Clinical progress in the development of CAR T cells to treat malignant glioma.

Context: Chimeric antigen receptor (CAR) T cell therapy is an exciting modality of immunotherapy that has revolutionized the treatment of hematologic malignancies. However, translating this success to malignant gliomas such as glioblastoma (GBM) and diffuse midline glioma (DMG) remains a formidable challenge due to multiple biologic, anatomic, and immunologic factors. Despite these hurdles, a number of clinical trials deployed over the last decade have increased optimism for the potential of CAR T cell therapy in glioma treatment.

Immunotherapy for Brain Tumors: Where We Have Been, and Where Do We Go From Here?

Immunotherapy for glioblastoma (GBM) remains an intensive area of investigation. Given the seismic impact of cancer immunotherapy across a range of malignancies, there is optimism that harnessing the power of immunity will influence GBM as well. However, despite several phase 3 studies, there are still no FDA-approved immunotherapies for GBM.

Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma.

In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, as well as the wild-type EGFR protein, through secretion of a T-cell-engaging antibody molecule (TEAM). Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects. Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants.

Discontinuation of Antiseizure Medications in Patients With Brain Tumors.

Patients with brain tumors will experience seizures during their disease course. While providers can use antiseizure medications to control these events, patients with brain tumors can experience side effects, ranging from mild to severe, from these medications. Providers in subspecialties such as neurology, neuro-oncology, neurosurgery, radiation oncology, and medical oncology often work with patients with brain tumor to balance seizure control and the adverse toxicity of antiseizure medications.

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.

Expert-centered Evaluation of Deep Learning Algorithms for Brain Tumor Segmentation.

Purpose To present results from a literature survey on practices in deep learning segmentation algorithm evaluation and perform a study on expert quality perception of brain tumor segmentation. Materials and Methods A total of 180 articles reporting on brain tumor segmentation algorithms were surveyed for the reported quality evaluation. Additionally, ratings of segmentation quality on a four-point scale were collected from medical professionals for 60 brain tumor segmentation cases.

The Role of Antibody-Based Therapies in Neuro-Oncology.

This review explores the evolving landscape of antibody-based therapies in neuro-oncology, in particular, immune checkpoint inhibitors and immunomodulatory antibodies. We discuss their mechanisms of action, blood-brain barrier (BBB) penetration, and experience in neuro-oncological conditions. Evidence from recent trials indicates that while these therapies can modulate the tumor immune microenvironment, their clinical benefits remain uncertain, largely due to challenges with BBB penetration and tumor-derived immunosuppression.

Not without Context-A Multiple Methods Study on Evaluation and Correction of Automated Brain Tumor Segmentations by Experts.

Rationale And Objectives: Brain tumor segmentations are integral to the clinical management of patients with glioblastoma, the deadliest primary brain tumor in adults. The manual delineation of tumors is time-consuming and highly provider-dependent. These two problems must be addressed by introducing automated, deep-learning-based segmentation tools.

BRAF-MEK Inhibition in Newly Diagnosed Papillary Craniopharyngiomas.

Background: Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy.

Bavituximab Decreases Immunosuppressive Myeloid-Derived Suppressor Cells in Newly Diagnosed Glioblastoma Patients.

Purpose: We evaluated the efficacy of bavituximab-a mAb with anti-angiogenic and immunomodulatory properties-in newly diagnosed patients with glioblastoma (GBM) who also received radiotherapy and temozolomide. Perfusion MRI and myeloid-related gene transcription and inflammatory infiltrates in pre-and post-treatment tumor specimens were studied to evaluate on-target effects (NCT03139916).

Patients And Methods: Thirty-three adults with IDH--wild-type GBM received 6 weeks of concurrent chemoradiotherapy, followed by 6 cycles of temozolomide (C1-C6).

Clinical management of seizures in patients with meningiomas: Efficacy of surgical resection for seizure control and patient-tailored postoperative anti-epileptic drug management.

Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms.

QU-BraTS: MICCAI BraTS 2020 Challenge on Quantifying Uncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results.

Deep learning (DL) models have provided state-of-the-art performance in various medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g.

Labeling T Cells to Track Immune Response to Immunotherapy in Glioblastoma.

While the advent of immunotherapy has revolutionized cancer treatment, its use in the treatment of glioblastoma (GBM) has been less successful. Most studies using immunotherapy in GBM have been negative and the reasons for this are still being studied. In clinical practice, interpreting response to immunotherapy has been challenging, particularly when trying to differentiate between treatment-related changes (i.

Imaging of Brain Tumors.

Objective: This article focuses on neuroimaging as an essential tool for diagnosing brain tumors and monitoring response to treatment.

Latest Developments: Neuroimaging is useful at all stages of brain tumor care. Technologic advances have improved the clinical diagnostic capability of neuroimaging as a vital complement to history, examination, and pathologic assessment.

Tandem chimeric antigen receptor (CAR) T cells targeting EGFRvIII and IL-13Rα2 are effective against heterogeneous glioblastoma.

Background: Chimeric antigen receptor (CAR) T cells have achieved remarkable responses in patients with hematological malignancies; however, the potential of this therapeutic platform for solid tumors like glioblastoma (GBM) has been limited, due in large part to the targeting of single antigens in a heterogeneous disease. Strategies that allow CAR T cells to engage multiple antigens concomitantly may broaden therapeutic responses and mitigate the effects of immune escape.

Methods: Here we have developed a novel, dual-specific, tandem CAR T (TanCART) cell with the ability to simultaneously target both EGFRvIII and IL-13Rα2, two well-characterized tumor antigens that are frequently found on the surface of GBM cells but completely absent from normal brain tissues.

Accelerated and quantitative three-dimensional molecular MRI using a generative adversarial network.

Purpose: To substantially shorten the acquisition time required for quantitative three-dimensional (3D) chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction.

Methods: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at three different sites, using three different scanner models and coils. A saturation transfer-oriented generative adversarial network (GAN-ST) supervised framework was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content.

Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic Mutations.

Purpose: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with loss. Given the predominance of mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas.