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

Radiosurgery for Unruptured Brain Arteriovenous Malformations: An International Multicenter Retrospective Cohort Study

Neurosurgery 80:888–898, 2017

The role of intervention in the management of unruptured brain arteriovenous malformations (AVM) is controversial.

OBJECTIVE: To analyze in a multicenter, retrospective cohort study, the outcomes following radiosurgery for unruptured AVMs and determine predictive factors.

METHODS: We evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes.

RESULTS: The unruptured AVM cohort comprised 938 patients with a median age of 35 yr. The median nidus volume was 2.4 cm3, 71% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 57%. The median radiosurgical margin dose was 21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 9% and 3%, respectively. Favorable outcome was achieved in 61%. In the multivariate logistic regression analysis, smaller AVM maximum diameter (P = .001), the absence of AVM-associated arterial aneurysms (P = .001), and higher margin dose (P = .002) were found to be independent predictors of a favorable outcome. A margin dose ≥ 20 Gy yielded a significantly higher rate of favorable outcome (70% vs 36%; P < .001)

CONCLUSION: Radiosurgery affords an acceptable risk to benefit profile for patients harboring unruptured AVMs. These findings justify further prospective studies comparing radiosurgical intervention to conservative management for unruptured AVMs.

 

Consensus guidelines for postoperative spine SBRT

J Neurosurg Spine 26:299–306, 2017

Although postoperative stereotactic body radiation therapy (SBRT) for spinal metastases is increasingly performed, few guidelines exist for this application. The purpose of this study is to develop consensus guidelines to promote safe and effective treatment for patients with spinal metastases.

METHODS Fifteen radiation oncologists and 5 neurosurgeons, representing 19 centers in 4 countries and having a collective experience of more than 1300 postoperative spine SBRT cases, completed a 19-question survey about postoperative spine SBRT practice. Responses were defined as follows: 1) consensus: selected by ≥ 75% of respondents; 2) predominant: selected by 50% of respondents or more; and 3) controversial: no single response selected by a majority of respondents.

RESULTS Consensus treatment indications included: radioresistant primary, 1–2 levels of adjacent disease, and previous radiation therapy. Contraindications included: involvement of more than 3 contiguous vertebral bodies, ASIA Grade A status (complete spinal cord injury without preservation of motor or sensory function), and postoperative Bilsky Grade 3 residual (cord compression without any CSF around the cord). For treatment planning, co-registration of the preoperative MRI and postoperative T1-weighted MRI (with or without gadolinium) and delineation of the cord on the T2-weighted MRI (and/or CT myelogram in cases of significant hardware artifact) were predominant. Consensus GTV (gross tumor volume) was the postoperative residual tumor based on MRI. Predominant CTV (clinical tumor volume) practice was to include the postoperative bed defined as the entire extent of preoperative tumor, the relevant anatomical compartment and any residual disease. Consensus was achieved with respect to not including the surgical hardware and incision in the CTV. PTV (planning tumor volume) expansion was controversial, ranging from 0 to 2 mm. The spinal cord avoidance structure was predominantly the true cord. Circumferential treatment of the epidural space and margin for paraspinal extension was controversial. Prescription doses and spinal cord tolerances based on clinical scenario, neurological compromise, and prior overlapping treatments were controversial, but reasonable ranges are presented. Fifty percent of those surveyed practiced an integrated boost to areas of residual tumor and density override for hardware within the beam path. Acceptable PTV coverage was controversial, but consensus was achieved with respect to compromising coverage to meet cord constraint and fractionation to improve coverage while meeting cord constraint.

CONCLUSIONS The consensus by spinal radiosurgery experts suggests that postoperative SBRT is indicated for radioresistant primary lesions, disease confined to 1–2 vertebral levels, and/or prior overlapping radiotherapy. The GTV is the postoperative residual tumor, and the CTV is the postoperative bed defined as the entire extent of preoperative tumor and anatomical compartment plus residual disease. Hardware and scar do not need to be included in CTV. While predominant agreement was reached about treatment planning and definition of organs at risk, future investigation will be critical in better understanding areas of controversy, including whether circumferential treatment of the epidural space is necessary, management of paraspinal extension, and the optimal dose fractionation schedules.

Staged-Volume Radiosurgery of Large Arteriovenous Malformations Improves Outcome by Reducing the Rate of Adverse Radiation Effects

Neurosurgery 80:180–192, 2017

The treatment of large arteriovenous malformations (AVMs) remains challenging. Recently, staged-volume radiosurgery (SVRS) has become an option.

OBJECTIVE: To compare the outcome of SVRS on large AVMs with our historical, single- stage radiosurgery (SSRS) series.

METHODS: We have been prospectively collecting data of patients treated by SVRS since 2007. There were 84 patients who had a median age of 37 years (range, 9-62 years) who were treated until July 2013. The outcomes of 76 of those who had follow-ups available were analyzed and compared with the outcomes of 122 patients treated with the best SSRS technique.

RESULTS: There were 21.5% of AVMs that were deep seated, and 44% presented with hemorrhage resulting in 45% fixed neurological deficit. There were 14% of patients who had undergone embolization before radiosurgery. The median nidus treatment volume was 19.7 cm 3 (6.65-68.7) and 17.5 Gy (13-22.5) prescription isodose was given. Of the 44 lesions having radiological follow-up at 4 years, 61.4% were completely obliterated. Previous embolization (50% with and 63% without) and higher Spetzler-Martin grades appeared to be the negative factors in successful obliteration, but treatment volume was not. Within 3 years after radiosurgery, the annual bleed rates of unruptured and previously ruptured AVMs were 3.2% and 5.6%, respectively. Three bleeds were fatal and 2 resulted in significant modified Rankin scale 3 morbidity. These rates differ little from SSRS. Temporary adverse radiation effects (AREs) did not change significantly, but permanent AREs dropped from 15% to 6.5% (P = .03) compared with SSRS.

CONCLUSION: Obliteration and hemorrhage rates of large AVMs treated by SVRS are similar to historical SSRS. However, SVRS offers a lower rate of AREs.

 

Long-Term Results of Stereotactic Radiosurgery for Skull Base Meningiomas

Long-Term Results of Stereotactic Radiosurgery for Skull Base Meningiomas

Neurosurgery 79:58–68, 2016

Gamma knife radiosurgery (GKRS) is well established in the management of inaccessible, recurrent, or residual benign skull base meningiomas. Most series report clinical outcome parameters and complications in the short intermediate period after radiosurgery. Reports of long-term tumor control and neurological status are still lacking.

OBJECTIVE: To report the presentation, treatment, and long-term outcome of skull base meningiomas after GKRS.

METHODS: From a prospectively collected institutional review board-approved database, we selected patients with a World Health Organization grade I skull base meningioma treated with a single-session GKRS and a minimum of 60 months follow-up. One hundred thirty-five patients, 54.1% males (n = 73), form the cohort. Median age was 54 years (19-80). Median tumor volume was 4.7 cm3 (0.5-23). Median margin dose was 15 Gy (7.5-36). Median follow-up was 102.5 months (60.1-235.4). Patient and tumor characteristics were assessed to determine the predictors of neurological function and tumor progression.

RESULTS: At last follow-up, tumor volume control was achieved in 88.1% (n = 119). Post- GKRS clinical improvement or stability was reported in 61.5%. The 5-, 10-, and 15-year actuarial progression-free survival rates were 100%, 95.4%, and 68.8%, respectively. Favorable outcome (both tumor control and clinical preservation/improvement) was attained in 60.8% (n = 79). Pre-GKRS performance status (Karnofsky Performance Scale) was shown to influence tumor progression (P = .001) and post-GKRS clinical improvement/preservation (P = .003).

CONCLUSION: GKRS offers a highly durable rate of tumor control for World Health Organization grade I skull base meningiomas, with an acceptably low incidence of neurological deficits. The Karnofsky Performance Scale at the time of radiosurgery serves as a reliable long-term predictor of overall outcome.

Radiation Therapy for Residual or Recurrent Atypical Meningioma

Radiation Therapy for Residual or Recurrent Atypical Meningioma

Neurosurgery 79:23–32, 2016

Optimal use of stereotactic radiosurgery (SRS) vs external beam radiation therapy (EBRT) for treatment of residual/recurrent atypical meningioma is unclear.

OBJECTIVE: To analyze features associated with progression after radiation therapy.

METHODS: Fifty radiation-naive patients who received SRS or EBRT for residual and/or recurrent atypical meningioma were examined for predictors of progression using Cox regression and Kaplan-Meier analyses.

RESULTS: Thirty-two patients (64%) received adjuvant radiation after subtotal resection, 12 patients (24%) received salvage radiation after progression following subtotal resection, and 6 patients (12%) received salvage radiation after recurrence following gross total resection. Twenty-one patients (42%) received SRS (median 18 Gy), and 7 (33%) had tumor progression. Twenty-nine patients (58%) received EBRT (median 54 Gy), and 13 (45%) had tumor progression. Whereas tumor volume (P = .53), SRS vs EBRT (P = .45), and adjuvant vs salvage (P = .34) were not associated with progression after radiation therapy, spontaneous necrosis (hazard ratio [HR] = 82.3, P < .001), embolization necrosis (HR = 15.6, P = .03), and brain invasion (HR = 3.8, P = .008) predicted progression in univariate and multivariate analyses. Tumors treated with SRS/EBRT had 2- and 5-year actuarial locoregional control rates of 91%/88% and 71%/69%, respectively. Tumors with spontaneous necrosis, embolization necrosis, and no necrosis had 2- and 5-year locoregional control rates of 76%, 92%, and 100% and 36%, 73%, and 100%, respectively (P < .001).

CONCLUSION: This study suggests that necrosis may be a negative predictor of radiation response regardless of radiation timing or modality.

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.

Pathological response of cavernous malformations following radiosurgery

Pathological response of cavernous malformations following radiosurgery

J Neurosurg 123:938–944, 2015

Stereotactic radiosurgery (SRS) is a therapeutic option for repeatedly hemorrhagic cavernous malformations (CMs) located in areas deemed to be high risk for resection. During the latency period of 2 or more years after SRS, recurrent hemorrhage remains a persistent risk until the obliterative process has finished. The pathological response to SRS has been studied in relatively few patients. The authors of the present study aimed to gain insight into the effect of SRS on CM and to propose possible mechanisms leading to recurrent hemorrhages following SRS.

Methods During a 13-year interval between 2001 and 2013, bleeding recurred in 9 patients with CMs that had been treated using Gamma Knife surgery at the authors’ institution. Microsurgical removal was subsequently performed in 5 of these patients, who had recurrent hemorrhages between 4 months and 7 years after SRS. Specimens from 4 patients were available for analysis and used for this report.

Results Histopathological analysis demonstrated that vascular sclerosis develops as early as 4 months after SRS. In the samples from 2 to 7 years after SRS, sclerotic vessels were prominent, but there were also vessels with incomplete sclerosis as well as some foci of neovascularization.

Conclusions: Recurrent bleeding after SRS for CM could be related to incomplete sclerosis of the vessels, but neovascularization may also play a role.

Stereotactic Radiosurgery for Intracranial Meningiomas: Current Concepts and Future Perspectives

Stereotactic Radiosurgery for Intracranial Meningiomas- Current Concepts and Future Perspectives

Neurosurgery 76:362–371, 2015

Meningiomas are among the most common adult brain tumors. Although the optimal management of meningiomas would provide complete elimination of the lesion, this cannot always be accomplished safely through resection. Therefore, other therapeutic modalities, such as stereotactic radiosurgery (as primary or adjunctive therapy), have emerged.

In the current review, we have provided an overview of the historical outcomes of various radiosurgical modalities applied in the management of meningiomas. Furthermore, we provide a discussion on key factors (eg World Health Organization grade, lesion size, and lesion location) that affect tumor control and adverse event rates. We discuss recent changes in our understanding of meningiomas, based on molecular and genetic markers, and how these will change our perspective on the management of meningiomas.

We conclude by outlining the areas in which knowledge gaps persist and provide suggestions as to how these can be addressed.

Factors Predicting Recurrence After Resection of Clival Chordoma

Clivus chordomas

Neurosurgery 76:179–186, 2015

Clival chordomas frequently recur because of their location and invasiveness.

OBJECTIVE: To investigate clinical, operative, and anatomic factors associated with clival chordoma recurrence.

METHODS: Retrospective review of clival chordomas treated at our center from 1993 to 2013.

RESULTS: Fifty patients (56% male) with median age of 59 years (range, 8-76) were newly diagnosed with clival chordoma of mean diameter 3.3 cm (range, 1.5-6.7). Symptoms included headaches (38%), diplopia (36%), and dysphagia (14%). Procedures included transsphenoidal (n = 34), transoral (n = 4), craniotomy (n = 5), and staged approaches (n = 7). Gross total resection (GTR) rate was 52%, with 83%mean volumetric reduction, values that improved over time.While the lower third of the clivus was the least likely superoinferior zone to contain tumor (upper third = 72%/middle third = 82%/lower third = 42%), it most frequently contained residual tumor (upper third = 33%/middle third = 38%/lower third = 63%; P , .05). Symptom improvement rates were 61% (diplopia) and 53% (headache). Postoperative radiation included proton beam (n = 19), cyberknife (n = 7), intensity-modulated radiation therapy (n = 6), external beam (n = 10), and none (n = 4). At last follow-up of 47 patients, 23 (49%) remain disease-free or have stable residual tumor. Lower third of clivus progressed most after GTR (upper/mid/lower third = 32%/ 41%/75%). In a multivariate Cox proportional hazards model, male gender (hazard ratio [HR] = 1.2/P = .03), subtotal resection (HR = 5.0/P = .02), and the preoperative presence of tumor in the middle third (HR = 1.2/P = .02) and lower third (HR = 1.8/P = .02) of the clivus increased further growth or regrowth, while radiation modality did not.

CONCLUSION: Our findings underscore long-standing support for GTR as reducing chordoma recurrence. The lower third of the clivus frequently harbored residual or recurrent tumor, despite staged approaches providing mediolateral (transcranial 1 endonasal) or superoinferior (endonasal 1 transoral) breadth. There was no benefit of proton-based over photonbased radiation, contradicting conventional presumptions.

Gamma Knife radiosurgery for meningiomas arising from the tentorium

Gamma Knife radiosurgery for meningiomas arising from the tentorium- a 22-year experienceJ Neurooncol (2015) 121:129–134

In order to evaluate long term clinical and imaging outcomes, the authors retrospectively reviewed our 22-year experience using stereotactic radiosurgery (SRS) for tentorial meningiomas.

Thirty-nine patients with tentorial meningiomas underwent SRS using various Gamma Knife technologies between 1988 and 2010. The most common presenting symptoms were headache, dizziness or disequilibrium, and ataxia. The median tumor volume was 4.6 cm3 (range 0.5–36.6 cm3) and the median radiation dose to the tumor margin was 14 Gy (range 8.9–18 Gy). The median follow-up period was 41 months (range 6–183 months).

At the last imaging follow-up, tumor volumes decreased in 22 patients (57 %), remained stable in 13 patients (33 %), and increased in 4 patients (10 %). The progression-free survival after SRS was 97 % at 1 year, and 92 % at 5 years. At the last clinical followup, 35 patients (90 %) showed no change in symptoms, 1 patient (2 %) showed improvement of their neurologic symptom, and 3 patients (8 %) demonstrated worsening symptoms. The rate of symptom worsening after SRS was 5 % at 1 year, and 10 % at 5 years. Asymptomatic peritumoral edema after SRS occurred in 2 patients (5 %). Symptomatic adverse radiation effect developed in 2 patients (5 %).

SRS for tentorial meningiomas provided long-term effective tumor control and a low risk of radiation related complications.

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.

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.

Using Higher Isodose Lines for Gamma Knife Treatment of 1 to 3 Brain Metastases Is Safe and Effective

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

Neurosurgery 74:360–366, 2014

Higher isodose lines (IDLs) in Gamma Knife (GK) Perfexion treatment of brain metastases (BMet) could result in lower local control (LC) or higher radiation necrosis (RN) rates, but reduce treatment time.

OBJECTIVE: To assess the impact of the heterogeneity index (HI) and conformality index (CFI) on local failure (LF) for patients treated with GK for 1 to 3 BMet.

METHODS: From an institutional review board—approved database, 320 patients with 496 BMet were identified, treated for 1 to 3 BMet from July 2007 to April 2011 on GK Perfexion. Cox proportional hazards regression was used to analyze significance of HI, CFI, IDL, dose, tumor diameter, recursive partitioning analysis class, tumor radioresistance, primary, smoking history, metastasis location, and whole-brain radiation therapy (WBRT) history with LF and RN.

RESULTS: Median follow-up by lesion was 6.8 months (range, 0-49.6). The series median survival was 14.2 months. Per RECIST, 9.5% of lesions failed, 33.9% were stable, 38.3% partially responded, 17.1% responded completely, and 1.2% could not be assessed. The 12-month LC rate was 87.3%. On univariate analysis, a dose less than 20 Gy (hazard ratio [HR]: 2.940, P , .001); tumor size (HR: 1.674, P , .001); and cerebellum/brainstem location vs other (HR: 1.891, P = .043) were significant for LF. Non-small cell lung cancer (HR: 0.333, P = .0097) was associated with better LC. On multivariate analysis, tumor size (HR: 1.696, P , .001) and cerebellum/brainstem location vs other (HR: 1.959, P = .033) remained significant for LF. Variables not significant for LF included CI, IDL, and HI.

CONCLUSION: Our study of patients with 1 to 3 BMet treated with GK demonstrated no difference in LC or RN with varying HI, indicating that physicians can treat to IDL at 70% or higher IDL to reduce treatment time without increased LF or RN.

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.

Solitary clival plasmocytomas

Solitary clival plasmocytomas

Acta Neurochir (2013) 155:1849–1856

Tumours of the clivus are exceptionally rare, representing a diagnostic and a therapeutic challenge. Clival solitary plasmocytomas have been described only as single case reports or included in small clinical series with other intracranial location.

Methods Authors report clinical, radiological, and survival data of four patients, who underwent surgery for clival plasmocytomas between 1989 and 2012 in a single centre. Current knowledge about solitary plasmocytomas of the clivus are reviewed.

Results Follow-up time was 54 months (range: 9–165). Mean age of patient was 57 years, no gender predilection was observed. Main symptoms were headache (75 %) and double vision (75 %), due to third or sixth cranial nerve palsy. Mean time to diagnosis was 8.2 months. All patients underwent surgery as primary treatment, through either a transsphenoidal (75 %) or a transmaxillary approach (25 %). In all cases adjuvant conventional radiotherapy was performed with a median delivered dose of 45 Gy. Only one case of progression into multiple myeloma was observed 13 months after surgery, and the patient died 9 months later. No other recurrences or progression were observed. Mean overall survival and progression free survival time were, respectively, 54 and 51.7 months.

Conclusions Although extremely rare, clival plasmocytomas have to be considered in the differential diagnosis of a solitary clival lesion. Biological and clinical features of these tumours strongly differ from those of similar lesions in other part of the body. Early diagnosis, extensive tumour removal, opportune indication of adjuvant treatment with radiotherapy and chemotherapy are the keys to manage these cases.

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.

Multisession Radiosurgery for Optic Nerve Sheath Meningiomas

Neurosurgery 69:1116–1123, 2011 DOI: 10.1227/NEU.0b013e31822932fe
Traditional treatment options for optic nerve sheath meningiomas (ONSMs) include observation, surgery, and radiotherapy, but to date none of these has become the clear treatment of choice.
OBJECTIVE: To evaluate the effectiveness and safety of multisession radiosurgery for ONSMs.
METHODS: From May 2004 to June 2008, 21 patients with ONSMs were treated by radiosurgery using the frameless CyberKnife system. Patient age ranged from 36 to 73 years (mean, 54 years). All patients were treated using multisession radiosurgery, with 5 fractions of 5 Gy each to a total dose of 25 Gy prescribed to the 75% to 85% isodose line. Patients were evaluated for tumor growth control and visual function.
RESULTS: The median pretreatment tumor volume was 2.8 mL (range, 0.3-23 mL). The mean follow-up was 30 months (range, 11-68 months). All patients tolerated treatment well, with only 1 patient in whom a mild optic neuropathy developed (which remitted after systemic steroid therapy). No other acute or late radiation-induced toxicities were observed. No patients showed ONSM progression on follow-up magnetic resonance imaging. Two patients (10%) had a partial response. No patients had worsening of visual function; visual function was stable in 65% and improved in 35% of patients.
CONCLUSION: Multisession radiosurgery for ONSMs was found to be safe and effective. The preliminary results from this study, in terms of growth control, visual function improvement, and toxicity, are quite promising. Further investigations are warranted.

Management of large vestibular schwannoma. Part II. Primary Gamma Knife surgery: radiological and clinical aspects

J Neurosurg 115:885–893, 2011.DOI: 10.3171/2011.6.JNS101963

In large vestibular schwannomas (VSs), microsurgery is the main treatment option. A wait-and-scan policy or radiosurgery are generally not recommended given concerns of further lesion growth or increased mass effect due to transient swelling. Note, however, that some patients do not present with symptomatic mass effect or may still have serviceable hearing. Moreover, others may be old, suffer from severe comorbidity, or refuse any surgery. In this study the authors report the results in patients with large, growing VSs primarily treated with Gamma Knife surgery (GKS), with special attention to volumetric growth, control rate, and symptoms.

Methods. The authors retrospectively analyzed 33 consecutive patients who underwent GKS for large, growing VSs, which were defined as > 6 cm3 and at least indenting the brainstem. Patients with neurofibromatosis Type 2 were excluded from analysis, as were patients who had undergone previous treatment. Volume measurements were performed on contrast-enhanced T1-weighted MR images at the time of GKS and during follow-up. Medical charts were analyzed for clinical symptoms.

Results. Radiological growth control was achieved in 88% of cases, clinical control (that is, no need for further treatment) in 79% of cases. The median follow-up was 30 months, and the mean VS volume was 8.8 cm3 (range 6.1–17.7 cm3). No major complications occurred, although ventriculoperitoneal shunts were placed in 2 patients. The preservation of serviceable hearing and facial and trigeminal nerve function was achieved in 58%, 91%, and 86% of patients, respectively, with any facial and trigeminal neuropathy being transient. In 92% of the patients presenting with trigeminal hypesthesia before GKS, the condition resolved during follow-up. No patient- or VS-related feature was correlated with growth.

Conclusions. Primary GKS for large VSs leads to acceptable radiological growth rates and clinical control rates, with the chance of hearing preservation. Although a higher incidence of clinical control failure and postradiosurgical morbidity is noted, as compared with that for smaller VSs, primary radiosurgery is suitable for a selected group of patients. The absence of symptomatology due to mass effect on the brainstem or cerebellum is essential, as are close clinical and radiological follow-ups, because there is little reserve for growth or swelling.

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

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