ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.

Purpose: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

Methods: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles.

Pembrolizumab alters the tumor immune landscape in a patient with dMMR glioblastoma.

Congenital DNA mismatch repair defects (dMMR), such as Lynch Syndrome, predispose patients to a variety of cancers and account for approximately 1% of glioblastoma cases. While few therapeutic options exist for glioblastoma, checkpoint blockade therapy has proven effective in dMMR tumors. Here we present a case study of a male in their 30s diagnosed with dMMR glioblastoma treated with pembrolizumab who experienced a partial response to therapy.

Phase I Study of High-Dose L-methylfolate in Combination with Temozolomide and Bevacizumab in Recurrent IDH wild-type High-Grade Glioma.

Purpose: mutations in low-grade gliomas (LGGs) results in improved survival and DNA hypermethylation compared to wild-type LGGs. -mutant LGGs become hypomethylated during progression. It's uncertain if methylation changes occur during wild-type GBM progression and if the methylome can be reprogrammed.

Impact of postoperative dexamethasone on survival, steroid dependency, and infections in newly diagnosed glioblastoma patients.

Background: We examined the effect of dexamethasone prescribed in the initial 3 postoperative weeks on survival, steroid dependency, and infection in glioblastoma patients.

Methods: In this single-center retrospective cohort analysis, we electronically retrieved inpatient administration and outpatient prescriptions of dexamethasone and laboratory values from the medical record of 360 glioblastoma patients. We correlated total dexamethasone prescribed from postoperative day (POD) 0 to 21 with survival, dexamethasone prescription from POD30 to POD90, and diagnosis of an infection by POD90.

NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017.

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options.

Preradiation Chemotherapy for Adult High-risk Medulloblastoma: A Trial of the ECOG-ACRIN Cancer Research Group (E4397).

Objectives: To assess the long-term outcomes and objective response (OR) to preradiation chemotherapy and radiation in adult high-risk medulloblastoma.

Materials And Methods: In this prospective phase II trial, adults with high-risk medulloblastoma were treated with 3 cycles of preradiation cisplatin, etoposide, cyclophosphamide, and vincristine followed by craniospinal radiation (CSI). OR, progression-free survival (PFS), overall survival (OS), and toxicities were assessed.

Response of silent corticotroph pituitary carcinoma to chemotherapy: case report.

Silent pituitary corticotroph carcinomas are rare, with only six previously described cases in the literature. We report a patient with a silent pituitary corticotroph adenoma treated with multiple trans-sphenoidal resections. Twelve years after her initial presentation, she returned with leptomeningeal metastases to the posterior fossa, foramen magnum, and numerous other subarachnoid locations involving the spine.

Valganciclovir and bevacizumab for recurrent glioblastoma: A single-institution experience.

Prolonged treatment with adjuvant valganciclovir has been shown in one retrospective study to exert a significant effect on overall survival (OS) in newly diagnosed patients with glioblastoma multiforme (GBM). However, studies evaluating the effectiveness of valganciclovir in the treatment of recurrent GBM have not been performed. We evaluated the effect of valganciclovir in the recurrent setting in combination with bevacizumab therapy.

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.

On the Use of DSC-MRI for Measuring Vascular Permeability.

Background And Purpose: Contrast agent extravasation has been shown to confound brain tumor perfusion measurements with DSC-MR imaging, necessitating the use of correction techniques (eg, Weisskoff, Bjornerud). Leakage parameters (K2 and K(a)) postulated to reflect vessel permeability can be extracted from these correction methods; however, the biophysical interpretation of these parameters and their relationship to commonly used MR imaging measures of vascular permeability (eg, contrast agent volume transfer constant, [K(trans)]) remain unclear. Given that vascular density, as assessed by blood volume, and vascular permeability, as reflected by K(trans) (and potentially K2 or K(a)), report on unique and clinically informative vascular characteristics, there is a compelling interest to simultaneously assess these features.

Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique.

Central nervous system cancers.

Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume.

Cancer susceptibility variants and the risk of adult glioma in a US case-control study.

Malignant gliomas are the most common and deadly brain tumors. Although their etiology remains elusive, recent studies have narrowed the search for genetic loci that influence risk. We examined variants implicated in recent cancer genome-wide association studies (GWAS) for associations with glioma risk in a US case-control study.

Molecular genetic analysis of a primitive neuroectodermal tumor arising after intracranial radiation and chemotherapy for leukemia.

Primitive neuroectodermal tumors are aggressive tumors of the central nervous system (CNS), yet their etiology remains unclear. We report a case of a primitive neuroectodermal tumor (PNET) arising in the cerebellum and pons 7 yr after intracranial radiation and chemotherapy for leukemia involving the CNS. This case suggests a possible link between radiation, chemotherapy, and the formation of these tumors, with a potential new pathogenetic role for somatic inactivation of the protooncogene RET.

Flecainide for the treatment of chronic neuropathic pain: a Phase II trial.

Background: Management of neuropathic pain is challenging. Medications that interfere with sodium channel transport, such as lidocaine, mexilitene and flecainide, are promising as analgesics.

Objective: In a general population of patients with a working diagnosis of neuropathic pain, whether if flecainide produces enough of an improvement in pain to warrant further clinical study is determined.

Differential responsiveness among "high risk" pediatric brain tumors in a pilot study of dose-intensive induction chemotherapy.

Background: These factors have been predictive for progressive disease on therapy (PDOT) among pediatric brain tumors: >1.5 cm(2) unresectable tumor, glioblastoma, supratentorial primitive neuroectodermal tumor, and metastatic medulloblastoma (MBL). This pilot study sought to correlate cytoreductive response with progression free survival.

Allelic losses in oligodendroglial and oligodendroglioma-like neoplasms: analysis using microsatellite repeats and polymerase chain reaction.

Context: Oligodendroglial tumors are heterogenous neoplasms with histologic features shared with other central nervous system tumors, such as dysembryoplastic neuroepithelial tumors.

Objective: We examined a series of tumors, identified as possessing oligodendroglial components at the time of intraoperative examination, to see if molecular subsets based on the oligodendroglial component could be recognized.

Design: DNA was extracted from fresh brain tumor tissue and corresponding peripheral blood or normal tissues.

Dural lesions mimicking meningiomas.

Recently, a number of neoplastic and nonneoplastic entities have been reported that radiographically and clinically mimic meningiomas. Because these lesions occur infrequently and may resemble a meningioma during intraoperative analysis, they may not be considered in the differential diagnosis. This review (and case illustrations) considers some of the newly recognized and notable lesions that can mimic meningiomas, including solitary fibrous tumors, gliosarcomas, leiomyosarcomas, hemangiopericytomas, melanocytomas, Hodgkin's disease, plasmacytomas, inflammatory pseudotumors, neurosarcoidosis, plasma cell granulomas, Rosai-Dorfman disease, Castleman's disease, xanthomas, rheumatoid nodules, and tuberculomas.

An open label trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis.

Drugs currently available for intrathecal administration are cleared rapidly from the CSF. DepoCyt is a slow-release formulation of cytarabine that maintains cytotoxic concentrations of free cytarabine in the CSF for >14 days following a single injection. DepoCyt was administered to 110 patients with a diagnosis of neoplastic meningitis based on either a positive CSF cytology (76) or neurologic and CT or MRI scan findings sufficient to document neoplastic meningitis (34).

Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers.

Recent studies from our laboratory suggest that gene-specific methylation changes in sputum could be good intermediate markers for the early detection of lung cancer and defining the efficacy of chemopreventive interventions. The purpose of our study was to determine the prevalence for aberrant promoter methylation of the p16, O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated protein (DAP) kinase, and Ras effector homologue (RASSFIA) genes in nonmalignant bronchial epithelial cells from current and former smokers in a hospital-based, case control study of lung cancer. The relationship between loss of heterozygosity, at 9p and p16 methylation in bronchial epithelium and the prevalence for methylation of these four genes in sputum from cancer-free, current and former smokers were also determined.