Phase II trial of blood-brain barrier permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma.

Background: This study is a phase II clinical trial to evaluate the efficacy, safety, and tolerability of the blood-brain barrier (BBB) permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma (HGG) (NCT01967810).

Methods: Seventy-three patients were enrolled in 3 separate arms-recurrent glioblastoma (GBM) (Arm 1), bevacizumab refractory GBM (Arm 2), and grade 3 anaplastic gliomas (AGs) (Arm 3). The study was started in October 2013, and the data were locked on September 29, 2017.

Quality of life after stereotactic radiosurgery for brain metastasis: an assessment from a prospective national registry.

Purpose: Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastasis patients. However, there is an urgent need to evaluate post-treatment outcomes and quality of life metrics for patients undergoing SRS for brain metastases.

Methods: The NeuroPoint Alliance (NPA) SRS Quality Registry conducted prospective enrollment of patients undergoing SRS from 2017 to 2024.

Defining the quality of interdisciplinary care for patients with brain metastases: modified Delphi panel recommendations.

The value of interdisciplinary teams in improving outcomes and quality of care of patients with brain metastases remains uncertain, partly due to the lack of consensus on key indicators to evaluate interprofessional care. We aimed to obtain expert consensus across disciplines on indicators that evaluate the quality and value of brain metastases care. A steering committee of key opinion leaders curated relevant outcomes and process indicators from a literature review and a stakeholder needs assessment, and an international panel of physicians rated the outcomes and process indicators using a modified Delphi method.

Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide.

Purpose: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy.

Methods: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ.

The role of microRNAs in brain metastasis.

Brain metastasis (BM) is the most common type of brain tumor and frequently foreshadows disease progression and poor overall survival with patients having a median survival of 6 months. 70,000 new cases of BM are diagnosed each year in the United States (US) and the incidence rate for BM is increasing with improved detection. MicroRNAs (miRNAs) are small non-coding RNAs that serve as critical regulators of gene expression and can act as powerful oncogenes and tumor suppressors.

Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases.

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019.

Systematic review of the management of brain metastases from hormone receptor positive breast cancer.

Introduction: Brain metastases are a common cause of morbidity and mortality in patients with breast cancer. Local central nervous system (CNS) directed therapies are usually the first line treatment for breast cancer brain metastases (BCBM), but those must be followed by systemic therapies to achieve long-term benefit. Systemic therapy for hormone receptor (HR) breast cancer has evolved in the last 10 years, but their role when brain metastases occur is uncertain.

Melanoma brain metastasis mimicking cortical laminar necrosis.

Background: Metastatic lesions to the brain are common in patients with melanoma. Imaging characteristics can support the diagnosis of metastatic melanoma, but alternative diagnoses should be considered.

Case Description: Here, we present a case of a 57-year-old man in whom a metastatic melanoma initially mimicked the imaging characteristics of cortical laminar necrosis.

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.

MRI features predict tumor grade in isocitrate dehydrogenase (IDH)-mutant astrocytoma and oligodendroglioma.

Purpose: Nearly all literature for predicting tumor grade in astrocytoma and oligodendroglioma pre-dates the molecular classification system. We investigated the association between contrast enhancement, ADC, and rCBV with tumor grade separately for IDH-mutant astrocytomas and molecularly-defined oligodendrogliomas.

Methods: For this retrospective study, 44 patients with IDH-mutant astrocytomas (WHO grades II, III, or IV) and 39 patients with oligodendrogliomas (IDH-mutant and 1p/19q codeleted) (WHO grade II or III) were enrolled.

The landscape of brain tumor mimics in neuro-oncology practice.

Background And Objective: Differentiating neoplastic and non-neoplastic brain lesions is essential to make management recommendations and convey prognosis, but the distinction between brain tumors and their mimics in practice may prove challenging. The aim of this study is to provide the incidence of brain tumor mimics in the neuro-oncology setting and describe this patient subset.

Methods: Retrospective study of adult patients referred to the Division of Neuro-oncology for a presumed diagnosis of brain tumor from January 1, 2005 through December 31, 2017, who later satisfied the diagnosis of a non-neoplastic entity based on neuroimaging, clinical course, and/or histopathology evaluation.

Proliferating CD8 T Cell Infiltrates Are Associated with Improved Survival in Glioblastoma.

Background: tumor-infiltrating lymphocytes are prognostic in many human cancers. However, the prognostic value of lymphocytes infiltrating glioblastoma (GBM), and roles in tumor control or progression are unclear. We hypothesized that B and T cell density, and markers of their activity, proliferation, differentiation, or function, would have favorable prognostic significance for patients with GBM.

Safety and Immune Effects of Blocking CD40 Ligand in Multiple Sclerosis.

Background And Objectives: Costimulation by CD40 and its ligand CD40L (CD154) is important for the functional differentiation of T cells. Preclinical studies have recognized the importance of this costimulatory interaction in the pathogenesis of experimental models of multiple sclerosis (MS). To determine safety, pharmacokinetics, and immune effect of a humanized monoclonal antibody (mAb) against CD40 ligand (toralizumab/IDEC-131) in patients with relapsing-remitting MS (RRMS).

Systemic coagulation is activated in patients with meningioma and glioblastoma.

Purpose: Up to 30% of patients with glioblastoma (GBM) develop venous thromboembolism (VTE) over the course of the disease. Although not as high, the risk for VTE is also increased in patients with meningioma. Direct measurement of peak thrombin generation (TG) allows quantitative assessment of systemic coagulation activation in patients with GBM and meningioma.

Imaging Mimics of Brain Tumors.

Nonneoplastic entities may closely resemble the imaging findings of primary or metastatic intracranial neoplasia, posing diagnostic challenges for the referring provider and radiologist. Prospective identification of brain tumor mimics is an opportunity for the radiologist to add value to patient care by decreasing time to diagnosis and avoiding unnecessary surgical procedures and medical therapies, but requires familiarity with mimic entities and a high degree of suspicion on the part of the interpreting radiologist. This article provides a framework for the radiologist to identify "brain tumor mimics," highlighting imaging and laboratory pearls and pitfalls, and illustrating unique and frequently encountered lesions.

Fluid attenuation in non-contrast-enhancing tumor (nCET): an MRI Marker for Isocitrate Dehydrogenase (IDH) mutation in Glioblastoma.

Purpose: The WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma.

Methods: This retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum).

Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases.

Purpose/objective(s): Tyrosine kinase inhibitors (TKIs) are commonly employed for patients with brain metastases from lung cancer and specific driver mutations. We sought to identify the correlation between intracranial tumor burden and outcomes in patients with brain metastases treated with TKIs.

Materials/methods: We identified and retrospectively reviewed cases of EGFR-mutant or ALK-rearranged lung cancer with brain metastases at any time during their cancer course.

Genesis of Quality Measurements to Improve the Care Delivered to Patients With Brain Metastases.

Purpose: High-value and high-quality health care requires outcome measurements to inform treatment decisions, but, to our knowledge, no standardized measurements exist to evaluate brain metastases (BMs) care. We propose a set of measurements and report on their implementation in the care of patients with BMs.

Methods: On the basis of a stakeholders' needs assessment and review of the literature, we identified outcome and process measurements to assess the care of patients with BMs according to treatment modality.

Diffuse large B-cell lymphoma relapse presenting as extensive neurolymphomatosis.

A 56-year-old woman with a history of diffuse large B-cell non-Hodgkin lymphoma (DLBCL-NHL) in remission for two years presented with weight loss and multifocal sensory/motor symptoms. Magnetic resonance imaging (MRI) of the neuraxis and whole-body FDG PET/CT led to a diagnosis of secondary neurolymphomatosis (NL). MRI demonstrated extensive thickening and enhancement of multiple cranial nerves and peripheral nerve plexuses with corresponding elevated metabolism on FDG PET/CT.

Adaptive dose-finding based on safety and feasibility in early-phase clinical trials of adoptive cell immunotherapy.

Background/aims: Dose feasibility is a challenge that may arise in the development of adoptive T cell therapies for cancer. In early-phase clinical trials, dose is quantified either by a fixed or per unit body weight number of cells infused. It may not be feasible, however, to administer a patient's assigned dose due to an insufficient number of cells harvested or functional heterogeneity of the product.