The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence.

Re-irradiation plus pembrolizumab: Phase II study for recurrent glioblastoma patients.

Purpose: Radiation therapy may enhance anti-tumor immune responses by several mechanisms including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.

Methods: Sixty recurrent glioblastoma patients received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n=30) or with bevacizumab continuation (cohort B, n=30).

Turnaway Study Report Unethically Violated Participants' Privacy and Misleads Public with a Non-Representative Sample, Selective Reporting, and Overstated Conclusions.

Results from the Turnaway Study, conducted by Advancing New Standards in Reproductive Health (ANSRH), have widely been represented as definitive proof that women denied access to abortion will suffer severe injury to their health and economic wellbeing. Yet a careful examination reveals that the study is based on a non-random, non-representative sample of women that grossly underrepresents the experiences of the majority of women undergoing abortions. In addition, a reanalysis of its reported results reveal that the effect size of the outcomes observed have been grossly overstated, leading to conclusions that are not supported by the results.

Central nervous system tumors in adolescents and young adults: A Society for Neuro-Oncology consensus review on diagnosis, management, and future directions.

Adolescents and young adults (AYAs; ages 15-39 years) are a vulnerable population facing challenges in oncological care, including access to specialized care, transition of care, unique tumor biology, and poor representation in clinical trials. Brain tumors are the second most common tumor type in AYA, with malignant brain tumors being the most common cause of cancer-related death. The 2021 WHO Classification for central nervous system (CNS) Tumors highlights the importance of integrated molecular characterization with histologic diagnosis in several tumors relevant to the AYA population.

A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine.

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens.

A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients.

Background: The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes.

Methods: Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2-4 gliomas, were collected from collaborating institutions between 2013 and 2019.

Welcomed Pregnancies: Characteristics and Patterns of Adjusting to Unwanted, Unplanned, Untimely or Otherwise Difficult Pregnancies.

Background Women facing problematic pregnancies, defined as "unplanned, mistimed, unwanted, or otherwise difficult," either have abortions or make adjustments to welcome these pregnancies. These adjustments are understudied. Pregnancy resource centers that provide counseling and services to assist in the process of welcoming pregnancies have been the focus of controversy due to their refusal to counsel or refer for abortions.

[F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue.

A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults.

Cavitation monitoring, treatment strategy, and acoustic simulations of focused ultrasound blood-brain barrier disruption in patients with glioblastoma.

Purpose: We report our experience disrupting the blood-brain barrier (BBB) to improve drug delivery in glioblastoma patients receiving temozolomide chemotherapy. The goals of this retrospective analysis were to compare MRI-based measures of BBB disruption and vascular damage to the exposure levels, acoustic emissions data, and acoustic simulations. We also simulated the cavitation detectors.

Case Report: Low-grade glioma with loss of function mimicking diffuse intrinsic pontine glioma.

Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG), which is now considered as diffuse midline glioma (DMG), H3K27-mutated of the pons. DIPG has limited treatment options and a poor prognosis, and the value of tissue diagnosis from an invasive biopsy remains controversial.

Non-Invasive Blood-Brain Barrier Disruption Using Acoustic Holography With a Clinical Focused Ultrasound System.

Objective: Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a hemispherical 1024-element phased array transducer and explored how it could benefit ultrasound-mediated blood-brain barrier (BBB) disruption.

Methods: With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory.

A Reanalysis of Mental Disorders Risk Following First-Trimester Abortions in Denmark.

Background: A previous Danish study of monthly and tri-monthly rates of first-time psychiatric contact following first induced abortions reported higher rates compared to first live births but similar rates compared to nine months pre-abortion. Therefore, the researchers concluded abortion has no independent effect on mental health; any differences between psychiatric contacts after abortion and delivery are entirely attributable to pre-existing mental health differences. However, these conclusions are inconsistent with similar studies that used longer time frames.

Effects of prior reproductive losses on risk of cardiovascular diseases within six months of a first live birth.

Objective: There is emerging evidence suggesting that pregnancy loss (induced or natural) is associated with an increased risk of cardiovascular diseases (CVD). This prospective longitudinal study investigates the effect of prior pregnancy losses on CVD risk during the first six months following a first live birth.

Methods: Medicaid claims of 1,002,556 low-income women were examined to identify history of pregnancy losses, CVD, diabetes, and hyperlipidemia prior to first live birth.

Auto-segmentation of Adult-Type Diffuse Gliomas: Comparison of Transfer Learning-Based Convolutional Neural Network Model vs. Radiologists.

Segmentation of glioma is crucial for quantitative brain tumor assessment, to guide therapeutic research and clinical management, but very time-consuming. Fully automated tools for the segmentation of multi-sequence MRI are needed. We developed and pretrained a deep learning (DL) model using publicly available datasets A (n = 210) and B (n = 369) containing FLAIR, T2WI, and contrast-enhanced (CE)-T1WI.

The Blood-Brain Barrier: Implications for Experimental Cancer Therapeutics.

The blood-brain barrier is critically important for the treatment of both primary and metastatic cancers of the central nervous system (CNS). Clinical outcomes for patients with primary CNS tumors are poor and have not significantly improved in decades. As treatments for patients with extracranial solid tumors improve, the incidence of CNS metastases is on the rise due to suboptimal CNS exposure of otherwise systemically active agents.

Clinical and Genomic Predictors of Adverse Events in Newly Diagnosed Glioblastoma.

Purpose: Adverse clinical events cause significant morbidity in patients with GBM (GBM). We examined whether genomic alterations were associated with AE (AE) in patients with GBM.

Experimental Design: We identified adults with histologically confirmed IDH-wild-type GBM with targeted next-generation sequencing (OncoPanel) at Dana Farber Cancer Institute from 2013 to 2019.

Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model.

Background: The GL261 and CT2A syngeneic tumor lines are frequently used as immunocompetent orthotopic mouse models of human glioblastoma (huGBM) but demonstrate distinct differences in their responses to immunotherapy.

Methods: To decipher the cell-intrinsic mechanisms that drive immunotherapy resistance in CT2A-luc and to define the aspects of human cancer biology that these lines can best model, we systematically compared their characteristics using whole exome and transcriptome sequencing, and protein analysis through immunohistochemistry, Western blot, flow cytometry, immunopeptidomics, and phosphopeptidomics.

Results: The transcriptional profiles of GL261-luc2 and CT2A-luc tumors resembled those of some huGBMs, despite neither line sharing the essential genetic or histologic features of huGBM.

Re-irradiation of recurrent IDH-wildtype glioblastoma in the bevacizumab and immunotherapy era: Target delineation, outcomes and patterns of recurrence.

Introduction And Background: While recurrent glioblastoma patients are often treated with re-irradiation, there is limited data on the use of re-irradiation in the setting of bevacizumab (BEV), temozolomide (TMZ) re-challenge, or immune checkpoint inhibition (ICI). We describe target delineation in patients with prior anti-angiogenic therapy, assess safety and efficacy of re-irradiation, and evaluate patterns of recurrence.

Materials And Methods: Patients with a histologically confirmed diagnosis of glioblastoma treated at a single institution between 2013 and 2021 with re-irradiation were included.