Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic ß-Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field.

A ß-cyclodextrin (ß-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the "Atkinson-Brezovich criterion". The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.

Multidisciplinary neurofibromatosis conference in the management of patients with neurofibromatosis type 1 and schwannomatosis in a single tertiary care institution.

OBJECTIVE: To evaluate the role of weekly neurofibromatosis (NF) multi-disciplinary conferences (MDC) on the diagnostic and therapeutic plan for patients with NF type 1 (NF1) and schwannomatosis (SWN). MATERIALS AND METHODS: This retrospective study reviewed patients with confirmed or suspected NF1 and SWN discussed in weekly MDC from March to July 2021. Demographic data collected included patient age, sex, pre-conference and post-conference diagnosis, radiological studies reviewed, and provider specialties in attendance. Outcomes reported included changes in imaging interpretation and treatment plans, changes in post-conference diagnosis relative to pre-conference diagnosis, and time to completion of the recommended change in treatment. RESULTS: Data from 17 MDC "pre-conference" lists included 75 patients (38 female, 37 males, mean age (years): 38 (range: 6-80)) with NF1 (52%, 39/75) and SWN (36%, 27/75) discussed over a total of 91 case reviews. 18.7% (14/75) of all patients had NF2-related SWN, and 17.3% (13/75) of all patients had non-NF2 SWN. The MDC led to changes in imaging interpretation in 18.7% and changes in patient management in 74.7% (diagnostic testing (n = 52), surgical plan (n = 24), medical treatment (n = 9), clinical trial status (n = 4), and radiation treatment (n = 1)) of cases. Among patients for whom a change in management was recorded, 91% (62/68) completed at least one recommendation (mean time to completion (days): 41.4 (range: 0-278)). CONCLUSION: Weekly MDC changes the diagnostic and therapeutic management of the majority of patients discussed (74.7%) and promotes a high adherence rate to recommendations (91%).

Conformational Changes of Poly(Maleic Anhydride-alt-styrene) Modified with Amino Acids in an Aqueous Medium and Their Effect on Cytocompatibility and Hemolytic Response.

The conformational changes of poly(maleic anhydride-alt-styrene) (PSMA) modified with different amino acids (PSMA-Aa) were studied in an aqueous medium as a function of ionic strength and pH. The specific viscosity of PSMA-Aa decreased with increasing salt concentration due to a more compact conformation. There was a decrease in surface tension with increasing concentrations of the modified polyelectrolyte having a greater effect for the PSMA modified with l-phenylalanine at pH 7.0, demonstrating a greater surface-active character. The conformational changes were also confirmed by molecular dynamics studies, indicating that PSMA-Aa exhibits a compact structure at pH 4.0 and a more extended structure at pH 7.0. On the other hand, the conformational changes of PSMA-Aa were related to its biological response, where the higher surface-active character of the PSMA modified with l-phenylalanine correlates very well with the higher hemolytic activity observed in red blood cells, in which the surface-active capacity supports lytic potency in erythrocytes. The cytocompatibility assays indicated that there were no significant cytotoxic effects of the PSMA-Aa. Additionally, in solvent-accessible surface area studies, it was shown that the carboxylate groups of the PSMA modified with l-phenylalanine are more exposed to the solvent at pH 7.0 and high salt concentrations, which correlates with lower fluorescence intensity, reflecting a loss of mitochondrial membrane potential. It is concluded that the study of the conformational changes in PE modified with amino acids is essential for their use as biomaterials and relevant to understanding the possible effects of PE modified with amino acids in biological systems.

COVID-19 cleaning protocol changes, experiences, and respiratory symptom prevalence among cleaning services personnel.

Introduction: Cleaning protocols were changed in response to the COVID-19 pandemic with unknown occupational health impacts. There is evidence that COVID-19 transmission risks from contaminated surfaces are low and that exposure to cleaning products can increase risks of work-related asthma. The study objective was to investigate relationships between reported COVID-19-related changes in cleaning protocols and prevalence of asthma-related respiratory symptoms for asthmatic and non-asthmatic janitors and maids. A secondary objective was to characterize experiences of respiratory symptoms associated with cleaning and barriers to personal protective equipment (PPE) use. Methods: Employees from two Tucson-based maid service companies (approximately 30 personnel in total) and one Phoenix-based school district (>300 janitors/custodians) were invited to participate in a written survey and/or a one-on-one interview in Spanish or English. Fisher's exact tests (α = 0.05) were used to test for statistically significant associations between reported respiratory symptoms by self-reported physician-diagnosed asthma status and changes in cleaning protocols. Interviews were transcribed and then analyzed by at least two researchers in English or Spanish. Results: Eighty-three percent reported that cleaning protocols had changed during COVID-19, with the two most reported changes including increased cleaning frequency (92%) and change of application type (e.g., fog, spray, wipe) (53%). There was a statistically significant association between multiple respiratory symptoms and self-reported physician diagnosed asthma. Reporting a type of application change (e.g., fog, spray, wipe) and being awakened during the night by attack/episode of cough were statistically significantly associated (p = 0.04). Interviews elucidated respiratory issues related to fogging devices. Discussion: This study provides preliminary evidence that changes in cleaning and disinfection protocols during COVID-19 (namely, the use of fogging/mechanical spraying devices) may have had negative impacts on the health of workers in the cleaning industry with little benefit to reducing COVID-19 risks. Further research is needed to evaluate the generalizability of our findings across larger geographical areas and to develop guidance for employers and employees on how to protect and promote respiratory health.

Current and Emerging Imaging Techniques for Neurofibromatosis Type 1-Associated Cutaneous Neurofibromas.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

Existing and Developing Preclinical Models for Neurofibromatosis Type 1-Related Cutaneous Neurofibromas.

Neurofibromatosis type 1 (NF1) is caused by a nonfunctional copy of the NF1 tumor suppressor gene that predisposes patients to the development of cutaneous neurofibromas (cNFs), the skin tumor that is the hallmark of this condition. Innumerable benign cNFs, each appearing by an independent somatic inactivation of the remaining functional NF1 allele, form in nearly all patients with NF1. One of the limitations in developing a treatment for cNFs is an incomplete understanding of the underlying pathophysiology and limitations in experimental modeling. Recent advances in preclinical in vitro and in vivo modeling have substantially enhanced our understanding of cNF biology and created unprecedented opportunities for therapeutic discovery. We discuss the current state of cNF preclinical in vitro and in vivo model systems, including two- and three-dimensional cell cultures, organoids, genetically engineered mice, patient-derived xenografts, and porcine models. We highlight the models' relationship to human cNFs and how they can be used to gain insight into cNF development and therapeutic discovery.

Cutaneous Neurofibroma Heterogeneity: Factors that Influence Tumor Burden in Neurofibromatosis Type 1.

Neurofibromatosis type 1 is one of the most common genetic disorders of the nervous system and predisposes patients to develop benign and malignant tumors. Cutaneous neurofibromas (cNFs) are NF1-associated benign tumors that affect nearly 100% of patients with NF1. cNFs dramatically reduce patients' QOL owing to their unaesthetic appearance, physical discomfort, and corresponding psychological burden. There is currently no effective drug therapy option, and treatment is restricted to surgical removal. One of the greatest hurdles for cNF management is the variability of clinical expressivity in NF1, resulting in intrapatient and interpatient cNF tumor burden heterogeneity, that is, the variability in the presentation and evolution of these tumors. There is growing evidence that a wide array of factors are involved in the regulation of cNF heterogeneity. Understanding the mechanisms underlying this heterogeneity of cNF at the molecular, cellular, and environmental levels can facilitate the development of innovative and personalized treatment regimens.

Target Product Profile for Cutaneous Neurofibromas: Clinical Trials to Prevent, Arrest, or Regress Cutaneous Neurofibromas.

Cutaneous neurofibromas (cNFs) are benign tumors of the skin that affect >95% of adults with neurofibromatosis type 1. Despite their benign histology, cNFs can significantly impact QOL due to disfigurement, pain, and pruritus. There are no approved therapies for cNFs. Existing treatments are limited to surgery or laser-based treatments that have had mixed success and cannot be readily applied to a large number of tumors. We review cNF treatment options that are currently available and under investigation, discuss the regulatory considerations specific to cNFs, and propose strategies to improve cNF clinical trial design and standardize clinical trial endpoints.

RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.

Cutaneous neurofibromas (cNFs) are the most common tumor in people with the rasopathy neurofibromatosis type 1. They number in hundreds or even thousands throughout the body, and currently, there are no effective interventions to prevent or treat these skin tumors. To facilitate the identification of novel and effective therapies, essential studies including a more refined understanding of cNF biology and the role of RAS signaling and downstream effector pathways responsible for cNF initiation, growth, and maintenance are needed. This review highlights the current state of knowledge of RAS signaling in cNF pathogenesis and therapeutic development for cNF treatment.

cNF-Skindex in Adults Living with Neurofibromatosis 1: Severity Strata in France and Validation in United States Adults.

Cutaneous neurofibromas (cNF) contribute to the impairment of QOL in individuals with neurofibromatosis 1. The cNF-Skindex, validated in a French population, specifically assesses the cNF-related QOL. In this study, we first defined severity strata using an anchoring approach on the basis of patient's burden. In total, 209 patients answered the anchor question and the cNF-Skindex. We tested the agreement among the three strata, generated by all potential couples of cut-off values of the cNF-Skindex and the three strata defined in the anchor question. The cut-off values 12 and 49 provided the highest Kappa value (κ = 0.685, 95% confidence interval = 0.604-0.765). Second, we validated the score and the strata in a United States population using the answers provided by 220 French and 148 United States adults. In the multivariable linear regression analysis, the country of origin was not a factor associated with the score (P = 0.297). The number of cNF along the different severity strata was similar between the French and the United States populations. In conclusion, stratification constitutes a powerful tool to better interpret the cNF-Skindex in daily practice and in clinical trials. This study validates its use in two populations that together constitute a large cohort of patients willing to participate in clinical research.

Whole body MRI with DWI in people with NF1 and Schwannomatosis: Are qualitative and quantitative imaging features of peripheral lesions comparable to localized MRI?

PURPOSE: To compare the qualitative and quantitative features of peripheral lesions on localized (L) and whole-body (WB) magnetic resonance imaging (MRI) in people with neurofibromatosis type 1 (NF1) and schwannomatosis. MATERIALS AND METHODS: This is a retrospective, HIPAA compliant study with twenty-seven patients (14 women, 13 men; mean age (years): 38 (3-67)) who underwent both L-MRI and WB-MRI without interval treatment. WB-MRI and L-MRI were comprised of T1-weighted, fat suppressed (FS) T2-weighted or short tau inversion recovery (STIR), diffusion-weighted imaging (DWI) using b-values of 50, 400, and 800 s/mm2, apparent diffusion coefficient (ADC) mapping and pre- and post-contrast FST1 sequences. Two readers recorded qualitative (T1 and T2/STIR signal intensity and heterogeneity, contrast enhancement and heterogeneity, perilesional enhancement, presence of a target sign and perilesional edema) and quantitative (size, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), ADC) features of peripheral lesions on L-MRI and WB-MRI.Descriptive statistics, Wilcoxon signed-rank test and McNemar's test were used. RESULTS: There were 31 peripheral lesions identified in 27 subjects, (mean size: 3.1 cm (range: 1-8.1 cm) on both L-MRI and WB-MRI).There were no differences in T1 signal and heterogeneity and T2/STIR signal and heterogeneity between WB-MRI and L-MRI ((p = 0.180, 0.083, 0.317 and 0.157 respectively). There were also no differences in contrast enhancement, heterogeneity and perilesional enhancement between WB-MRI and L-MRI (p = 1.000, 0.380 and 1.000 respectively). Presence of a target sign and perilesional edema did not differ between WB-MRI and L-MRI (p = 1.000 and 0.500 respectively). Craniocaudal (CC), mediolateral (ML) and anteroposterior (AP) size measurements on WB-MRI did not differ from CC, ML and AP size measurements on L-MRI (p = 0.597, 0.128 and 0.783 respectively). SNR on WB-DWI did not differ from SNR on L-DWI for b50, b400 and b800 images (p = 0.285, 0.166, and 0.974 respectively), and CNR on WB-DWI did not differ from CNR on L-DWI for b50, b400 and b800 images (p = 0.600, 0.124, and 0.787 respectively). There was no significant difference in minimum, mean and maximum ADC values between WB-DWI and L-DWI (p = 0.234, 0.481, and 0.441 respectively). Median minimum, mean and maximum ADC (×10(-3)mm(2)/s) differences between WB-DWI and L-DWI were 0.0 (range -1 to 0.7), 0.0 (range -0.5 to 0.6), and 0.1 (range -1.2 to 0.8) respectively. Relative ADC difference averages were 29.1% for minimum values, 10.1% for mean values, and 14.8% for maximum values. CONCLUSION: WB-MRI yields qualitative and quantitative features for peripheral lesions, including DWI and ADC measurements, that are comparable to L-MRI scans. WB-DWI can be reliably used for the assessment of peripheral nerve sheath tumors, obviating the need for a repeat follow-up L-DWI acquisition.

Clinical, histological, and molecular features of gliomas in adults with neurofibromatosis type 1.

BACKGROUND: People with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research. METHODS: Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified. Retrospective data were collated, and pathology was reviewed centrally. RESULTS: Forty-five patients, comprising 23 females (51%), met eligibility criteria, with a median of age 37 (18-68 years) and performance status of 80% (30%-100%). Tissue was available for 35 patients. Diagnoses included infiltrating (low-grade) astrocytoma (9), glioblastoma (7), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), high-grade astrocytoma (3), WHO diagnosis not reached (4) and one each of gliosarcoma, ganglioglioma, embryonal tumor, and diffuse midline glioma. Seventy-one percent of tumors were midline and underwent biopsy only. All 27 tumors evaluated were IDH1-wild-type, independent of histology. In the 10 cases with molecular testing, the most common genetic variants were NF1, EGFR, ATRX, CDKN2A/B, TP53, TERT, and MSH2/3 mutation. While the treatments provided varied, the median overall survival was 24 months [2-267 months] across all ages, and 38.5 [18-109] months in individuals with grade 1-2 gliomas. CONCLUSIONS: Non-OPGs in adults with NF1, including low-grade tumors, often have an aggressive clinical course, indicating a need to better understand the pathobiology of these NF1-associated gliomas.

Timely Surgery in Intermittent Exotropia.

INTRODUCTION: Surgical treatment of intermittent exotropia is indicated when periods of monocular deviation become longer or control over deviation deteriorates. However, there is no consensus on the ideal age to perform surgery in patients with intermittent exotropia. PURPOSE: To evaluate ocular alignment and sensory results at 12 months of follow-up, in patients who received surgical treatment for intermittent exotropia at ≤4 years or >4 years. METHODS: A retrospective, observational, analytical, and comparative cohort study was carried out, which included 97 patients treated surgically for X(T), divided into two groups, ≤4 years and >4 years. The motor and sensory results of the patients were evaluated on the first day, 1 month and 12 months of postoperative follow-up. RESULTS: In this study, no statistically significant differences were observed in ocular alignment and postoperative sensory results at 1 year of follow-up between both groups. CONCLUSION: Age is not a variable that influences surgical results in patients with intermittent exotropia. Instead of early or delayed surgery, we propose to use the term "timely surgery."

Quantitation of terameprocol in human plasma by liquid chromatography-tandem mass spectrometry.

The global transcription inhibitor terameprocol is being evaluated clinically as an oral formulation to treat high-grade glioma. A sensitive, reliable method was developed to quantitate terameprocol using LC-MS/MS to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of terameprocol and the internal standard, Sorafenib-methyl-d3, was achieved with a Zorbax XDB C18 column (2.1 × 50 mm, 3.5 µm) and gradient elution over a 2-minute total analytical run time. A SCIEX 4500 or SCIEX 5500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for terameprocol detection. The assay range of 5-1000 ng/mL was demonstrated to be accurate (92.7-107.4%) and precise (CV ≤ 11.3%). A sample diluted 1:10 (v/v) was accurately quantitated. Terameprocol in plasma has been proven stable for at least 20 months when stored at -70 °C. The method was applied to the measurement of total plasma concentrations of terameprocol in a patient with a high-grade glioma receiving a 300 mg oral dose.

Broadening learning communities during COVID-19: developing a curricular framework for telemedicine education in neurology.

BACKGROUND: In response to the cancellation of clinical clerkships due to COVID-19, the Johns Hopkins (JH) Neurology Education Team developed a virtual elective to enhance medical students' clinical telemedicine skills and foster community between academic institutions. METHODS: This two-week clinical elective, entitled "Virtual Patient Rounds in Neurology," was administered once in April 2020 and once in May 2020. The curriculum included attending/fellow-led Virtual Rounds, Student Presentations, and Asynchronous Educational Activities. We also developed a new lecture series entitled JHNeuroChats, which consisted of live synchronous lectures presented by JH faculty and Virtual Visiting Professors. Trainees and faculty from outside institutions were invited to participate in the JHNeuroChats. Students and faculty completed pre- and post-elective surveys to assess the educational impact of the elective. Student's t-tests were used to compare scores between pre- and post-elective surveys. RESULTS: Seven JH medical students enrolled in each iteration of the elective, and an additional 337 trainees and faculty, representing 14 different countries, registered for the JHNeuroChats. We hosted 48 unique JHNeuroChats, 32 (66.7%) of which were led by invited Virtual Visiting Professors. At the end of the elective, students reported increased confidence in virtually obtaining a history (P < 0.0001) and performing a telehealth neurological physical exam (P < 0.0001), compared to the start of the course. In addition, faculty members reported increased confidence in teaching clinical medicine virtually, although these findings were not statistically significant (P = 0.15). CONCLUSIONS: Despite the constraints imposed by COVID-19, this virtual Neurology elective increased medical students' confidence in certain telemedicine skills and successfully broadened our learning community to encompass learners from around the world. As virtual medical education becomes more prevalent, it is important that we are intentional in creating opportunities for shared learning across institutions. We believe that this elective can serve as a model for these future educational collaborations.

Management of glioblastoma: a perspective from Mexico.

Access to healthcare in Mexico is available to its population via publicly and privately funded institutions. The public sector, administered by both the local and federal government under the jurisdiction of the Department of Health, provides healthcare to the majority of the country's population. Privately funded institutions vary in size and scope of practice, ranging from small clinics focused on family practice, to large tertiary hospitals with capacity for treating patients with complex conditions and performing clinical research. The evaluation and treatment of patients with cancer in Mexico is also available through both sectors. In the country's capital, Mexico City, patients with glioblastoma are primarily treated at the National Institute of Neurology and Neurosurgery and the National Institute of Oncology. Epidemiological data is incomplete due to the lack of a national cancer registry. In the case of neoplasms of the central nervous system, the available information suggests that gliomas represent 33% of all intracranial tumors. The treatment of patients in Mexico diagnosed with glioblastoma has not been standardized owing to the lack of resources in some communities and the expense of antineoplastic agents. Current options range from a biopsy only to maximal safe resection followed by adjuvant treatment with radiation and chemotherapy. Currently, basic science and clinical research is being conducted in academic institutions associated with universities and in private hospitals. Studies include the evaluation of tumor biology, neuroimaging biomarkers and new treatment options such as the use of chloroquine.

Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Adult Medulloblastoma Workshop.

BACKGROUND: Medulloblastoma (MB) is a rare brain tumor occurring more frequently in children in whom research has been primarily focused. Treatment recommendations in adults are mainly based on retrospective data and pediatric experience; however, molecular features and treatment tolerance differ between the 2 age groups. In adults, prognostic tools are suboptimal, late recurrences are typical, and long-term sequelae remain understudied. Treatment has not adapted to molecular classification advances; thus, the survival rate of adult MB has not improved. METHODS: In 2017, the National Cancer Institute (NCI) received support from the Cancer Moonshot℠ to address the challenges and unmet needs of adults with rare central nervous system tumors through NCI-CONNECT, a program that creates partnerships among patients, health care professionals, researchers, and advocacy organizations. On November 25, 2019, NCI-CONNECT convened leading clinicians and scientists in a workshop to review advances in research, share scientific insights, and discuss clinical challenges in adult MB. RESULTS: Working groups identified unmet needs in clinical trial design, tissue acquisition and testing, tumor modeling, and measurement of clinical outcomes. CONCLUSIONS: Participants identified opportunities for collaboration; discussed plans to create a working group of clinicians, researchers, and patient advocates; and developed specific action items to expedite progress in adult MB.

Quantifying the utility of a multidisciplinary neuro-oncology tumor board.

OBJECTIVE: There has been limited research on the efficacy of multidisciplinary tumor boards (MDTBs) in improving the treatment of patients with tumors affecting the nervous system. The objective of the present study was to quantify the utility of MDTBs in providing alternative diagnostic interpretations and treatment plans for this patient population. METHODS: The authors performed a prospective study of patients in 4 hospitals whose cases were discussed at MDTBs between July and November 2019. Patient demographic data, diagnoses, treatment plans, and eligibility for clinical trials were recorded, among other variables. RESULTS: A total of 176 cases met eligibility criteria for study inclusion. The majority (53%) of patients were male, and the mean patient age was 52 years. The most frequent diagnosis was glioblastoma (32.4%). Among the evaluable cases, MDTBs led to 38 (21.6%) changes in image interpretation and 103 (58.2%) changes in patient management. Additionally, patients whose cases were discussed at MDTBs had significantly shorter referral times than patients whose cases were not discussed (p = 0.024). CONCLUSIONS: MDTB discussions led to significant numbers of diagnostic and treatment plan changes as well as shortened referral times, highlighting the potential clinical impact of multidisciplinary care for patients with nervous system tumors.