Stereotactic Radiosurgery for Intermediate (III) or High (IV-V) Spetzler-Martin Grade Arteriovenous Malformations: International Stereotactic Radiosurgery Society Practice Guideline.

BACKGROUND AND OBJECTIVES: Consensus guidelines do not exist to guide the role of stereotactic radiosurgery (SRS) in the management of patients with Spetzler-Martin Grade III-V arteriovenous malformations (AVMs). We sought to establish SRS practice guidelines for Grade III-V AVMs based on a critical systematic review of the published literature. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant search of Medline, Embase, and Scopus, 1986 to 2023, for publications reporting post-SRS outcomes in ≥10 Grade III-V AVMs with the median follow-up ≥24 months was performed. Primary end points were AVM obliteration and post-SRS hemorrhage. Secondary end points included dosimetric variables, Spetzler-Martin parameters, and neurological outcome. RESULTS: : In total, 2463 abstracts were screened, 196 manuscripts were reviewed, and 9 met the strict inclusion criteria. The overall sample of 1634 AVMs consisted of 1431 Grade III (88%), 186 Grade IV (11%), and 11 Grade V lesions (1%). Total median post-SRS follow-up was 53 months for Grade III and 43 months for Grade IV-V AVMs (ranges, 2-290; 12-262). For Grade III AVMs, the crude obliteration rate was 72%, and among Grade IV-V lesions, the crude obliteration rate was 46%. Post-SRS hemorrhage was observed in 7% of Grade III compared with 17% of Grade IV-V lesions. Major permanent deficits or death from hemorrhage or radiation-induced complications occurred in 86 Grade III (6%) and 22 Grade IV-V AVMs (12%). CONCLUSION: Most patients with Spetzler-Martin Grade III AVMs have favorable SRS treatment outcomes; however, the obliteration rate for Grade IV-V AVMs is less than 50%. The available studies are heterogenous and lack nuanced, long-term, grade-specific outcomes.

Repeat Single-Session Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Systematic Review, Meta-Analysis, and International Stereotactic Radiosurgery Society Practice Guidelines.

BACKGROUND AND OBJECTIVES: Repeat stereotactic radiosurgery (SRS) for residual arteriovenous malformations (AVMs) can be considered as a salvage approach after failure of initial SRS. There are no published guidelines regarding patient selection, timing, or SRS parameters to guide clinical practice. This systematic review aimed to review outcomes and complications from the published literature to inform practice recommendations provided on behalf of the International Stereotactic Radiosurgery Society. METHODS: We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of MEDLINE, Scopus, Web of Science, and Embase was conducted. Fourteen studies with 925 patients met the inclusion criteria. Patients were treated between 1985 and 2022. All studies were retrospective, except for one prospective cohort. RESULTS: The median patient age at repeat SRS ranged from 32 to 60 years. Four studies (630 patients) reported detailed information on Spetzler-Martin grade at the time of repeat SRS; 12.54% of patients had Spetzler-Martin grade I AVMs (79/630 patients), 46.51% had grade II (293/630), 34.92% had grade III (220/630), 5.08% had grade IV (32/630), and 0.95% had grade V (6/630). The median prescription doses varied between 15 and 25 Gy (mean, 13.06-22.8 Gy). The pooled overall obliteration rate at the last follow-up after repeat SRS was 59% (95% CI 51%-67%) with a median follow-up between 21 and 50 months. The pooled hemorrhage incidence at the last follow-up was 5% (95% CI 4%-7%), and the pooled overall radiation-induced change incidence was 12% (95% CI 7%-20%). CONCLUSION: For an incompletely obliterated AVM, repeat radiosurgery after 3 to 5 years of follow-up from the first SRS provides a reasonable benefit to the risk profile. After repeat SRS, obliteration is achieved in the majority of patients. The risk of hemorrhage or radiation-induced change appears low, and International Stereotactic Radiosurgery Society recommendations are presented.

Dosimetric Comparison of Dedicated Radiosurgery Platforms for the Treatment of Essential Tremor: Technical Report.

Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing. Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being "reversible", deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by high-intensity focused ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a "second look". While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this brief technical report we compare the dosimetric profiles of three major radiosurgical platforms (Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS)) for the treatment of ET. In general, the GRS and Gamma Knife were shown to have the best theoretical dosimetric profiles for VIM lesioning. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

Management of sporadic intracanalicular vestibular schwannomas: A critical review and International Stereotactic Radiosurgery Society (ISRS) practice guidelines.

BACKGROUND: The choice of an appropriate strategy for intracanalicular vestibular schwannoma (ICVS) is still debated. We conducted a systematic review and meta-analysis with the aim to compare treatment outcomes amongst management strategies (conservative surveillance (CS), microsurgical resection (MR), or stereotactic radiosurgery (SRS)) aiming to inform guideline recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2021 referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies or case series reporting a cohort of ICVS managed with CS, MR, or SRS. Primary outcome measures included tumor control, the need for additional treatment, hearing outcomes, and posttreatment neurological deficits. These were pooled using meta-analytical techniques and compared using meta-regression with random effect. RESULTS: Forty studies were included (2371 patients). The weighted pooled estimates for tumor control were 96% and 65% in SRS and CS series, respectively (P < .001). Need for further treatment was reported in 1%, 2%, and 25% for SRS, MR, and CS, respectively (P = .001). Hearing preservation was reported in 67%, 68%, and 55% for SRS, MR, and CS, respectively (P = .21). Persistent facial nerve deficit was reported in 0.1% and 10% for SRS and MR series, respectively (P = .01). CONCLUSIONS: SRS is a noninvasive treatment with at least equivalent rates of tumor control and hearing preservation as compared to MR, with the caveat of better facial nerve preservation. As compared to CS, upfront SRS is an effective treatment in achieving tumor control with similar rates of hearing preservation.

Single-fraction radiosurgery outcomes for large vestibular schwannomas in the upfront or post-surgical setting: a systematic review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines.

PURPOSE: To perform a systematic review of literature specific to single-fraction stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS), maximum diameter ≥ 2.5 cm and/or classified as Koos Grade IV, and to present consensus recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach. We considered eligible prospective and retrospective studies, written in the English language, reporting treatment outcomes for large VS; SRS for large post-operative tumors were analyzed in aggregate and separately. RESULTS: 19 of the 229 studies initially identified met the final inclusion criteria. Overall crude rate of tumor control was 89% (93.7% with no prior surgery vs 87.7% with prior surgery). Rates of salvage microsurgical resection, need for shunt, and additional SRS in all series versus those with no prior surgery were 9.6% vs 3.3%, 4.7% vs 6.4% and 1% vs 0.9%, respectively. Rates of facial palsy and hearing preservation in all series versus those with no prior surgery were 1.3% vs 3.4% and 34.2% vs 40.4%, respectively. CONCLUSIONS: Upfront SRS resulted in high rates of tumor control with acceptable rates of facial palsy and hearing preservation as compared to the results in those series including patients with prior surgery (level C evidence). Therefore, although large VS are considered classic indication for microsurgical resection, upfront SRS can be considered in selected patients and we recommend a prescribed marginal dose from 11 to 13 Gy (level C evidence).

Benchmarking Tests of Contemporary SRS Platforms: Have Technological Developments Resulted in Improved Treatment Plan Quality?

PURPOSE: Stereotactic radiosurgery treatment delivery can be performed with a range of devices, each of which have evolved over recent years. We sought to evaluate the differences in performance of contemporary stereotactic radiosurgery platforms and also to compare them with earlier platform iterations from a previous benchmarking study. METHODS AND MATERIALS: The following platforms were selected as "state of the art" in 2022: Gamma Knife Icon (GK), CyberKnife S7 (CK), Brainlab Elements (Elekta VersaHD and Varian TrueBeam), Varian Edge with HyperArc (HA), and Zap-X. Six benchmarking cases were used from a 2016 study. To reflect the evolution of increasing numbers of metastases treated per patient, a 14-target case was added. The 28 targets among the 7 patients ranged from 0.02 to 7.2 cc in volume. Participating centers were sent images and contours for each patient and asked to plan them to the best of their ability. Although some variation in local practice was allowed (eg, margins), groups were asked to prescribe a specified dose to each target and tolerance doses to organs at risk were agreed upon. Parameters compared included coverage, selectivity, Paddick conformity index, gradient index (GI), R50%, efficiency index, doses to organs at risk, and planning and treatment times. RESULTS: Mean coverage for all targets ranged from 98.2% (Brainlab/Elekta) to 99.7% (HA-6X). Paddick conformity index values ranged from 0.722 (Zap-X) to 0.894 (CK). GI ranged from a mean of 3.52 (GK), representing the steepest dose gradient, to 5.08 (HA-10X). The GI appeared to follow a trend with beam energy, with the lowest values from the lower energy platforms (GK, 1.25 MeV; Zap-X, 3 MV) and the highest value from the highest energy (HA-10X). Mean R50% values ranged from 4.48 (GK) to 5.98 (HA-10X). Treatment times were lowest for C-arm linear accelerators. CONCLUSIONS: Compared with earlier studies, newer equipment appears to deliver higher quality treatments. CyberKnife and linear accelerator platforms appear to give higher conformity whereas lower energy platforms yield a steeper dose gradient.

Improving the Accuracy of Biologically Effective Dose Estimates, from a Previously Published Study, After Radiosurgery for Acoustic Neuromas.

OBJECTIVE: To recalculate biological effective dose values (BED) for radio-surgical treatments of acoustic neuroma from a previous study. BEDs values were previously overestimated by only using beam-on times in calculations, so excluding the important beam-off-times (when deoxyribonucleic acid repair continues) which contribute to the overall treatment time. Simple BED estimations using a mono-exponential approximation may not always be appropriate but if used should include overall treatment time. METHODS: Time intervals between isocenters were estimated. These were especially important for the Gamma Knife Model 4C cases since manual changes significantly increase overall treatment times. Individual treatment parameters, such as iso-center number, beam-on-time, and beam-off-time, were then used to calculate BED values using a more appropriate bi-exponential model that includes fast and slow components of DNA damage repair over a wider time range. RESULTS: The revised BED estimates differed significantly from previously published values. The overestimates of BED, obtained using beam-on-time only, varied from 0%-40.3%. BED subclasses, each with a BED range of 5 Gy2.47, indicated that revised values were consistently reduced when compared with originally quoted values, especially for 4C compared with Perfexion cases. Furthermore, subdivision of 4C cases by collimator number further emphasized the impact of scheduled gap times on BED. Further analysis demonstrated important limitations of the mono-exponential model. Target volume was a major confounding factor in the interpretation of the results of this study. CONCLUSIONS: BED values should be estimated by including beam-on and beam-off times. Suggestions are provided for more accurate BED estimations in future studies.

Dosimetric accuracy of the Convolution algorithm for Leksell Gamma Plan radiosurgery treatment planning: Evaluation in the presence of clinically relevant inhomogeneities.

PURPOSE: The Leksell Gamma Plan Convolution algorithm (LGP-Convolution) has not been widely adopted. This mainly stems from the higher calculated beam-on times relative to the standard ray tracing-based LGP-TMR10 dose calculation algorithm. This study aims to evaluate the accuracy of the LGP-Convolution in scenarios where the treated lesions are in the vicinity of or encompassed by bone and/or air inhomogeneities. METHODS: The solid water dosimetry phantom provided by the vendor was modified to include bone and air inhomogeneities. Two treatment planning scenarios were investigated involving a single shot and multiple shots, respectively. Treatment planning and dose prescription were performed using the LGP-Convolution algorithm. Triple channel film dosimetry was performed using GafChromic EBT3 films calibrated in terms of absorbed dose to water in a 60 Co beam. Monte Carlo (MC) simulation dosimetry was also performed in the inhomogeneous experimental geometry using the EGSnrc MC platform and a previously validated sector-based phase-space source model. MC simulations were also employed to determine correction factors required for converting EBT3 measurements at points within the bone and air inhomogeneities from dose-to-water values to the corresponding dose to medium values. RESULTS AND CONCLUSIONS: EBT3 dose to medium correction factors ranged with field size (4, 8, or 16 mm) within 0.941-0.946 for bone and 0.745-0.749 for air inhomogeneities. An excellent agreement was found between the LGP-Convolution calculations with corresponding EBT3 and MC dose to medium results at all measurement points, except those located inside the air inhomogeneity. The latter is of no clinical importance and excluding them yielded gamma index passing rates of nearly 100% for 3% local dose difference and 1 mm distance-to-agreement criteria. The excellent agreement observed between LGP-Convolution calculations and film as well as MC results of dose to medium indicates that the latter is the quantity reported by the LGP-Convolution.

ISRS Technical Guidelines for Stereotactic Radiosurgery: Treatment of Small Brain Metastases (≤1 cm in Diameter).

PURPOSE: The objective of this literature review was to develop International Stereotactic Radiosurgery Society (ISRS) consensus technical guidelines for the treatment of small, ≤1 cm in maximal diameter, intracranial metastases with stereotactic radiosurgery. Although different stereotactic radiosurgery technologies are available, most of them have similar treatment workflows and common technical challenges that are described. METHODS AND MATERIALS: A systematic review of the literature published between 2009 and 2020 was performed in Pubmed using the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) methodology. The search terms were limited to those related to radiosurgery of brain metastases and to publications in the English language. RESULTS: From 484 collected abstract 37 articles were included into the detailed review and bibliographic analysis. An additional 44 papers were identified as relevant from a search of the references. The 81 papers, including additional 7 international guidelines, were deemed relevant to at least one of five areas that were considered paramount for this report. These areas of technical focus have been employed to structure these guidelines: imaging specifications, target volume delineation and localization practices, use of margins, treatment planning techniques, and patient positioning. CONCLUSIONS: This systematic review has demonstrated that Stereotactic Radiosurgery (SRS) for small (1 cm) brain metastases can be safely performed on both Gamma Knife (GK) and CyberKnife (CK) as well as on modern LINACs, specifically tailored for radiosurgical procedures, However, considerable expertise and resources are required for a program based on the latest evidence for best practice.

Toward semi-automatic biologically effective dose treatment plan optimisation for Gamma Knife radiosurgery.

Objective.Dose-rate effects in Gamma Knife radiosurgery treatments can lead to varying biologically effective dose (BED) levels for the same physical dose. The non-convex BED model depends on the delivery sequence and creates a non-trivial treatment planning problem. We investigate the feasibility of employing inverse planning methods to generate treatment plans exhibiting desirable BED characteristics using the per iso-centre beam-on times and delivery sequence.Approach.We implement two dedicated optimisation algorithms. One approach relies on mixed-integer linear programming (MILP) using a purposely developed convex underestimator for the BED to mitigate local minima issues at the cost of computational complexity. The second approach (local optimisation) is faster and potentially usable in a clinical setting but more prone to local minima issues. It sequentially executes the beam-on time (quasi-Newton method) and sequence optimisation (local search algorithm). We investigate the trade-off between time to convergence and solution quality by evaluating the resulting treatment plans' objective function values and clinical parameters. We also study the treatment time dependence of the initial and optimised plans using BED95(BED delivered to 95% of the target volume) values.Main results.When optimising the beam-on times and delivery sequence, the local optimisation approach converges several orders of magnitude faster than the MILP approach (minutes versus hours-days) while typically reaching within 1.2% (0.02-2.08%) of the final objective function value. The quality parameters of the resulting treatment plans show no meaningful difference between the local and MILP optimisation approaches. The presented optimisation approaches remove the treatment time dependence observed in the original treatment plans, and the chosen objectives successfully promote more conformal treatments.Significance.We demonstrate the feasibility of using an inverse planning approach within a reasonable time frame to ensure BED-based objectives are achieved across varying treatment times and highlight the prospect of further improvements in treatment plan quality.

Stereotactic Radiosurgery for Dural Arteriovenous Fistulas: A Systematic Review and Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) are often treated with stereotactic radiosurgery (SRS) to achieve complete obliteration (CO), prevent future hemorrhages, and ameliorate neurological symptoms. OBJECTIVE: To summarize outcomes after SRS for dAVFs and propose relevant practice recommendations. METHODS: Using a PICOS/PRISMA/MOOSE protocol, we included patients with dAVFs treated with SRS and data for at least one of the outcomes of the study. Relevant outcomes were CO, symptom improvement and cure, and post-SRS hemorrhage or permanent neurological deficits (PNDs). Estimated outcome effect sizes were determined using weighted random-effects meta-analyses using DerSimonian and Laird methods. To assess potential relationships between patient and lesion characteristics and clinical outcomes, mixed-effects weighted regression models were used. RESULTS: Across 21 published studies, we identified 705 patients with 721 dAVFs treated with SRS. The CO rate was 68.6% (95% CI 60.7%-76.5%) with symptom improvement and cure rates of 97.2% (95% CI 93.2%-100%) and 78.8% (95% CI 69.3%-88.2%), respectively. Estimated incidences of post-SRS hemorrhage and PNDs were 1.1% (95% CI 0.6%-1.6%) and 1.3% (95% CI 0.8%-1.8%), respectively. Noncavernous sinus (NCS) dAVFs were associated with lower CO (P = .03) and symptom cure rates (P = .001). Higher grade was also associated with lower symptom cure rates (P = .04), whereas previous embolization was associated with higher symptom cure rates (P = .01). CONCLUSION: SRS for dAVFs results in CO in the majority of patients with excellent symptom improvement rates with minimal toxicity. Patients with NCS and/or higher-grade dAVFs have poorer symptom cure rates. Combined therapy with embolization and SRS is recommended when feasible for clinically aggressive dAVFs or those refractory to embolization to maximize the likelihood of symptom cure.

Improving on whole-brain radiotherapy in patients with large brain metastases: A planning study to support the AROMA clinical trial.

PURPOSE: To develop a novel dose-escalated volumetric modulated arc therapy (VMAT) strategy for patients with single or multiple large brain metastases which can deliver a higher dose to individual lesions for better local control (LC), and to compare dosimetry between whole brain radiotherapy (WBRT), hippocampal-sparing whole brain radiotherapy (HS-WBRT) and different VMAT-based focal radiotherapy approaches. METHODS AND MATERIALS: We identified 20 patients with one to ten brain metastases and at least one lesion larger than 15 cm3 who had received WBRT as part of routine care. For each patient, we designed and evaluated five radiotherapy treatment plans, including WBRT, HS-WBRT and three VMAT dosing models. A dose of 20 Gy in 5 fractions was prescribed to the whole brain or target volumes depending on the plan, with higher doses to smaller lesions and dose-escalated inner planning target volumes (DE-iPTV) in VMAT plans, respectively. Treatment plans were evaluated using the efficiency index, mean dose and D0.1 cc to the target volumes and organs at risk. RESULTS: Compared with WBRT, VMAT plans achieved a significantly more efficient dose distribution in brain lesions, especially with our DE-iPTV model, while minimising the dose to the normal brain and other organs at risks (OARs) (p < 0.05). CONCLUSIONS: VMAT plans obtained higher doses to brain metastases and minimised doses to OARs. Dose-escalated VMAT for larger lesions allows higher radiotherapy doses to be delivered to larger lesions while maintaining safe doses to OARs.

Automated Koos Classification of Vestibular Schwannoma.

Objective: The Koos grading scale is a frequently used classification system for vestibular schwannoma (VS) that accounts for extrameatal tumor dimension and compression of the brain stem. We propose an artificial intelligence (AI) pipeline to fully automate the segmentation and Koos classification of VS from MRI to improve clinical workflow and facilitate patient management. Methods: We propose a method for Koos classification that does not only rely on available images but also on automatically generated segmentations. Artificial neural networks were trained and tested based on manual tumor segmentations and ground truth Koos grades of contrast-enhanced T1-weighted (ceT1) and high-resolution T2-weighted (hrT2) MR images from subjects with a single sporadic VS, acquired on a single scanner and with a standardized protocol. The first stage of the pipeline comprises a convolutional neural network (CNN) which can segment the VS and 7 adjacent structures. For the second stage, we propose two complementary approaches that are combined in an ensemble. The first approach applies a second CNN to the segmentation output to predict the Koos grade, the other approach extracts handcrafted features which are passed to a Random Forest classifier. The pipeline results were compared to those achieved by two neurosurgeons. Results: Eligible patients (n = 308) were pseudo-randomly split into 5 groups to evaluate the model performance with 5-fold cross-validation. The weighted macro-averaged mean absolute error (MA-MAE), weighted macro-averaged F1 score (F1), and accuracy score of the ensemble model were assessed on the testing sets as follows: MA-MAE = 0.11 ± 0.05, F1 = 89.3 ± 3.0%, accuracy = 89.3 ± 2.9%, which was comparable to the average performance of two neurosurgeons: MA-MAE = 0.11 ± 0.08, F1 = 89.1 ± 5.2, accuracy = 88.6 ± 5.8%. Inter-rater reliability was assessed by calculating Fleiss' generalized kappa (k = 0.68) based on all 308 cases, and intra-rater reliabilities of annotator 1 (k = 0.95) and annotator 2 (k = 0.82) were calculated according to the weighted kappa metric with quadratic (Fleiss-Cohen) weights based on 15 randomly selected cases. Conclusions: We developed the first AI framework to automatically classify VS according to the Koos scale. The excellent results show that the accuracy of the framework is comparable to that of neurosurgeons and may therefore facilitate management of patients with VS. The models, code, and ground truth Koos grades for a subset of publicly available images (n = 188) will be released upon publication.

Planning of gamma knife radiosurgery (GKR) for brain arteriovenous malformations using triple magnetic resonance angiography (triple-MRA).

PURPOSE: Intra-arterial Digital Subtraction Angiography (DSA) is the gold standard technique for radiosurgery target delineation in brain Arterio-Venous Malformations (AVMs). This study aims to evaluate whether a combination of three Magnetic Resonance Angiography sequences (triple-MRA) could be used for delineation of brain AVMs for Gamma Knife Radiosurgery (GKR). METHODS: Fifteen patients undergoing DSA for GKR targeting of brain AVMs also underwent triple-MRA: 4D Arterial Spin Labelling based angiography (ASL-MRA), Contrast-Enhanced Time-Resolved MRA (CE-MRA) and High Definition post-contrast Time-Of-Flight angiography (HD-TOF). The arterial phase of the AVM nidus was delineated on triple-MRA by an interventional neuroradiologist and a consultant neurosurgeon (triple-MRA volume). Triple-MRA volumes were compared to AVM targets delineated by the clinical team for delivery of GKR using the current planning paradigm, i.e., stereotactic DSA and volumetric MRI (DSA volume). Difference in size, degree of inclusion (DI) and concordance index (CcI) between DSA and triple-MRA volumes are reported. RESULTS: AVM target volumes delineated on triple-MRA were on average 9.8% smaller than DSA volumes (95%CI:5.6-13.9%; SD:7.14%; p = .003). DI of DSA volume in triple-MRA volume was on average 73.5% (95%CI:71.2-76; range: 65-80%). The mean percentage of triple-MRA volume not included on DSA volume was 18% (95%CI:14.7-21.3; range: 7-30%). CONCLUSION: The technical feasibility of using triple-MRA for visualisation and delineation of brain AVMs for GKR planning has been demonstrated. Tighter and more precise delineation of AVM target volumes could be achieved by using triple-MRA for radiosurgery targeting. However, further research is required to ascertain the impact this may have in obliteration rates and side effects.

Stereotactic Radiosurgery for Postoperative Spine Malignancy: A Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines.

PURPOSE: To determine safety and efficacy of postoperative spine stereotactic body radiation therapy (SBRT) in the published literature, and to present practice recommendations on behalf of the International Stereotactic Radiosurgery Society. METHODS AND MATERIALS: A systematic review of the literature was performed, specific to postoperative spine SBRT, using PubMed and Embase databases. A meta-analysis for 1-year local control (LC), overall survival (OS), and vertebral compression fracture probability was conducted. RESULTS: The literature search revealed 251 potentially relevant articles after duplicates were removed. Of these 56 were reviewed in-depth for eligibility and 12 met all the inclusion criteria for analysis. 7 studies were retrospective, 2 prospective observational and 3 were prospective phase 1 and 2 clinical trials. Outcomes for a total of 461 patients and 499 spinal segments were reported. Ten studies used a magnetic resonance imaging (MRI) scan fused to computed tomography (CT) simulation for treatment planning, and 2 investigations reported on all patients receiving a CT-myelogram at the time of planning. Meta-analysis for 1 year LC and OS was 88.9% and 57%, respectively. The crude reported vertebral compression fracture rate was 5.6%. One case of myelopathy was described in a patient with a previously irradiated spinal segment. One patient developed an esophageal fistula requiring surgical repair. CONCLUSIONS: Postoperative spine SBRT delivers a high 1-year LC with acceptably low toxicity. Patients who may benefit from this include those with oligometastatic disease, radioresistant histology, paraspinal masses, or those with a history of prior irradiation to the affected spinal segment. The International Stereotactic Radiosurgery Society recommends a minimum interval of 8 to 14 days after invasive surgery before simulation for SBRT, with initiation of radiation therapy within 4 weeks of surgery. An MRI fused to the planning CT, or the use of a CT-myelogram, are necessary for target and organ-at-risk delineation. A planning organ-at-risk volume (PRV) of 1.5 to 2 mm for the spinal cord is advised.

Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and International Stereotactic Radiosurgery Society practice recommendations.

OBJECTIVE: A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations. METHODS: The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing's disease, and prolactinomas were selected and included in the analysis. RESULTS: For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%-98.0%), 44.0% (95% CI 35.0%-53.0%), and 17.0% (95% CI 13.0%-23.0%), respectively. For Cushing's disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%-95.0%), 48.0% (95% CI 35.0%-61.0%), and 21.0% (95% CI 13.0%-31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%-95.0%), 28.0% (95% CI 19.0%-39.0%), and 12.0% (95% CI 6.0%-24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes. CONCLUSIONS: SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.