MTAP and p16 IHC as Markers for CDKN2A/B Loss in Meningiomas.

Background: Homozygous cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss is one of the parameters that support the designation of meningiomas as Central Nervous System (CNS) WHO grade 3 tumors. Evaluation of CDKN2A/B by sequencing or Fluorescence in situ hybridization (FISH) is costly and not always readily accessible. An immunohistochemistry (IHC)-based marker for the evaluation of CDKN2A/B loss would provide faster results at a lower cost.

Immune landscape of isocitrate dehydrogenase-stratified primary and recurrent human gliomas.

Background: Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear.

Methods: In this study, we used sequential single-cell transcriptomics on 144 678 and spectral cytometry on over 2 million immune cells encompassing 48 human gliomas to decipher their immune landscape.

Results: We identified 22 distinct immune cell types that contribute to glioma immunity.

Accelerated tumor progression after COVID-19 infection in patients with glioblastoma: A retrospective case-control study.

Background: We observed rapid tumor progression following COVID-19 infection among patients with glioblastoma and sought to systematically characterize their disease course in a retrospective case-control study.

Methods: Using an institutional database, we retrospectively identified a series of COVID-19-positive glioblastoma cases and matched them by age and sex 1:2 to glioblastoma controls who had a negative COVID-19 test during their disease course. Demographic and clinical data were analyzed.

Therapeutic Strategies for Gliomas Associated With Cancer Predisposition Syndromes.

Purpose: The purpose of this article was to provide an overview of syndromic gliomas.

Design: The authors conducted a nonsystematic literature review.

Results: Cancer predisposition syndromes (CPSs) are genetic conditions that increase one's risk for certain types of cancer compared with the general population.

The risk and burden of thromboembolic and hemorrhagic events in patients with malignant gliomas receiving bevacizumab.

Purpose: Bevacizumab has evolved as an integral treatment option for patients with high-grade gliomas. Little is known about clinical risk factors that predispose patients with high-grade gliomas receiving bevacizumab to VTE or ICH. We sought to characterize the clinical risk factors associated with risk of either event.

The Role of Immunotherapy in the Treatment of Rare Central Nervous System Tumors.

Establishing novel therapies for rare central nervous system (CNS) tumors is arduous due to challenges in conducting clinical trials in rare tumors. Immunotherapy treatment has been a rapidly developing field and has demonstrated improvements in outcomes for multiple types of solid malignancies. In rare CNS tumors, the role of immunotherapy is being explored.

Impact of salvage surgery with or without reirradiation for skull base meningiomas recurring after prior radiotherapy.

Objective: Long-term follow-up of meningiomas has demonstrated recurrence rates ranging from 2.5% to 48% after 10 years, depending on histology grade. There are limited data available to guide the management of recurrent and previously irradiated skull base meningiomas, and challenges related to salvage surgery, reirradiation, and lack of clear systemic therapy strategies remain.

Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials.

Although targeting oxidative phosphorylation (OXPHOS) is a rational anticancer strategy, clinical benefit with OXPHOS inhibitors has yet to be achieved. Here we advanced IACS-010759, a highly potent and selective small-molecule complex I inhibitor, into two dose-escalation phase I trials in patients with relapsed/refractory acute myeloid leukemia (NCT02882321, n = 17) and advanced solid tumors (NCT03291938, n = 23). The primary endpoints were safety, tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D) of IACS-010759.

Neoadjuvant Pembrolizumab in Localized Microsatellite Instability High/Deficient Mismatch Repair Solid Tumors.

Purpose: Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space.

Methods: This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation.

Molecular, Histological, and Clinical Characteristics of Oligodendrogliomas: A Multi-Institutional Retrospective Study.

Background: Reports suggest that phosphatidylinositol 3-kinase pathway alterations confer increased risk of progression and poor prognosis in oligodendroglioma, IDH-mutant, and 1p/19q-codeleted molecular oligodendrogliomas (mODG). However, factors that affect prognosis in mODG have not been thoroughly studied. In addition, the benefits of adjuvant radiation and temozolomide (TMZ) in mODGs remain to be determined.

Prolonged survival after laser interstitial thermal therapy in glioblastoma.

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Management includes surgical resection followed by chemoradiation, and prognosis remains poor. Surgical resection is not possible for some deep-seated or eloquent tumors.

Outcome of patients with primary glioblastoma in Chile: single centre series.

Background: Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumour. The standard of care is surgical resection, followed by radiotherapy with concurrent and adjuvant temozolomide. In Latin America, there is scarcity of information about the incidence of GBM and even less data regarding outcomes.

Laser Interstitial Thermal Therapy for Glioblastoma: A Single-Center Experience.

Background: Surgical resection has been shown to prolong survival in patients with glioblastoma multiforme (GBM), although this benefit has not been demonstrated for reoperation following tumor recurrence. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has been shown to effectively reduce tumor burden in some patients with intracranial malignancy. The aim of this study was to describe the safety and efficacy of LITT for recurrent and newly diagnosed GBM at a large tertiary referral center.

Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study.

Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region. Symptoms can be debilitating due to hormonal excess and survival is poor. Pituitary carcinomas recur despite conventional multimodality treatments.

Pineal parenchymal tumor of intermediate differentiation: a single-institution experience.

Background: Pineal parenchymal tumors are exceedingly rare brain tumors responsible for less than 1% of all adult primary intracranial malignancies in the United States. In this study, we describe the clinicopathologic features, management, and outcomes of patients with pineal parenchymal tumor of intermediate differentiation (PPTID).

Methods: We describe a single-center, multidisciplinary team experience in managing PPTID patients over a 15-year period (January 2000 to January 2015) at The University of Texas MD Anderson Cancer Center (MDACC).

Association Between Facility Volume and Overall Survival for Patients with Grade II Meningioma after Gross Total Resection.

Background: The role of adjuvant radiation after gross total resection (GTR) for grade II meningioma is evolving, prompting further evaluation in NRG-BN003, a phase 3 national trial. Furthermore, the relationship between facility volume and outcomes in patients with grade II meningioma after GTR has not been examined at a national level. We aim to assess overall survival (OS) of patients with grade II meningioma after GTR by surgical case volume and OS by receipt of adjuvant radiation.

Glioblastoma-mediated Immune Dysfunction Limits CMV-specific T Cells and Therapeutic Responses: Results from a Phase I/II Trial.

Purpose: Cytomegalovirus (CMV) antigens occur in glioblastoma but not in normal brains, making them desirable immunologic targets.

Patients And Methods: Highly functional autologous polyclonal CMV pp65-specific T cells from patients with glioblastoma were numerically expanded under good manufacturing practice compliant conditions and administered after 3 weeks of lymphodepleting dose-dense temozolomide (100 mg/m) treatment. The phase I component used a 3+3 design, ascending through four dose levels (5 × 10-1 × 10 cells).

Impact of adverse events of bevacizumab on survival outcomes of patients with recurrent glioblastoma.

Background: Bevacizumab is widely used for treatment of recurrent glioblastoma (rGB). It is well known that adverse events (AEs) due to bevacizumab can cause early discontinuation of treatment. However, the association between AEs and survival outcomes is not well defined.

Genetic and immune profiling for potential therapeutic targets in adult human craniopharyngioma.

Craniopharyngioma is a rare tumor in adults. Although histologically benign, it can be locally aggressive and may require additional therapeutic modalities to surgical resection. Analyses including next generation sequencing, chromogenic and hybridization, immunohistochemistry, and gene amplification were used to profile craniopharyngiomas (n=6) for frequently altered therapeutic targets.

The path forward for anti-programmed cell death-1 therapy in gliomas.

Purpose Of Review: Checkpoint inhibitors (CPIs) represent the forefront of novel immunotherapeutic approaches for the treatment of solid cancers. However, the clinical development of CPIs in glioblastoma (GBM) has been challenging owing to an immunosuppressive tumor microenvironment and, possibly, low tumor mutation burden. Here, we review possible mechanisms responsible for the success of programmed cell death-1 (PD-1) blockade in patients with hypermutated GBM, recent clinical trials of anti-PD-1 monotherapy, trials incorporating neoadjuvant strategies, and trials of immunotherapy combination approaches in GBM.

Treatment and long-term outcomes in pituitary carcinoma: a cohort study.

Background: Pituitary carcinoma (PC) is an aggressive neuroendocrine tumor diagnosed when a pituitary adenoma (PA) becomes metastatic. PCs are typically resistant to therapy and develop multiple recurrences despite surgery, radiotherapy and chemotherapy. Recently, treatment with temozolomide (TMZ) has shown promising results, although the lack of prospective trials limits assessment of benefit.

Clinical trial participation of patients with glioblastoma at The University of Texas MD Anderson Cancer Center.

Background: It is estimated only 8-11% of patients with glioblastoma (GBM) enrol in clinical trials, limiting treatment development. We analysed the clinical and demographic features of patients with GBM enroled in clinical trials at the University of Texas MD Anderson Cancer Center (MDACC).

Methods: We reviewed the records of adult patients treated for primary GBM between 2007 and 2012 at the MDACC.