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Abstract BACKGROUND 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 Spetzler-Martin 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.

Abstract BACKGROUND Stereotactic radiosurgery (SRS) for benign intracranial meningiomas is an established treatment. OBJECTIVE To summarize the literature and provide evidence-based practice guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS Articles in English specific to SRS for benign intracranial meningioma, published from January 1964 to April 2018, were systematically reviewed. Three electronic databases, PubMed, EMBASE, and the Cochrane Central Register, were searched. RESULTS Out of the 2844 studies identified, 305 had a full text evaluation and 27 studies met the criteria to be included in this analysis. All but one were retrospective studies. The 10-yr local control (LC) rate ranged from 71% to 100%. The 10-yr progression-free-survival rate ranged from 55% to 97%. The prescription dose ranged typically between 12 and 15 Gy, delivered in a single fraction. Toxicity rate was generally low. CONCLUSION The current literature supporting SRS for benign intracranial meningioma lacks level I and II evidence. However, when summarizing the large number of level III studies, it is clear that SRS can be recommended as an effective evidence-based treatment option (recommendation level II) for grade 1 meningioma.

Abstract BACKGROUND: The risk of radiation-induced optic neuropathy (RION) is the primary limitation of single-fraction stereotactic radiosurgery (SRS) for many patients with parasellar lesions. OBJECTIVE: To define the normal tissue complication probability of the anterior visual pathways (AVPs) after single-fraction SRS. METHODS: Retrospective review comparing visual function before and after SRS in 133 patients (266 sides) with pituitary adenomas having SRS between October 2007 and July 2012. Patients with prior radiation therapy or SRS were excluded. The median follow-up after SRS was 32 months. RESULTS: The median maximum point dose to the AVP was 9.2 Gy (interquartile range [IQR], 6.9-10.8). One hundred seventy-four sides (65%) received >8 Gy: the median 8-Gy volume was 15.8 mm3 (IQR, 3.7-36.2). Ninety-four sides (35%) received >10 Gy; the median 10-Gy volume was 1.6 mm3 (IQR, 0.5-5.3). Twenty-nine sides (11%) received >12 Gy; the median 12-Gy volume was 0.1 mm3 (IQR, 0.1-0.6). No patient had a RION after SRS. The chances of developing a RION at the 8-Gy, 10-Gy, and 12-Gy volumes (95% confidence interval) in this series were 0% to 2.6%, 0% to 4.7%, and 0% to 13.9%, respectively. CONCLUSION: The AVP in patients without prior radiation treatments can safely receive radiation doses up to 12 Gy with a low risk of RION. Although additional studies are needed to better delineate the normal tissue complication probability of the AVP, adherence to the AVP radiation tolerance guidelines developed 20 years ago (8 Gy) limits the applicability and potentially the effectiveness of single-fraction SRS for patients with lesions in the parasellar region.

Abstract BACKGROUND Late adverse radiation effects (ARE) typically occur many years after stereotactic radiosurgery (SRS) of intracranial arteriovenous malformations (AVM). They are characterized by perilesional edema or cyst formation and are distinct from radiation-induced changes (RIC) noted in the first 1 to 2 years after AVM SRS and radiation necrosis. OBJECTIVE To determine the incidence of late ARE after AVM SRS. METHODS Retrospective review of 233 AVM patients having SRS from 1990 to 2009. Patients had sporadic AVM, no prior radiation, and a minimum of 5 years of magnetic resonance imaging (MRI) follow-up. The median MRI follow-up after SRS was 9.8 years (range, 5-24.2). RESULTS Late ARE were observed in 16 patients (6.9%) at a median of 8.7 years after SRS (range, 2.0-16.1). The 5-, 10-, and 15-year incidence of late ARE was 0.4%, 7.7%, and 12.5%, respectively. Eight patients (3.4%) were symptomatic at the time of ARE detection. Three of 8 patients who were initially asymptomatic had documented cyst progression (at 11, 40, and 42 months), for an overall symptomatic rate of 4.7%. Five patients with asymptomatic ARE have been observed for a median of 9.3 years (range, 2.0-14.1) without progression. Patients having early RIC (hazard ratio [HR] = 2.11, P < .001), patients having obliteration (HR = 1.24, P = .02), and patients having SRS before April 1997 (HR = 1.12, P = .02) were more likely to develop late ARE. CONCLUSION Late ARE are common in AVM patients who develop early RIC after SRS. Resection of the thrombosed AVM and the adjacent damaged tissue is effective at eliminating the mass effect and improving patients’ neurological condition.

Abstract BACKGROUND: Stereotactic radiosurgery (SRS) of benign intracranial meningiomas is an accepted management option for well-selected patients. OBJECTIVE: To analyze patients who had single-fraction SRS for benign intracranial meningiomas to determine factors associated with tumor control and neurologic complications. METHODS: Retrospective review was performed of 416 patients (304 women/112 men) who had single-fraction SRS for imaging defined (n = 252) or confirmed World Health Organization grade I (n = 164) meningiomas from 1990 to 2008. Excluded were patients with radiation-induced tumors, multiple meningiomas, neurofibromatosis type 2, and previous or concurrent radiotherapy. The majority of tumors (n = 337; 81%) involved the cranial base or tentorium. The median tumor volume was 7.3 cm3; the median tumor margin dose was 16 Gy. The median follow-up was 60 months. RESULTS: The disease-specific survival rate was 97% at 5 years and 94% at 10 years. The 5- and 10-year local tumor control rate was 96% and 89%, respectively. Male sex (hazard ratio [HR]: 2.5, P = .03), previous surgery (HR: 6.9, P = .002) and patients with tumors located in the parasagittal/falx/convexity regions (HR: 2.8, P = .02) were negative risk factors for local tumor control. In 45 patients (11%) permanent radiation-related complications developed at a median of 9 months after SRS. The 1- and 5-year radiation-related complication rate was 6% and 11%, respectively. Risk factors for permanent radiation-related complication rate were increasing tumor volume (HR: 1.05, P = .008) and patients with tumors of the parasagittal/falx/convexity regions (HR: 3.0, P = .005). CONCLUSION: Single-fraction SRS at the studied dose range provided a high rate of tumor control for patients with benign intracranial meningiomas. Patients with small volume, nonoperated cranial base or tentorial meningiomas had the best outcomes after single-fraction SRS.

PurposeTo clarify the role of stereotactic radiosurgery (SRS) for atypical meningiomas (AM).MethodsA retrospective analysis of 68 patients with AM having SRS from 1995 until 2019.ResultsNineteen patients (28%) had undergone prior external beam radiation therapy (EBRT) (median dose, 54 Gy). The median follow-up period was 52 months. Eighteen (26%), 17 (25%), and 33 (49%) patients received SRS as an upfront adjuvant (≤ 6 months), early salvage (7–18 months), or late salvage treatment (> 18 months), respectively. The 3-, 5-, and 10-year progression-free survivals (PFSs) were 52%, 35%, and 25%, respectively. The 3-, 5-, and 10-year disease-specific survivals were 85%, 78%, and 61%, respectively. Adverse radiation events (AREs) were observed in 12 patients (18%), with increased or new seizures being the most frequent complication (n = 7). Prior EBRT was associated with reduced PFS (HR 5.92, P < 0.01), reduced DSS (HR 5.84, P < 0.01), and an increased risk of ARE (HR 3.31, P = 0.04). Timing of SRS was correlated with reduced PFS for patients having early salvage treatment compared to upfront adjuvant (HR 3.17, P = 0.01) or late salvage treatment (HR 4.39, P < 0.01).ConclusionPFS for patients with residual/recurrent AM remains poor despite SRS. Prior EBRT was associated with worse tumor control, higher tumor-related mortality, and an increased risk of ARE. Further study on the timing of SRS is needed to determine if upfront adjunctive SRS improves tumor control compared to salvage SRS.

Although considered slow-growing, low-grade malignancies, chordomas are locally aggressive and destructive tumors with high recurrence rates. To assess patient survival, tumor control, complications, and selected variables that predict outcome in patients who underwent Gamma Knife stereotactic radiosurgery (SRS) as primary, adjuvant, or salvage management for chordomas of the skull base. Six participating centers of the North American Gamma Knife Consortium identified 71 patients who underwent SRS for chordoma. The median patient age was 45 years (range, 7-80 years). The median SRS target volume was 7.1 cm³ (range, 0.9-109 cm³), and median margin dose was 15.0 Gy (range, 9-25 Gy). At a median follow-up of 5 years (range, 0.6-14 years) after SRS, 23 patients died of tumor progression. The 5-year actuarial overall survival after SRS was 80% for the entire group, 93% for the no prior fractionated radiation therapy (RT) group (n = 50), and 43% for the prior RT group (n = 21). Younger age, longer interval between initial diagnosis and SRS, no prior RT, < 2 cranial nerve deficits, and smaller total tumor volume were significantly associated with longer patient survival. The 5-year treated tumor control rate after SRS was 66% for the entire group, 69% for the no prior RT group, and 62% for the prior RT group. Older age, recurrent group, prior RT, and larger tumor volume were significantly associated with worse tumor control. Stereotactic radiosurgery is a potent treatment option for small sized chordomas, especially in younger patients and as part of a multipronged attack that includes surgical resection when possible.

Stereotactic radiosurgery is a frequently performed procedure for patients with benign intracranial tumors. Benign tumors are good candidates for radiosurgery because they are generally non-invasive, are well visualized by magnetic resonance imaging, and their slow rate of proliferation makes conventional radiation dose fractionation unnecessary. Stereotactic radiosurgery is now an important part of both neurosurgical and radiation oncology training. This chapter will review the indications and results of radiosurgery for patients with intracranial meningiomas, vestibular schwannomas, and pituitary adenomas having single-fraction radiosurgery at the Mayo Clinic since 1990.

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. OBJECTIVE To improve understanding of clinical and dosimetric factors predicting biochemical remission. METHODS A single-institution cohort study of nonsyndromic, radiation-naïve patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or <24 mo of follow-up. The primary outcome was biochemical remission—defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppression. Biochemical remission was assessed using Cox proportional hazards. Prior studies reporting IGF-1i were assessed via systematic literature review and meta-analysis using random-effect modeling. RESULTS A total of 102 patients met study criteria. Of these, 46 patients (45%) were female. The median age was 49 yr (interquartile range [IQR] = 37-59), and the median follow-up was 63 mo (IQR = 29-100). The median pre-SRS IGF-1i was 1.66 (IQR = 1.37-3.22). The median margin dose was 25 Gy (IQR = 21-25); the median estimated biologically effective dose (BED) was 169.49 Gy (IQR = 124.95-196.00). Biochemical remission was achieved in 58 patients (57%), whereas 22 patients (22%) had medication-controlled disease. Pre-SRS IGF-1i ≥ 2.25 was the strongest predictor of treatment failure, with an unadjusted hazard ratio (HR) of 0.51 (95% CI = 0.26-0.91, P = .02). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained significant—and was independently associated with outcome in continuous (HR = 1.01, 95% CI = 1.00-1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39-5.22, P = .002). A total of 24 patients (29%) developed new post-SRS hypopituitarism. Pooled HR for biochemical remission given subthreshold IGF-1i was 2.25 (95% CI = 1.33-3.16, P < .0001). CONCLUSION IGF-1i is a reliable predictor of biochemical remission after SRS. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed. Graphical Abstract Graphical Abstract

Intracranial vascular malformations are seen increasingly in clinical practice, primarily because of advances in cross-sectional brain and spinal cord imaging. Commonly encountered lesion types include arteriovenous malformations, cavernous malformations, venous malformations, dural arteriovenous fistulas, and capillary telangiectasias. Patients can experience various symptoms and signs at presentation. The natural history of vascular malformations depends on lesion type, location, size, and overall hemodynamics. The natural history for each lesion subtype is reviewed, with special consideration of the risk of hemorrhage or other adverse outcomes after the lesion is detected and any known predictors of hemorrhage or other outcomes. In practice, these data are compared with the risk of available treatment options as the optimal management is clarified. A multidisciplinary approach including neurosurgery, radiosurgery, interventional neuroradiology, and vascular neurology is most useful in determining the best management strategy.