Wenya Linda Bi

Background: Mechanisms driving aggressive meningiomas remain poorly understood. Given the pivotal role of the immune microenvironment in tumor progression, we developed a comprehensive atlas of the meningioma microenvironment, with a view toward identifying modifiable opportunities. Methods: The immune microenvironment of 2,727 meningiomas was profiled using orthogonal methodologies, including 24 with mass cytometry, 24 single-cell RNAseq, 1,437 bulk RNAseq, 1,125 DNA methylation, 117 multiplex immunofluorescence, as well as that of 5 paired peripheral blood samples and 10 human meninges. Patient-derived organotypic tumor spheroids (PDOTS) were established to assess the effect of STING stimulation combined with anti-PD-1 treatment. Results: We revealed a rich immune infiltration in meningioma, among the highest across 34 human cancer types (n = 12,188). Macrophages predominated in meningioma microenvironment, in contrast to the lymphoid dominance of peripheral blood, with meninges exhibiting an intermediate immune profile between meningiomas and peripheral blood. Cellular states and phenotypes of both immune and tumor cells shifted during tumor progression, with aggressive meningiomas possessing earlier-stage, immunosuppressive immune cells and proliferative tumor cells. Using ex vivo meningioma PDOTS, we demonstrated inducible responses to STING activation, marked by elevated cytokine release, which were synergistic when combined with PD-1 blockade. Conclusions: These findings offer an extensive resource on the cellular heterogeneity of the meningioma microenvironment and provide a framework for rational therapeutic modeling and strategy development.

Injury of lower cranial nerves XI and X poses significant morbidity and mortality to patients. Appropriate recognition, timely intervention, and appreciation of the natural history for recovery potential are critical to achieve safe outcomes when such injury occurs. To outline the most effective ways to assess and manage lower cranial nerve injuries, we propose a sequential approach to the management of preoperative and postoperative voice and swallow deficiencies from lower cranial nerve injuries. Injury of cranial nerves IX and X from neoplastic pathologies and following surgical intervention poses significant morbidity and mortality to patients. Appropriate recognition, timely intervention, and appreciation of the natural history for recovery potential are critical to achieve safe outcomes when such injury occurs. Patients with injury of cranial nerves IX through XII from neoplastic pathologies and following surgical intervention. In this narrative review, we outline the anatomy and physiology of the lower cranial nerves IX and X and the functional consequences of their injury, with an emphasis on the time course of available therapeutic options for voice and swallow dysfunction. We propose a sequential approach to the management of preoperative and postoperative voice and swallow deficiencies. With this knowledge, surgeons will be better equipped to anticipate and manage perioperative lower cranial nerve injuries to optimize outcome in patients.

The emergence of modern adjuvant therapies has significantly improved outcomes for patients with brain metastases. However, treatment-related side effects present an ongoing challenge, particularly, treatment-induced necrosis characterized by perilesional edema and inflammation. Standard management with steroids compromises the efficacy of otherwise efficacious immunotherapeutic approaches. This position paper critiques traditional management strategies that rely heavily on systemic corticosteroid therapy—often ineffective in providing lasting relief and associated with serious side effects—and proposes a paradigm shift that prioritizes surgical resection. Resection facilitates prompt edema reduction with a low recurrence rate of symptoms and mitigates the adverse effects of prolonged corticosteroid use. We propose increased consideration for resecting symptomatic radiation necrosis to facilitate improved efficacy of immunotherapies in patients with brain metastases.

Chromosome-arm copy number alterations (CNAs) are an important component of cancer molecular classifiers. CNAs are often translated into binary chromosome arm calls (arm gain/loss) using an arm call threshold before integration into classification schemes. However, substantial variability exists in thresholds used to define arm calls from CNA data. Here, we analyze 1042 meningiomas with whole-genome microarray data and 13 meningiomas with multifocal sampling to characterize how CNA thresholds influence molecular classification and prognostication. Changing arm call thresholds shifts the association of chromosomal arm calls with meningioma recurrence in an arm-dependent manner and upgrades 21.5% of cases from low-grade to high-grade in a molecularly Integrated Grade (IG) scheme. The impact of threshold differences in IG prediction of recurrence is most evident amongst intermediate grade (IG-2) tumors and CNA call thresholds approaching whole-chromosome arm length (>95%). The designation of chromosome loss or gain remains stable across a majority of thresholds, although this varies in a chromosome-dependent manner. CNAs fluctuate among paired primary-recurrent tumors, mostly growing on recurrence, but cluster in discrete sizes within a tumor. Appreciation of the impact of chromosome arm call thresholds can help ensure robustness of molecular classification paradigms.

Since its first activities in 2008 and 2009, the Response Assessment in NeuroOncology (RANO) group has given guidance on response assessment, trial design, and trial procedures to improve and standardize the way clinical trials in neurooncological studies are performed. To achieve its objectives, a variety of working groups have been initiated that cover many aspects of clinical trial design and outcome assessment in patients with tumors affecting the Central Nervous System. The RANO working groups are built on expertise without a formal structure, which makes rapid responses to new developments possible. RANO is aiming at evidence-based guidelines and recommendations, but in the absence of evidence will provide consensus-based guidance achieved by inviting recognized international experts. In its 15 years of existence, more than 60 RANO papers have been published mostly in high-ranking journals, and its recommendations have been accepted by regulators and industry as guiding principles. RANO organizes two meetings per year, one in conjunction with the annual American Society for Clinical Oncology (ASCO) meeting, and one during the annual Society for Neuro-Oncology meeting. These meetings are open, as are the working groups of RANO. New initiatives are welcomed.

Background: Patients with pituitary lesions often present with visual deficits attributable to mass effect along the optic pathway or on the cranial nerves controlling extraocular muscles. While symptoms often improve after treatment, persistent symptoms negatively impact quality of life. Methods: We reviewed the literature on emerging concepts in visual monitoring and recovery during and after pituitary surgery. Results: Rigorous preoperative laboratory testing, neuro-ophthalmologic examination, and imaging abet planning of safe surgery. Intraoperative visual evoked potentials may provide an adjunct to monitor impending damage to vision during surgery, particularly for recurrent tumors that may have scarred onto visual structures. Treatment of persistent visual deficits depends on the physiological cause of the deficit, the duration of symptoms, and the degree and pace of spontaneous recovery. Management ranges from observation to corrective oculoplastic surgery, often in the context of a multidisciplinary team. There are several gaps in knowledge on the reasons why visual deficits remain after adequate decompression during surgery, and further study will reveal new therapies and devices. Conclusion: Postoperative visual deficits following pituitary surgery can cause a considerable reduction in quality of life. Multidisciplinary neurosurgery, neuro-ophthalmologic, and neuro-endocrine teams should work in concert to provide an individualized approach for each patient.

Brainstem tumors are bounded by a compact topography of eloquent tracts, cranial nerves, and nuclei. Reliable intraoperative neuromonitoring aids microneurosurgical technique to optimize safe resection. The authors present a case of motor mapping–guided resection of a recurrent brainstem pilocytic astrocytoma. They demonstrate reliable and continuous responses from the corticospinal tract at the level of the midbrain to the pons with dynamic subcortical motor mapping using a monopolar stimulating suction. Contralateral limb and ipsilateral face muscles can be simultaneously detected and tumor resected until a threshold of less than 1 mA, corresponding to 1 mm or less from the corticospinal tracts. The video can be found here: https://stream.cadmore.media/r10.3171/2024.10.FOCVID24110