopsy procedures are an everyday part of neurosurgery. The procedure provides an accurate histological diagnosis with the least possible morbidity. Robotic stereotactic biopsy needs to be an accurate, safe, frameless, and rapid technique. This article reports the clinical results of a series of 100 frameless robotic biopsies using a Medtech ROSA device.

Methods The authors retrospectively analyzed their first 100 frameless stereotactic biopsies performed with the robotic ROSA device: 84 biopsies were performed by frameless robotic surface registration, 7 were performed by robotic bone fiducial marker registration, and 9 were performed by scalp fiducial marker registration. Intraoperative flat-panel CT scanning was performed concomitantly in 25 cases. The operative details of the robotic biopsies, the diagnostic yield, and mortality and morbidity data observed in this series are reported.

Results A histological diagnosis was established in 97 patients. No deaths or permanent morbidity related to surgery were observed. Six patients experienced transient neurological worsening. Six cases of bleeding within the lesion or along the biopsy trajectory were observed on postoperative CT scans but were associated with transient clinical symptoms in only 2 cases. Stereotactic surgery was performed with patients in the supine position in 93 cases and in the prone position in 7 cases. The use of fiducial markers was reserved for posterior fossa biopsy via a transcerebellar approach, via an occipital approach, or for pediatric biopsy.

Conclusions ROSA frameless stereotactic biopsies appear to be accurate and safe robotized frameless procedures.

Jugulotympanic paragangliomas treated with Gamma Knife radiosurgery

Jugulotympanic paragangliomas treated with Gamma Knife radiosurgery- a single-center review of 58 cases

J Neurosurg 121:1158–1165, 2014

Jugulotympanic paragangliomas (JTPs) are rare benign tumors whose surgical treatment is usually associated with partial resection of the lesion, high morbidity, and even death. Gamma Knife radiosurgery (GKRS) has been reported as a useful treatment option. The goal of this retrospective study is to analyze the role of GKRS in tumor volume control and clinical outcomes of these patients.

Methods. A total of 75 patients with JTPs were treated with GKRS at the authors’ center from 1995 to 2012. The authors analyzed those treated during this period to allow for a minimal observation time of 2 years. The MR images and clinical reports of these patients were reviewed to assess clinical and volumetric outcomes of the tumors. The radiological and clinical assessments, along with a group of prognostic factors measured, were analyzed using descriptive methods. The time to volumetric and clinical progression was analyzed using the Kaplan-Meier method. Prognostic factors were identified using log-rank statistics and multivariate Cox regression models.

Results. The mean follow-up was 86.4 months. The authors observed volumetric tumor control in 94.8% of cases. In 67.2% of cases, tumor volume decreased by a mean of 40.1% from the original size. Of patients with previous tinnitus, 54% reported complete recovery. Improvement of other symptoms was observed in 34.5% of cases. Overall, clinical control was achieved in 91.4% of cases. Previous embolization and familial history of paraganglioma were selected as significant prognostic factors for volumetric response to GKRS treatment in the univariate analysis. In multivariate analysis, no factors were significantly correlated with progression-free survival. No patient died of side effects related to GKRS treatment or tumor progression.

Conclusions. Gamma Knife radiosurgery is an effective, safe, and efficient therapeutic option for the treatment of these tumors as a first-line treatment or in conjunction with traditional surgery, endovascular treatment, or conventional fractionated radiotherapy.

Results for a Series of 697 Arteriovenous Malformations Treated by Gamma Knife

AVM frontal

Neurosurgery 75:568–583, 2014

Stereotactic radiosurgery (RS) is an effective tool in treating brain arteriovenous malformations (AVMs). Careful study of AVM angiographic characteristics may improve results.

OBJECTIVE: To report the long-term outcomes of Gamma Knife RS (GKRS) in brain AVMs, focusing on how the angioarchitectural and hemodynamic parameters of AVMs affect the post-RS results.

METHODS: This was a retrospective, longitudinal study of 697 consecutive GKRS treatments of brain AVMs in 662 patients performed at a single center between 1993 and 2005. The mean age of the patients was 37 years; the median AVM volume was 3.6 cm3; and the mean follow-up was 11 years. Forty-five percent of patients presented with intracranial hemorrhage; 44% underwent embolization; and 7% had multiple RSs. AVM characteristics in the RS-planning angiograms were analyzed, and their relationship to the post-RS obliteration rate was determined by univariate and multivariate analyses.

RESULTS: The obliteration rate after a single RS was 69.3%; after multiple RS, it was 75%. Positive predictors of obliteration included compact nidus (odds ratio = 3.16; 95% confidence interval, 1.92-5.22), undilated feeders (odds ratio = 0.36; 95% confidence interval, 0.23-0.57), smaller AVM volume (odds ratio = 0.95; 95% confidence interval, 0.92-0.99), and higher marginal dose (odds ratio = 1.16; 95% confidence interval, 1.06-1.27). Improvement or clinical stability was observed in 89.3% of patients; postprocedural bleeding was noted in 6.1%; and clinical worsening attributable to RS was seen in 3.8%. The annual risk of hemorrhage in the 4 years after RS was 1.2%.

CONCLUSION: GKRS yielded a good long-term clinical outcome in most patients. Certain angiographic features of brain AVMs such as a well-defined nidus and undilated feeder arteries contribute to AVM occlusion by RS. GKRS can be regarded as the treatment of choice for AVMs <6 cm3, even after bleeding.

Gamma knife radiosurgery for brainstem cavernous malformations: should a patient wait for the rebleed?

Gamma knife radiosurgery for brainstem cavernous malformations- should a patient wait for the rebleed?

Acta Neurochir (2014) 156:1937–1946

The effectiveness of stereotactic radiosurgery (SRS) for cavernous malformation (CM) has not been fully assessed. Consequently, observation is usually recommended when a bleeding CM is initially discovered. Recurrent bleeding occurs with CMs, and these repeat hemorrhages can result in additional morbidity.

Methods From 1992 to 2011, 49 patients with brainstem CMs were treated with Gamma Knife radiosurgery (GKS). We classified patients into two groups: Group A (n=31), patients who underwent GKS for a CM following a single symptomatic bleed, and group B (n=18), patients who underwent GKS for a CM following two or more symptomatic bleeds. The mean marginal dose of radiation was 13.1 Gy (range 9.0- 16.8 Gy): 12.8 Gy in group A and 13.7 Gy in group B. The mean follow-up period was 64.0 months (range 1-171 months).

Results In group A, the annual hemorrhage rate (AHR) following GKS was 7.06 % within the first 2 years and 2.03 % after 2 years. In group B, four patients (22.2 %) developed new or worsening neurologic deterioration as a result of repeat hemorrhages. In group B, the AHR was 38.36 % prior to GKS, 9.84 % within the first two years, and 1.50 % after two years. There was no statistically significant difference in the AHRs at each follow-up period after GKS between the two groups. Adverse radiation effects (AREs) developed in a total of four patients (8.2%); among them, one patient (2.0 %) developed a permanent case of diplopia. No mortality occurred in this series.

Conclusion In this study, GKS was demonstrated to be a safe and effective alternative treatment for brain stem CMs that resulted in a reduction in the AHR. Consequently, we suggest that even CM patients who have suffered only a single bleed should not be contraindicated for SRS.

Stereotactic radiosurgery for Spetzler-Martin Grade III arteriovenous malformations

Spetzler-Martin grade III AVMs

J Neurosurg 120:973–981, 2014

The purpose of this study was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs).

Methods. Between 1987 and 2009, SRS was performed in 474 patients with SM Grade III AVMs. The AVMs were categorized by scoring the size (S), drainage (D), and location (L): IIIa was a small AVM (S1D1L1, N = 282); IIIb was a medium/deep AVM (S2D1L0, N = 44); and IIIc was a medium/eloquent AVM (S2D0L1, N = 148). The median target volume was 3.8 ml (range 0.1–26.3 ml) and the margin dose was 20 Gy (range 13–25 Gy). Eighty-one patients (17%) underwent prior embolization, and 58 (12%) underwent prior resection.

Results. At a mean follow-up of 89 months, the total obliteration rates documented by angiography or MRI for all SM Grade III AVMs increased from 48% at 3 years to 69% at 4 years, 72% at 5 years, and 77% at 10 years. The SM Grade IIIa AVMs were more likely to obliterate than other subgroups. The cumulative rate of hemorrhage was 2.3% at 1 year, 4.4% at 2 years, 5.5% at 3 years, 6.4% at 5 years, and 9% at 10 years. The SM Grade IIIb AVMs had a significantly higher cumulative rate of hemorrhage. Symptomatic adverse radiation effects were detected in 6%.

Conclusions. Treatment with SRS was an effective and relatively safe management option for SM Grade III AVMs. Although patients with residual AVMs remained at risk for hemorrhage during the latency interval, the cumulative 10-year 9% hemorrhage risk in this series may represent a significant reduction compared with the expected natural history.

Radiosurgery for Spetzler-Martin Grade III arteriovenous malformations

Multimodality management of Spetzler-Martin Grade III arteriovenous malformations

J Neurosurg 120:959–969, 2014

Intracranial arteriovenous malformations (AVMs) are most commonly classified based on their Spetzler- Martin grades. Due to the composition of the Spetzler-Martin grading scale, Grade III AVMs are the most heterogeneous, comprising 4 distinct lesion subtypes. The management of this class of AVMs and the optimal treatment approach when intervention is indicated remain controversial. The authors report their experience with radiosurgery for the treatment of Grade III AVMs in a large cohort of patients.

Methods. All patients with Spetzler-Martin Grade III AVMs treated with radiosurgery at the University of Virginia over the 20-year span from 1989 to 2009 were identified. Patients who had less than 2 years of radiological follow-up and did not have evidence of complete obliteration during that period were excluded from the study, leaving 398 cases for analysis. The median patient age at treatment was 31 years. The most common presenting symptoms were hemorrhage (59%), seizure (20%), and headache (10%). The median AVM volume was 2.8 cm3, and the median prescription dose was 20 Gy. The median radiological and clinical follow-up intervals were 54 and 68 months, respectively. Univariate and multivariate Cox proportional hazards and logistic regression analysis were used to identify factors associated with obliteration, postradiosurgery radiation-induced changes (RIC), and favorable outcome.

Results. Complete AVM obliteration was observed in 69% of Grade III AVM cases at a median time of 46 months after radiosurgery. The actuarial obliteration rates at 3 and 5 years were 38% and 60%, respectively. The obliteration rate was higher in ruptured AVMs than in unruptured ones (p < 0.001). Additionally, the obliteration rate for Grade III AVMs with small size (< 3 cm diameter), deep venous drainage, and location in eloquent cortex was higher than for the other subtypes (p < 0.001). Preradiosurgery AVM rupture (p = 0.016), no preradiosurgery embolization (p = 0.003), increased prescription dose (p < 0.001), fewer isocenters (p = 0.006), and a single draining vein (p = 0.018) were independent predictors of obliteration. The annual risk of postradiosurgery hemorrhage during the latency period was 1.7%. Two patients (0.5%) died of hemorrhage during the radiosurgical latency period. The rates of symptomatic and permanent RIC were 12% and 4%, respectively. Absence of preradiosurgery AVM rupture (p < 0.001) and presence of a single draining vein (p < 0.001) were independent predictors of RIC. Favorable outcome was observed in 63% of patients. Independent predictors of favorable outcome were no preradiosurgery hemorrhage (p = 0.014), increased prescription dose (p < 0.001), fewer isocenters (p = 0.014), deep location (p = 0.014), single draining vein (p = 0.001), and lower Virginia radiosurgery AVM scale score (p = 0.016).

Conclusions. Radiosurgery for Spetzler-Martin Grade III AVMs yields relatively high rates of obliteration with a low rate of adverse procedural events. Small and ruptured lesions are more likely to become obliterated after radiosurgery than large and unruptured ones.

Stereotactic radiosurgery for arteriovenous malformations of the cerebellum

Bowden et al

J Neurosurg 120:583–590, 2014

Arteriovenous malformations (AVMs) of the posterior fossa have an aggressive natural history and propensity for hemorrhage. Although the cerebellum accounts for the majority of the posterior fossa volume, there is a paucity of stereotactic radiosurgery (SRS) outcome data for AVMs of this region. The authors sought to evaluate the long-term outcomes and risks of cerebellar AVM radiosurgery.

Methods. This single-institution retrospective analysis reviewed the authors’ experience with Gamma Knife surgery during the period 1987–2007. During this time 64 patients (median age 47 years, range 8–75 years) underwent SRS for a cerebellar AVM. Forty-seven patients (73%) presented with an intracranial hemorrhage. The median target volume was 3.85 cm3 (range 0.2–12.5 cm3), and the median marginal dose was 21 Gy (range 15–25 Gy).

Results. Arteriovenous malformation obliteration was confirmed by MRI or angiography in 40 patients at a median follow-up of 73 months (range 4–255 months). The actuarial rates of total obliteration were 53% at 3 years, 69% at 4 years, and 76% at 5 and 10 years. Elevated obliteration rates were statistically higher in patients who underwent AVM SRS without prior embolization (p = 0.005). A smaller AVM volume was also associated with a higher rate of obliteration (p = 0.03). Four patients (6%) sustained a hemorrhage during the latency period and 3 died. The cumulative rates of AVM hemorrhage after SRS were 6% at 1, 5, and 10 years. This correlated with an overall annual hemorrhage rate of 2.0% during the latency interval. One patient experienced a hemorrhage 9 years after confirmed MRI and angiographic obliteration. A permanent neurological deficit due to adverse radiation effects developed in 1 patient (1.6%) and temporary complications were seen in 2 additional patients (3.1%).

Conclusions. Stereotactic radiosurgery proved to be most effective for patients with smaller and previously nonembolized cerebellar malformations. Hemorrhage during the latency period occurred at a rate of 2.0% per year until obliteration occurred.

Optimizing Contrast-Enhanced Magnetic Resonance Imaging Characterization of Brain Metastases: Relevance to Stereotactic Radiosurgery

Optimizing_Contrast_Enhanced_Magnetic_Resonance

Neurosurgery 72:691–701, 2013

Intracranial metastases are the most common form of intra-axial brain tumor. Management approaches to brain metastases include surgical resection, whole-brain radiotherapy, and stereotactic radiosurgery (SRS). The management approach that is selected is based typically on algorithms that incorporate the number, size, and location of lesions.

SRS is the treatment of choice when metastases detected on imaging are few (maximum, 3-5) and/or of small size (#30 mm) and offers the advantages of noninvasiveness and the ability to treat inaccessible lesions compared with surgical resection.

Contrast-enhanced magnetic resonance imaging (MRI) is the standard imaging technique for determining the number, size, and location of metastatic lesions. In SRS, the capability of MRI to delineate lesion borders precisely in 3 dimensions helps reduce recurrence rates and minimize radiation necrosis in surrounding tissue.

Optimization of the MRI protocol, including selection of the appropriate gadolinium-based contrast agent (GBCA), is paramount for accurate lesion imaging. GBCAs differ in their safety, tolerability, and efficacy because of their diverse physicochemical properties. Gadobutrol and gadobenate dimeglumine are high-relaxivity GBCAs that demonstrate superior efficacy for imaging metastatic lesions compared with other GBCAs, whereas gadobutrol additionally provides macrocyclic stability.

This article reviews recent comparative trials of GBCAs and discusses their relevance for optimizing MRI protocols in the management of brain metastases, with particular relevance to SRS.

Long-term Outcomes After Staged-Volume Stereotactic Radiosurgery for Large Arteriovenous Malformations

Neurosurgery 71:632–644, 2012 DOI: 10.1227/NEU.0b013e31825fd247

Stereotactic radiosurgery is an effective treatment modality for small arteriovenous malformations (AVMs) of the brain. For larger AVMs, the treatment dose is often lowered to reduce potential complications, but this decreases the likelihood of cure. One strategy is to divide large AVMs into smaller anatomic volumes and treat each volume separately.

OBJECTIVE: To prospectively assess the long-term efficacy and complications associated with staged-volume radiosurgical treatment of large, symptomatic AVMs.

METHODS: Eighteen patients with AVMs larger than 15 mL underwent prospective staged-volume radiosurgery over a 13-year period. The median AVM volume was 22.9 mL (range, 15.7-50 mL). Separate anatomic volumes were irradiated at 3- to 9-month intervals (median volume, 10.9 mL; range, 5.3-13.4 mL; median marginal dose, 15 Gy; range, 15-17 Gy). The AVM was divided into 2 volumes in 10 patients, 3 volumes in 5 patients, and 4 volumes in 3 patients. Seven patients underwent retreatment for residual disease.

RESULTS: Actuarial rates of complete angiographic occlusion were 29% and 89% at 5 and 10 years. Five patients (27.8%) had a hemorrhage after radiosurgery. Kaplan-Meier analysis of cumulative hemorrhage rates after treatment were 12%, 18%, 31%, and 31% at 2, 3, 5, and 10 years, respectively. One patient died after a hemorrhage (5.6%).

CONCLUSION: Staged-volume radiosurgery for AVMs larger than 15 mL is a viable treatment strategy. The long-term occlusion rate is high, whereas the radiation-related complication rate is low. Hemorrhage during the lag period remains the greatest source of morbidity and mortality.

Stereotactic radiosurgery after embolization for AVMs

J Neurosurg 117:265–275, 2012

In this paper the authors’ goal was to define the long-term benefits and risks of stereotactic radiosurgery (SRS) for patients with arteriovenous malformations (AVMs) who underwent prior embolization.

Methods. Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 120 patients underwent embolization followed by SRS. In this series, 64 patients (53%) had at least one prior hemorrhage. The median number of embolizations varied from 1 to 5. The median target volume was 6.6 cm3 (range 0.2–26.3 cm3). The median margin dose was 18 Gy (range 13.5–25 Gy).

Results. After embolization, 25 patients (21%) developed symptomatic neurological deficits. The overall rates of total obliteration documented by either angiography or MRI were 35%, 53%, 55%, and 59% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration were smaller target volume, smaller maximum diameter, higher margin dose, timing of embolization during the most recent 10-year period (1997–2006), and lower Pollock-Flickinger score. Nine patients (8%) had a hemorrhage during the latency period, and 7 patients died of hemorrhage. The actuarial rates of AVM hemorrhage after SRS were 0.8%, 3.5%, 5.4%, 7.7%, and 7.7% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 2.7%. Factors associated with a higher risk of hemorrhage after SRS were a larger target volume and a larger number of prior hemorrhages. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 3 patients (2.5%) after SRS, and 1 patient had delayed cyst formation 210 months after SRS. No patient died of AREs. A larger 12-Gy volume was associated with higher risk of symptomatic AREs. Using a case-control matched approach, the authors found that patients who underwent embolization prior to SRS had a lower rate of total obliteration (p = 0.028) than patients who had not undergone embolization.

Conclusions. In this 20-year experience, the authors found that prior embolization reduced the rate of total obliteration after SRS, and that the risks of hemorrhage during the latency period were not affected by prior embolization. For patients who underwent embolization to volumes smaller than 8 cm3, success was significantly improved. A margin dose of 18 Gy or more also improved success. In the future, the role of embolization after SRS should be explored.

Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations

J Neurosurg 116:54–65, 2012. DOI: 10.3171/2011.9.JNS11177

The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery.

Methods. In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm3. Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8–13.8 months). The median target volume was 11.5 cm3 (range 4.0–26 cm3) in the first-stage SRS and 9.5 cm3 in the second-stage SRS. The median margin dose was 16 Gy (range 13–18 Gy) for both stages.

Results. In 17 patients, AVM obliteration was confirmed after 2–4 SRS procedures at a median follow-up of 87 months (range 0.4–209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33–113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0–1, 1–5, and 5–10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS.

Conclusions. Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volumestaged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.

Neurosurgery Department. “La Fe” University Hospital. Valencia, Spain

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