Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.

Assessing survival in non-small cell lung cancer brain metastases after stereotactic radiosurgery: before and after the start of the targetable mutation era.

Purpose: Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations.

Methods: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021.

D-TERMINED, a phase 1 trial in newly diagnosed high-grade glioma with temozolomide, radiation, and minocycline followed by adjuvant minocycline/temozolomide.

Background: Standard treatment for newly diagnosed high-grade gliomas remains suboptimal. Preclinical data indicate that mesenchymal transition and radiation resistance in glioblastoma are driven by NF-κB and microglia activation, which can be inhibited by minocycline. We assessed the safety and efficacy of minocycline combined with standard radiation and temozolomide in newly diagnosed high-grade gliomas.

Gross Tumor and Intracranial Control Benefits with Fractionated Radiotherapy Compared with Stereotactic Radiosurgery for Patients with WHO Grade 2 Meningioma.

Objective: Surgical resection is the mainstay of treatment for WHO grade 2 meningioma. Fractionated radiation therapy (RT) is frequently used after surgery, though many centers utilize stereotactic radiosurgery (SRS) for recurrence or progression. Herein, we report disease control outcomes from an institutional cohort with adjuvant fractionated RT versus salvage SRS.

Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas.

Unlabelled: Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema.

Patterns of failure after radiosurgery for WHO grade 1 or imaging defined meningiomas: Long-term outcomes and implications for management.

Background: We analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors' affiliated institution.

Methods: 96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression.

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.

Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma.

Purpose: We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial.

Patients And Methods: One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m or 125 mg/m (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review.

An evaluation of biobanking and therapeutic clinical trial representation among adult glioma patients from rural and urban Utah.

Background: Social determinants of health (SDOHs)-specifically those related to rurality, health care accessibility, and income-may play as-yet-unidentified roles in prognosis for glioma patients, and their impact on access to clinical trials is important to understand. We examined SDOHs of patients enrolled in glioma clinical trials and evaluate disparities in trial participation and outcomes between rural and urban patients.

Methods: We retrospectively identified patients enrolled in glioma clinical trials at Huntsman Cancer Institute (HCI) from May 2012 to May 2022 to evaluate clinical trial participation.

High-Throughput Screening of Epigenetic Inhibitors in Meningiomas Identifies HDAC, G9a, and Jumonji-Domain Inhibition as Potential Therapies.

 Epigenetics may predict treatment sensitivity and clinical course for patients with meningiomas more accurately than histopathology. Nonetheless, targeting epigenetic mechanisms is understudied for pharmacotherapeutic development for these tumors. The bio-molecular insights and potential therapeutic development of meningioma epigenetics led us to investigate epigenetic inhibition in meningiomas.

Modeling Meningiomas: Optimizing Treatment Approach.

Preclinical meningioma models offer a setting to test molecular mechanisms of tumor development and targeted treatment options but historically have been challenging to generate. Few spontaneous tumor models in rodents have been established, but cell culture and in vivo rodent models have emerged along with artificial intelligence, radiomics, and neural networks to differentiate the clinical heterogeneity of meningiomas. We reviewed 127 studies using PRISMA guideline methodology, including laboratory and animal studies, that addressed preclinical modeling.

High-grade glioma imaging volumes and survival: a single-institution analysis of 101 patients after resection using intraoperative MRI.

Purpose: Intraoperative magnetic resonance imaging (iMRI) has been efficacious in maximizing resection of high-grade gliomas (HGGs). In this single-institution study of patients with HGGs who underwent resection using iMRI, the authors present a volumetric-based survival analysis to evaluate progression-free survival (PFS) and overall survival (OS), as well as the impact of additional resection on survival.

Methods: This retrospective analysis included patients with HGGs who underwent resection using iMRI from 2011 to 2021.

A Longitudinal, Qualitative Examination of Participant Intent-To-Change Statements that do not Match the Stated Learning Objectives of American Association of Neurological Surgeons-Sponsored Continuing Medical Education Activities.

Objective: Continuing medical education (CME) programs are planned to provide medical professionals with the opportunity to stay abreast of new developments in their field. After each program, CME attendees are given the chance to evaluate the success of the activity in meeting its defined learning objectives. Over one-third of intent-to-change statements from CME evaluations do not match the stated learning objectives.

Survival After Resection of Newly-Diagnosed Intracranial Grade II Ependymomas: An Initial Multicenter Analysis and the Logistics of Intraoperative Magnetic Resonance Imaging.

Objective: To identify factors, including the use of intraoperative magnetic resonance imaging (iMRI), impacting overall survival (OS) and progression-free survival (PFS) after resections of newly diagnosed intracranial grade II ependymomas performed across 4 different institutions.

Methods: Analyses of a multicenter mixed retrospective/prospective database assessed the impact of patient, treatment, and tumor characteristics on OS and PFS. iMRI workflow and logistics were also outlined.

Development of a residents-as-teachers curriculum for neurosurgical training programs.

Neurosurgery residents spend a significant amount of their time teaching patients, families, students, residents, and other health professionals. To help ensure competence in their residents' teaching abilities, many specialties have established formal residents-as-teachers (RAT) curricula; however, such formalized curricula are often lacking in neurosurgery programs. The authors' goal was to develop and implement a formal RAT curriculum, designed with neurosurgery residents' other responsibilities in mind, to improve residents' formal and informal teaching abilities.

Outcomes using linear accelerator stereotactic radiosurgery for the treatment of trigeminal neuralgia: A single-center, retrospective study.

Background: Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) treatment of trigeminal neuralgia (TN) may have similar efficacy to Gamma Knife SRS (GK-SRS), but the preponderance of data comes from patients treated with GK-SRS. Our objective was to analyze the outcomes for LINAC-based treatment of TN in patients at our institution.

Methods: We retrospectively analyzed data for patients who underwent LINAC-based SRS for TN from 2006 to 2018.

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively.

Targeting DNA Methyl Transferases with Decitabine in Cultured Meningiomas.

Objective: Meningiomas are a common primary central nervous system tumor that lack a U.S. Food and Drug Administration-approved pharmacotherapy.