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).

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.

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.

Extracranial dose and the risk of radiation-induced malignancy after intracranial stereotactic radiosurgery: is it time to establish a therapeutic reference level?

BACKGROUND: To measure extracranial doses from Gamma Knife Perfexion (GKP) intracranial stereotactic radiosurgery (SRS) and model the risk of malignancy after SRS for different treatment platforms. METHODS: Doses were measured for 20 patients undergoing SRS on a GKP at distances of 18, 43 and 75 cm from the target, corresponding to the approximate positions of the thyroid, breast and gonads respectively. A literature review was conducted to collect comparative data from other radiosurgery platforms. All data was used to calculate the dose to body organs. The National Cancer Institute (NCI) RadRAT calculator was used to estimate excess lifetime cancer risk from this exposure. Five different age groups covering childhood and younger adults were modelled for both sexes. RESULTS: Extracranial doses delivered during SRS with the GKP were a median 0.04%, 0.008% and 0.002% of prescription dose at 18 cm, 43 cm and 70 cm from the isocentre respectively. Comparison with the literature revealed that the extracranial dose was lowest from GKP, then linacs equipped with micro-multileaf collimators (mMLC), then linacs equipped with circular collimators (cones), and highest from Cyberknife (CK). Estimated lifetime risks of radiation-induced malignancy in the body for patients treated with SRS aged 5-45 years were 0.03-0.88%, 0.36-11%, 0.61-18% and 2.2-39% for GKP, mMLC, cones and CK respectively. CONCLUSIONS: We have compared typical extracranial doses from different platforms and quantified the lifetime risk of radiation-induced malignancy. The risk varies with platform. This should be taken into account when treating children and young adults with SRS. The concept of a therapeutic reference level (TRL), similar to the diagnostic reference level (DRL) established in radiology, is proposed.

Evolution of gamma knife capsulotomy for intractable obsessive-compulsive disorder.

For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

IntuitivePlan inverse planning performance evaluation for Gamma Knife radiosurgery of AVMs.

PURPOSE: To compare planning indices achieved using manual and inverse planning approaches for Gamma Knife radiosurgery of arterio-venous malformations (AVMs). METHODS AND MATERIALS: For a series of consecutive AVM patients, treatment plans were manually created by expert planners using Leksell GammaPlan (LGP). Patients were re-planned using a new commercially released inverse planning system, IntuitivePlan. Plan quality metrics were calculated for both groups of plans and compared. RESULTS: Overall, IntuitivePlan created treatment plans of similar quality to expert planners. For some plan quality metrics statistically significant higher scores were achieved for the inversely generated plans (Coverage 96.8% vs 96.3%, P = 0.027; PCI 0.855 vs 0.824, P = 0.042), but others did not show statistically significant differences (Selectivity 0.884 vs 0.856, P = 0.071; GI 2.85 vs 2.76, P = 0.096; Efficiency Index 47.0% vs 48.1%, P = 0.242; Normal Brain V12 (cc) 5.81 vs 5.79, P = 0.497). Automatic inverse planning demonstrated significantly shorter planning times over manual planning (3.79 vs 11.58 min, P < 10-6 ) and greater numbers of isocentres (40.4 vs 10.8, P < 10-6 ), with an associated cost of longer treatment times (57.97 vs 49.52 min, P = 0.009). When planning and treatment time were combined, there was no significant difference in the overall time between the two methods (61.76 vs 61.10, P = 0.433). CONCLUSIONS: IntuitivePlan can offer savings on the labor of treatment planning. In many cases, it achieves higher quality indices than those achieved by an "expert planner".

Investigation of dosimetric differences between the TMR 10 and convolution algorithm for Gamma Knife stereotactic radiosurgery.

Since its inception, doses applied using Gamma Knife Radiosurgery (GKR) have been calculated using a simple TMR algorithm, which assumes the patient's head is of even density, the same as water. This results in a significant approximation of the dose delivered by the Gamma Knife. We investigated how GKR dose cal-culations varied when using a new convolution algorithm clinically available for GKR planning that takes into account density variations in the head compared with the established calculation algorithm. Fifty-five patients undergoing GKR and harboring 85 lesions were voluntarily and prospectively enrolled into the study. Their clinical treatment plans were created and delivered using TMR 10, but were then recalculated using the density correction algorithm. Dosimetric differences between the planning algorithms were noted. Beam on time (BOT), which is directly proportional to dose, was the main value investigated. Changes of mean and maximum dose to organs at risk (OAR) were also assessed. Phantom studies were performed to investigate the effect of frame and pin materials on dose calculation using the convolution algorithm. Convolution yielded a mean increase in BOT of 7.4% (3.6%-11.6%). However, approximately 1.5% of this amount was due to the head contour being derived from the CT scans, as opposed to measurements using the Skull Scaling Instrument with TMR. Dose to the cochlea calculated with the convolution algorithm was approximately 7% lower than with the TMR 10 algorithm. No significant difference in relative dose distribution was noted and CT artifact typically caused by the stereotactic frame, glue embolization material or different fixation pin materials did not systematically affect convolu-tion isodoses. Nonetheless, substantial error was introduced to the convolution calculation in one target located exactly in the area of major CT artifact caused by a fixation pin. Inhomogeneity correction using the convolution algorithm results in a considerable, but consistent, dose shift compared to the TMR 10 algorithm traditionally used for GKR. A reduction of the prescription dose may be neces-sary to obtain the same clinical effect with the convolution algorithm. Head shape definition using CT outlining can reduce treatment uncertainty from head shape approximations.

Evaluation of the stability of the stereotactic Leksell Frame G in Gamma Knife radiosurgery.

The purpose of this study was to evaluate the stability of the Leksell Frame G in Gamma Knife radiosurgery (GKR). Forty patients undergoing GKR underwent pretreatment stereotactic MRI for GKR planning and stereotactic CT immediately after GKR. The stereotactic coordinates of four anatomical landmarks (cochlear apertures and the summits of the anterior post of the superior semicircular canals, bilaterally) were measured by two evaluators on two separate occasions in the pre-treatment MRI and post-treatment CT scans and the absolute distance between the observations is reported. The measurement method was validated with an indepen-dent group of patients who underwent both stereotactic MRI and CT imaging before treatment (negative controls; n: 5). Patients undergoing GKR for arteriovenous malformations (AVM) also underwent digital subtraction angiography (DSA), which could result in extra stresses on the frame. The distance between landmark local-ization in the scans for the negative control group (0.63 mm; 95% CI: 0.57-0.70; SD: 0.29) represents the overall consistency of the evaluation method and provides an estimate of the minimum displacement that could be detected by the study. Two patients in the study group had the fiducial indicator box accidentally misplaced at post-treatment CT scanning. This simulated the scenario of a frame displacement, and these cases were used as positive controls to demonstrate that the evaluation method is capable of detecting a discrepancy between the MRI and CT scans, if there was one. The mean distance between the location of the landmarks in the pretreatment MRI and post-treatment CT scans for the study group was 0.71 mm (95% CI: 0.68-0.74; SD:0.32), which was not statistically different from the over-all uncertainty of the evaluation method observed in the negative control group (p = 0.06). The subgroup of patients with AVM (n: 9), who also underwent DSA, showed a statistically significant difference between the location of the landmarks compared to subjects with no additional imaging: 0.78 mm (95% CI: 0.72-0.84) vs. 0.69 mm (95% CI: 0.66-0.72), p = 0.016. This is however a minimal differ-ence (0.1 mm) and the mean difference in landmark location for each AVM patient remained submillimeter. This study demonstrates submillimeter stability of the Leksell Frame G in GKR throughout the treatment procedure.

Stereotactic Radiosurgery for Intracranial Cavernous Malformations: International Stereotactic Radiosurgery Society, Systematic Review, Meta-Analysis, and Practice Guidelines.

OBJECTIVE: The International Stereotactic Radiosurgery Society (ISRS) aims to establish evidence-based guidelines for single-fraction stereotactic radiosurgery (SRS) in treating intracranial cavernous malformations. METHODS: We conducted a systematic review following PRISMA and MOOSE guidelines, searching electronic databases up to January 2024 to assess SRS's impact on post-treatment hemorrhage rates. Pooled risk ratios (RR) and confidence intervals were utilized to quantify this effect, along with assessments of lesion volume changes, seizure outcomes, and SRS-related adverse effects. RESULTS: Our meta-analysis included 32 studies with 2672 patients. A significant decrease in annual hemorrhage rates was observed post-treatment (RR=0.17), with rates of RR=0.29 in the first 2 years and RR=0.11 thereafter. Hemorrhage rates significantly differed before and after 2 years post-SRS (RR=0.36). Among epileptic patients, 20.2% had epilepsy pre-treatment, and 49.9% were seizure-free post-SRS, while 30.6% experienced reduced seizure frequency. Lesion volume changes showed a reduction in 46.9%, stability in 47.1%, and an increase in 6.7%. Symptomatic radiation effects affected 8% of patients. Subgroup analysis revealed symptomatic change rates of 6% at doses ≤13Gy compared to 9% at doses >13Gy. Permanent clinical deficits were rare (2%). CONCLUSION: This meta-analysis suggests SRS is an effective intervention for intracranial cavernous malformations, significantly reducing hemorrhage rates and improving seizure outcomes. ISRS practice guidelines are provided.

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.

Experience of Gamma Knife radiosurgery for treatment of brain metastases in pregnancy with literature review.

Brain metastases during pregnancy poses complex conundrum in management. Stereotactic radiosurgery (SRS) offers valuable option to clinicians in this scenario. We reviewed and described the safety and effectiveness of Gamma Knife (GK) SRS in treating a solitary cerebellar metastasis in a patient with recurrent breast cancer at 28 weeks of gestation. Following multidisciplinary discussion, she consented for urgent single session GK SRS to the brain metastasis with 2 cycles of 3-weekly paclitaxel chemotherapy prior to planned delivery at term. Prior to the frame-based treatment, a trial run with dosimeters placed on the superior and inferior parts of foam knee support showed radiation exposure of 3.12 mSv and 1.06 mSv respectively. A prescription dose of 16 Gy at the 50% isodose was delivered using 24 isocentres over 39.7' of beam on time. The treatment plan had 98% coverage, 89% selectivity and a gradient index of 2.98. Dosimeters placed near the uterine fundus and suprapubic region (consistent with location of fetal head) during the actual treatment recorded 2.83 mSv and 0.27 mSv, which is lower than the trial dosimeter readings. The patient successfully completed SRS treatment and gave birth to a healthy baby two months later. Follow-up MRI at three months interval showed total resolution of the lesion. GK SRS is known for the lowest extracranial dose compared to other SRS modalities. This report and literature review confirmed that GK is a sharp and effective, yet gentle and safe treatment for pregnant patients with brain metastases.

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.

Pediatric Cranial Stereotactic Radiosurgery: Meta-Analysis and International Stereotactic Radiosurgery Society Practice Guidelines.

BACKGROUND: There are limited data on the use of stereotactic radiosurgery (SRS) for pediatric patients. The aim of this systematic review was to summarize indications and outcomes specific to pediatric cranial SRS to inform consensus guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: A systematic review, using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), analyzed English-language articles on SRS, published between 1989 and 2021, that included outcomes for at least 5 pediatric patients. MEDLINE database terms included tumor types and locations, and radiosurgical and age-specific terms. We excluded nonclinical reports, expert opinions, commentaries, and review articles. Meta-regressions for associations with local control were performed for medulloblastoma, craniopharyngioma, ependymoma, glioma, and arteriovenous malformation (AVM). RESULTS: Of the 113 articles identified for review, 68 met the inclusion criteria. These articles described approximately 400 pediatric patients with benign and malignant brain tumors and 5119 with AVMs who underwent cranial SRS. The rates of local control for benign tumors, malignant tumors, and AVMs were 89% (95% CI, 82%-95%), 71% (95% CI, 59%-82%), and 65% (95% CI, 60%-69%), respectively. No significant associations were identified for local control with patient-, tumor-, or treatment-related variables. CONCLUSIONS: This review is the first to summarize outcomes specific to SRS for pediatric brain tumors and AVMs. Although data reporting is limited for pediatric patients, SRS appears to provide acceptable rates of local control. We present ISRS consensus guidelines to inform the judicious use of cranial SRS for pediatric patients.

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.

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.

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.

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.

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.