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Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

Papillary craniopharyngioma (PCP) is a rare type of tumor, comprising ∼20% of all craniopharyngioma (CP) cases. It is now recognized as a separate pathological entity from the adamantinomatous type. PCPs are benign tumors, classified as World Health Organization grade 1, characterized by nonkeratinizing squamous epithelium. They typically grow as solid and round papillomatous masses or as unilocular cysts with a cauliflower-like excrescence. PCPs primarily occur in adults (95%), with increased frequency in males (60%), and predominantly affect the hypothalamus. Over 80% of these tumors are located in the third ventricle, expanding either above an anatomically intact infundibulum (strictly third ventricle tumors) or within the infundibulo-tuberal region of the third ventricle floor. Clinical manifestations commonly include visual deficits and a wide range of psychiatric disturbances (45% of patients), such as memory deficits and odd behavior. Magnetic resonance imaging can identify up to 50% of PCPs by the presence of a basal duct-like recess. Surgical management is challenging, requiring complex approaches to the third ventricle and posing significant risk of hypothalamic injury. The endoscopic endonasal approach allows radical tumor resection and yields more favorable patient outcomes. Of intriguing pathogenesis, over 90% of PCPs harbor the somatic BRAFV600E mutation, which activates the mitogen-activated protein kinase signaling pathway. A phase 2 clinical trial has demonstrated that PCPs respond well to proto-oncogene B-Raf/MAPK/ERK kinase inhibitors. This comprehensive review synthesizes information from a cohort of 560 well-described PCPs and 99 large CP series including PCP cases published from 1856 to 2023 and represents the most extensive collection of knowledge on PCPs to date.

The molecular weight cutoff for glomerular filtration is thought to be 30—50 kDa. Here we report rapid and efficient filtration of molecules 10—20 times that mass and a model for the mechanism of this filtration. We conducted multimodal imaging studies in mice to investigate renal clearance of a single-walled carbon nanotube (SWCNT) construct covalently appended with ligands allowing simultaneous dynamic positron emission tomography, near-infrared fluorescence imaging, and microscopy. These SWCNTs have a length distribution ranging from 100 to 500 nm. The average length was determined to be 200—300 nm, which would yield a functionalized construct with a molecular weight of ∼350—500 kDa. The construct was rapidly (t 1/2 ∼ 6 min) renally cleared intact by glomerular filtration, with partial tubular reabsorption and transient translocation into the proximal tubular cell nuclei. Directional absorption was confirmed in vitro using polarized renal cells. Active secretion via transporters was not involved. Mathematical modeling of the rotational diffusivity showed the tendency of flow to orient SWCNTs of this size to allow clearance via the glomerular pores. Surprisingly, these results raise questions about the rules for renal filtration, given that these large molecules (with aspect ratios ranging from 100:1 to 500:1) were cleared similarly to small molecules. SWCNTs and other novel nanomaterials are being actively investigated for potential biomedical applications, and these observations—that high aspect ratio as well as large molecular size have an impact on glomerular filtration—will allow the design of novel nanoscale-based therapeutics with unusual pharmacologic characteristics.

Radiation is a mainstay of treatment for central nervous system (CNS) tumors. Brachytherapy involves the placement of a localized/interstitial radiation source into a tumor or resection bed and has distinct advantages that can make it an attractive form of radiation when used in the appropriate setting. However, the data supporting use of brachytherapy is clouded by variability in radiation sources, techniques, delivered doses, and trial designs. The goal of this manuscript is to identify consistent themes, review the highest-level evidence and potential indications for brachytherapy in CNS tumors, as well as highlight avenues for future work. Improved understanding of the underlying biology, indications, complications, and evolving industry-academic collaborations, place brachytherapy on the brink of a resurgence.

Background Leptomeningeal metastasis (LM) occurs in 3–5% of patients with solid metastatic tumors and often portends a severe prognosis including symptomatic hydrocephalus and intracranial hypertension. Cerebrospinal fluid (CSF) shunting can provide symptomatic relief in this patient subset; however, few studies have examined the role of shunting in the palliation, prognosis and overall oncologic care of these patients. Objective To identify and evaluate risk factors associated with prognosis after CSF diversion and assess surgical, symptomatic and oncologic outcomes in this population. Methods A retrospective study was conducted on patients with solid-malignancy LM treated with a shunt at a NCI-designated Comprehensive Cancer Center between 2010 and 2019. Results One hundred and ninety patients with metastatic LM underwent CSF diversion. Overall survival was 4.14 months from LM diagnosis (95% CI: 3.29–4.70) and 2.43 months (95% CI: 2.01–3.09) from shunting. Karnofsky performance status (KPS) at time of shunting and brain metastases (BrM) number at LM diagnosis demonstrated significant associations with survival (HR = 0.66; 95% CI [0.51–0.86], p = 0.002; HR = 1.40; 95% CI [1.01–1.93] per 10 BrM, p = 0.04, respectively). Eighty-three percent of patients experienced symptomatic relief, and 79% were discharged home or to rehabilitation facilities post-shunting. Post-shunt, 56% of patients received additional systemic therapy or started or completed WBRT. Complications included infection (5%), symptomatic subdural hygroma/hematoma (6.3%), and shunt externalization/removal/repair (8%). Abdominal seeding was not identified. Conclusions CSF diversion for LM with hydrocephalus and intracranial hypertension secondary to metastasis can achieve symptomatic relief, hospital discharge, and return to further oncologic therapy, with a complication profile unique to this pathophysiology. However, decision-making in this population must incorporate end-of-life goals of care given limited prognosis.

Purpose Molecular data has become an essential part of the updated World Health Organization (WHO) grading of central nervous system tumors. However, stereotactic needle biopsies provide only small volume specimens and limit the extent of histologic and molecular testing that can be performed. We assessed the use of a tubular retractor-based minimally invasive biopsy technique to provide improved tissue yield and diagnostic data compared to needle biopsy. Methods Eighteen patients underwent an open transtubular biopsy compared to 146 stereotactic biopsies during the years of 2010–2018. Results Tubular biopsies resulted in a higher volume of tissue provided to the pathologist than needle biopsies (1.26 cm 3 vs. 0.3 cm 3 ; p < 0.0001). There was a higher rate of non-diagnostic sample with stereotactic compared to transtubular biopsy (13% vs. 0%; p = 0.13). Six patients who underwent stereotactic biopsy required reoperation for diagnosis, while no transtubular biopsy patient required reoperation in order to obtain a diagnostic specimen. Postoperative hematoma was the most common post-operative complication in both groups. Conclusions Stereotactic transtubular biopsies are a viable alternative to stereotactic needle biopsies with excellent rates of diagnostic success and acceptable morbidity relative to the needle biopsy technique. As molecular data begins to increasingly drive treatment decisions, additional biopsy techniques that afford large tissue volumes may be necessary to adapt to the new needs of pathologists and treating oncologists.

Purpose Extra-central nervous system metastasis (ECM) from glioblastoma and other high-grade gliomas (HGGs) is exceedingly rare, likely due to central nervous system barriers and the short overall survival (OS) in HGG patients, limiting the timeframe for metastasis. Improved treatments have extended survival, potentially increasing ECM incidence, though mechanisms remain unclear. Methods This retrospective study examines HGG patients ( n  = 16) with ECM treated at The University of Texas M. D. Anderson Cancer Center from 1993 to 2023. Results Median age at HGG and ECM diagnoses were 33.6 and 35.1 years, respectively, with a slight female predominance. Diagnoses included glioblastoma, IDH -wildtype WHO Grade 4 ( n  = 11), epithelioid glioblastoma WHO Grade 4 ( n  = 2), astrocytoma IDH -mutant WHO Grade 4 ( n  = 2), and H3K27-altered diffuse midline glioma ( n  = 1). Median interval from HGG to ECM diagnosis was 10 months. The temporal lobe was the most common HGG site, with ECM primarily in cervical lymph nodes, bone, parotid gland, and cranial soft tissues. Genomic profiling identified TP53 , EGFR , RB1 , NF1 , TERT promoter, and BRAF V600E mutations. Median OS from HGG diagnosis was 23.4 months, and median OS following ECM diagnosis was 5.9 months. Chemotherapy and radiotherapy to ECM sites extended survival. Leptomeningeal disease was present in 50% of cases and correlated with worse prognosis. ECM typically developed in advanced disease stages. Conclusion This study highlights genomic alterations, management, and outcomes associated with ECM in HGG. Tumor spread may stem from neurosurgical manipulation and occur via hematogenous and/or lymphatic routes. Multimodal treatment extends survival. Targeted therapies based on molecular profiles should be explored.

Background The introduction of Cesium-131 (Cs-131) as a radiation source has led to a resurgence of brachytherapy for central nervous system (CNS) tumors. The aim of this study was to evaluate the safety and efficacy of the largest cohort of Cs-131 patients to-date. Methods A retrospective review of all CNS tumors treated with resection and adjuvant Cs-131 brachytherapy at New York-Presbyterian/Weill Cornell from 2010 to 2021 was performed. Overall survival (OS) and local control (LC) were assessed with Kaplan-Meier methodology. Univariable analysis was conducted to identify patient factors associated with local recurrence or radiation necrosis. Results Adjuvant Cs-131 brachytherapy following resection was performed in 119 patients with a median follow-up time of 11.8 (IQR 4.7–23.6) months and a mean of 22.3 +/-30.3 months. 1-year survival rates were 53.3% (95%CI 41.9–64.6%) for brain metastases (BrM), 45.9% (95%CI 24.8–67.0%) for gliomas, and 73.3% (95%CI 50.9–95.7%) for meningiomas. 1-year local control rates were 84.7% for BrM, 34.1% for gliomas, and 83.3% for meningiomas (p < 0.001). For BrM, local control was superior in NSCLC relative to other BrM pathologies (90.8% versus 76.5%, p = 0.039). Radiographic radiation necrosis (RN) was identified in 10 (8.4%) cases and demonstrated an association with smaller median tumor size (2.4 [IQR 1.8-2.7 cm] versus 3.1 [IQR 2.4-3.8 cm], p = 0.034). Wound complications occurred in 14 (11.8%) patients. Conclusions Cs-131 brachytherapy demonstrated a favorable safety and efficacy profile characterized by high rates of local control for all treated pathologies. The concept of brachytherapy has seen a resurgence given the excellent results when Cs-131 is used as a source.

Introduction Evidence-based medicine guidelines are increasingly published and sanctioned by organized neurosurgery. However, implementation, interpretation, and use of clinical guidelines may vary substantially on a regional, national and international basis. Survey research can help bridge the gap by providing a snapshot of neurosurgeon attitudes, knowledge, and practices. The American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Section on Tumors formed a Survey Committee to formalize the process by which surveys are submitted and reviewed before distribution to our membership. The goal of this committee is to provide peer-review so that collected information will be scientifically robust and useful to the neurosurgical community. Methods Surveys submitted to the AANS/CNS tumor section between 2015 and 2019 were reviewed and metrics such as response rate and publication status assessed. Results Six surveys were submitted to the Survey Committee of the AANS/CNS section on tumors between 2015 and 2019. Four have been circulated to section members, of which three have been published. Response rate has averaged 19% (range 16–23%), a majority of respondents (mean 70%) practice in academic settings. Conclusions The AANS/CNS Section on Tumors Survey Committee has and continues to help promote and improve the practice of surveying our community to answer important questions that can advance future training, research, and practice. There remains significant room for improvement in response rates, but ongoing tumor section efforts to increase member engagement will likely improve these numbers.