Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion.

Fatty acid synthesis (FAS) has been shown to play a key role in the survival of brain-metastatic (BM) breast cancer. We demonstrate that the fatty acid synthase inhibitor TVB-2640 synergizes with the topoisomerase inhibitor SN-38 in triple-negative breast cancer (TNBC) BM cell lines, upregulates FAS and downregulates cell cycle progression gene expression, and slows the motility of TNBC BM cell lines. The combination of SN-38 and TVB-2640 warrants further consideration as a potential therapeutic option in TNBC BMs.

Optimizing Precision Medicine for Breast Cancer Brain Metastases with Functional Drug Response Assessment.

Unlabelled: The development of novel therapies for brain metastases is an unmet need. Brain metastases may have unique molecular features that could be explored as therapeutic targets. A better understanding of the drug sensitivity of live cells coupled to molecular analyses will lead to a rational prioritization of therapeutic candidates.

Milestones for neurosurgery sub-interns: a novel evaluation tool to quantitatively differentiate residency applicants.

Objective: The study objective was to create a novel milestones evaluation form for neurosurgery sub-interns and assess its potential as a quantitative and standardized performance assessment to compare potential residency applicants. In this pilot study, the authors aimed to determine the form's interrater reliability, relationship to percentile assignments in the neurosurgery standardized letter of recommendation (SLOR), ability to quantitatively differentiate tiers of students, and ease of use.

Methods: Medical student milestones were either adapted from the resident Neurological Surgery Milestones or created de novo to evaluate a student's medical knowledge, procedural aptitude, professionalism, interpersonal and communication skills, and evidence-based practice and improvement.

Artificial-intelligence-based molecular classification of diffuse gliomas using rapid, label-free optical imaging.

Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. However, timely molecular diagnostic testing for patients with brain tumors is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment. In this study, we developed DeepGlioma, a rapid (<90 seconds), artificial-intelligence-based diagnostic screening system to streamline the molecular diagnosis of diffuse gliomas.

Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.

Purpose: Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities.

Experimental Design: We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR).

Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.

Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.

IMPACT the Brain: A Team-Based Approach to Management of Metastatic Breast Cancer With CNS Metastases.

Purpose: CNS metastases are associated with decreased survival and quality of life for patients with metastatic breast cancer (MBC). Team-based care can optimize outcomes. IMPACT the Brain is a care coordination program that aims to improve access to team-based care for patients with MBC and CNS metastases.

Rapid Automated Analysis of Skull Base Tumor Specimens Using Intraoperative Optical Imaging and Artificial Intelligence.

Background: Accurate specimen analysis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative specimen interpretation can be challenging because of the wide range of skull base pathologies and lack of intraoperative pathology resources.

Objective: To develop an independent and parallel intraoperative workflow that can provide rapid and accurate skull base tumor specimen analysis using label-free optical imaging and artificial intelligence.

Correlation between brain tissue oxygen tension and regional cerebral oximetry in uninjured human brain under conditions of changing ventilation strategy.

Controversy surrounds regional cerebral oximetry (rSO) because extracranial contamination and unmeasured changes in cerebral arterial:venous ratio confound readings. Correlation of rSO with brain tissue oxygen (PbrO), a "gold standard" for cerebral oxygenation, could help resolve this controversy but PbrO measurement is highly invasive. This was a prospective cohort study.

G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cell immunosuppression and enhances the efficacy of immunotherapy.

Mutant isocitrate-dehydrogenase 1 () synthesizes the oncometabolite 2-hydroxyglutarate (2HG), which elicits epigenetic reprogramming of the glioma cells’ transcriptome by inhibiting DNA and histone demethylases. We show that the efficacy of immune-stimulatory gene therapy (TK/Flt3L) is enhanced in gliomas, due to the reprogramming of the myeloid cells’ compartment infiltrating the tumor microenvironment (TME). We uncovered that the immature myeloid cells infiltrating the TME are mainly nonsuppressive neutrophils and preneutrophils.

A customized 3D implant to target laser interstitial thermal therapy ablation of a posterior fossa mass.

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique that has been demonstrated to successfully ablate intracranial tumors. While LITT for supratentorial lesions can often be straightforward, ablation of infratentorial lesions can be difficult with current targeting technologies and instrumentation. The anatomical difficulty of targeting posterior fossa masses can be further complicated in patients who have had a prior craniectomy or other procedure that removed the bone that is required to set the surgical trajectory.

Introduction to special issue dedicated to the 35th anniversary of the joint section on tumors.

The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Section on Tumors was formed in December of 1984 as the first professional organization devoted to the study and treatment of brain tumors. One year earlier, the Journal of Neuro-Oncology had been established and went on to be sponsored by the Joint Section on Tumors. To celebrate the 35th anniversary of the founding of the Section, we are thrilled to bring you this special issue of Journal of Neuro-Oncology in which current leaders of the Joint Section on Tumors highlight their work and the work of others that have led to significant recent advances in the management of tumors of the central nervous system.

A Phase 2 Study of Dose-intensified Chemoradiation Using Biologically Based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma.

Purpose: We hypothesized that dose-intensified chemoradiation therapy targeting adversely prognostic hypercellular (TV) and hyperperfused (TV) tumor volumes would improve outcomes in patients with glioblastoma.

Methods And Materials: This single-arm, phase 2 trial enrolled adult patients with newly diagnosed glioblastoma. Patients with a TV/TV >1 cm, identified using high b-value diffusion-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced perfusion MRI, were treated over 30 fractions to 75 Gy to the TV/TV with temozolomide.

Rapid, label-free detection of diffuse glioma recurrence using intraoperative stimulated Raman histology and deep neural networks.

Background: Detection of glioma recurrence remains a challenge in modern neuro-oncology. Noninvasive radiographic imaging is unable to definitively differentiate true recurrence versus pseudoprogression. Even in biopsied tissue, it can be challenging to differentiate recurrent tumor and treatment effect.

Utilization of a Resuscitative Care Unit for Initial Triage, Management, and Disposition of Minor Intracranial Hemorrhage.

Unlabelled: Management of minor intracranial hemorrhage typically involves ICU admission. ICU capacity is increasingly strained, resulting in increased emergency department boarding of critically ill patients. Our objectives were to implement a novel protocol using our emergency department-based resuscitative care unit for management of management of minor intracranial hemorrhage patients in the emergency department setting, to provide timely and appropriate critical care, and to decrease inpatient ICU utilization.

Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce.

Outcomes in Patients Treated with Laser Interstitial Thermal Therapy for Primary Brain Cancer and Brain Metastases.

Laser interstitial thermal therapy (LITT) is an emerging modality to treat benign and malignant brain lesions. LITT is a minimally invasive method to ablate tissue using laser-induced tissue heating and serves as both a diagnostic and therapeutic modality for progressive brain lesions. We completed a single-center retrospective analysis of all patients with progressive brain lesions treated with LITT since its introduction at our center in August of 2015.

Thirty-Day Hospital Readmission and Surgical Complication Rates for Shunting in Normal Pressure Hydrocephalus: A Large National Database Analysis.

Background: Research on age-related complications secondary to shunts in normal pressure hydrocephalus (NPH) is primarily limited to single-center studies and small cohorts.

Objective: To determine the rates of hospital readmission and surgical complications, and factors that predict them, following shunt surgery for NPH in a large healthcare network.

Methods: Surgical procedures, complications, and readmissions for adults undergoing ventricular shunting for NPH were determined using de-identified claims from a privately insured United States healthcare network in years 2007-2014.

Dose-intensified chemoradiation is associated with altered patterns of failure and favorable survival in patients with newly diagnosed glioblastoma.

Background And Purpose: We evaluated whether dose-intensified chemoradiation alters patterns of failure and is associated with favorable survival in the temozolomide era.

Materials And Methods: Between 2003 and 2015, 82 patients with newly diagnosed glioblastoma were treated with 66-81 Gy in 30 fractions using conventional magnetic resonance imaging. Progression-free (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods.