Adult Atypical Teratoid/Rhabdoid Tumors.

Background: Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant neoplasms that rarely occur in adults. Due to the complex histology of AT/RTs, the differential diagnosis of these tumors is quite challenging and increasingly relies on demonstration of characteristic SMARCB1/INI1 inactivation in tumor cells.

Case Description: A 51-year-old man presented with diplopia, lethargy, and memory deficit owing to Parinaud syndrome and hydrocephalus.

A prognostic cytogenetic scoring system to guide the adjuvant management of patients with atypical meningioma.

Background: The appropriate use of adjuvant therapy in patients with gross totally resected atypical meningioma requires an accurate assessment of recurrence risk. We sought to determine whether cytogenetic/genetic characterization may facilitate better estimation of the probability of recurrence.

Methods: We first analyzed our clinical database, including high-resolution DNA copy number data, to identify 11 common copy number aberrations in a pilot cohort of meningiomas of all grades.

Extent of resection and overall survival for patients with atypical and malignant meningioma.

Background: The prognosis for patients with atypical and malignant meningioma is guarded; whether the extent of resection is associated with survival-based outcomes in this population remains poorly defined. This study investigated the association between gross total resection (GTR) and all-cause mortality in patients with atypical and malignant meningioma.

Methods: The Surveillance, Epidemiology, and End Results program was used to identify 575 and 64 patients betweens the ages of 18 and 70 years who were diagnosed with atypical and malignant meningioma, respectively, between 2004 and 2009.

Prospects of immune checkpoint modulators in the treatment of glioblastoma.

Glioblastoma is the most common primary brain tumour in adults. Prognosis is poor: even with the current gold-standard first-line treatment—maximal safe resection and combination of radiotherapy with temozolomide chemotherapy—the median overall survival time is only approximately 15-17 months, because the tumour recurs in virtually all patients, and no commonly accepted standard treatment for recurrent disease exists. Several targeted agents have failed to improve patient outcomes in glioblastoma.

Brachytherapy in the treatment of recurrent aggressive falcine meningiomas.

Recurrent aggressive falcine meningiomas are uncommon tumors that recur despite receiving extensive surgery and radiation therapy (RT). We have utilized brachytherapy as a salvage treatment in two such patients with a unique implantation technique. Both patients had recurrence of WHO Grade II falcine meningiomas despite multiple prior surgical and RT treatments.

Rapid Intraoperative Molecular Characterization of Glioma.

Importance: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1).

One size should not fit all: advancing toward personalized glioblastoma therapy.

Over the past few years, understanding the genetic abnormalities associated with glioblastoma, the most common malignant primary tumor of the central nervous system, has increased dramatically. Mutation types and frequencies have been comprehensively assessed, glioblastoma subclasses have been defined based on gene expression and methylation analyses, and novel mutations implicated in gliomagenesis have been identified. Nonetheless, a critical disconnect exists between achieved scientific advances and failure to improve patient outcome.

Incidence, risk factors, and reasons for hospitalization among glioblastoma patients receiving chemoradiation.

Despite a high symptom burden, little is known about the incidence or predictors of hospitalization among glioblastoma patients, including risks during chemoradiation (CRT). We studied 196 consecutive newly diagnosed glioblastoma patients treated at our institution from 2006-2010. Toxicity data were reviewed during and after the CRT phase, defined as the period between diagnosis and 6 weeks after radiotherapy completion.

Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma.

Lessons Learned: Trials focusing on unresectable multifocal glioblastoma are needed because of the extremely poor prognosis and challenges in receiving standard therapy, such as concurrent radiation and chemotherapy.Developing a strategy to chemically debulk tumors before radiation and/or surgery is warranted.

Background: Extent of resection remains a key prognostic factor in glioblastoma (GBM), with gross total resection providing a better prognosis than biopsy or subtotal resection.

Multicentric Low-Grade Gliomas.

Background: Multicentric low-grade gliomas are rare entities that occur in disparate regions of the brain. They can present with distinct pathologic and imaging findings and may harbor a worse prognosis. We present a case of multicentric low-grade gliomas and highlight their pathogenesis, imaging characteristics, and molecular signatures, with implications for clinical management.

A phase 1 study of ABT-806 in subjects with advanced solid tumors.

Purpose: ABT-806, a humanized recombinant monoclonal antibody, binds a unique epidermal growth factor receptor (EGFR) epitope exposed in the EGFRde2-7 (EGFRvIII) deletion mutant and other EGFR proteins in the activated state. This phase I study evaluated the safety, pharmacokinetics, and recommended phase two dose (RP2D) of ABT-806 in patients with solid tumors that commonly overexpress activated EGFR or EGFRvlll.

Methods: Patients with advanced solid tumors, including glioblastoma, were eligible.

Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients.

Purpose: Older patients with newly diagnosed glioblastoma have poor outcomes, and optimal treatment is controversial. Hypofractionated radiation therapy (HRT) is frequently used but has not been compared to patients receiving standard fractionated radiation therapy (SRT) and temozolomide (TMZ).

Methods And Materials: We conducted a retrospective analysis of patients ≥65 years of age who received radiation for the treatment of newly diagnosed glioblastoma from 1994 to 2013.

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study.

Background: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter.

Methods: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89).

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood.

Pitfalls in the neuroimaging of glioblastoma in the era of antiangiogenic and immuno/targeted therapy - detecting illusive disease, defining response.

Glioblastoma, the most common malignant primary brain tumor in adults is a devastating diagnosis with an average survival of 14-16 months using the current standard of care treatment. The determination of treatment response and clinical decision making is based on the accuracy of radiographic assessment. Notwithstanding, challenges exist in the neuroimaging evaluation of patients undergoing treatment for malignant glioma.

Clinical implementation of integrated whole-genome copy number and mutation profiling for glioblastoma.

Background: Multidimensional genotyping of formalin-fixed paraffin-embedded (FFPE) samples has the potential to improve diagnostics and clinical trials for brain tumors, but prospective use in the clinical setting is not yet routine. We report our experience with implementing a multiplexed copy number and mutation-testing program in a diagnostic laboratory certified by the Clinical Laboratory Improvement Amendments.

Methods: We collected and analyzed clinical testing results from whole-genome array comparative genomic hybridization (OncoCopy) of 420 brain tumors, including 148 glioblastomas.

How treatment monitoring is influencing treatment decisions in glioblastomas.

Glioblastoma (GBM), the most common malignant primary tumor in adults, carries a dismal prognosis with an average median survival of 14-16 months. The current standard of care for newly diagnosed GBM consists of maximal safe resection followed by fractionated radiotherapy combined with concurrent temozolomide and 6 to 12 cycles of adjuvant temozolomide. The determination of treatment response and clinical decision-making in the treatment of GBM depends on accurate radiographic assessment.

Re-defining response and treatment effects for neuro-oncology immunotherapy clinical trials.

In much of medical oncology, including neuro-oncology, there is great interest to evaluate the therapeutic potential of immune-based therapies including vaccines, adoptive T cell strategies and modulators of immune checkpoint regulators such as cytotoxic T lymphocyte antigen 4 and programmed death 1. Immune-based treatments exert an indirect anti-tumor effect by generating potent, tumor-targeting immune responses. Robust anti-tumor immune responses have been shown to achieve encouraging radiographic responses across the spectrum of applied immunotherapeutics which are felt to be indicative of a bona fide anti-tumor effect.

Implementation of a Hemostatic and Antithrombotic Stewardship program.

Hemostatic and antithrombotic (HAT) agents are high risk, high cost products. They require close monitoring and dose titration to adequately treat or prevent thrombosis while avoiding bleeding events. Incorporating the principles of inpatient anticoagulation management service into a stewardship program not only improves outcomes and decreases cost, but also improves transitions of care, exposes gaps in therapy management, and leads to the development of institution specific protocols and guidelines.

Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma.

There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors.

A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study.

Background: The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin. In previous phase II trials (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival.