A phase I study of convection-enhanced delivery (CED) of liposomal-irinotecan using real-time magnetic resonance imaging in patients with recurrent high-grade glioma.

Background: Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial.

NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy.

Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental. Resistance to radiotherapy is common in high-grade meningiomas, and the cell types and signaling mechanisms driving meningioma tumorigenesis or resistance to radiotherapy are incompletely understood.

Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Background: Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and current indications for postoperative radiotherapy are controversial. Recent studies have proposed prognostic meningioma classification systems using DNA methylation profiling, copy number variants, DNA sequencing, RNA sequencing, histology, or integrated models based on multiple combined features. Targeted gene expression profiling has generated robust biomarkers integrating multiple molecular features for other cancers, but is understudied for meningiomas.

Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.

Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities.

A single institution retrospective analysis on survival based on treatment paradigms for patients with anaplastic oligodendroglioma.

Introduction: Anaplastic oligodendrogliomas are high-grade gliomas defined molecularly by 1p19q co-deletion. There is no curative therapy, and standard of care includes surgical resection followed by radiation and chemotherapy. However, the benefit of up-front radiation with chemotherapy compared to chemotherapy alone has not been demonstrated in a randomized control trial.

Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma.

Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas.

DNA methylation profiling demonstrates superior diagnostic classification to RNA-sequencing in a case of metastatic meningioma.

Meningiomas are the most common primary intracranial tumors, but meningioma metastases are rare. Accordingly, the clinical workup, diagnostic testing, and molecular classification of metastatic meningioma is incompletely understood. Here, we present a case report of multiply recurrent meningioma complicated by liver metastasis.

Integrated models incorporating radiologic and radiomic features predict meningioma grade, local failure, and overall survival.

Background: We investigated prognostic models based on clinical, radiologic, and radiomic feature to preoperatively identify meningiomas at risk for poor outcomes.

Methods: Retrospective review was performed for 303 patients who underwent resection of 314 meningiomas (57% World Health Organization grade I, 35% grade II, and 8% grade III) at two independent institutions, which comprised primary and external datasets. For each patient in the primary dataset, 16 radiologic and 172 radiomic features were extracted from preoperative magnetic resonance images, and prognostic features for grade, local failure (LF) or overall survival (OS) were identified using the Kaplan-Meier method, log-rank tests and recursive partitioning analysis.

The Effect of Molecular Diagnostics on the Treatment of Glioma.

Purpose Of Review: This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions.

Recent Findings: Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions.

Current and future strategies for treatment of glioma.

Gliomas are one of the most common types of primary brain tumors and have remained particularly challenging to treat. This review illustrates a multidisciplinary approach to the treatment of glioma and glioblastoma. We will review current advances in surgical approaches, novel imaging techniques, advanced molecular characterization of tumors and translational efforts for treatment.