Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

OBJECTIVE: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

Clinical and Imaging Outcomes After Trigeminal Schwannoma Radiosurgery: Results From a Multicenter, International Cohort Study.

BACKGROUND AND OBJECTIVES: An international, multicenter, retrospective study was conducted to evaluate the long-term clinical outcomes and tumor control rates after stereotactic radiosurgery (SRS) for trigeminal schwannoma. METHODS: Patient data (N = 309) were collected from 14 international radiosurgery centers. The median patient age was 50 years (range 11-87 years). Sixty patients (19%) had prior resections. Abnormal facial sensation was the commonest complaint (49%). The anatomic locations were root (N = 40), ganglion (N = 141), or dumbbell type (N = 128). The median tumor volume was 4 cc (range, 0.2-30.1 cc), and median margin dose was 13 Gy (range, 10-20 Gy). Factors associated with tumor control, symptom improvement, and adverse radiation events were assessed. RESULTS: The median and mean time to last follow-up was 49 and 65 months (range 6-242 months). Greater than 5-year follow-up was available for 139 patients (45%), and 50 patients (16%) had longer than 10-year follow-up. The overall tumor control rate was 94.5%. Tumors regressed in 146 patients (47.2%), remained unchanged in 128 patients (41.4%), and stabilized after initial expansion in 20 patients (6.5%). Progression-free survival rates at 3 years, 5 years, and 10 years were 91%, 86%, and 80 %. Smaller tumor volume (less than 8 cc) was associated with significantly better progression-free survival ( P = .02). Seventeen patients with sustained growth underwent further intervention at a median of 27 months (3-144 months). Symptom improvement was noted in 140 patients (45%) at a median of 7 months. In multivariate analysis primary, SRS ( P = .003) and smaller tumor volume ( P = .01) were associated with better symptom improvement. Adverse radiation events were documented in 29 patients (9%). CONCLUSION: SRS was associated with long-term freedom (10 year) from additional management in 80% of patients. SRS proved to be a valuable salvage option after resection. When used as a primary management for smaller volume tumors, both clinical improvement and prevention of new deficits were optimized.

Contingency, repeatability, and predictability in the evolution of a prokaryotic pangenome.

Pangenomes exhibit remarkable variability in many prokaryotic species, much of which is maintained through the processes of horizontal gene transfer and gene loss. Repeated acquisitions of near-identical homologs can easily be observed across pangenomes, leading to the question of whether these parallel events potentiate similar evolutionary trajectories, or whether the remarkably different genetic backgrounds of the recipients mean that postacquisition evolutionary trajectories end up being quite different. In this study, we present a machine learning method that predicts the presence or absence of genes in the Escherichia coli pangenome based on complex patterns of the presence or absence of other accessory genes within a genome. Our analysis leverages the repeated transfer of genes through the E. coli pangenome to observe patterns of repeated evolution following similar events. We find that the presence or absence of a substantial set of genes is highly predictable from other genes alone, indicating that selection potentiates and maintains gene-gene co-occurrence and avoidance relationships deterministically over long-term bacterial evolution and is robust to differences in host evolutionary history. We propose that at least part of the pangenome can be understood as a set of genes with relationships that govern their likely cohabitants, analogous to an ecosystem's set of interacting organisms. Our findings indicate that intragenomic gene fitness effects may be key drivers of prokaryotic evolution, influencing the repeated emergence of complex gene-gene relationships across the pangenome.

Third Stereotactic Radiosurgery for Residual Arteriovenous Malformations: A Retrospective Multicenter Study.

BACKGROUND AND OBJECTIVES: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual. METHODS: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC. RESULTS: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up. CONCLUSION: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs.

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

Stereotactic radiosurgery in the management of non-small cell lung cancer brain metastases: a prospective study using the NeuroPoint Alliance Stereotactic Radiosurgery Registry.

OBJECTIVE: The literature on non-small cell lung cancer (NSCLC) brain metastases (BMs) managed using stereotactic radiosurgery (SRS) relies mainly on single-institution studies or randomized controlled trials (RCTs). There is a literature gap on clinical and radiological outcomes of SRS for NSCLC metastases in real-world practice. The objective of this study was to benchmark mortality and progression outcomes in patients undergoing SRS for NSCLC BMs and identify risk factors for these outcomes using a national quality registry. METHODS: The SRS Registry of the NeuroPoint Alliance was used for this study. This registry included patients from 16 enrolling sites who underwent SRS from 2017 to 2022. Data are prospectively collected without a prespecified research purpose. The main outcomes of this analysis were overall survival (OS), out-of-field recurrence, local progression, and intracranial progression. All time-to-event investigations included Kaplan-Meier analyses and multivariable Cox regressions. RESULTS: Two hundred sixty-four patients were identified, with a mean age of 66.7 years and a female proportion of 48.5%. Most patients (84.5%) had a Karnofsky Performance Status (KPS) score of 80-100, and the mean baseline EQ-5D score was 0.539 quality-adjusted life years. A single lesion was present in 53.4% of the patients, and 29.1% of patients had 3 or more lesions. The median OS was 28.1 months, and independent predictors of mortality included no control of primary tumor (hazard ratio [HR] 2.1), KPS of 80 (HR 2.4) or lower (HR 2.4), coronary artery disease (HR 2.8), and 5 or more lesions present at the time of SRS treatment (HR 2.3). The median out-of-field progression-free survival (PFS) was 24.8 months, and the median local PFS was unreached. Intralesional hemorrhage was an independent risk factor of local progression, with an HR of 6.0. The median intracranial PFS was 14.0 months and was predicted by the number of lesions at the time of SRS (3-4 lesions, HR 2.2; 5-14 lesions, HR 2.5). CONCLUSIONS: In this real-world prospective study, the authors used a national quality registry and found favorable OS in patients with NSCLC BMs undergoing SRS compared with results from previously published RCTs. The intracranial PFS was mainly driven by the emergence of new lesions rather than local progression. A greater number of lesions at baseline was associated with out-of-field progression, while intralesional hemorrhage at baseline was associated with local progression.

Rigidity percolation in a random tensegrity via analytic graph theory.

Functional structures from across the engineered and biological world combine rigid elements such as bones and columns with flexible ones such as cables, fibers, and membranes. These structures are known loosely as tensegrities, since these cable-like elements have the highly nonlinear property of supporting only extensile tension. Marginally rigid systems are of particular interest because the number of structural constraints permits both flexible deformation and the support of external loads. We present a model system in which tensegrity elements are added at random to a regular backbone. This system can be solved analytically via a directed graph theory, revealing a mechanical critical point generalizing that of Maxwell. We show that even the addition of a few cable-like elements fundamentally modifies the nature of this transition point, as well as the later transition to a fully rigid structure. Moreover, the tensegrity network displays a collective avalanche behavior, in which the addition of a single cable leads to the elimination of multiple floppy modes, a phenomenon that becomes dominant at the transition point. These phenomena have implications for systems with nonlinear mechanical constraints, from biopolymer networks to soft robots to jammed packings to origami sheets.

Cerebrotendinous xanthomatosis tremor successfully controlled post-ventral intermediate nucleus-deep brain stimulation: a case report.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by a deficiency of the sterol 27-hydroxylase enzyme. This deficiency results in excess production and accumulation of cholestanol, which can lead to many clinical findings within the first three decades of life, including progressive neurological dysfunction. This is a treatable condition with improvements in neurological and non-neurological symptoms upon the early initiation of replacement therapy. This case report details a 42 years-old left-handed male in whom deep brain stimulation (DBS) intervention was pursued due to a limiting tremor related to delayed diagnosis and treatment of CTX at 22 years old. The application of DBS in treating tremors in a CTX patient has not previously been reported. For our patient, application of DBS led to meaningful and longstanding tremor control benefits that have required minimal changes to stimulation parameters post-DBS. These improvements to tremor were achieved without negative impact to his other CTX related comorbidities.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

BACKGROUND: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

Prokaryotic Pangenomes Act as Evolving Ecosystems.

Understanding adaptation to the local environment is a central tenet and a major focus of evolutionary biology. But this is only part of the adaptionist story. In addition to the external environment, one of the main drivers of genome composition is genetic background. In this perspective, I argue that there is a growing body of evidence that intra-genomic selective pressures play a significant part in the composition of prokaryotic genomes and play a significant role in the origin, maintenance and structuring of prokaryotic pangenomes.

Band Theory and Boundary Modes of High-Dimensional Representations of Infinite Hyperbolic Lattices.

Periodic lattices in hyperbolic space are characterized by symmetries beyond Euclidean crystallographic groups, offering a new platform for classical and quantum waves, demonstrating great potential for a new class of topological metamaterials. One important feature of hyperbolic lattices is that their translation group is nonabelian, permitting high-dimensional irreducible representations (irreps), in contrast to abelian translation groups in Euclidean lattices. Here we introduce a general framework to construct wave eigenstates of high-dimensional irreps of infinite hyperbolic lattices, thereby generalizing Bloch's theorem, and discuss its implications on unusual mode counting and degeneracy, as well as bulk-edge correspondence in hyperbolic lattices. We apply this method to a mechanical hyperbolic lattice, and characterize its band structure and zero modes of high-dimensional irreps.

Omnimodal topological polarization of bilayer networks: Analysis in the Maxwell limit and experiments on a 3D-printed prototype.

Periodic networks on the verge of mechanical instability, called Maxwell lattices, are known to exhibit zero-frequency modes localized to their boundaries. Topologically polarized Maxwell lattices, in particular, focus these zero modes to one of their boundaries in a manner that is protected against disorder by the reciprocal-space topology of the lattice's band structure. Here, we introduce a class of mechanical bilayers as a model system for designing topologically protected edge modes that couple in-plane dilational and shearing modes to out-of-plane flexural modes, a paradigm that we refer to as "omnimodal polarization." While these structures exhibit a high-dimensional design space that makes it difficult to predict the topological polarization of generic geometries, we are able to identify a family of mirror-symmetric bilayers that inherit the in-plane modal localization of their constitutive monolayers, whose topological polarization can be determined analytically. Importantly, the coupling between the layers results in the emergence of omnimodal polarization, whereby in-plane and out-of-plane edge modes localize on the same edge. We demonstrate these theoretical results by fabricating a mirror-symmetric, topologically polarized kagome bilayer consisting of a network of elastic beams via additive manufacturing and confirm this finite-frequency polarization via finite element analysis and laser-vibrometry experiments.

Discrete symmetries control geometric mechanics in parallelogram-based origami.

Geometric compatibility constraints dictate the mechanical response of soft systems that can be utilized for the design of mechanical metamaterials such as the negative Poisson's ratio Miura-ori origami crease pattern. Here, we develop a formalism for linear compatibility that enables explicit investigation of the interplay between geometric symmetries and functionality in origami crease patterns. We apply this formalism to a particular class of periodic crease patterns with unit cells composed of four arbitrary parallelogram faces and establish that their mechanical response is characterized by an anticommuting symmetry. In particular, we show that the modes are eigenstates of this symmetry operator and that these modes are simultaneously diagonalizable with the symmetric strain operator and the antisymmetric curvature operator. This feature reveals that the anticommuting symmetry defines an equivalence class of crease pattern geometries that possess equal and opposite in-plane and out-of-plane Poisson's ratios. Finally, we show that such Poisson's ratios generically change sign as the crease pattern rigidly folds between degenerate ground states and we determine subfamilies that possess strictly negative in-plane or out-of-plane Poisson's ratios throughout all configurations.

Robotic swimming in curved space via geometric phase.

Locomotion by shape changes or gas expulsion is assumed to require environmental interaction, due to conservation of momentum. However, as first noted in [J. Wisdom, Science 299, 1865-1869 (2003)] and later in [E. Guéron, Sci. Am. 301, 38-45 (2009)] and [J. Avron, O. Kenneth, New J. Phys, 8, 68 (2006)], the noncommutativity of translations permits translation without momentum exchange in either gravitationally curved spacetime or the curved surfaces encountered by locomotors in real-world environments. To realize this idea which remained unvalidated in experiments for almost 20 y, we show that a precision robophysical apparatus consisting of motors driven on curved tracks (and thereby confined to a spherical surface without a solid substrate) can self-propel without environmental momentum exchange. It produces shape changes comparable to the environment's inverse curvatures and generates movement of [Formula: see text] cm per gait. While this simple geometric effect predominates over short time, eventually the dissipative (frictional) and conservative forces, ubiquitous in real systems, couple to it to generate an emergent dynamics in which the swimming motion produces a force that is counter-balanced against residual gravitational forces. In this way, the robot both swims forward without momentum and becomes fixed in place with a finite momentum that can be released by ceasing the swimming motion. We envision that our work will be of use in a broad variety of contexts, such as active matter in curved space and robots navigating real-world environments with curved surfaces.

Hemorrhage and Recurrence of Obliterated Brain Arteriovenous Malformations Treated With Stereotactic Radiosurgery.

BACKGROUND: Although complete nidal obliteration of brain arteriovenous malformations (AVM) is generally presumed to represent durable cure, postobliteration hemorrhage, and AVM recurrence have become increasingly recognized phenomena. The goal of the study was to define hemorrhage and nidal recurrence risks of obliterated AVMs treated with stereotactic radiosurgery (SRS). METHODS: This is a retrospective cohort study from the International Radiosurgery Research Foundation comprising AVM patients treated between 1987 and 2020. Patients with AVM obliteration on digital subtraction angiography (DSA) were included. Outcomes were (1) hemorrhage and (2) AVM recurrence. Follow-up duration began at the time of AVM obliteration and was censored at subsequent hemorrhage, AVM recurrence, additional AVM treatment, or loss to follow-up. Annualized risk and survival analyses were performed. A sensitivity analysis comprising patients with AVM obliteration on magnetic resonance imaging or DSA was also performed for postobliteration hemorrhage. RESULTS: The study cohort comprised 1632 SRS-treated patients with AVM obliteration on DSA. Pediatric patients comprised 15% of the cohort, and 42% of AVMs were previously ruptured. The mean imaging follow-up after AVM obliteration was 22 months. Among 1607 patients with DSA-confirmed AVM obliteration, 16 hemorrhages (1.0%) occurred over 2223 patient-years of follow-up (0.72%/y). Of the 1543 patients with DSA-confirmed AVM obliteration, 5 AVM recurrences (0.32%) occurred over 2071 patient-years of follow-up (0.24%/y). Of the 16 patients with postobliteration hemorrhage, AVM recurrence was identified in 2 (12.5%). In the sensitivity analysis comprising 1939 patients with post-SRS AVM obliteration on magnetic resonance imaging or DSA, 16 hemorrhages (0.83%) occurred over 2560 patient-years of follow-up (0.63%/y). CONCLUSIONS: Intracranial hemorrhage and recurrent arteriovenous shunting after complete nidal obliteration are rare in AVM patients treated with SRS, and each phenomenon harbors an annual risk of <1%. Although routine postobliteration DSA cannot be recommended to SRS-treated AVM patients, long-term neuroimaging may be advisable in these patients.

Prokaryote pangenomes are dynamic entities.

Prokaryote pangenomes are influenced heavily by environmental factors and the opportunity for gene gain and loss events. As the field of pangenome analysis has expanded, so has the need to fully understand the complexity of how eco-evolutionary dynamics shape pangenomes. Here, we describe current models of pangenome evolution and discuss their suitability and accuracy. We suggest that pangenomes are dynamic entities under constant flux, highlighting the influence of two-way interactions between pangenome and environment. New classifications of core and accessory genes are also considered, underscoring the need for continuous evaluation of nomenclature in a fast-moving field. We conclude that future models of pangenome evolution should incorporate eco-evolutionary dynamics to fully encompass their dynamic, changeable nature.

Factors associated with progression and mortality among patients undergoing stereotactic radiosurgery for intracranial metastasis: results from a national real-world registry.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been increasingly employed in recent years to treat intracranial metastatic lesions. However, there is still a need for optimization of treatment paradigms to provide better local control and prevent progressive intracranial disease. In the current study, the authors utilized a national collaborative registry to investigate the outcomes of patients with intracranial metastatic disease who underwent SRS and to determine factors associated with lesion treatment response, overall progression, and mortality. METHODS: The NeuroPoint Alliance SRS registry was queried for all patients with intracranial metastatic lesions undergoing single- or multifraction SRS at participating institutions between 2016 and 2020. The main outcomes of interest included lesion response (lesion-level analysis), progression using Response Assessment for Neuro-Oncology criteria, and mortality (patient-level analysis). Kaplan-Meier analysis was used to report time to progression and overall survival, and multivariable Cox proportional hazards analysis was used to investigate factors associated with lesion response, progression, and mortality. RESULTS: A total of 501 patients (1447 intracranial metastatic lesions) who underwent SRS and had available follow-up were included in the current analyses. The most common primary tumor was lung cancer (49.5%, n = 248), followed by breast (15.4%, n = 77) and melanoma (12.2%, n = 61). Most patients had a single lesion (44.9%, n = 225), 29.3% (n = 147) had 2 or 3 lesions, and 25.7% (n = 129) had > 3 lesions. The mean sum of baseline measurements of the lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) was 35.54 mm (SD 25.94). At follow-up, 671 lesions (46.4%) had a complete response, 631 (43.6%) had a partial response (≥ 30% decrease in longest diameter) or were stable (< 30% decrease but < 20% increase), and 145 (10%) showed progression (> 20% increase in longest diameter). On multivariable Cox proportional hazards analysis, melanoma-associated lesions (HR 0.48, 95% CI 0.34-0.67; p < 0.001) and larger lesion size (HR 0.94, 95% CI 0.93-0.96; p < 0.001) showed lower odds of lesion regression, while a higher biologically effective dose was associated with higher odds (HR 1.001, 95% CI 1.0001-1.00023; p < 0.001). A total of 237 patients (47.3%) had overall progression (local failure or intracranial progressive disease), with a median time to progression of 10.03 months after the index SRS. Factors found to be associated with increased hazards of progression included male sex (HR 1.48, 95% CI 1.108-1.99; p = 0.008), while administration of immunotherapy (before or after SRS) was found to be associated with lower hazards of overall progression (HR 0.62, 95% CI 0.460-0.85; p = 0.003). A total of 121 patients (23.95%) died during the follow-up period, with a median survival of 19.4 months from the time of initial SRS. A higher recursive partitioning analysis score (HR 21.3485, 95% CI 1.53202-3.6285; p < 0.001) was found to be associated with higher hazards of mortality, while single-fraction treatment compared with hypofractionated treatment (HR 0.082, 95% CI 0.011-0.61; p = 0.015), administration of immunotherapy (HR 0.385, 95% CI 0.233-0.64; p < 0.001), and presence of single compared with > 3 lesions (HR 0.427, 95% CI 0.187-0.98; p = 0.044) were found to be associated with lower risk of mortality. CONCLUSIONS: The comparability of results between this study and those of previously published clinical trials affirms the value of multicenter databases with real-world data collected without predetermined research purpose.