Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Hydrocephalus after Gamma Knife® stereotactic radiosurgery (SRS) for vestibular schwannomas is a rare but manageable occurrence. Most series report post-SRS communicating hydrocephalus in about 1% of patients, thought to be related to a release of proteinaceous substances into the cerebrospinal fluid. While larger tumor size and older patient age have been associated with post-SRS hydrocephalus, the influence of baseline ventricular anatomy on hydrocephalus risk remains poorly defined. METHODS:A single-institution retrospective cohort study examining patients who developed symptomatic communicating hydrocephalus after undergoing Gamma Knife® SRS for unilateral vestibular schwannomas from 2011 to 2021 was performed. Patients with prior hydrocephalus and cerebrospinal fluid diversion or prior surgical resection were excluded. Baseline tumor volume, third ventricle width, and Evans Index (EI)-maximum width of the frontal horns of the lateral ventricles/maximum internal diameter of the skull-were measured on axial postcontrast T1-weighted magnetic resonance imaging. RESULTS:A total of 378 patients met the inclusion criteria; 14 patients (3.7%) developed symptomatic communicating hydrocephalus and 10 patients (2.6%) underwent shunt placement and 4 patients (1.1%) were observed with milder symptoms. The median age of patients who developed hydrocephalus was 69 years (IQR, 67-72) and for patients younger than age 65 years, the risk was 1%. For tumor volumes <1 cm3, the risk of requiring shunting was 1.2%. The odds of developing symptomatic hydrocephalus were 5.0 and 7.7 times higher in association with a baseline EI > 0.28 (P = .024) and tumor volume >3 cm3 (P = .007), respectively, in multivariate analysis. Fourth ventricle distortion on pre-SRS imaging was significantly associated with hydrocephalus incidence (P < .001). CONCLUSION/CONCLUSIONS:Patients with vestibular schwannoma with higher baseline EI, larger tumor volumes, and fourth ventricle deformation are at increased odds of developing post-SRS hydrocephalus. These patients should be counseled regarding risk of hydrocephalus and carefully monitored after SRS.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) with neoadjuvant embolization is a treatment strategy for brain arteriovenous malformations (AVMs), especially for those with large nidal volume or concomitant aneurysms. The aim of this study was to assess the effects of pre-SRS embolization in AVMs with an associated intracranial aneurysm (IA). METHODS:The International Radiosurgery Research Foundation AVM database from 1987 to 2018 was retrospectively reviewed. SRS-treated AVMs with IAs were included. Patients were categorized into those treated with upfront embolization (E + SRS) vs stand-alone SRS (SRS). Primary end point was a favorable outcome (AVM obliteration + no permanent radiation-induced changes or post-SRS hemorrhage). Secondary outcomes included AVM obliteration, mortality, follow-up modified Rankin Scale, post-SRS hemorrhage, and radiation-induced changes. RESULTS:Forty four AVM patients with associated IAs were included, of which 23 (52.3%) underwent pre-SRS embolization and 21 (47.7%) SRS only. Significant differences between the E + SRS vs SRS groups were found for AVM maximum diameter (1.5 ± 0.5 vs 1.1 ± 0.4 cm3, P = .019) and SRS treatment volume (9.3 ± 8.3 vs 4.3 ± 3.3 cm3, P = .025). A favorable outcome was achieved in 45.4% of patients in the E + SRS group and 38.1% in the SRS group (P = .625). Obliteration rates were comparable (56.5% for E + SRS vs 47.6% for SRS, P = .555), whereas a higher mortality rate was found in the SRS group (19.1% vs 0%, P = .048). After adjusting for AVM maximum diameter, SRS treatment volume, and maximum radiation dose, the likelihood of achieving favorable outcome and AVM obliteration did not differ between groups (P = .475 and P = .820, respectively). CONCLUSION/CONCLUSIONS:The likelihood of a favorable outcome and AVM obliteration after SRS with neoadjuvant embolization in AVMs with concomitant IA seems to be comparable with stand-alone SRS, even after adjusting for AVM volume and SRS maximum dose. However, the increased mortality among the stand-alone SRS group and relatively low risk of embolization-related complications suggest that these patients may benefit from a combined treatment approach.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Pediatric spine surgery has evolved considerably over the past century. No previous study conducted a bibliometric analysis of the corpus of pediatric spine surgery. We used big data and advanced bibliometric analyses to evaluate trends in the progression of pediatric spine surgery as a distinct field since the beginning of the 20th century. METHODS:A Web of Science query was designed to capture the representative corpus of pediatric spine literature. Statistical and bibliometric analyses were performed using various Python packages and the Bibliometrix R package. RESULTS:The collection, published from 1902 to 2023, comprised a total of 11 861 articles from 61 journals and 32 715 unique authors. The overall growth rate annually for publications was 5.08%. An upsurge in publications was seen in the 1980s, after the advent of specialty and subspecialty journals. Illustratively, over 90% of all articles pertaining to pediatric spine surgery were published in the past 3 decades. International and domestic collaboration also increased exponentially over this time period. Reference publication year spectroscopy allowed us to identify 75 articles that comprise the historical roots of modern pediatric spine surgery. There was a recent lexical evolution of topics and terms toward alignment, outcomes, and patient-centric terms. Coauthorship among under-represented groups increased since 1990, but remains low, with disparities persisting across journals. CONCLUSION/CONCLUSIONS:This comprehensive bibliometric analysis on the corpus of pediatric spine surgery offers insight into the evolving landscape of research, authorship, and publication trends over the past century. Advancements in the understanding of the natural history and technology have led the field to become increasingly outcomes focused, all of which have been fueled by pioneering authors. While diversity among authors improves, under-representation of various groups continues to persist, indicating a critical role for further outreach and promotion.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Vestibular schwannomas demonstrate different responses after stereotactic radiosurgery (SRS), commonly including a transient loss of internal enhancement on postcontrast T1-weighted MRI thought to be due to an early reduction in tumor vascularity. We used dynamic contrast-enhanced based golden-angle radial sparse parallel (GRASP) MRI to characterize the vascular permeability changes underlying this phenomenon, with correlations to long-term tumor regression. METHODS:Consecutive patients with vestibular schwannoma who underwent SRS between 2017 and 2019, had a transient loss of enhancement after SRS, and had long-term longitudinal GRASP studies (6, 18, and 30 months) were included in this retrospective cohort analysis (n = 19). Using GRAVIS ( https://gravis-imaging.org/gravis/ ), an analysis pipeline for GRASP studies, we extracted the key parameters normalized to the venous sinus from a region of interest within the tumor. RESULTS:The peak, area under the curve (AUC), and wash-in phase slope were significantly reduced at 6, 18, and 30 months after SRS (corrected P < .05), even while the internal enhancement returned in the tumors. Larger pre-SRS tumors were more likely to have a greater reduction in peak ( P = .013) and AUC ( P = .029) at 6 months. In a subset of patients (N = 13) with long-term follow-up, the median percentage reduction in tumor volume was 58% at a median of 62 months. These patients showed a strong correlation between peak, AUC, and wash-in phase slope changes at 6 months and tumor volume at the last follow-up. CONCLUSION/CONCLUSIONS:After SRS and loss of internal contrast uptake within vestibular schwannomas, a slow vascular permeability dynamic persisted, suggesting the presence of postradiation processes such as fibrosis. We show for the first time, using GRASP, a quantitative assessment of the vascular radiobiological effect.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy. METHODS:We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell. We searched the literature for qualitative and quantitative work identifying and quantifying potential sources of inaccuracy and describing each system's implementation using Standards for Reporting Qualitative Research guidelines. Our literature search spanned 1969 to 2024, and various studies were included, with formats ranging from phantom studies to systematic reviews. Keyword searches were conducted, and the details about each system were used to create a framework for identifying and describing the unique targeting error profile of each system. RESULTS:We describe and illustrate the details of various sources of stereotactic inaccuracies and generate a framework to unify these sources into a single framework. This framework entails 5 domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. This framework was applied to 10 stereotactic systems. CONCLUSION/CONCLUSIONS:This framework provides a rubric to analyze the sources of error for any stereotactic system. Illustrations allow the reader to understand sources of error conceptually so that they may apply them to their practice.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Pineocytomas are grade 1 tumors arising from the pineal parenchyma. Gross total resection can potentially cure these benign lesions but can be associated with morbidity. This study was designed to provide multi-institutional data to evaluate the results of stereotactic radiosurgery (SRS) for pineocytomas. METHODS:Centers participating in the International Radiosurgery Research Foundation were asked to review their database and provide data for patients who had SRS for histology confirmed grade 1 pineocytomas, for whom clinical and imaging follow-up of at least 6 months was available. RESULTS:In total, 38 patients underwent SRS as part of the management of a pineocytoma. The median age at SRS was 39 years (range 8-76). SRS was performed as primary approach in 68%, adjuvant after partial resection 19%, and at recurrence in 13% of patients. The median margin dose was 15 Gy (range 11-25 Gy). The median treatment volume was 3.35 cc (range 0.1-17.9 cc). Local tumor control was achieved in 92% of patients, with a mean actuarial progression-free survival of 21.6 years (median not reached). At last follow-up, 82% were still controlled, 8% had local recurrence, and 10% had cerebrospinal fluid dissemination. Tumor control was significantly better when SRS was used as primary care compared with the adjuvant or recurrent setting (P = .016). Five patients (13%) died during follow-up, all from tumor progression. The actuarial mean survival duration was 24.3 years, with a 5-year survival rate of 91%, and an estimated rate of 76% at 29 years. Larger tumor volume at SRS was found to be correlated to increased risk of death (P = .045). Transient symptomatic adverse radiation effects were observed in 4 patients (11%). CONCLUSION/CONCLUSIONS:SRS appears safe and effective for the management of pineocytomas. Long-term tumor control is achieved in most cases. SRS can be offered to selected patients as an alternative to surgical resection.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The management of World Health Organization (WHO) grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited but suggests that a higher dose is better for tumor control. We characterize the predictors of post-SRS outcomes that can help guide planning and management. METHODS:We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. RESULTS:Ninety-nine patients (median age 62 years) underwent SRS, 11 of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received previous irradiation. The median follow-up was 49 months. The median overall survival was 119 months (95% CI 92-NA) with estimated 5- and 10-year survival of 83% and 27%, respectively. The median progression-free survival (PFS) was 40 months (95% CI 32-62), with 3- and 5-year rates at 54% and 35%, respectively. The median locomarginal PFS was 63 months (95% CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 Common Terminology Criteria for Adverse Events grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session cohort, Ki-67 significantly predicted both overall survival and intracranial PFS. Tumors with Ki-67 >10% had 2.17 times the risk of locomarginal progression compared with Ki-67 ≤10% (P = .018) adjusting for covariates. Sex, prescription dose, tumor volume, and location also predicted tumor control. In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control but not for tumors with Ki-67 ≤10%. CONCLUSION/CONCLUSIONS:The management of WHO grade 2 meningiomas requires a multimodality approach. This study demonstrates the value of a targeted SRS approach in patients with limited disease and further establishes predictive biomarkers that can guide planning through a personalized approach.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections. METHODS:Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (≥2) before SRS were reviewed and analyzed. The treatment interval spanned the period of 1992 to 2022. Cox regression and Kaplan-Meier curves were used to assess predictive factors and the probability of tumor control and hypopituitarism. RESULTS:Among the 311 patients (median age: 50.2 [IQR: 18.0] years), 226 (72.7%) had undergone ≥2 previous resections. The median margin dose was 14 Gy (IQR: 4.0 Gy), and the median tumor volume 3.6 cm3 (IQR: 4.8). Overall, the probability of tumor control after SRS was 93.3% (CI 95%: 89.9-96.9) and 86.7% (CI 95%: 81.1-92.6) at 5 and 10 years, respectively. A margin dose >14 Gy was associated with a decreased risk of tumor progression (hazard ratio = 0.33, CI 95% = 0.15-0.75, P = .008). At a last clinical follow-up of 4.1 (IQR 6.1) years, 10.1% (30/296) developed at least 1 new hormone deficiency after SRS. The cumulative probability of new hormone deficiency was 6.1% (95% CI: 3.0-9.1), 10.3% (95% CI: 5.8-14.6), and 18.9% (95% CI: 11.5-25.8) at 3, 5, and 10 years after SRS, respectively. The average latency between SRS and development of new hormone deficiencies was 3.3 years (IQR 4.1). A maximum point dose to the pituitary stalk >10 Gy was associated with a new deficiency (hazard ratio = 4.06, CI 95% = 1.57-10.5, P-value = .004). CONCLUSION/CONCLUSIONS:For patients with NFPA with multiple previous resections, SRS offers effective local tumor control and a low risk of delayed hypopituitarism for managing these challenging adenomas. SRS should be strongly considered in patients with NFPA with 2 previous resections compared with considering a third resection.

Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients (n = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p < 0.001) using recurrent multivariate analysis. The annual hemorrhage rate decreased from 14.8 per 100 CCM-years before SRS to 2.3 after treatment. Using univariate Cox-analysis, the probability of a new hemorrhages after SRS was reduced for patient older than 35 years (HR = 0.21, p = 0.002) and increased with a margin dose > 13 Gy (HR = 2.57, p = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status.