Electromagnetic Neuronavigation for CNS Tumors

Abstract BACKGROUND Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are a class of compounds found in marijuana. Numerous studies in adults have examined cannabinoid use in management of cancer-related symptoms such as nausea, anorexia, and pain. Less is known about the use in the pediatric oncology population. METHODS A prospective observational study has been ongoing since 2016 at Children’s Hospital Colorado to evaluate cannabinoids’ impact using PedsQL™ modules on quality of life of pediatric patients with central nervous system (CNS) tumors who are 2–18 years old. Laboratory assessments of T-cell activity and pharmacokinetics of CBD, THC and associated metabolites are in process. Diaries with exploratory information on cannabinoid use patterns are being collected. RESULTS Thirty-three patients (14:19; male:female) have been enrolled with a median age of 6.4 years (range, 2.9–17.7 years). The most common tumor type in enrolled patients is embryonal tumors (13/33; 39%). Nine (27%) patients have low-grade glial/glioneuronal tumors, and eight (24%) had high-grade/diffuse midline gliomas. The remaining patients had ependymoma or craniopharyngioma. The median time on cannabinoids is 9 months. Most (n=20) patients have used oral products with CBD and THC. One patient continues on cannabinoid therapy in follow up. Preliminary immune function analyses identified impaired neutrophil superoxide anion production and chemotaxis in patients taking cannabinoids at early time points on therapy. CONCLUSIONS Families of children with various CNS tumors are pursuing cannabinoid therapy for both antitumor and supportive care purposes. Analysis of the impact of cannabinoids on patients’ quality of life is ongoing.

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PATH-27. MUTATION DETECTION USING PLASMA CELL-FREE DNA IN CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.662 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii430-iii430

Author(s):

Ross Mangum ◽

Jacquelyn Reuther ◽

Koel Sen Baksi ◽

Ryan C Zabriskie ◽

Ilavarasi Gandhi ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Plasma Cell ◽

Pediatric Patients ◽

Cns Tumors ◽

Cell Free Dna ◽

Pilot Studies ◽

Dna And Rna ◽

Free Dna ◽

Initial Cohort

Abstract BACKGROUND The role of plasma cell-free DNA (cfDNA) as a cancer biomarker for tracking treatment response and detecting early relapse has been well described for solid tumors outside the central nervous system (CNS). However, the presence of a blood-brain barrier complicates the application of plasma cfDNA analysis for patients with CNS malignancies. METHODS cfDNA was extracted from plasma of pediatric patients with CNS tumors utilizing a QIAmp® MinElute® kit and quantitated with Qubit 2.0 Fluorometer. Extensive genomic testing, including targeted DNA and RNA solid tumor panels, exome and transcriptome sequencing, as well as copy number array, was performed on matched tumor samples as part of the Texas KidsCanSeq study. An Archer® Reveal ctDNA28 NGS kit was then used for assaying the sensitivity of detecting tumor-specific mutations in the plasma of these patients. RESULTS A median of 10.7ng cfDNA/mL plasma (Interquartile range: 6.4 – 15.3) was extracted from 78 patients at time of study enrollment. Longitudinal samples from 24 patients exhibited a median yield of 7.7ng cfDNA/mL plasma (IQR: 5.9 – 9.1). An initial cohort of 6 patients was identified with 7 somatic variants covered by the Archer® Reveal kit. Four of seven mutations identified in matched tumor specimens were detected in patient plasma at variant allele frequencies ranging from 0.2–1%. CONCLUSIONS While challenging, detection of cfDNA in the plasma of pediatric patients with CNS tumors is possible and is being explored in a larger patient cohort along with pilot studies investigating cerebrospinal fluid as an additional source for tumor-specific cfDNA.

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LINC-42. EPIDEMIOLOGICAL OVERVIEW OF CHILDHOOD CNS TUMORS IN THE NEUROSURGICAL UNIT IN YEREVAN, ARMENIA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.475 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii386-iii386

Author(s):

Nune Karapetyan ◽

Samvel Danielyan ◽

Gevorg Tamamyan ◽

Armen Tananyan ◽

Liana Safaryan ◽

...

Keyword(s):

Medical Center ◽

Survival Rates ◽

Developed Countries ◽

Cns Tumors ◽

Malignant Neoplasms ◽

Low Grade ◽

Embryonal Tumors ◽

Low Grade Gliomas ◽

Neurosurgical Treatment

Abstract BACKGROUND Central nervous system (CNS) tumors are the second most common malignant neoplasms among children worldwide. The current paper aims to analyze the situation in pediatric neuro-oncology in Armenia from the neurosurgical perspective. METHODS We have collected data of pediatric patients with CNS tumors treated in the Neurosurgery department of “Surb Astvasamayr” Medical Center from 01.01.2010 till 01.12.2019. Incidence by gender, age at diagnosis, and histopathology results were calculated. Survival rates were calculated based on the follow-up results performed until 30.12.2019. RESULTS Hospital-based data showed that during the previous 10 years 47 patients with CNS tumors received neurosurgical treatment in the unit, among them 66% were females. 38.3%, 31.9% and 29.8% of diagnosed patients were aged 0–4, 5–9, and 10–18 respectively. In 41 cases, the disease was not disseminated at diagnosis. The most common observed malignancies were low-grade gliomas (21.3%) and embryonal tumors (19.1%), followed by high-grade gliomas (14.9%) and ependymal tumors (8.5%). Follow-up information only for 33 patients is available. From them, 14 are dead and 19 alive. Survival rates in most common groups were 62.5%, 80%, 50%, and 50% respectively. The median follow-up time was 18 months (range 1–113 months). CONCLUSION Similar to the data reported in the literature, low-grade gliomas, and embryonal tumors are the most frequent pediatric CNS tumors in Armenia. On the other hand, the pediatric CNS tumor survival rates are lower compared to those reported in developed countries.

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Raman Spectral Signatures of Serum-Derived Extracellular Vesicle-Enriched Isolates May Support the Diagnosis of CNS Tumors

Cancers ◽

10.3390/cancers13061407 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1407

Author(s):

Matyas Bukva ◽

Gabriella Dobra ◽

Juan Gomez-Perez ◽

Krisztian Koos ◽

Maria Harmati ◽

...

Keyword(s):

Lumbar Disc ◽

Area Under The Curve ◽

Principal Component ◽

Extracellular Vesicle ◽

Classification Performance ◽

Cns Tumors ◽

Clinical Samples ◽

Support Vector ◽

Serum Samples ◽

Raman Spectroscopic

Investigating the molecular composition of small extracellular vesicles (sEVs) for tumor diagnostic purposes is becoming increasingly popular, especially for diseases for which diagnosis is challenging, such as central nervous system (CNS) malignancies. Thorough examination of the molecular content of sEVs by Raman spectroscopy is a promising but hitherto barely explored approach for these tumor types. We attempt to reveal the potential role of serum-derived sEVs in diagnosing CNS tumors through Raman spectroscopic analyses using a relevant number of clinical samples. A total of 138 serum samples were obtained from four patient groups (glioblastoma multiforme, non-small-cell lung cancer brain metastasis, meningioma and lumbar disc herniation as control). After isolation, characterization and Raman spectroscopic assessment of sEVs, the Principal Component Analysis–Support Vector Machine (PCA–SVM) algorithm was performed on the Raman spectra for pairwise classifications. Classification accuracy (CA), sensitivity, specificity and the Area Under the Curve (AUC) value derived from Receiver Operating Characteristic (ROC) analyses were used to evaluate the performance of classification. The groups compared were distinguishable with 82.9–92.5% CA, 80–95% sensitivity and 80–90% specificity. AUC scores in the range of 0.82–0.9 suggest excellent and outstanding classification performance. Our results support that Raman spectroscopic analysis of sEV-enriched isolates from serum is a promising method that could be further developed in order to be applicable in the diagnosis of CNS tumors.

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Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Cancers ◽

10.3390/cancers13123028 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3028

Author(s):

George I. Lambrou ◽

Apostolos Zaravinos ◽

Maria Braoudaki

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cns Tumors ◽

Normal Brain ◽

Cns Tumor ◽

Different Types ◽

Receiver Operator Curve Analysis ◽

The Central Nervous System ◽

Tumor Types ◽

Operator Curve

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.

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Unexpected Binding of Tozuleristide “Tumor Paint” to Cerebral Vascular Malformations: A Potentially Novel Application of Fluorescence-Guided Surgery

Neurosurgery ◽

10.1093/neuros/nyab106 ◽

2021 ◽

Author(s):

Andrew J Kobets ◽

David Nauen ◽

Amy Lee ◽

Alan R Cohen

Keyword(s):

Near Infrared ◽

Vascular Malformations ◽

Cns Tumors ◽

Matrix Metalloproteinase 2 ◽

Cerebrovascular Lesions ◽

Cavernous Malformations ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

Cerebral Vascular Malformations ◽

Cerebral Vascular

Abstract BACKGROUND Fluorescence-guided surgery (FGS) is under investigation as a means to improve the extent of resection for primary central nervous system (CNS) tumors. Tozuleristide, known also as “Tumor Paint,” is an investigational tumor-targeting agent covalently conjugated to a derivative of the fluorescent dye indocyanine green. OBJECTIVE To report the finding of avid intraoperative fluorescence of tozuleristide on cerebral vascular malformations. METHODS Our institution is participating in a phase 2/3 study of intraoperative near-infrared fluorescence detection of pediatric primary CNS tumors in patients receiving intravenous tozuleristide and imaged with the Canvas system. Our site enrolled 2 patients with intracranial lesions, suspected preoperatively of possibly being gliomas that proved to be cavernous vascular malformations after resection. RESULTS Each lesion had a dark blue mulberry appearance and each fluoresced avidly with tozuleristide. Each was completely resected, and the patients recovered without deficit. Pathological assessment showed cavernous angioma for both cases. Tozuleristide fluorescence is postulated to result from binding to matrix metalloproteinase-2 and annexin A2, and literature review demonstrates expression of both these ligands on multiple cerebrovascular lesions, including cavernous malformations. CONCLUSION This finding deserves further investigation to determine if tozuleristide “Tumor Paint” may have a wider role in the identification of non-neoplastic intracranial pathologies.

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