ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma.

Purpose: Zolbetuximab, an IgG1 monoclonal antibody, binds to claudin 18.2 (CLDN18.2) and mediates tumor cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.

NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma.

Purpose: To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities.

Methods: NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone.

A multi-institutional phase II trial of bevacizumab for recurrent and refractory meningioma.

Background: Systemic therapies for refractory meningiomas are limited with no FDA-approved therapeutics. Vascular endothelial growth factor (VEGF) is a signaling protein associated with neovascularization, peritumoral edema, and meningioma tumorigenesis.

Methods: This phase II study investigates the efficacy of bevacizumab (BEV), a VEGF binding monoclonal antibody, in patients with progressive Grade I (G1M), Grade II (G2M), Grade III (G3M) meningioma, and other non-parenchymal tumors including vestibular schwannoma ( = 4) and hemangiopericytoma ( = 4) with the primary endpoint of progression-free survival rate at 6-months (PFS-6).

A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics.

Background: Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD).

Methods: This multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab.

Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.

Purpose: FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ∼8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study of a selective FGFR1-3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas.

Patients And Methods: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles.

Advanced Age Increases Immunosuppression in the Brain and Decreases Immunotherapeutic Efficacy in Subjects with Glioblastoma.

Purpose: Wild-type isocitrate dehydrogenase-expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% of all GBMs and has a median overall survival (OS) of <15 months. Although immune checkpoint blockade (ICB) therapy has achieved remarkable survival benefits in a variety of aggressive malignancies, similar success has yet to be achieved for GBM among phase III clinical trials to date.

The Impact of Perioperative Arterial Infarct on Recurrence, Functional Outcomes, and Survival in Glioblastoma Patients.

Perioperative infarcts are a known complication that can occur during the resection of glioblastoma (GBM). Recent studies suggest that gross total and even "supra-total" resections may be associated with an increased survival but the rate of complications, including perioperative ischemia, may increase with these more aggressive resection strategies. However, little is known about the impact that perioperative infarcts have on survival, functional outcomes, and tumor recurrence patterns.

NRG/RTOG 1122: A phase 2, double-blinded, placebo-controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma.

Background: Targeting vascular endothelial growth factor (VEGF) alone does not improve overall survival (OS) in recurrent glioblastoma (rGBM). The angiopoiein (Ang)-TIE2 system may play a role in tumor survival under VEGF inhibition. We conducted a phase 2, double-blinded, placebo-controlled trial of bevacizumab plus trebananib (a novel Fc fusion protein that sequesters Ang1/Ang2) over bevacizumab alone in rGBM.

Extensive brainstem infiltration, not mass effect, is a common feature of end-stage cerebral glioblastomas.

Background: Progress in extending the survival of glioblastoma (GBM) patients has been slow. A better understanding of why patient survival remains poor is critical to developing new strategies. Postmortem studies on GBM can shed light on why patients are dying.

Response assessment of meningioma: 1D, 2D, and volumetric criteria for treatment response and tumor progression.

Background: Meningiomas are the most common primary brain tumors in adults. Due to their variable growth rates and irregular tumor shapes, response assessment in clinical trials remains challenging and no standard criteria have been defined. We evaluated 1D, 2D, and volume imaging criteria to assess whether a volumetric approach might be a superior surrogate for overall survival (OS).

Primary Central Nervous System Lymphoma-PART 2: Modern Therapeutic Management and Future Directions.

Primary central nervous system (CNS) lymphoma, a rare CNS neoplasm associated with high mortality, is responsive to therapeutic interventions. In Part 1 of our two-part coverage of this entity, we provided an overview of the epidemiology of primary CNS lymphoma, followed by a discussion of the diagnostic and staging evaluation, and a review of current prognostication systems. In Part 2, we discuss the management of primary CNS lymphoma, focusing in particular on systemic therapies and radiation.

Primary Central Nervous System Lymphoma-PART 1: Epidemiology, Diagnosis, Staging, and Prognosis.

Primary central nervous system (CNS) lymphoma is a rare CNS neoplasm. Its highest incidence is in the elderly and the immunocompromised. The initial steps in establishing a diagnosis involve CNS imaging.

Improving vaccine efficacy against malignant glioma.

The effective treatment of adult and pediatric malignant glioma is a significant clinical challenge. In adults, glioblastoma (GBM) accounts for the majority of malignant glioma diagnoses with a median survival of 14.6 mo.

A phase II trial evaluating the effects and intra-tumoral penetration of bortezomib in patients with recurrent malignant gliomas.

One resistance mechanism in malignant gliomas (MG) involves nuclear factor-κB (NF-κB) activation. Bortezomib prevents proteasomal degradation of NF-κB inhibitor α (NFKBIA), an endogenous regulator of NF-κB signaling, thereby limiting the effects of NF-κB on tumor survival and resistance. A presurgical phase II trial of bortezomib in recurrent MG was performed to determine drug concentration in tumor tissue and effects on NFKBIA.

Central Nervous System Cancers, Version 1.2015.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update.

The kynurenine to tryptophan ratio as a prognostic tool for glioblastoma patients enrolling in immunotherapy.

We hypothesized that peripheral tryptophan (Trp) and/or kynurenine (Kyn) levels would provide prognostic value for physicians planning to enroll glioblastoma multiforme (GBM) patients in immunotherapy. GBM is the most common form of malignant glioma in adults. Despite aggressive surgical resection, irradiation and chemotherapy, patients with GBM have a median survival of only 14.

Managing Disease and Therapy-Related Complications in Patients with Central Nervous System Tumors.

Treating patients with brain tumors can be divided into tumor-directed therapies, the management of tumor-related symptoms and complications and the psychosocial aspect of patient care. In this review, we will discuss the management of disease and treatment-related complications, which can negatively impact patient quality of life and functional status. Brain edema is a common complication or brain tumors and often causes more symptoms than the tumor itself.

Financial burden experienced by patients undergoing treatment for malignant gliomas.

Background: Patients undergoing treatment for malignant gliomas (MGs) can encounter medical costs beyond what their insurance covers. The magnitude and type of costs experienced by patients are unknown. The purpose of this study was to have patients or their families report on the medical costs incurred during the patients MG treatment.

Concordance of patient and caregiver reports in evaluating quality of life in patients with malignant gliomas and an assessment of caregiver burden.

Background: Given the neurocognitive impairment experienced by many patients with malignant gliomas, caregiver reports can be critical in assessing the quality of life (QOL) of these patients. In this study, we explored whether assessment of patient QOL by the primary caregiver shows concordance with the patient's self-reported QOL, and we quantified the burden faced by caregivers.

Methods: QOL of 45 patients was evaluated by both the patient and primary caregiver on 3 or more separate occasions using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) instrument, and concordance between the 2 reports was evaluated.

Bevacizumab in high-grade gliomas: past, present, and future.

The survival of patients with high-grade gliomas (anaplastic gliomas and glioblastoma) remains poor despite current treatment modalities. However, an enhanced understanding of gliomagenesis is supporting the development of targeted molecular therapies with the potential for improving clinical outcomes. Glioblastoma (GBM) is characterized by extensive microvascular proliferation and the production of large amounts of VEGF.

Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma.

Background: Panobinostat is a histone deacetylase inhibitor with antineoplastic and antiangiogenic effects in glioma that may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat combined with bevacizumab in patients with recurrent high-grade glioma (HGG).

Methods: Patients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per week, every other week, in combination with bevacizumab 10 mg/kg every other week.