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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. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N= 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P< 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P= 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses.

Since the early descriptions of language function based on observations of patients with language deficits by Broca and Wernicke, neurosurgeons have been focused on characterizing the anatomic regions necessary for language perception and production, and preserving these structures during surgery to minimize patient deficits post operatively. In this supplementary issue on awake intraoperative mapping, we review language processing across multiple domains, highlighting key advances in direct electrical stimulation of different cortical and subcortical regions involved in naming, repetition, reading, writing, and syntax. We then discuss different intraoperative tasks for assessing the function of a given area and avoiding injury to critical, eloquent regions.

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions. Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function. Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients. A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions. Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function. Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients. A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

Gliomas are often in close proximity to functional regions of the brain; therefore, electrocortical stimulation (ECS) mapping is a common technique utilized during glioma resection to identify functional areas. Stimulation-induced seizure (SIS) remains the most common reason for aborted procedures. Few studies have focused on oncological factors impacting cortical stimulation thresholds.

Intraoperative functional mapping of tumor and peri-tumor tissue is a well-established technique for avoiding permanent neurologic deficits and maximizing extent of resection. Motor, language, and other cognitive domains may be assessed with intraoperative tasks. This article describes techniques used for motor and language mapping including awake mapping considerations in addition to less traditional intraoperative testing paradigms for cognition. It also discusses complications associated with mapping and insights into complication avoidance.

Gliomas are a major cause of morbidity. Direct cortical stimulation mapping offers the ability to identify functional areas within the broader neural network both cortically and subcortically. Since the World Health Organization (WHO) 2016 classification categorized gliomas into molecular subgroups with varied molecular signatures and clinical behavior, it is possible that gliomas may demonstrate rates of functional network integration. We therefore retrospectively reviewed a data registry of 181 patients with dominant hemisphere frontal, parietal, insular, or temporal gliomas. Our goal was to test the hypothesis that WHO glioma histopathology and molecular subtype influences functional language or motor sites identified within the tumor. Intratumoral function as determined by direct cortical and subcortical stimulation mapping was identified at the highest rate in isocitrate dehydrogenase mutant astrocytomas and oligodendrogliomas. Finally, we reviewed the emerging literature exploring the interface between functional neural networks and gliomas. These data shed light on glioma molecular and histological characteristics most commonly associated within intratumoral function.

Glioblastoma has been shown to have many different genetic mutations found both within and between tumor samples. Molecular testing and genomic sequencing has helped to classify diagnoses and clarify difficult to interpret histopathological specimens. Genomic information also plays a critical role in prognostication for patients, with IDH mutations and MGMT methylation having significant impact of the response to chemotherapy and overall survival of patients. Unfortunately, personalized medicine and targeted therapy against specific mutations have not been shown to improve patient outcomes. As technology continues to improve, exome and RNA sequencing will play a role in the design of clinical trials, classification of patient subgroups and identification of rare mutations that can be targeted by small-molecule inhibitors and biologic agents.

Introduction:A limitation of small molecule inhibitors, nanoparticles (NPs) and therapeutic adenoviruses is their incomplete distribution within the entirety of solid tumors such as malignant gliomas. Currently, cell-based carriers are making their way into the clinical setting as they offer the potential to selectively deliver many types of therapies to cancer cells.Areas covered:Here, we review the properties of stem cells, induced pluripotent stem cells and engineered cells that possess the tumor-tropic behavior necessary to serve as cell carriers. We also report on the different types of therapeutic agents that have been delivered to tumors by these cell carriers, including: i) therapeutic genes; ii) oncolytic viruses; iii) NPs; and iv) antibodies. The current challenges and future promises of cell-based drug delivery are also discussed.Expert opinion:While the emergence of stem cell-mediated therapy has resulted in promising preclinical results and a human clinical trial utilizing this approach is currently underway, there is still a need to optimize these delivery platforms. By improving the loading of therapeutic agents into stem cells and enhancing their migratory ability and persistence, significant improvements in targeted cancer therapy may be achieved.

The use of stem cells (SCs) as carriers for therapeutic agents has now progressed to early clinical trials. These clinical trials exploring SC‐mediated delivery of oncolytic adenoviruses will commence in the near future, hopefully yielding meritorious results that can provoke further scientific inquiry. Preclinical animal studies have demonstrated that SCs can be successfully loaded with conditionally‐replicative adenoviruses and delivered to the tumor, whereupon they may evoke pronounced therapeutic efficacy. In this protocol, we describe the maintenance of SCs, provide an analysis of optimal adenoviral titers for SC loading, and evaluate the optimized viral loading on SCs. © 2015 by John Wiley & Sons, Inc.