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.

Gamma Knife Stereotactic Radiosurgery for Trigeminal Neuralgia Secondary to Multiple Sclerosis

Neurosurgery 93:453–461, 2023

The efficacy of stereotactic radiosurgery (SRS) for the relief of trigeminal neuralgia (TN) is well established. Much less is known, however, about the benefit of SRS for multiple sclerosis (MS)–related TN (MS-TN). OBJECTIVE: To compare outcomes in patients who underwent SRS for MS-TN vs classical/idiopathic TN and identify relative risk factors for failure.

METHODS: We conducted a retrospective, case-control study of patients who underwent Gamma Knife radiosurgery at our center for MS-TN between October 2004 and November 2017. Cases were matched 1:1 to controls using a propensity score predicting MS probability using pretreatment variables. The final cohort consisted of 154 patients (77 cases and 77 controls). Baseline demographics, pain characteristics, and MRI features were collected before treatment. Pain evolution and complications were obtained at follow-up. Outcomes were analyzed using the Kaplan-Meir estimator and Cox regressions.

RESULTS: There was no statistically significant difference between both groups with regards to initial pain relief (modified Barrow National Institute IIIa or less), which was achieved in 77% of patients with MS and 69% of controls. In responders, 78% of patients with MS and 52% of controls eventually had recurrence. Pain recurred earlier in patients with MS (29 months) than in controls (75 months). Complications were similarly distributed in each group and consisted, in the MS group, of 3% of new bothersome facial hypoesthesia and 1% of new dysesthesia.

CONCLUSION: SRS is a safe and effective modality to achieve pain freedom in MS-TN. However, pain relief is significantly less durable than in matched controls without MS.

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.

Gamma Knife Central Lateral Thalamotomy for Chronic Neuropathic Pain

Neurosurgery 92:363–369, 2023

Chronic neuropathic pain can be severely disabling and is difficult to treat. The medial thalamus is believed to be involved in the processing of the affectivemotivational dimension of pain, and lesioning of the medial thalamus has been used as a potential treatment for neuropathic pain. Within the medial thalamus, the central lateral nucleus has been considered as a target for stereotactic lesioning.

OBJECTIVE: To study the safety and efficacy of central lateral thalamotomy using Gamma Knife radiosurgery (GKRS) for the treatment of neuropathic pain.

METHODS: We retrospectively reviewed all patients with neuropathic pain who underwent central lateral thalamotomy using GKRS. We report on patient outcomes, including changes in pain scores using the Numeric Pain Rating Scale and Barrow Neurological Institute pain intensity score, and adverse events.

RESULTS: Twenty-one patients underwent central lateral thalamotomy using GKRS between 2014 and 2021. Meaningful pain reduction occurred in 12 patients (57%) after a median period of 3 months and persisted in 7 patients (33%) at the last follow-up (the median follow-up was 28 months). Rates of pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared with all other patients (P = .009). No patient had treatment-related adverse events.

CONCLUSION: Central lateral thalamotomy using GKRS is remarkably safe. Pain reduction after this procedure occurs in a subset of patients and is more frequent in those with trigeminal deafferentation pain; however, pain recurs frequently over time.


Stereotactic radiosurgery for Koos grade IV vestibular schwannoma in patients ≥ 65 years old

Acta Neurochirurgica (2023) 165:211–220

Surgery is the preferred treatment for large vestibular schwannomas (VS). Good tumor control and cranial nerve outcomes were described in selected Koos IV VS after single-session stereotactic radiosurgery (SRS), but outcomes in elderly patients have never been specifically studied. The aim of this study is to report clinical and radiological outcomes after single-session SRS for Koos IV VS in patients ≥ 65 years old.

Method This multicenter, retrospective study included patients ≥ 65 years old, treated with primary, single-session SRS for a Koos IV VS, and at least 12 months of follow-up. Patients with life-threatening or incapacitating symptoms were excluded. Tumor control rate, hearing, trigeminal, and facial nerve function were studied at last follow-up.

Results One-hundred and fifty patients (median age of 71.0 (IQR 9.0) years old with a median tumor volume of 8.3 cc (IQR 4.4)) were included. The median prescription dose was 12.0 Gy (IQR 1.4). The local tumor control rate was 96.0% and 86.2% at 5 and 10 years, respectively. Early tumor expansion occurred in 6.7% and was symptomatic in 40% of cases. A serviceable hearing was present in 16.1% prior to SRS and in 7.4% at a last follow-up of 46.5 months (IQR 55.8). The actuarial serviceable hearing preservation rate was 69.3% and 50.9% at 5 and 10 years, respectively. Facial nerve function preservation or improvement rates at 5 and 10 years were 98.7% and 91.0%, respectively. At last follow-up, the trigeminal nerve function was improved in 14.0%, stable in 80.7%, and worsened in 5.3% of the patients. ARE were noted in 12.7%. New hydrocephalus was seen in 8.0% of patients.

Conclusion SRS can be a safe alternative to surgery for selected Koos IV VS in patients ≥ 65 years old. Further follow-up is warranted.

Risk for Hemorrhage the First 2 Years After Gamma Knife Surgery for Arteriovenous Malformations: An Update

Neurosurgery 91:920–927, 2022

Knowledge about the natural course of brain arteriovenous malformations (AVMs) have increased during the past 20 years, as has the number of AVMs treated, especially larger ones. It is thus timely to again analyze the risk for hemorrhage after Gamma Knife Surgery (GKS).

OBJECTIVE: To confirm or contradict conclusions drawn 20 years ago regarding factors that affect the risk for post-GKS hemorrhage.

METHODS: The outcome after GKS was studied in 5037 AVM patients followed for up to 2 years. The relation between post-treatment hemorrhage rate and a number of patient, AVM, and treatment parameters was analyzed. The results were also compared with the results from our earlier study.

RESULTS: The annual post-treatment hemorrhage rate was 2.4% the first 2 years after GKS. Large size, low treatment dose, and old age were independent risk factors for AVM hemorrhage. After having compensated for the factors above, peripheral AVM location and female sex, at least during their child bearing ages, were factors associated with a lower post-GKS hemorrhage rate.

CONCLUSION: Large AVMs (>5 cm3) treated with low doses (≤16 Gy) had higher and small AVMs treated with high doses a lower risk for hemorrhage as compared with untreated AVMs. This was detectable within the first 6 months after GKS. No difference in hemorrhage rate could be detected for the other AVMs. Based on our findings, it is advisable to prescribe >16 Gy to larger AVMs, assuming that the risk for radiation-induced complications can be kept at an acceptable level.

Management of cavernous sinus meningiomas: Consensus statement on behalf of the EANS skull base section

Brain and Spine 2 (2022) 100864

The evolution of cavernous sinus meningiomas (CSMs) might be unpredictable and the efficacy of their treatments is challenging due to their indolent evolution, variations and fluctuations of symptoms, heterogeneity of classifications and lack of randomized controlled trials. Here, a dedicated task force provides a consensus statement on the overall management of CSMs. Research question: To determine the best overall management of CSMs, depending on their clinical presentation, size, and evolution as well as patient characteristics.

Material and methods: Using the PRISMA 2020 guidelines, we included literature from January 2000 to December 2020. A total of 400 abstracts and 77 titles were kept for full-paper screening.

Results: The task force formulated 8 recommendations (Level C evidence). CSMs should be managed by a highly specialized multidisciplinary team. The initial evaluation of patients includes clinical, ophthalmological, endocrinological and radiological assessment. Treatment of CSM should involve experienced skull-base neurosurgeons or neuro-radiosurgeons, radiation oncologists, radiologists, ophthalmologists, and endocrinologists.

Discussion and conclusion: Radiosurgery is preferred as first-line treatment in small, enclosed, pauci-symptomatic lesions/in elderly patients, while large CSMs not amenable to resection or WHO grade II-III are candidates for radiotherapy. Microsurgery is an option in aggressive/rapidly progressing lesions in young patients presenting with oculomotor/visual/endocrinological impairment. Whenever surgery is offered, open cranial approaches are the current standard. There is limited experience reported about endoscopic endonasal approach for CSMs and the main indication is decompression of the cavernous sinus to improve symptoms. Whenever surgery is indicated, the current trend is to offer decompression followed by radiosurgery.

Stereotactic radiosurgery as the primary management for patients with Koos grade IV vestibular schwannomas

J Neurosurg 135:1058–1066, 2021

While extensive long-term outcome studies support the role of stereotactic radiosurgery (SRS) for smaller volume vestibular schwannomas (VSs), its role in the management for larger-volume tumors remains controversial.

METHODS Between 1987 and 2017, the authors performed single-session SRS on 170 patients with previously untreated Koos grade IV VSs (volumes ranged from 5 to 20 cm3). The median tumor volume was 7.4 cm3. The median maximum extracanalicular tumor diameter was 27.5 mm. All tumors compressed the middle cerebellar peduncle and distorted the fourth ventricle. Ninety-three patients were male, 77 were female, and the median age was 61 years. Sixtytwo patients had serviceable hearing (Gardner-Robertson [GR] grades I and II). The median margin dose was 12.5 Gy.

RESULTS At a median follow-up of 5.1 years, the progression-free survival rates of VSs treated with a margin dose ≥ 12.0 Gy were 98.4% at 3 years, 95.3% at 5 years, and 90.7% at 10 years. In contrast, the tumor control rate after delivery of a margin dose < 12.0 Gy was 76.9% at 3, 5, and 10 years. The hearing preservation rates in patients with serviceable hearing at the time of SRS were 58.1% at 3 years, 50.3% at 5 years, and 35.9% at 7 years. Younger age (< 60 years, p = 0.036) and initial GR grade I (p = 0.006) were associated with improved serviceable hearing preservation rate. Seven patients (4%) developed facial neuropathy during the follow-up interval. A smaller tumor volume (< 10 cm3, p = 0.002) and a lower margin dose (≤ 13.0 Gy, p < 0.001) were associated with preservation of facial nerve function. The probability of delayed facial neuropathy when the margin dose was ≤ 13.0 Gy was 1.1% at 10 years. Nine patients (5%) required a ventriculoperitoneal shunt because of delayed symptomatic hydrocephalus. Fifteen patients (9%) developed detectable trigeminal neuropathy. Delayed resection was performed in 4% of patients.

CONCLUSIONS Even for larger-volume VSs, single-session SRS prevented the need for delayed resection in almost 90% at 10 years. For patients with minimal symptoms of tumor mass effect, SRS should be considered an effective alternative to surgery in most patients, especially those with advanced age or medical comorbidities.

Stereotactic radiosurgery for clinoid meningiomas: a multi‐institutional study

Acta Neurochirurgica (2021) 163:2861–2869

Resection of clinoid meningiomas can be associated with significant morbidity. Experience with stereotactic radiosurgery (SRS) for clinoid meningiomas remains limited. We studied the safety and effectiveness of SRS for clinoid meningiomas.

Methods From twelve institutions participating in the International Radiosurgery Research Foundation, we pooled patients treated with SRS for radiologically suspected or histologically confirmed WHO grade I clinoid meningiomas.

Results Two hundred seven patients (median age: 56 years) underwent SRS for clinoid meningiomas. Median treatment volume was 8.02 cm3, and 87% of tumors were immediately adjacent to the optic apparatus. The median tumor prescription dose was 12 Gy, and the median maximal dose to the anterior optic apparatus was 8.5 Gy. During a median post-SRS imaging follow-up of 51.1 months, 7% of patients experienced tumor progression. Greater margin SRS dose (HR = 0.700, p = 0.007) and pre-SRS radiotherapy (HR = 0.004, p < 0.001) were independent predictors of better tumor control. During median visual follow-up of 48 months, visual function declined in 8% of patients. Pre-SRS visual deficit (HR=2.938, p=0.048) and maximal radiation dose to the optic apparatus of ≥ 10 Gy (HR = 11.297, p = 0.02) independently predicted greater risk of post-SRS visual decline. Four patients experienced new post-SRS cranial nerve V neuropathy.

Conclusions SRS allows durable control of clinoid meningiomas and visual preservation in the majority of patients. Greater radiosurgical prescription dose is associated with better tumor control. Radiation dose to the optic apparatus of ≥ 10 Gy and visual impairment before the SRS increase risk of visual deterioration.

Stereotactic radiosurgery as the first-line treatment for intracanalicular vestibular schwannomas

J Neurosurg 135:1051–1057, 2021

This report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs).

METHODS Between 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22–85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015–0.63 cm3). The median margin dose was 12.5 Gy (range 11.0–25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7–50.0 Gy).

RESULTS The progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569–5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059–4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS.

CONCLUSIONS SRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

Gamma Knife central lateral thalamotomy for the treatment of neuropathic pain

J Neurosurg 135:228–236, 2021

The goal of this study was to assess the safety and efficacy of stereotactic central lateral thalamotomy with Gamma Knife radiosurgery in patients with neuropathic pain.

METHODS Clinical and radiosurgical data were prospectively collected and analyzed in patients with neuropathic pain who underwent Gamma Knife central lateral thalamotomy. The safety and efficacy of the lesioning procedure were evaluated by neurological examination and standardized scales for pain intensity and health-related quality of life. Visual analog scale (VAS) for pain, McGill Pain Questionnaire (MPQ), EuroQol–5 dimensions (EQ-5D), and the 36-Item Short Form Health Survey, version 2 (SF-36v2) were measured during baseline and postoperative follow-up evaluations at 3, 6, 12, 24, and 36 months.

RESULTS Eight patients with neuropathic pain underwent Gamma Knife central lateral thalamotomy. Four patients suffered from trigeminal deafferentation pain, 2 from brachial plexus injury, 1 from central poststroke facial neuropathic pain, and 1 from postherpetic neuralgia. No lesioning-related adverse effect was recorded during the follow-up periods. All patients had pain reduction following thalamotomy. The mean follow-up time was 24 months. At the last follow-up visits, 5 patients reported ≥ 50% VAS pain reduction. The overall mean VAS pain score was 9.4 (range 8–10) before radiosurgery. After 1 year, the mean VAS pain score decreased significantly, from 9.4 (range 8–10) to 5.5 (mean -41.33%, p = 0.01). MPQ scores significantly decreased (mean -22.18%, p = 0.014). Statistically significant improvements of the SF-36v2 quality of life survey (mean +48.16%, p = 0.012) and EQ-5D (+45.16%, p = 0.012) were observed. At 2 years after radiosurgery, the VAS pain score remained significantly reduced to a mean value of 5.5 (p = 0.027). Statistically significant improvements were also observed for the MPQ (mean -16.05%, p = 0.034); the EQ-5D (mean +35.48%, p = 0.028); and the SF-36v2 (mean +35.84%, p = 0.043). At the last follow-up visits, pain had recurred in 2 patients, who were suffering from central poststroke neuropathic pain and brachial plexus injury, respectively.

CONCLUSIONS Safe, nonpharmacological therapies are imperative for the management of refectory chronic pain conditions. The present series demonstrates that Gamma Knife central lateral thalamotomy is safe and potentially effective in the long term for relieving chronic neuropathic pain refractory to pharmacotherapy and for restoring quality of life.


Stereotactic Radiosurgery for Spetzler-Martin Grade I and II Arteriovenous Malformations: International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline

Neurosurgery 87:442–452, 2020

No guidelines have been published regarding stereotactic radiosurgery (SRS) in the management of Spetzler-Martin grade I and II arteriovenous malformations (AVMs).

OBJECTIVE: To establish SRS practice guidelines for grade I-II AVMs on the basis of a systematic literature review.

METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant search of Medline, Embase, and Scopus, 1986-2018, for publications reporting post-SRS outcomes in ≥ 10 grade I-II AVMs with a follow-up of ≥ 24 mo. Primary endpoints were obliteration and hemorrhage; secondary outcomes included SpetzlerMartin parameters, dosimetric variables, and “excellent” outcomes (defined as total obliteration without new post-SRS deficit).

RESULTS: Of 447 abstracts screened, 8 were included (n = 1, level 2 evidence; n = 7, level 4 evidence), representing 1102 AVMs, of which 836 (76%) were grade II. Obliteration was achieved in 884 (80%) at a median of 37 mo; 66 hemorrhages (6%) occurred during a median follow-up of 68 mo. Total obliteration without hemorrhage was achieved in 78%. Of 836 grade II AVMs, Spetzler-Martin parameters were reported in 680: 377 were eloquent brain and 178 had deep venous drainage, totaling 555/680 (82%) high-risk SRS-treated grade II AVMs.

CONCLUSION: The literature regarding SRS for grade I-II AVM is low quality, limiting interpretation. Cautiously, we observed that SRS appears to be a safe, effective treatment for grade I-II AVM and may be considered a front-line treatment, particularly for lesions in deep or eloquent locations. Preceding publications may be influenced by selection bias, with favorable AVMs undergoing resection, whereas those at increased risk of complications and nonobliteration are disproportionately referred for SRS.

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.

Biologically effective dose and prediction of obliteration of unruptured arteriovenous malformations treated by upfront Gamma Knife radiosurgery: a series of 149 consecutive cases

Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs.

METHODS A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12–154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18–25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7–246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9–138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313–3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4–2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed.

RESULTS A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (−0.013689 × beam-on time) + (0.021 × age) − 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03).

CONCLUSIONS The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.


Petroclival meningiomas: long-term outcomes of multimodal treatments and management strategies based on 30 years of experience at a single institution

J Neurosurg 132:1675–1682, 2020

A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution.

METHODS Ninety-two patients with petroclival meningiomas were treated surgically at the authors’ institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1–368 months) and 105 months (range 1–348 months), respectively.

RESULTS A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively.

CONCLUSIONS The authors’ preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.


Frameless Stereotactic Radiosurgery on the Gamma Knife Icon: Early Experience From 100 Patients

Neurosurgery 86:509–516, 2020

The Gamma Knife (GK) Icon (Elekta AB) uses a cone-beam computed tomography (CBCT) scanner and an infrared camera system to support the delivery of frameless stereotactic radiosurgery (SRS). There are limited data on patients treated with frameless GK radiosurgery (GKRS).

OBJECTIVE: To describe the early experience, process, technical details, and short-term outcomes with frameless GKRS at our institution.

METHODS: We reviewed our patient selection and described the workflow in detail, including image acquisition, treatment planning, mask-based immobilization, stereotactic CBCT localization, registration, treatment, and intrafraction monitoring. Because of the short interval of follow-up, we provide crude rates of local control.

RESULTS: Data from 100 patients are reported. Median age is 67 yr old. 56 patients were treated definitively, 21 postoperatively, and 23 had salvage GKRS for recurrence after surgery. Forty-two patients had brain metastases, 26 meningiomas, 16 vestibular schwannomas, 9 high-grade gliomas, and 7 other histologies. Median doses to metastases were 20 Gy in 1 fraction (range: 14-21), 24 Gy in 3 fractions (range: 19.5-27), and 25 Gy in 5 fractions (range: 25-30 Gy). Thirteen patients underwent repeat SRS to the same area. Median treatment time was 17.7 min (range: 5.8-61.7). We found an improvement in our workflow and a greater number of patients eligible for GKRS because of the ability to fractionate treatments.

CONCLUSION: We report a large cohort of consecutive patients treated with frameless GKRS. We look forward to studies with longer follow-up to provide valuable data on clinical outcomes and to further our understanding of the radiobiology of hypofractionation in the brain.

Is There a Need for a 6-Month Postradiosurgery Magnetic Resonance Imaging in the Treatment of Vestibular Schwannoma?

Neurosurgery, Volume 86, Issue 2, February 2020, Pages 250–256

Stereotactic radiosurgery (SRS) is a common treatment modality for vestibular schwannoma (VS), with a role in primary and recurrent/progressive algorithms. At our institution, routine magnetic resonance imaging (MRI) is obtained at 6 and 12 mo following SRS for VS.

OBJECTIVE: To analyze the safety and financial impact of eliminating the 6-mo post-SRS MRI in asymptomatic VS patients. METHODS: A prospectively maintained SRS database was retrospectively reviewed for VS patients with 1 yr of post-treatment follow-up, 2005 to 2015. Decisions at 6-mo MRI were binarily categorized as routine follow-up vs clinical action—defined as a clinical visit, additional imaging, or an operation as a direct result of the 6-mo study.

RESULTS: A total of 296 patients met screening criteria, of whom 53 were excluded for incomplete follow-up and 8 for NF-2. Nine were reimaged prior to 6 mo due to clinical symptoms. Routine 6-mo post-SRS MRI was completed by 226 patients (76% of screened cohort), following from which zero instances of clinical action occurred.When scaled using national insurance database-derived financials—which estimated the mean per-study charge for MRI of the brain with and without contrast at $1767—the potential annualized national charge reduction was approximated as $1 611 504.

CONCLUSION: For clinically stable VS, 6-mo post-SRS MRI does not contribute significantly to management. We recommend omitting routine MRI before 12 mo, in patients without new or progressive neurological symptoms. If extrapolated nationally to the more than 100 active SRS centers, thousands of patients would be spared an inconvenient, nonindicated study, and national savings in health care dollarswouldbe on the order ofmillions annually.

An International Radiosurgery Research Foundation Multicenter Retrospective Study of Gamma Ventral Capsulotomy for Obsessive Compulsive Disorder

Neurosurgery, Volume 85, Issue 6, December 2019, Pages 808–816

Obsessive compulsive disorder (OCD) across its full spectrum of severity is a psychiatric illness affecting ∼2% to 3% of the general population and results in significant functional impairment. There are few large patient series regarding Gamma ventral capsulotomy (GVC).
OBJECTIVE: To evaluate clinical outcomes of severe medically refractory OCD treated with GVC.
METHODS: This is an international, multicenter, retrospective cohort study. Forty patients with pre-GVC Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores ≥ 24 (indicating severe OCD) were included. GVC was performed with 1 or 2 isocenters with a median maximum dose of 135 Gy (range, 120-180 Gy). Patients were deemed “responders” to GVC if there was ≥35% reduction of follow-up Y-BOCS scores, and considered in remission if their Y-BOCS scores were ≤16. The median follow-up was 36 mo (range, 6-96 mo).
RESULTS: The median pre-SRS Y-BOCS score was 35 (range, 24-40). Eighteen patients (45%) were considered “responders,” and 16 (40%) of them were in remission at their last follow-up. Nineteen patients (47.5%) remained stable with Y-BOCS of 33 (range, 26-36) following GVC, whereas 3 patients (7.5%) experienced worsening in Y-BOCS scores. Patients treated with 2 isocenters were more likely to have improvement in Y-BOCS score at 3 and 5 yr (P < .0005). Ten patients (25%) experienced post-GVC mood disturbance and neurological complications in 3 patients (7.5%). One patient developed radiation necrosis with edema that improved with steroids.
CONCLUSION: GVC serves as a reasonable treatment strategy for severe medical refractory OCD. Patients treated with 2 isocenters were more likely to have substantial improvement in OCD.

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.

Gamma Knife Radiosurgery for Multiple Sclerosis-Associated Trigeminal Neuralgia


Neurosurgery 85:E933–E939, 2019

Trigeminal neuralgia in the setting of multiple sclerosis (MS-TN) is a challenging condition to manage that is commonly treated with Gamma Knife radiosurgery (GKRS; Elekta AB). However, data regarding the efficacy of this treatment are somewhat limited, particularly for repeat GKRS.

OBJECTIVE: To report outcomes of GKRS for MS-TN from a cohort study.

METHODS: Retrospective review of our GKRS database identified 77 cases of unilateral MS-TN (UMSTN) in 74 patients treated with GKRS between 2001 and 2016, with 37 cases undergoing repeat GKRS. Background medical history, treatment outcomes and complications, and dosimetric data were obtained by retrospective chart reviews and telephone interviews.

RESULTS:Eighty two percent of UMSTN cases achieved Barrow Neurological Institute (BNI) IIIb or better pain relief following initial GKRS for a median duration of 1.1 yr. Estimated rates ofpainreliefat1,3,and5yr were 51,39,and29% respectively.Eighty-eightpercentachieved BNI IIIb or better pain relief after repeat GKRS for a median duration of 4.0 yr. Estimated rates of pain relief at 1 and 3 yr were 70 and 54%, respectively. Median doses for initial and repeat GKRS were 85 and 80 Gy to the 100% isodose line, respectively. Those with MS-TN had a shorter duration of BNI IIIb or better pain relief after initial (4.6 vs 1.1 yr), but not repeat GKRS (3.8 vs 4.0 yr) compared to a historical cohort from our institution.

CONCLUSION: GKRS is an effective, well-tolerated treatment for patientswith MS-TN. More durable relief is often achieved with repeat GKRS.


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