Association Between Pseudoprogression of Vestibular Schwannoma After Radiosurgery and Radiological Features of Solid and Cystic Components

Neurosurgery 93:1383–1392, 2023

The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic resonance images may help predict VS pseudoprogression. This study used VS radiological features quantified using an automated segmentation algorithm to predict pseudoprogression after GKRS treatment.

METHODS: This is a retrospective study comprising 330 patients with VS who received GKRS. After image preprocessing and T2W/contrast-enhanced T1-weighted image (CET1W) image generation, with fuzzy C-means clustering, VSs were segmented into solid and cystic components and classified as solid and cystic. Relevant radiological features were then extracted. The response to GKRS was classified into “nonpseudoprogression” and “pseudoprogression/fluctuation”. The Z test for two proportions was used to compare solid and cystic VS for the likelihood of pseudoprogression/fluctuation. Logistic regression was used to assess the correlation between clinical variables and radiological features and response to GKRS.

RESULTS: The likelihood of pseudoprogression/fluctuation after GKRS was significantly higher for solid VS compared with cystic VS (55% vs 31%, P < .001). For the entire VS cohort, multivariable logistic regression revealed that a lower mean tumor signal intensity (SI) in T2W/CET1W images was associated with pseudoprogression/fluctuation after GKRS (P = .001). For the solid VS subgroup, a lower mean tumor SI in T2W/CET1W images (P = .035) was associated with pseudoprogression/fluctuation after GKRS. For the cystic VS subgroup, a lower mean SI of the cystic component in T2W/ CET1W images (P = .040) was associated with pseudoprogression/fluctuation after GKRS.

CONCLUSION: Pseudoprogression is more likely to occur in solid VS compared with cystic VS. Quantitative radiological features in pretreatment magnetic resonance images were associated with pseudoprogression after GKRS. In T2W/ CET1W images, solid VS with a lower mean tumor SI and cystic VS with a lower mean SI of cystic component were more likely to have pseudoprogression after GKRS. These radiological features can help predict the likelihood of pseudoprogression after GKRS.

Vestibular Schwannoma Stereotactic Radiosurgery in Octogenarians

Neurosurgery 93:1099–1105, 2023

The management of octogenarians with vestibular schwannomas (VS) has received little attention. However, with the increase in octogenarian population, more effort is needed to clarify the value of stereotactic radiosurgery (SRS) in this population. The aim of this study was to evaluate the safety and efficacy of SRS in this patient age group.

METHODS: A retrospective study of 62 patients aged 80 years or older who underwent single-session SRS for symptomatic VS during a 35-year interval was performed. The median patient age was 82 years, and 61.3% were male. SRS was performed as planned adjuvant management or for delayed progression after prior partial resection in 5 patients.

RESULTS: SRS resulted in a 5-year tumor control rate of 95.6% with a 4.8% risk of adverse radiation effects (ARE). Tumor control was unrelated to patient age, tumor volume, Koos grade, sex, SRS margin dose, or prior surgical management. Four patients underwent additional management including 1 patient with symptomatic progression requiring surgical resection, 2 patients with symptomatic hydrocephalus requiring cerebrospinal fluid diversion, and 1 patient whose tumor-related cyst required delayed cyst aspiration. Three patients developed ARE, including 1 patient with permanent facial weakness (House-Brackmann grade II), 1 who developed trigeminal neuropathy, and 1 who had worsening gait disorder. Six patients had serviceable hearing preservation before SRS, and 2 maintained serviceable hearing preservation after 4 years. A total of 44 (71%) patients died at an interval ranging from 6 to 244 months after SRS.

CONCLUSION: SRS resulted in tumor and symptom control in most octogenarian patients with VS.

Formation of internal carotid artery aneurysms following gamma knife radiosurgery for pituitary adenomas

Acta Neurochirurgica (2023) 165:2257–2265

Only two aneurysm formations in the internal carotid artery after gamma knife radiosurgery (GKRS) for pituitary adenomas are reported so far.

Here, out of the 482 patients who underwent GKRS for pituitary adenomas at our institute, at least five developed aneurysms within the area of high single-dose irradiation. Three patients presented with epistaxis due to aneurysmal rupture and one presented with abducens paralysis due to nerve compression, while one was asymptomatic.

The interval between irradiation and aneurysmal detection ranged from 14 to 21 years. Aneurysm formation in those conditions may be higher than previously thought.

The longitudinal volumetric response of vestibular schwannomas after Gamma Knife radiosurgery

J Neurosurg 138:1273–1280, 2023

Gamma Knife radiosurgery (GKRS) is an effective treatment for vestibular schwannomas (VSs) and has been used in > 100,000 cases worldwide. In the present study the authors sought to define the serial volumetric tumor response of Koos grade I–IV VS after radiosurgery.

METHODS A total of 201 consecutive VS patients underwent GKRS at a single institution between 2015 and 2019. All patients had a minimum follow-up of 18 months and at least 2 interval postprocedure MRI scans. The contrast-enhanced tumor volumes were contoured manually and compared between pre- and post-GKRS imaging. The percentages of tumor volume change at 18 months (short-term follow-up) and up to 5 years after GKRS (long-term follow-up) were compared with the baseline tumor volume. An increase of 20% was considered a significant increase of tumor volume. Trends of tumor volume over time were assessed with linear models using time as a continuous variable. A test for linear trend was evaluated according to the initial Koos tumor classification.

RESULTS Koos grade II VS was the most frequently occurring tumor (n = 74, 36.8%), followed by grade III (n = 57, 28.4%), grade I (n = 41, 20.4%), and grade IV (n = 29, 14.4%). The mean tumor volume at the time of GKRS was 2.12 ±2.82 cm 3 (range 0.12–18.77 cm 3 ) and the median margin dose was 12 Gy. Short-term follow-up revealed that tumor volumes transiently increased in 34.2% and 28.4% of patients at 6 and 18 months, respectively, regardless of Koos grade. Linear regression analysis of Koos grade II, III, and IV tumors showed a significant longitudinal volume decrease on long-term follow-up. At last follow-up (median 30 months, range 18–54 months), 19 patients (9.4%) showed a persistent increase of tumor volume. Five patients received additional management after GKRS.

CONCLUSIONS Although selected VS patients demonstrate an early and measurable transient volumetric increase after GKRS, > 90% have stable or reduced tumor volumes over an observed period of up to 5 years. Volumetric regression is most pronounced in Koos grade II, III, and IV tumors and may not be fully detectable until 3 years after GKRS.

Results of three or more Gamma Knife radiosurgery procedures for recurrent trigeminal neuralgia

J Neurosurg 135:1789–1798, 2021

Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN.

METHODS The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III).

RESULTS A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up.

CONCLUSIONS The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of longterm pain relief, recurrence, and adverse effects.


Efficacy and safety of gamma knife radiosurgery for posterior cranial fossa meningioma

Neurosurgical Review (2020) 43:1089–1099

The management of posterior cranial fossa meningioma [PCFM] is challenging and many neurosurgeons advise gamma knife radiosurgery [GKRS] as a modality for its upfront or adjuvant treatment. Due to the varying radiosurgical response based on lesion location, tumor biology, and radiation dosage, we performed a pioneer attempt in doing a systematic review analyzing the treatment efficacy and safety profile of GKRS for PCFM based on current literature.

A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines. A thorough literature search was conducted on PubMed, Web of science, and Cochrane data base; articles were selected systematically based on PRISMA protocol, reviewed completely, and relevant data was summarized and discussed.

A total of 18 publications pertaining to GKRS for PCFM were included with a pooled sample size of 2131 patients. The median pre-GKRS tumor volume ranged from 2.28 to 10.5 cm [3]. Primary GKRS was administered in 61.1% of the pooled study cohorts, adjuvant treatment in 32.9%, and salvage therapy in 6.5% patients. Majority of the meningiomas were WHO grade 1 tumors (99.7%). The pooled mean marginal dose in the studies was 13.6 Gy (range 12–15.2 Gy) while the mean of maximum doses was 28.6 Gy (range 25–35 Gy). Most studies report an excellent radiosurgical outcome including the tumor control rate and the progression-free survival [PFS] of over 90%. The tumor control, PFS, and adverse radiation effect [ARE] rates in author’s series were 92.3%, 91%, and 9.6%, respectively. The favorable radiosurgical outcome depends on multiple factors such as small tumor volume, absence of previous radiotherapy, tumor location, elderly patients, female gender, longer time from symptom onset, and decreasing maximal dose.

GKRS as primary or adjuvant treatment modality needs to be considered as a promising management strategy for PCFM in selected patients in view of the growing evidence of high tumor control rate, improved neurological functions, and low incidence of ARE. The use of multiple isocenters, 3-D image planning, and limit GKRS treatment to tumors less than 3.5 cm help to avoid complications and achieve the best results. The treatment decisions in PCFM cases must be tailored and should consider the factors such as radiological profile, symptom severity, performance level, and patient preference for a good outcome.

Treatment Outcomes and Dose Rate Effects Following Gamma Knife Stereotactic Radiosurgery for Vestibular Schwannomas

Neurosurgery 85:E1084–E1094, 2019

Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored.

OBJECTIVE: To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas.

METHODS: We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression.

RESULTS: The study cohort included 227 patientswith available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rateswere 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044).

CONCLUSION:Whereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effectsmay impact post-treatment functional outcomes. Further research remains warranted.

Early postsurgical diffusivity metrics for prognostication of long-term pain relief after Gamma Knife radiosurgery for trigeminal neuralgia

J Neurosurg 131:539–548, 2019

Gamma Knife radiosurgery (GKRS) is an important treatment modality for trigeminal neuralgia (TN). Current longitudinal assessment after GKRS relies primarily on clinical diagnostic measures, which are highly limited in the prediction of long-term clinical benefit. An objective, noninvasive, predictive tool would be of great utility to advance the clinical management of patients. Using diffusion tensor imaging (DTI), the authors’ aim was to determine whether early (6 months post-GKRS) target diffusivity metrics can be used to prognosticate long-term pain relief in patients with TN.

METHODS Thirty-seven patients with TN treated with GKRS underwent 3T MRI scans at 6 months posttreatment. Diffusivity metrics of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were extracted bilaterally from the radiosurgical target of the affected trigeminal nerve and its contralateral, unaffected nerve. Early (6 months post-GKRS) diffusivity metrics were compared with long-term clinical outcome. Patients were identified as long-term responders if they achieved at least 75% reduction in preoperative pain for 12 months or longer following GKRS.

RESULTS Trigeminal nerve diffusivity at 6 months post-GKRS was predictive of long-term clinical effectiveness, where long-term responders (n = 19) showed significantly lower fractional anisotropy at the radiosurgical target of their affected nerve compared to their contralateral, unaffected nerve and to nonresponders. Radial diffusivity and mean diffusivity, correlates of myelin alterations and inflammation, were also significantly higher in the affected nerve of long-term responders compared to their unaffected nerve. Nonresponders (n = 18) did not exhibit any characteristic diffusivity changes after GKRS.

CONCLUSIONS The authors demonstrate that early postsurgical target diffusivity metrics have a translational, clinical value and permit prediction of long-term pain relief in patients with TN treated with GKRS. Importantly, an association was found between the footprint of radiation and clinical effectiveness, where a sufficient level of microstructural change at the radiosurgical target is necessary for long-lasting pain relief. DTI can provide prognostic information that supplements clinical measures, and thus may better guide the postoperative assessment and clinical decision-making for patients with TN.

Results of Gamma Knife anterior capsulotomy for refractory obsessive-compulsive disorder

J Neurosurg 131:376–383, 2019

Obsessive-compulsive disorder (OCD) is a severe psychiatric condition. The authors present their experience with Gamma Knife radiosurgery (GKRS) in the treatment of patients with OCD resistant to any medical therapy.

METHODS Patients with severe OCD resistant to all pharmacological and psychiatric treatments who were treated with anterior GKRS capsulotomy were retrospectively reviewed. These patients were submitted to a physical, neurological, and neuropsychological examination together with structural and functional MRI before and after GKRS treatment. Strict study inclusion criteria were applied. Radiosurgical capsulotomy was performed using two 4-mm isocenters targeted at the midputaminal point of the anterior limb of the capsule. A maximal dose of 120 Gy was prescribed for each side. Clini- cal global changes were assessed using the Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) scale, EQ-5D, Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAI). OCD symptoms were determined by the Yale–Brown Obsessive Compulsive Scale (Y-BOCS).

RESULTS Ten patients with medically refractory OCD (5 women and 5 men) treated between 2006 and 2015 were included in this study. Median age at diagnosis was 22 years, median duration of illness at the time of radiosurgery was 14.5 years, and median age at treatment was 38.8 years. Before GKRS, the median Y-BOCS score was 34.5 with a me- dian obsession score of 18 and compulsion score of 17. Seven (70%) of 10 patients achieved a full response at their last follow-up, 2 patients were nonresponders, and 1 patient was a partial responder. Evaluation of the Y-BOCS, BDI, STAI- Trait, STAI-State, GAF, and EQ-5D showed statistically significant improvement at the last follow-up after GKRS. Neurological examinations were normal in all patients at each visit. At last follow-up, none of the patients had experienced any significant adverse neuropsychological effects or personality changes.

CONCLUSIONS GKRS anterior capsulotomy is effective and well tolerated with a maximal dose of 120 Gy. It reduces both obsessions and compulsions, improves quality of life, and diminishes depression and anxiety.

Volumetric changes and clinical outcome for petroclival meningiomas after primary treatment with Gamma Knife radiosurgery

J Neurosurg 129:1623–1629, 2018

Petroclival meningiomas (PCMs) can cause devastating clinical symptoms due to mass effect on cranial nerves (CNs); thus, patients harboring these tumors need treatment. Many neurosurgeons advocate for microsurgery because removal of the tumor can provide relief or result in symptom disappearance. Gamma Knife radiosurgery (GKRS) is often an alternative for surgery because it can cause tumor shrinkage with improvement of symptoms. This study evaluates qualitative volumetric changes of PCM after primary GKRS and its impact on clinical symptoms.

METHODS The authors performed a retrospective study of patients with PCM who underwent primary GKRS between 2003 and 2015 at the Gamma Knife Center of the Elisabeth-Tweesteden Hospital in Tilburg, the Netherlands. This study yields 53 patients. In this study the authors concentrate on qualitative volumetric tumor changes, local tumor control rate, and the effect of the treatment on trigeminal neuralgia (TN).

RESULTS Local tumor control was 98% at 5 years and 93% at 7 years (Kaplan-Meier estimates). More than 90% of the tumors showed regression in volume during the first 5 years. The mean volumetric tumor decrease was 21.2%, 27.1%, and 31% at 1, 3, and 6 years of follow-up, respectively. Improvement in TN was achieved in 61%, 67%, and 70% of the cases at 1, 2, and 3 years of follow-up, respectively. This was associated with a mean volumetric tumor decrease of 25% at the 1-year follow-up to 32% at the 3-year follow-up.

CONCLUSIONS GKRS for PCMs yields a high tumor control rate with a low incidence of neurological deficits. Many patients with TN due to PCM experienced improvement in TN after radiosurgery. GKRS achieves significant volumetric tumor decrease in the first years of follow-up and thereafter.


Long-Term Outcome Following Stereotactic Radiosurgery for Glomus Jugulare Tumors

Neurosurgery 83:1007–1014, 2018

Glomus jugulare tumors (GJTs) are rare benign tumors, which pose significant treatment challenges due to proximity to critical structures.

OBJECTIVE: To evaluate the long-term clinical and radiological outcomein patients undergoing stereotactic radiosurgery (SRS) for GJTs through retrospective study.

METHODS: Forty-two patientswith 43 GJTswere treated using Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) at our institute from 1997 to 2016. Clinical, imaging, and radiosurgery data were collected from an institutional review board approved database.

RESULTS: Most patients were females (n = 35, 83.3%) and median age was 61 yr (range 23- 88 yr).Median tumor volume and diameterwere 5 cc and 3 cm, respectively,with a median follow-up of 62.3 mo (3.4-218.6 mo). Overall, 20 patients (47.6%) improved clinically and 14 (33.3%) remained unchanged at last follow-up. New onset or worsening of hearing loss was noted in 6 patients (17.2%) after SRS. The median prescription dose to the tumor margin was 15 Gy (12-18 Gy). Median reduction in tumor volume and maximum tumor diameter at last follow-up was 33.3% and 11.54%, respectively. The 5-yr and 10-yr tumor control rates were 87%±6% and 69%±13%, respectively. There was no correlation between maximum or mean dose to the internal acoustic canal and post-GK hearing loss (P > .05).

CONCLUSION: SRS is safe and effective in patients with GJTs and results in durable, longterm control. SRS has lower morbidity than that associated with surgical resection, particularly lower cranial nerve dysfunction, and can be a first-line management option in these patients.

Outcomes of stereotactic radiosurgery for foramen magnum meningiomas: an international multicenter study

J Neurosurg 129:383–389, 2018

Meningiomas are the most common benign extramedullary lesions of the foramen magnum; however, their optimal management remains undefined. Given their location, foramen magnum meningiomas (FMMs) can cause significant morbidity, and complete microsurgical removal can be challenging. Anterior and anterolateral FMMs carry greater risks with surgery, but they comprise the majority of these lesions. As an alternative to resection, stereotactic radiosurgery (SRS) has been used to treat FMMs in small case series. To more clearly define the outcomes of SRS and to delineate a rational management paradigm for these lesions, the authors analyzed the safety and efficacy of SRS for FMM in an international multicenter trial.

METHODS Seven medical centers participating in the International Gamma Knife Research Foundation (IGKRF) provided data for this retrospective cohort study. Patients who were treated with Gamma Knife radiosurgery and whose clinical and radiological follow-up was longer than 6 months were eligible for study inclusion. Data from pre- and post- SRS radiological and clinical evaluations were analyzed. Stereotactic radiosurgery treatment variables were recorded.

RESULTS Fifty-seven patients (39 females and 18 males, with a median age of 64 years) met the study inclusion criteria. Thirty-two percent had undergone prior microsurgical resection. Patients most frequently presented with cranial neuropathy (39%), headache (35%), numbness (32%), and ataxia (30%). Median pre-SRS tumor volume was 2.9 cm3. Median SRS margin dose was 12.5 Gy (range 10–16 Gy). At the last follow-up after SRS, 49% of tumors were stable, 44% had regressed, and 7% had progressed. Progression-free survival rates at 5 and 10 years were each 92%. A greater margin dose was associated with a significantly increased likelihood of tumor regression, with 53% of tumors treated with > 12 Gy regressing. Fifty-two percent of symptomatic patients noted some clinical improvement. Adverse radiation effects were limited to hearing loss and numbness in 1 patient (2%).

CONCLUSIONS Stereotactic radiosurgery for FMM frequently results in tumor control or tumor regression, as well as symptom improvement. Margin doses > 12 Gy were associated with increased rates of tumor regression. Stereotactic radiosurgery was generally safe and well tolerated. Given its risk-benefit profile, SRS may be particularly useful in the management of small- to moderate-volume anterior and anterolateral FMMs.


Magnetic resonance imaging characteristics and the prediction of outcome of vestibular schwannomas following Gamma Knife radiosurgery

J Neurosurg 127:1384–1391, 2017

Gamma Knife surgery (GKS) is a promising treatment modality for patients with vestibular schwannomas (VSs), but a small percentage of patients have persistent postradiosurgical tumor growth. The aim of this study was to determine the clinical and quantitative MRI features of VS as predictors of long-term tumor control after GKS.

METHODS The authors performed a retrospective study of all patients with VS treated with GKS using the Leksell Gamma Knife Unit between 2005 and 2013 at their institution. A total of 187 patients who had a minimum of 24 months of clinical and radiological assessment after radiosurgery were included in this study. Those who underwent a craniotomy with tumor removal before and after GKS were excluded. Study patients comprised 85 (45.5%) males and 102 (54.5%) females, with a median age of 52.2 years (range 20.4–82.3 years). Tumor volumes, enhancing patterns, and apparent diffusion coefficient (ADC) values were measured by region of interest (ROI) analysis of the whole tumor by serial MRI before and after GKS.

RESULTS The median follow-up period was 60.8 months (range 24–128.9 months), and the median treated tumor volume was 3.54 cm3 (0.1–16.2 cm3). At last follow-up, imaging studies indicated that 150 tumors (80.2%) showed decreased tumor volume, 20 (10.7%) had stabilized, and 17 (9.1%) continued to grow following radiosurgery. The postradiosurgical outcome was not significantly correlated with pretreatment volumes or postradiosurgical enhancing patterns. Tumors that showed regression within the initial 12 months following radiosurgery were more likely to have a larger volume reduction ratio at last follow-up than those that did not (volume reduction ratio 55% vs 23.6%, respectively; p < 0.001). Compared with solid VSs, cystic VSs were more likely to regress or stabilize in the initial postradiosurgical 6–12-month period and during extended follow-up. Cystic VSs exhibited a greater volume reduction ratio at last follow-up (cystic vs solid: 67.6% ± 24.1% vs 31.8% ± 51.9%; p < 0.001). The mean preradiosurgical maximum ADC (ADCmax) values of all VSs were significantly higher for those with tumor regression or stabilization at last follow-up compared with those with progression (2.391 vs 1.826 × 10-3 mm2/sec; p = 0.010).

CONCLUSIONS Loss of central enhancement after radiosurgery was a common phenomenon, but it did not correlate with tumor volume outcome. Preradiosurgical MRI features including cystic components and ADCmax values can be helpful as predictors of treatment outcome.

Control of vestibular schwannomas treated with Gamma Knife


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.

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.

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.

Computational Fractal-Based Analysis of Brain Arteriovenous Malformation Angioarchitecture

Computational Fractal-Based Analysis of Brain Arteriovenous Malformation Angioarchitecture

Neurosurgery 75:72–79, 2014

Neuroimaging is the gold standard for diagnosis and follow-up of brain arteriovenous malformations (bAVMs), but no objective parameter has been validated for the assessment of the nidus angioarchitecture and for prognostication following treatment. The fractal dimension (FD), which is a mathematical parameter able to quantify the space-filling properties and roughness of natural objects, may be useful in quantifying the geometrical complexity of bAVMs nidus.

OBJECTIVE: To propose FD as a neuroimaging biomarker of the nidus angioarchitecture, which might be related to radiosurgical outcome.

METHODS: We retrospectively analyzed 54 patients who had undergone stereotactic radiosurgery for the treatment of bAVMs. The quantification of the geometric complexity of the vessels forming the nidus, imaged in magnetic resonance imaging, was assessed by means of the box-counting method to obtain the fractal dimension.

RESULTS: FD was found to be significantly associated with the size (P = .03) and volume (P , .001) of the nidus, in addition to several angioarchitectural parameters. A nonsignificant association between clinical outcome and FD was observed (area under the curve, 0.637 [95% confidence interval, 0.49-0.79]), indicative of a potential inverse relationship between FD and bAVM obliteration.

CONCLUSION: In our exploratory methodological research, we showed that the FD is an objective computer-aided parameter for quantifying the geometrical complexity and roughness of the bAVM nidus. The results suggest that more complex bAVM angioarchitecture, having higher FD values, might be related to decreased response to radiosurgery and that the FD of the bAVM nidus could be used as a morphometric neuroimaging biomarker.

Vestibular Schwannoma: Surgery or Gamma-Knife radiosurgery?. A prospective, non-randomized study

Neurosurgery 64:654–663, 2009 DOI: 10.1227/01.NEU.0000340684.60443.55

OBJECTIVE: To conduct a prospective, open, nonrandomized study of treatment- associated morbidity in patients undergoing microsurgery or gamma knife radiosurgery (GKRS) for vestibular schwannomas.

METHODS: Ninety- one patients with vestibular schwannomas with a maximum tumor diameter of 25 mm in the cerebellopontine angle were treated according to a prospective protocol either by GKRS (63 patients) or open microsurgery (28 patients) using the suboccipital approach. Primary end points included hearing function, according to the Gardner- Robertson scale, and facial nerve function, according to the House- Brackmann scale at 2 years. Clinical data included a balance platform test, score for tinnitus and vertigo using a visual analog scale, and working ability. Patients responded to the qualityof- life questionnaires Short- Form 36 and Glasgow Benefit Inventory.

RESULTS: Three elderly GKRS patients withdrew; all remaining patients were followed for 2 years. Both primary end points were highly significant in favor of GKRS (P<0.001). Evidence of reduced facial nerve function (House- Brackmann grade 2 or poorer) at 2 years was found in 13 of 28 open microsurgery patients and 1 of 60 GKRS patients. Thirteen of 28 patients who underwent surgery had serviceable hearing (Gardner- Robertson grade A or B) preoperatively, but none had serviceable hearing postoperatively. Twentyfive of 60 GKRS patients had serviceable hearing before treatment, and 17 (68%) of them had serviceable hearing 2 years after treatment. The tinnitus and vertigo visual analog scale score, as well as balance platform tests, did not change significantly after treatment, and working status did not differ between the groups at 2 years. Quality of life was significantly better in the GKRS group at 2 years, based on the Glasgow Benefit Inventory questionnaire. One GKRS patient required operative treatment within the 2-year study period.

CONCLUSION: This is the second prospective study to demonstrate better facial nerve and hearing outcomes from GKRS than from open surgery for small- and medium- sized vestibular schwannomas.

Gamma knife radiosurgery for the treatment of glomus jugulare tumors

Journal of Neuro-Oncology. doi:10.1007/s11060-009-0002-6

The treatment of glomus jugulare tumors represents a challenge for the neurosurgeon, since they invade major vessels and compress critical cranial nerves, resulting in significant morbidity from tumor resection. Among alternative and complementary treatment options, gamma knife radiosurgery is a less invasive procedure and may provide better protection of vital structures. This study aimed to evaluate the efficacy and long-term outcomes of gamma knife surgery in the treatment of these tumors in a large series with the longest follow-up period compared with previous reports. A total of 18 patients with glomus jugulare tumors that underwent gamma knife radiosurgery (GKS) were included. Eleven patients had a history of previous microsurgical treatment. The mean marginal radiation dose was 15.6 Gy (median 15 Gy, range 13–20 Gy). Patients were followed for a mean period of 52.7 months (median 41.5 months); the effect of gamma knife radiosurgery was evaluated using magnetic resonance (MR) images. Based on the last MR images, tumor control could be achieved in 17 out of 18 patients (94.4%). No complications such as radiation-induced peritumoral edema or radiation necrosis occurred. Neurological follow-up examinations revealed improved clinical status in ten patients (55.6%), stable neurological status in seven (38.9%), and deterioration in one patient (5.5%). At the last visit, 17 out of 18 patients were alive. Our results indicate that stereotactic radiosurgery is an effective and safe treatment modality in the management of glomus jugulare tumors, particularly for residual or previously untreated small tumors.