Neuraxis metastases from central nervous system tumors: a review of clinicopathological and radiographic characters of 198 cases in a single center

Abstract Background Neuraxis metastases (NM) from systemic and central nervous system (CNS) tumors have become increasingly common. However, a lack of systematic information restricts the development of the accurate diagnosis and treatment. The aim of this study is to facilitate the understanding of NM arising from CNS tumors in the largest cohort. Methods Based on the clinicopathological and neuroimaging findings, we retrospectively analyze the epidemiological characters, radiographic classification, therapeutic strategies and prognostic factors. Results A total of 198 cases are enrolled and the most common primary tumor is medulloblastoma (34.34%). The median age is 15.0 years and the majority of NM (79.29%) occur in the children and young adult groups. 149 (75.25%) cases suffer from intracranial metastases, and 169 (85.35%) have the intraspinal NM. The whole leptomeninges and cauda equine are the most preferential disseminated sites. Upon MRI parameters, the massive and miliary subgroup occur most frequently in the intracranial and intraspinal NM, respectively. Treatment includes surgery (21.71%), chemotherapy alone (19.19%), radiation alone (10.10%) and combined therapy (55.56%). Operations are performed in order to identify pathology and relive masses, as well as the triple chemotherapeutic scheme consisting of ifosfamide, carboplatin and etoposide is recommended to most of NM. The median overall survival is 11.6 months. The younger age, coexistence of NM with primary tumors, shorter interval from primaries to metastases, glioma, leptomeningeal seeding and nodal subtype on MRI are significantly associated with the poor prognosis. Conclusion In spite of the controversial therapies and poor outcomes, the neuroimaging classification and comprehensive treatment contribute to the efficient administration of NM.

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Cytology of Extraneural Metastases of Nonhematolymphoid Primary Central Nervous System Tumors: Six Cases with Histopathological Correlation and Literature Update

Acta Cytologica ◽

10.1159/000517480 ◽

2021 ◽

Vol 65 (6) ◽

pp. 529-540

Author(s):

Joerg Schwock ◽

Lorna Mirham ◽

Zeina Ghorab

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tertiary Care ◽

Case Series ◽

Cns Tumors ◽

Salivary Gland Neoplasm ◽

Time Interval ◽

Myxopapillary Ependymoma ◽

Primary Tumor Site ◽

Primary Tumors

Introduction: Extraneural/-cranial metastases (ENM) of primary central nervous system (CNS) tumors are rare and may be diagnostically challenging. We describe the cytomorphological and pertinent clinical features of ENM in a case series assessed by fine-needle aspiration (FNA). A search of the laboratory information systems of 2 tertiary care centers in Toronto (2000–2015) was performed. Cases with direct extracranial/-spinal extension of CNS neoplasms were excluded. Microscopic slides of FNA and surgical specimens were reviewed. Demographic and clinicopathological data were retrieved. Case Presentation: Six cases were identified with the original diagnoses of glioblastoma, glioblastoma with primitive neuroectodermal tumor-like components, anaplastic ependymoma, myxopapillary ependymoma, atypical meningioma, and hemangiopericytoma. Median patient age at first diagnosis was 44 years (range 22–56). The time interval between initial diagnosis and first metastatic disease manifestation was 3 months to 19 years. All FNA diagnoses were rendered correctly. In 4 cases, immunohistochemistry was used to support the diagnosis. All cases had prior surgical intervention at the primary tumor site. In 4 cases, the ENM location was the ipsilateral parotid or buccal area. Two primary tumors in midline location developed ENM in the scapular area. Discussion/Conclusion: ENM are a rare manifestation of a range of different primary CNS tumors and may involve the ipsilateral head and neck mimicking clinically a salivary gland neoplasm. FNA can rapidly discriminate ENM from other, potentially more indolent conditions. Awareness of the clinical history is paramount to avoid diagnostic confusion.

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QOL-36. USE OF CANNABINOIDS IN THE PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR POPULATION

Neuro-Oncology ◽

10.1093/neuonc/noaa222.695 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii438-iii438

Author(s):

Kathleen Dorris ◽

Jessica Channell ◽

Ashley Mettetal ◽

Molly Hemenway ◽

Natalie Briones ◽

...

Keyword(s):

Quality Of Life ◽

Central Nervous System ◽

Nervous System ◽

Cell Activity ◽

Cns Tumors ◽

Low Grade ◽

Tumor Type ◽

Central Nervous System Tumor ◽

The Impact

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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Development of the Cerebrospinal Fluid in Early Stage after Hemorrhage in the Central Nervous System

Life ◽

10.3390/life11040300 ◽

2021 ◽

Vol 11 (4) ◽

pp. 300

Author(s):

Petr Kelbich ◽

Aleš Hejčl ◽

Jan Krejsek ◽

Tomáš Radovnický ◽

Inka Matuchová ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Early Stage ◽

Rank Test ◽

Signed Rank ◽

Signed Rank Test ◽

The Central Nervous System ◽

Poor Outcomes ◽

Molecular Patterns

Extravasation of blood in the central nervous system (CNS) represents a very strong damaged associated molecular patterns (DAMP) which is followed by rapid inflammation and can participate in worse outcome of patients. We analyzed cerebrospinal fluid (CSF) from 139 patients after the CNS hemorrhage. We compared 109 survivors (Glasgow Outcome Score (GOS) 5-3) and 30 patients with poor outcomes (GOS 2-1). Statistical evaluations were performed using the Wilcoxon signed-rank test and the Mann–Whitney U test. Almost the same numbers of erythrocytes in both subgroups appeared in days 0–3 (p = 0.927) and a significant increase in patients with GOS 2-1 in days 7–10 after the hemorrhage (p = 0.004) revealed persistence of extravascular blood in the CNS as an adverse factor. We assess 43.3% of patients with GOS 2-1 and only 27.5% of patients with GOS 5-3 with low values of the coefficient of energy balance (KEB < 15.0) in days 0–3 after the hemorrhage as a trend to immediate intensive inflammation in the CNS of patients with poor outcomes. We consider significantly higher concentration of total protein of patients with GOS 2-1 in days 0–3 after hemorrhage (p = 0.008) as the evidence of immediate simultaneously manifested intensive inflammation, swelling of the brain and elevation of intracranial pressure.

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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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Defining and Timing of Palliative Opportunities in Children with Central Nervous System Tumors

Neuro-Oncology Practice ◽

10.1093/nop/npab020 ◽

2021 ◽

Author(s):

A McCauley Massie ◽

Jonathan Ebelhar ◽

Kristen E Allen ◽

Nicholas P DeGroote ◽

Karen Wasilewski-Masker ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

End Of Life ◽

Phase 1 ◽

Marrow Transplant ◽

Cns Tumors ◽

Do Not Resuscitate ◽

Intensive Care Admission ◽

Repeated Events

Abstract Background Children with brain and central nervous system (CNS) tumors experience substantial challenges to their quality of life during their disease course. These challenges are opportunities for increased subspecialty palliative care (PC) involvement. Palliative opportunities have been defined in the pediatric oncology population, but the frequency, timing, and factors associated with palliative opportunities in pediatric patients with CNS tumors are unknown. Methods A single-institution retrospective review was performed on children ages 0-18 diagnosed with a CNS tumor who died between 01/01/2012-11/30/2017. Nine palliative opportunities were defined prior to data collection (progression; relapse; admission for severe symptoms; intensive care admission; bone marrow transplant; phase 1 trial; hospice; do-not-resuscitate (DNR) order). Demographic, disease, treatment, palliative opportunity, and end-of-life data were collected. Opportunities were evaluated over quartiles from diagnosis to death. Results Amongst 101 patients with a median age at death of eight years (Interquartile range, IQR=8.0, range 0-22), there was a median of seven (IQR=6) palliative opportunities per patient, which increased closer to death. PC consultation occurred in 34 (33.7%) patients, at a median of 2.2 months before death, and was associated with having a DNR order (p=0.0028). Hospice was involved for 72 (71.3%) patients. Conclusion Children with CNS tumors suffered repeated events warranting PC yet received PC support only one-third of the time. Mapping palliative opportunities over the cancer course promotes earlier timing of PC consultation which can decrease suffering and resuscitation attempts at the end-of-life.

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Clinical utility of comprehensive genomic profiling in central nervous system tumors of children and young adults

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab037 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Jianling Ji ◽

Kristiyana Kaneva ◽

Matthew C Hiemenz ◽

Girish Dhall ◽

Tom Belle Davidson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Utility ◽

Adolescent And Young Adult ◽

Cns Tumors ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Genomic Profiling ◽

Comprehensive Genomic Profiling ◽

Clinically Significant

Abstract Background Recent large-scale genomic studies have revealed a spectrum of genetic variants associated with specific subtypes of central nervous system (CNS) tumors. The aim of this study was to determine the clinical utility of comprehensive genomic profiling of pediatric, adolescent and young adult (AYA) CNS tumors in a prospective setting, including detection of DNA sequence variants, gene fusions, copy number alterations (CNAs), and loss of heterozygosity. Methods OncoKids, a comprehensive DNA- and RNA-based next-generation sequencing (NGS) panel, in conjunction with chromosomal microarray analysis (CMA) was employed to detect diagnostic, prognostic, and therapeutic markers. NGS was performed on 222 specimens from 212 patients. Clinical CMA data were analyzed in parallel for 66% (146/222) of cases. Results NGS demonstrated clinically significant alterations in 66% (147/222) of cases. Diagnostic markers were identified in 62% (138/222) of cases. Prognostic information and targetable genomic alterations were identified in 22% (49/222) and 18% (41/222) of cases, respectively. Diagnostic or prognostic CNAs were revealed by CMA in 69% (101/146) of cases. Importantly, clinically significant CNAs were detected in 57% (34/60) of cases with noncontributory NGS results. Germline cancer predisposition testing was indicated for 27% (57/212) of patients. Follow-up germline testing was performed for 20 patients which confirmed a germline pathogenic/likely pathogenic variant in 9 cases: TP53 (2), NF1 (2), SMARCB1 (1), NF2 (1), MSH6 (1), PMS2 (1), and a patient with 47,XXY Klinefelter syndrome. Conclusions Our results demonstrate the significant clinical utility of integrating genomic profiling into routine clinical testing for pediatric and AYA patients with CNS tumors.

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LINC-39. PERFORMANCE STATUS OF PEDIATRIC PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS TREATED IN MEXICO, A SINGLE-CENTER EXPERIENCE

Neuro-Oncology ◽

10.1093/neuonc/noaa222.472 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii385-iii386

Author(s):

Claudia Madrigal-Avila ◽

Alfonso Perez-Bañuelos ◽

Rafael Ruvalcaba-Sanchez ◽

Lourdes Vega-Vega ◽

Gabriela Escamilla-Asiain

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Multidisciplinary Approach ◽

Pediatric Patients ◽

Performance Status ◽

Retrospective Chart Review ◽

Cns Tumors ◽

Surgical Morbidity ◽

Tertiary Center

Abstract BACKGROUND Central nervous system (CNS) tumors are the most common solid neoplasms in the pediatric age, they comprise about a quarter of all cancers at this age. Little is known about the specific epidemiology of this group in Mexico and there are no reports of results focused on the Performance Status of patients who are treated in a multidisciplinary setting. OBJECTIVE To describe the Performance Status of CNS pediatric patients after being treated with a multidisciplinary approach in a tertiary center. METHODS We report a retrospective chart review of all pediatric patients who presented to the Neuro-Oncology Clinic at Teleton Pediatric Oncology Hospital in Queretaro, Mexico, from December 2014 to January 2020. We analyzed age, gender, the extent of surgical resection and histopathology. Performance Status was assessed using ECOG and Karnofsky/Lansky scores during every patient’s last follow-up visit. RESULTS A total of 56 patients were treated, epidemiology and histopathology variants are similar to those described in the international literature. With a median follow-up of 33 months, 35 patients are alive (62.5%), 28 of them (74.2%) have an excellent Performance Status (ECOG score 0 or Lansky/Karnofsky ≥ 90), 5 (14.2%) scored ECOG 1–2 and only 4 (11.4%) scored ECOG 3–4. CONCLUSIONS A multidisciplinary approach with a focus on Performance Status and the potential for neurological recovery is essential in the management of pediatric patients with CNS tumors. Efforts should be aimed at reducing post-surgical morbidity and early rehabilitation to reintegrate patients into society in the long term.

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CASE STUDY ON CIRCUMSCRIBED GLIOMAS, THEIR CLINICOPATHOLOGICAL CORRELATION IN A TERTIARY CARE CENTER

10.36106/ijsr/6424584 ◽

2021 ◽

pp. 42-45

Author(s):

Esther Alffi Papang ◽

K. Rama

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Tertiary Care ◽

Biological Behavior ◽

Low Grade ◽

Lower Grade ◽

Who Grade ◽

Primary Tumors ◽

Short Period ◽

The Impact

The histogenesis and biological behavior of primary tumors of the central nervous system(CNS) are very diverse. The majority of present gliomas as benign, slow growing lesions classied as by the WHO classicati grade I or II (Low grade gliomas) on of CNS tumors. However, a signicant fraction of gliomas develop over a short period of time and progress rapidly and are therefore classied as WHO grade III or IV(High grade gliomas). Astrocytomas are primary central nervous system tumours that can develop in adults or in children. They arise from the Astrocytes. They can be divided into diffuse that generally have a higher grade and poorer prognosis and those that are localised that tend to be of a lower grade and have a better prognosis. In this study, we outline the basic histological spectrum and features, epidemiological aspects and grade of circumscribed gliomas (localised) or other Astrocytic tumours according to WHO classication . These are the Pilocytic Astrocytoma, Pilomyxoid Astrocytoma, Subependymal giant cell Astrocytoma, Pleomorphic xanthoastrocytoma and Anaplastic astrocytoma . The knowledge of these tumours are important as they are one of the commonest cause of mortality and morbidity in both the young and old, accounting for about 60% of the glial tumours. Therefore neuropathological diagnosis and tumour characteristics will therefore profoundly inuence the impact of treatment strategies.

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Long-term medical imaging use in children with central nervous system tumors

PLoS ONE ◽

10.1371/journal.pone.0248643 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248643

Author(s):

Erin J. A. Bowles ◽

Diana L. Miglioretti ◽

Marilyn L. Kwan ◽

Ute Bartels ◽

Adam Furst ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Medical Imaging ◽

Tumor Grade ◽

Tumor Diagnosis ◽

Cns Tumors ◽

Cns Tumor ◽

Longitudinal Imaging ◽

The U.S

Background Children with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis. Procedure We conducted a retrospective cohort study of children aged 0–20 years diagnosed with CNS tumors between 1996–2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade. Results We observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09–1.13) and 2.14 MRIs (95%CI 2.12–2.16) in the U.S., and 1.67 CTs (95%CI 1.65–1.68) and 1.86 MRIs (95%CI 1.85–1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities. Conclusions MRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.

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