Height after photon craniospinal irradiation in pediatric patients treated for central nervous system embryonal tumors

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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hTERT Gene Amplification and Increased mRNA Expression in Central Nervous System Embryonal Tumors

American Journal Of Pathology ◽

10.1016/s0002-9440(10)64311-8 ◽

2003 ◽

Vol 162 (6) ◽

pp. 1763-1769 ◽

Cited By ~ 48

Author(s):

Xing Fan ◽

Yunyue Wang ◽

John Kratz ◽

Dan J. Brat ◽

Yves Robitaille ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mrna Expression ◽

Gene Amplification ◽

Embryonal Tumors ◽

Htert Gene

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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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CHRONIC LEAD ENCEPHALOPATHY

PEDIATRICS ◽

10.1542/peds.25.2.309 ◽

1960 ◽

Vol 25 (2) ◽

pp. 309-315

Author(s):

Harry H. White ◽

Fred D. Fowler

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Pediatric Patients ◽

Early Recognition ◽

Central Nervous System Involvement ◽

Fast Screening ◽

The Central Nervous System ◽

Lead Encephalopathy ◽

Urinary Coproporphyrin

Chronic lead encephalopathy must be considered in the differential diagnosis of pediatric patients who present with manifestations of schizophrenia, behavior disorders or degenerative diseases of the central nervous system. Determination of urinary coproporphyrin is a simple, fast screening procedure applicable to office practice. The prognosis for normal mental development following encephalopathy is poor. It is hoped that early recognition of the more subtle signs of central nervous system involvement will allow treatment to be instituted soon enough to prevent the crippling mental deterioration which is so often a sequela of lead poisoning.

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Polo-Like Kinase 4 (PLK4) Is Overexpressed in Central Nervous System Neuroblastoma (CNS-NB)

Bioengineering ◽

10.3390/bioengineering5040096 ◽

2018 ◽

Vol 5 (4) ◽

pp. 96 ◽

Cited By ~ 5

Author(s):

Anders Bailey ◽

Amreena Suri ◽

Pauline Chou ◽

Tatiana Pundy ◽

Samantha Gadd ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Brain Tumors ◽

Meta Analysis ◽

P Value ◽

Embryonal Tumors ◽

Expression Levels ◽

Embryonal Brain

Neuroblastoma (NB) is the most common extracranial solid tumor in pediatrics, with rare occurrences of primary and metastatic tumors in the central nervous system (CNS). We previously reported the overexpression of the polo-like kinase 4 (PLK4) in embryonal brain tumors. PLK4 has also been found to be overexpressed in a variety of peripheral adult tumors and recently in peripheral NB. Here, we investigated PLK4 expression in NBs of the CNS (CNS-NB) and validated our findings by performing a multi-platform transcriptomic meta-analysis using publicly available data. We evaluated the PLK4 expression by quantitative real-time PCR (qRT-PCR) on the CNS-NB samples and compared the relative expression levels among other embryonal and non-embryonal brain tumors. The relative PLK4 expression levels of the NB samples were found to be significantly higher than the non-embryonal brain tumors (p-value < 0.0001 in both our samples and in public databases). Here, we expand upon our previous work that detected PLK4 overexpression in pediatric embryonal tumors to include CNS-NB. As we previously reported, inhibiting PLK4 in embryonal tumors led to decreased tumor cell proliferation, survival, invasion and migration in vitro and tumor growth in vivo, and therefore PLK4 may be a potential new therapeutic approach to CNS-NB.

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