bluuebunny/crossref_metadata_2025_split huggingface dataset:
NURS-02. CLINICAL MANAGEMENT OF PATIENTS RECEIVING CAR T CELL THERAPY FOR CNS TUMORS
Authors: Holtzclaw Susan , Hoeppner Corrine 
Published: December 2020

Abstract
Chimeric antigen receptor (CAR) T cells are an innovative new therapy with proven efficacy in some pediatric cancers such as leukemia and lymphoma, but much less experience in solid tumors, especially tumors of the central nervous system (CNS). Seattle Children’s has three open Phase 1 CAR T cell studies (BrainChild-01, -02, and -03 targeting HER2, EGFR, and B7-H3, respectively) for recurrent/refractory CNS tumors and DIPG (BrainChild-03 only). As of December 2019, four patients have been treated at Seattle Children’s Hospital with CAR T cells infused on a weekly schedule through indwelling catheters into the tumor resection cavity or ventricular system. Given the scrutiny of clinical care needed for Phase 1 studies, we are now able to report detailed clinical information that we have learned during the treatment of these patients. Clinical care includes the judicious use of steroids, the clinical support of patient’s symptoms pre- and post-infusion, and the management of peritumoral edema. We will also discuss the psychosocial support needed for families who travel long distances to receive this therapy compounded by the many emotional components of being enrolled on any Phase 1 trial. Case studies and experience from a Nurse Practitioner role will be provided and discussed.
OTHR-09. CENTRAL DIABETES INSIPIDUS: A RARE UNREPORTED SIDE EFFECT OF TEMOZOLOMIDE IN PEDIATRICS
Authors: Kuo Christopher , Waters Kaaren , Cheung Clement , Margol Ashley 
Published: December 2020

Abstract
Temozolomide is a chemotherapeutic agent commonly used in the treatment of central nervous system tumors. While there are case reports of temozolomide associated central diabetes insipidus (CDI) in adults, this has not been reported in children. We describe the first case of temozolomide associated CDI in a pediatric patient. The patient was a previously healthy 12yr old male diagnosed with anaplastic astroblastoma. He underwent gross total resection of the lesion and was subsequently treated with focal radiation therapy and concurrent temozolomide. On day 21 of therapy he developed thrombocytopenia, severe polyuria and polydipsia. Temozolomide was held and he underwent a preliminary evaluation for CDI. Initial laboratory findings were concerning for CDI, and he was admitted for further work-up and to assess the need for desmopressin. Additional laboratory tests demonstrated normal anterior pituitary function and his serum sodium normalized when allowed to drink to thirst, mitigating the need for desmopressin. Temozolomide was not restarted and the symptoms of polyuria and polydipsia resolved and did not recur. Upon review, the tumor did not involve the pituitary or hypothalamus. Additionally, these areas were not involved in the irradiation field. CDI is a rare but clinically significant side effect of temozolomide, reported in adults. Given this is the first report of CDI secondary to temozolomide in a pediatric patient, we speculate that this is likely under-recognized in children. Prompt recognition and treatment is necessary to prevent severe sequelae of hypernatremia.
PATH-17. INTRAGENIC COPY NUMBER BREAKPOINT ANALYSIS OF METHYLATION DATA FROM CNS TUMOURS IDENTIFIES NOVEL SUBGROUP-SPECIFIC CANDIDATE FUSION GENE ENRICHMENTS
Authors: Mackay Alan , Grabovska Yura , Clarke Matthew , Carvalho Diana , Temelso Sara , Jones Chris 
Published: December 2020

Abstract
Methylation array-based molecular profiling has redefined the classification of brain tumours and now forms an important part of their integrated diagnosis, providing both subgroup assignment and genome wide DNA copy number profiles. These latter data can be used to identify intragenic breakpoints which are frequently associated with structural variations resulting in therapeutically targetable oncogenic fusion genes. To systematically assess the landscape of these alterations, we combined publicly available methylation datasets resulting in a total of 5660 CNS tumours, around half paediatric, and including &gt;1000 high grade glioma and DIPG. These were analysed by standard methodology (MNP, conumee), and intragenic breakpoint enrichment was compared within methylation subgroups, superfamilies, and tumours with no high-scoring classification. Benchmarking included sequence-verified cases such as infant hemispheric gliomas (IHG) with ALK(15%) and ROS1(7%) fusions, and pathognomic alterations associated with specific entities such as RELA-EPN, MYB-LGG and HGNET-MN1. We identified previously unreported enrichments of well-recognised fusion targets such as NTRK2in GBM_MID and NTRK3in DMG_K27 (both 5%), METin A_IDH / A_IDH_HG (3–5%), and FGFR1/3in GBM_G34 (8–9%). Novel recurrent kinase gene candidates to be verified and explored further include IGF1Rin 2–12% cases spanning glioma subgroups, and TIE1in poorly classified tumours. This latter ‘NOS’ group were also enriched in various transcription factor targets of breakpoints, including TCF4and PLAGL2. Despite limitations due to sample quality, resolution or balanced translocations, breakpoint analysis of methylation copy number profiles provides simple screening for structural rearrangements which may directly influence targeted therapy in paediatric CNS tumours.
PATH-18. HIGH-GRADE NEUROEPITHELIAL TUMOR (HGNET) IN A PEDIATRIC CASE-SERIES
Authors: Sanders Felipe Hada , Azambuja Alessandra , Frasseto Fernando , Rosemberg Sergio , Matushita Hamilton 
Published: December 2020

Abstract
The central nervous system (CNS) high-grade neuroepithelial tumor is a recently described molecular entity. We report 2 new CNS HGNET cases sharing common clinical presentation and pathologic features. In summary, CNS HGNET represents a rare tumor occurring in young patients with dismal prognosis. We think it is important to report these cases to spread the experience and raise the knowledge of the medical community.
PATH-19. MOLECULAR CLASSIFICATION BASED ON THE DNA METHYLATION PROFILE OF CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN CHILDREN: TWO-YEARS EXPERIENCE AT THE BAMBINO GESÙ HOSPITAL
Authors: Miele Evelina , Rossi Sabrina , Pedace Lucia , Camassei Francesca Diomedi , Antonelli Manila , Cacchione Antonella , Colafati Giovanna Stefania , Carai Andrea , Gianno Francesca , Alzoubi Hiba , Gessi Marco , Tartaglia Marco , Giangaspero Felice , Locatelli Franco , Mastronuzzi Angela 
Published: December 2020

Abstract

INTRODUCTION
Pediatric brain tumors (PBT) represent the second most common pediatric cancer, with the highest mortality rate among childhood malignancies. Improvement of PBT diagnostic accuracy is fundamental to optimize treatment strategy. OBJECTIVES: We aimed to explore the impact of DNA methylation arrays implementation in PBT clinical practice.

METHODS
214 PBT were analyzed by Illumina 850KEPICmethylation array. Low score and discordant cases were collegially reviewed.

RESULTS
Calibrated score was 0.8 or higher in 159 cases (74.3%), with pathological diagnosis confirmation in 132 cases and molecular subgroup definition in 47 of them, including cases of medulloblastoma, CNS neuroblastoma FOXR2, HGNET MN1; methylation profiling amended diagnosis in 10 cases, e.g. HGNET BCOR and anaplastic PXA, was non-contributory in 4 and misleading in 12 cases, including glioneural tumors and tumors arising in syndromic contexts. Calibrated score ranged between 0.8 and 0.3 in 37 cases (17.3%) and was below 0,3 (no match) in 18 cases (8.4%). Calibrated score below 0,8 was more frequently assigned to low grade gliomas and low grade glioneural tumors (p &lt;0.0006). Challenging/very rare cases, e.g. intracranial AFH with EWSR1:CREM fusion and nonRELA supratentorial ependymomas, were assigned to “no match subgroup”; in syndromic patients the score tended to be lower (p=0.07); no correlation between score and age &lt; 3-years was found (p=0.1).

CONCLUSION
Methylation profiling refine on diagnostic accuracy in PBT classification. Improvements are needed in classifying low grade glioma/glioneuronal tumors and challenging/very rare PBT. In syndromic cases, there is a high rate of misleading profiles and/or low scores.
PATH-27. MUTATION DETECTION USING PLASMA CELL-FREE DNA IN CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMORS
Authors: Mangum Ross , Reuther Jacquelyn , Baksi Koel Sen , Zabriskie Ryan C , Gandhi Ilavarasi , Recinos Alva , Potter Samara L , Lin Frank Y , Chintagumpala Murali , Muzny Donna M , Fisher Kevin , Plon Sharon E , Roy Angshumoy , Parsons D Williams 
Published: December 2020

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.
PATH-29. HIGH FREQUENCY OF CLINICALLY-RELEVANT TUMOR VARIANTS DETECTED BY MOLECULAR TESTING OF HIGH-RISK PEDIATRIC CNS TUMORS – PRELIMINARY FINDINGS FROM THE TEXAS KidsCanSeq STUDY
Authors: Lin Frank Y , Mangum Ross , Reuther Jacquelyn , Potter Samara L , López-Terrada Dolores H , Adesina Adekunle M , Mohila Carrie A , Aldave Guillermo , Chintagumpala Murali M , Muzny Donna M , Bernini Juan Carlos , Gill Jonathan , Griffin Timothy , Tomlinson Gail , Vallance Kelly , Fisher Kevin E , Roy Angshumoy , Plon Sharon E , Parsons D Williams 
Published: December 2020

Abstract

BACKGROUND
DNA and RNA-based tumor sequencing tests have the potential to guide the clinical management of children with CNS tumors. However, data describing the utility of these tests are limited.

METHODS
Children with high-risk or recurrent CNS tumors are included in the diverse cohort of patients enrolling in the KidsCanSeq study from six Texas sites. DNA and RNA from FFPE tumor is subjected to targeted sequencing using a 124-gene mutation panel and an 81-gene fusion panel. Tumor capture transcriptome sequencing, exome sequencing, and copy number array (as well as germline panel and exome testing) are also performed. Tumor variants are classified using AMP/ASCO/CAP consensus guidelines.

RESULTS
A total of 74 children with high-risk/recurrent CNS tumors enrolled as of 1/28/20. Targeted tumor DNA and RNA panel testing was completed for 57 patients with varied diagnoses. At least one tumor variant with strong or potential clinical significance was identified in 43 of 57 (75%) tumors, with therapeutic significance in 20 of 57 (35%) tumors. The 38 therapeutically-relevant variants most frequently affected MAPK signaling (BRAF x9, EGFR x3, FGFR2, FGFR3, KRAS, NF1, NTRK2) and the AKT/mTOR pathway (PIK3CA x3, PTEN x2, mTOR, TSC1, PIK3R1). Most had not been detected by prior targeted diagnostic testing (27/38, 71%).

CONCLUSION
Integrated DNA and RNA-based panel testing identified variants with potential to impact clinical decision-making in a majority of children with high-risk/recurrent CNS tumors. The comparative yield of panel testing vs. exome/transcriptome/array will be evaluated in the KidsCanSeq study cohort.
QOL-05. TUMOR LOCATION IS LESS LIKELY INFLUENCE ON COGNITIVE DYSFUNCTION IN CHILDREN
Authors: Nakajima Riho , Kinoshita Masashi , Tanaka Shingo , Nakada Mitsutoshi 
Published: December 2020

Abstract

INTRODUCTION
Though several factors are known to influence on long-term cognitive function in children with brain tumor, the impact of tumor localization to specific cognitive function was not well known. Here we investigated the influence of local brain resection by surgery on postoperative cognitive outcome in school-aged children.

METHODS
Participants were seven pediatric patients who underwent craniotomy for tumor resection in our hospital (mean age, 13.9 years). Their diagnosis were WHO grade 1 or 2 glioma (n=6) and hemangioma (n=1). Tumor were mainly located in following regions; frontal, n=2; parietal, n=2; temporal, n=3 (These lesions included hippocampus or were located very close to it). Temporal assessments for cognitive function of several functional domains were performed according to tumor location until post-op 1 year. Based on MRI, we estimated cognitive dysfunctions and compared them to observational symptoms.

RESULTS
Preoperative cognitive function was normal in all patients. Cognitive dysfunctions estimated from resected area were as follows (cumulative total number); memory or working memory disorder, n=4; visuospatial cognitive disorder, n=3; disorder of processing speed, n=2; facial or topographical agnosia, n=2; Gerstman syndrome, n=1. Just after surgery, cognitive function was declined in two functional domains of two patients, which were only 16.7% of estimated deficit from resected region. They recovered completely until 3 months postoperatively, and returned to school without any deficits.

CONCLUSIONS
In pediatric lower-grade tumor, focal cognitive symptom was unlikely to be induced by local resection.
QOL-07. CORTICAL VOLUME AND THICKNESS IN ADULT SURVIVORS OF CHILDHOOD POSTERIOR FOSSA TUMORS
Authors: Sleurs Charlotte , Lemiere Jurgen , Blommaert Jeroen , Deprez Sabine , Van Beek Karen , Uyttebroeck Anne , Jacobs Sandra 
Published: December 2020

Abstract

PURPOSE
A brain tumor treatment including cranial radiotherapy has previously been associated with long-term neurocognitive sequelae. Since underlying neurological mechanisms remain inconclusive, we investigated cortical features in childhood posterior fossa tumor survivors.

METHODS
T1-weighted MRI (MPRAGE, resolution=.98x.98x1.2mm) was acquired to investigate the cortical structure in adult survivors of childhood infratentorial tumors (n=19, 15males) (16.4–34.8 years old, &gt;2years after treatment). These scans were compared to age- and gender- matched controls. Supratentorial cortical volume and thickness were investigated using voxel-based morphometry (VBM) and surface-based morphometry (SBM), respectively. We compared patients and controls, irradiated (n=13) versus non-irradiated patients, and investigated the age at radiotherapy (peak level: p&lt;.001).

RESULTS
Lower GM volumes were encountered in multiple brain areas of patients compared to controls, with the largest clusters in the right and left occipital fusiform gyri. Irradiated patients showed lower GM volumes then non-irradiated patients in the superior and middle frontal gyri, the right supramarginal gyrus and precuneus. Age at radiotherapy was associated with GM volume in the inferior frontal gyrus. SBM yielded larger cortical thickness in patients in the left precuneus, inferior temporal and fusiform gyrus. The opposite effect was only marginally significant, in the left temporal lingual gyrus. Age at radiotherapy was not associated with cortical thickness, but radiotherapy was associated with lower thickness of the left pars opercularis.

CONCLUSION
Widespread differences in cortical volumes and thickness were observed in posterior fossa tumor survivors. Both radiotherapy and age at radiotherapy could be suggested as risk factors for long-term cortical development.
QOL-09. WHOLE-BRAIN WHITE MATTER NETWORK CONNECTIVITY IS DISRUPTED BY PEDIATRIC BRAIN TUMOR TREATMENT
Authors: Oyefiade Adeoye , Beera Kiran , Moxon-Emre Iska , Skocic Jovanka , Bartels Ute , Laughlin Suzanne , Ramaswamy Vijay , Mabbott Donald 
Published: December 2020

Abstract

INTRODUCTION
Treatments for pediatric brain tumors (PBT) are neurotoxic and lead to long-term deficits that are driven by the perturbation of underlying white matter (WM). It is unclear if and how treatment may impair WM connectivity across the entire brain.

METHODS
Magnetic resonance images from 41 PBT survivors (mean age: 13.19 years, 53% M) and 41 typically developing (TD) children (mean age: 13.32 years, 51% M) were analyzed. Image reconstruction, segmentation, and node parcellation were completed in FreeSurfer. DTI maps and probabilistic streamline generation were completed in MRtrix3. Connectivity matrices were based on the number of streamlines connecting two nodes and the mean DTI (FA) index across streamlines. We used graph theoretical analyses to define structural differences between groups, and random forest (RF) analyses to identify hubs that reliably classify PBT and TD children.

RESULTS
For survivors treated with radiation, betweeness centrality was greater in the left insular (p &lt; 0.000) but smaller in the right pallidum (p &lt; 0.05). For survivors treated without radiation (surgery-only), betweeness centrality was smaller in the right interparietal sulcus (p &lt; 0.05). RF analyses showed that differences in WM connectivity from the right pallidum to other parts of the brain reliably classified PBT survivors from TD children (classification accuracy = 77%).

CONCLUSIONS
The left insular, right pallidum, and right inter-parietal sulcus are structurally perturbed hubs in PBT survivors. WM connectivity from the right pallidum is vulnerable to the long-term effects of treatment for PBT.
QOL-33. THE PROMOTE STUDY: DEVELOPMENT AND TESTING OF KLIK-UK, AN ONLINE PLATFORM, TO ENHANCE OUTPATIENT COMMUNICATION ABOUT HEALTH-RELATED QUALITY OF LIFE (HRQOL) AT THREE UK CHILDREN’S BRAIN TUMOUR TREATMENT CENTRES (CBTTCs)
Authors: Bull Kim , Stubley Shelly , Kouzoupi Natalia , Darlington Anne-Sophie , Grootenhuis Martha , Hargrave Darren , Liossi Christina , Morris Christopher , Walker David , Kennedy Colin 
Published: December 2020

Abstract

BACKGROUND
The HRQoL of survivors of childhood brain tumour is significantly reduced into adulthood but is not systematically assessed. In the UK, referral for appropriate support is often reactive rather than proactive. We developed KLIK, the online Dutch platform, for use to enable the systematic assessment of HRQoL in the UK NHS using patient-reported outcomes measures (PROMs) which could be fed back to clinicians during outpatient review appointments.

METHODS
PARTICIPANTS: Children aged 5–17.9 years, receiving outpatient care &gt;6 monthly for a brain tumour diagnosed within preceding 5 years and their parents and clinicians. SETTING: Three UK CBTTCs – UHS, Southampton; GOSH, London; and QMC, Nottingham. PROCEDURE: KLIK-UK was developed throughout the study and barriers and opportunities for its use logged. A. Development phase: relevant PROMs were identified through systematic literature review1 and families’ views regarding choice of PROMs, communication needs within consultations, and KLIK-UK were obtained by interview. B: Feasibility phase: KLIK-UK was tested in outpatient review appointments followed by interviews with the family and clinician.

RESULTS
57 families and 10 clinicians participated. The PedsQL-Core module was preferred by families. Communication needs and barriers were identified. All clinicians reported that they could see the potential value of using KLIK-UK but views differed as to whether they could use it within their current timetable. Analysis of interviews from the feasibility phase will be reported.

CONCLUSION
KLIK-UK is ready for use in the UK but will need to be adapted according to local resources, needs, and preferences. 1Bull et al. 2019 https://doi.org/10.1093/nop/npz064
QOL-38. USE OF COMPUTERIZED NEUROPSYCHOLOGICAL MEASURES TO ASSESS COGNITIVE MORBIDITY IN SURVIVORS OF CHILDHOOD BRAIN TUMORS
Authors: Dickson Duncan , Channell Jessica , Mettetal Ashley , Chick Elizabeth , Wilkening Greta , Liu Arthur , Hankinson Todd , Foreman Nicholas , Hutaff-Lee Christa 
Published: December 2020

Abstract
Treatment of central nervous system (CNS) tumors in pediatric populations is associated with significant cognitive morbidity. Documentation of neuropsychological deficits is vital to treatment and educational planning. We investigated the feasibility and utility of a computerized neuropsychological measure (NIH Toolbox Cognitive Battery) in differentiating individuals who received tumor treatment from healthy controls. Participants included pediatric CNS tumor survivors (N = 85; Mean Age = 13.47; SD = 4.76) at least 1-year post-completion of treatment and healthy sibling controls (N = 20; Mean Age = 10.2; SD = 3.21) who completed the NIH Toolbox. Ninety-eight percent of the participants enrolled completed the computerized tasks. The overall logistical regression model, with NIH Toolbox tests as predictors, was statistically significant [χ2 (7, N = 105) = 26.176; p &lt; .001] and improved correct group classification from 81% to 82.9%. Picture Sequencing (β = -0.059; Wald = 6.942; p = .008) and Flanker (β = -0.083; Wald = 7.473; p = .006) were both statistically significant and negatively predictive of membership in the treatment group. For each 1 unit increase in standard score on measures of working memory and inhibition, odds of membership in the treatment group decreased by 6.2% and 8.7%, respectively. Consistent with the literature, worse performance on computerized measures of cognitive functioning mediated by executive functioning was correlated with a history of brain tumor treatment. Further investigation will focus on comparing computerized neuropsychological tools to traditional comprehensive neuropsychological evaluations and clarifying the trajectory of these deficits across recovery.