bluuebunny/crossref_metadata_2025_split huggingface dataset:
QOL-48. INTERDISCIPLINARY SPIRITUAL CARE TRAINING IN PEDIATRIC NEURO-ONCOLOGY
Authors: Lion Alex , Maiko Saneta , Szilagyi Csaba , Slaven James , Puchalski Christina 
Published: December 2020

Abstract

INTRODUCTION
Pediatric neuro-oncology requires attention to not only cancer biology and therapeutics, but also to the suffering of the patient. In addressing patient suffering, consensus guidelines direct attention to the spiritual distress and resources of patients and families. A lack of training has been a key barrier to integrating this aspect of health into patient care.

METHODS
A neuro-oncologist and a chaplain participated in a train the trainer for the Interprofessional Spiritual Care Education Curriculum (ISPEC) through the George Washington University’s Institute for Spirituality and Health. After the train the trainer, the online curriculum was offered to interdepartmental team members, combined with in-person discussion groups, which met weekly for six sessions. A survey was given before and after the training, and Likert scores were analyzed using the Wilcoxon rank-sum non-parametric test. OUTCOMES: 17 interdisciplinary members participated in the training. These members included neuro-oncologists, neuro-surgeons, rehabilitation physicians, nurse practitioners, nurses, physical therapists, music therapists, a child life specialist, a school liaison, and a patient experience specialist. The training resulted in multiple improvements, including increased ability to identify spiritual issues (p=.0278) and increased ability to respond to these issues (p=.0056).

CONCLUSION
ISPEC addressed a key barrier to providing generalist spiritual care to patients with pediatric brain tumors. Diverse disciplines were represented during the training. With implementation of interdisciplinary spiritual care, outcomes that may be measured in the future include improved quality of life, patient satisfaction, and the resilience of both patients and team members.
QOL-55. INTEGRATED MULTI-SCALE MODEL FOR PEDIATRIC BRAIN TUMOR SURVIVAL PREDICTION
Authors: Qiu Yeping Lina , Sabran Amaury , Zheng Hong , Gevaert Olivier 
Published: December 2020

Abstract
Brain tumors are the most common solid tumors affecting children, and its prognosis has been a great challenge for physicians and researchers. With the advances in high-throughput sequencing technology and digital pathology, more quantitative data is now becoming available and more information may potentially be discovered in whole slide images (WSIs) and molecular tumor characteristics to determine survival and treatment. Imaging and genomic data, though very different in nature, both may contain different aspects of disease characteristics that are important for survival prediction. Hence our work aims to build a framework to integrate two data modules, whole-slide histopathology image data, and RNA sequencing data, for a unified model to improve pediatric brain tumor survival outcome prediction. The imaging data and genomic data are both of high dimensions and on different scales. We use two independent modules, each of which consists of a deep neural network, to extract lower dimensional features from imaging and genomic data respectively. We concatenate the extracted features and use a third neural network to train a Cox regression model using the merged feature as input. Each module is first pre-trained with TCGA adult brain tumor data, and subsequently fine-tuned with pediatric brain tumor data. The entire pipeline is tested on the holdout pediatric brain tumor dataset. Preliminary results suggest that the integrated framework achieves improved prediction performance than using each single data module alone. The concordance index (C-index) of integrated model is 0.68, compared to 0.62 with imaging data only, and 0.66 with genomic data only.
QOL-57. SOUTHERN CALIFORNIA KAISER PERMANENTE PEDIATRIC NEURO-ONCOLOGY PROGRAM DEVELOPMENT
Authors: Tran Hung 
Published: December 2020

Abstract

KEY MESSAGE
Standardization of care for subspecialty patients require centralization and support across multi-disciplinary groups within the Kaiser Permanente medical group, which is a large health maintenance organization (HMO) in the United States.

BACKGROUND
Prior to the development of a Pediatric Neuro-Oncology program, Southern California Kaiser Permanente pediatric neuro-oncology patients were routinely referred to respective regional academic centers for consultation. The process was not standard across the region, resulting in additional costs and differences in treatment recommendations, potentially affecting outcomes.

METHODS
A Pediatric Neuro-Oncology program was established, July 2017, based at the Kaiser Permanente Los Angeles Medical Center (LAMC), consisting of pediatric neuro-oncology, pediatric neurosurgery, pediatric neuro-radiology, pediatric radiation oncology, and pediatric neuro-oncology case management.

RESULTS
A Pediatric Neuro-Oncology tumor board was established to meet on a bi-monthly basis. Pediatric neuro-oncology patients across the Southern California now have their magnetic resonance imaging (MRI) reviewed by the same pediatric neuro radiologists. Neuropathology is standardized and sent to Children’s Hospital Los Angeles and reviewed at the molecular neuropathology tumor board attended by the pediatric neuro-oncologist. Cases discussions regarding the patients include the regional pediatric neurosurgeons, the pediatric radiation oncologists, and the pediatric neuro-oncologist, and treatment plans are recommended and recorded by the case manager.

CONCLUSIONS
Centralization of care has allowed for more consistent and standard care across the Southern California Region, but requires support from multi-disciplinary groups.
QOL-58. ASSESSING FATIGUE EXPERIENCED BY PEDIATRIC PATIENTS WITH INTRACRANIAL NEOPLASMS
Authors: Eccles Eamon , Han Yan , Liu Hao , Holmes Jordan , Coven Scott 
Published: December 2020

Abstract

BACKGROUND
Indiana University possessed one of the earliest clinical proton facilities in the United States. The purpose of this study was to assess fatigue and nausea/vomiting in children with central nervous system (CNS) tumors undergoing radiation therapy as part of their treatment regimen, and to understand what factors influence fatigue. DESIGN: The study was approved by the institutional review board at Indiana University and consent and/or assent from eligible participants was obtained prior to enrollment. The validated Fatigue Scale is scored on a 5-point Likert scale. Surveys were completed 1) prior to radiation therapy, 2) week three of radiation therapy, and 3) week six of radiation therapy. A score of 41 or higher for the Fatigue Scale-Parent (&lt; 7 years), 12 or higher for the Fatigue Scale-Child (8–12 years), and 17 or higher for the Fatigue Scale-Adolescent (13–18 years), indicates significant cancer-related fatigue.

RESULTS
The study aimed to recruit a total of 50 patients during the eligible period; however, data on 31 individual participants were available for analysis. 25 patients underwent proton radiation therapy, while 6 patients underwent conventional photon therapy. The mean age of children was 8.8 years. Of the 31 patients, 22 recorded scores indicating significant cancer-related fatigue at some point during radiation therapy.

CONCLUSIONS
Cancer related fatigue continues to be a challenge, with limited understanding of factors that might predict clinically relevant fatigue This work demonstrates the feasibility of conducting symptom research for children undergoing radiation therapy; further research is needed to characterize predictors of fatigue.
RARE-11. QUANTITATIVE MR IMAGING FEATURES ASSOCIATED WITH UNIQUE TRANSCRIPTIONAL CHARACTERISTICS IN PEDIATRIC ADAMANTINOMATOUS CRANIOPHARYNGIOMA: A POTENTIAL GUIDE FOR THERAPY
Authors: Mirsky David , Prince Eric , Staulcup Susan , Hengartner Astrid , Vijmasi Trinka , Johnston James , Massimi Luca , Anderson Richard , Souweidane Mark , Naftel Robert , Limbrick David , Grant Gerald , Niazi Toba , Dudley Roy , Kilburn Lindsay , Jackson Eric , Jallo George , Ginn Kevin , Smith Amy , Chern Joshua , Lee Amy , Drapeau Annie , Krieger Mark , Handler Michael , Hankinson Todd 
Published: December 2020

Abstract

METHODS
Through the Advancing Treatment for Pediatric Craniopharyngioma (ATPC) consortium we accumulated preoperative MRIs and tumor RNA for 50 unique ACP patients. MRIs were assessed quantitatively for 28 different features and analyzed using Multiple Factor Analysis (MFA) and optimal clustering was determined via maximization of Bayesian Information Criterion (BIC). Following bulk RNAseq, differential expression and pathway enrichment were performed using standard methodologies (i.e., DESeq2 and GSEA).

RESULTS
MRI features were well represented in the first 3 dimensions of MFA (variance explained=67.32%); specifically tumor/cyst size, ventricular size, and cyst fluid diffusivity. Using this three-way axis, we identified 3 patient subgroups. Transcriptional differences between these subgroups indicated one group was enriched for DNA damage response and MYC related pathways, one group enriched for SHH, and one group enriched for WNT/β-catenin and EMT-related pathways.

CONCLUSION
This preliminary work suggests that there may be unique gene expression variants within ACP, which may be identified preoperatively using easily quantifiable MRI parameters. These radiogenomic signatures could provide prognostic information and/or guidance in the selection of antitumor therapies for children with ACP.
RARE-37. NOONAN SYNDROME AND GLIONEURONAL TUMORS: A CENTRAL NERVOUS SYSTEM CANCER PREDISPOSITION ASSOCIATION?
Authors: Shatara Margaret , Varga Elizabeth A , Boué Daniel R , Martin Lisa , Rusin Jerome A , Rodriguez Diana P , Jones Jeremy , McAllister Aaron , Leonard Jeffrey R , Pindrik Jonathan , Schieffer Kathleen M , Leraas Kristen M , Lichtenberg Tara M , Mardis Elaine R , Cottrell Catherine E , Osorio Diana S , AbdelBaki Mohamed S , Finlay Jonathan L 
Published: December 2020

Abstract

BACKGROUND
Noonan syndrome (NS) is associated with germline Ras signaling pathway mutations, RAS overactivation and increased tumorigenesis risk. Rosette-forming glioneuronal tumors (RFGT) are rare indolent tumors. We report the molecular profiling of two patients with NS and RFGT. PATIENT 1: A 22-year-old male with NS was diagnosed with RFGT after partial tumor resection followed by focal irradiation. He was enrolled on a comprehensive genomic profiling study involving paired tumor-normal whole exome sequencing and RNA sequencing of the disease-involved tissue, revealing a germline PTPN11 alteration (p.Gly60Ala) consistent with NS, and a somatic deletion (p.Ile442_Thr454del) in PIK3R1 and a somatic variant (p.Lys656Glu) in FGFR1 with concomitant increased expression of PIK3R1 and FGFR1 by RNA-sequencing. The patient remains without tumor progression now nine months since irradiation. PATIENT 2: A 19-year-old male with persistent headaches, underwent a brain MRI demonstrated multiple abnormal signals in the pineal region and midbrain. He had a stereotactic biopsy revealing RFGT. He was enrolled on the genomic study revealing a germline PTPN11 alteration (p.Asn308Asp) resulting in a new diagnosis of NS. Several family members were subsequently identified with clinical features of NS, including his mother and two siblings, enabling appropriate counseling. Two somatic variants were found in trans in PIK3R1 (p.Thr454_Phe456del and p.Glu451_Asn453delinsAsp), and a somatic variant (p.Val695Met) in FGFR1, with resultant overexpression of PIK3R1. The patient is monitored with surveillance imaging.

CONCLUSION
We report the molecular profiling of two patients with NS and RFGT; strongly suggesting their connection to RASopathies through the overactivation of the MAPK and PI3K/AKT/mTOR signaling pathways.
RARE-49. CHOROID PLEXUS ADENOMA WITHOUT ASSOCIATED HYDROCEPHALUS PRESENTING AS PRECOCIOUS PUBERTY
Authors: Utley Kaylyn , Dedekian Michael , Wilson James , Chaleff Stanley 
Published: December 2020

Abstract
Precocious puberty (PP) is a rare presentation of intracranial pathology unrelated to the pituitary. PP in this setting is considered a paraneoplastic phenomenon, achieved through synthesis of sex-hormones by the tumor itself or via alterations in the release of gonadotrophins from the pituitary. The latter has been described with masses adjacent to the pituitary or with those which cause hydrocephalus. We describe a case of a choroid plexus papilloma (CPP) without hydrocephalus presenting as precocious puberty. An 18 month-old female presented with 4-months of weight loss, bilateral galactorrhea and constipation. Her weight decreased from the 15th to below the 1st percentile. CBC, celiac and thyroid studies were normal. Prolactin was at the upper limit of normal (25.8;ref 3.3–26.3). Breast ultrasound demonstrated symmetric breast tissue development. She was referred to pediatric gastroenterology for constipation and failure to thrive. Caloric supplementation, bowel regimen and barium enema were recommended. One week later, she was admitted with dehydration, painful constipation and further weight loss in the setting of an acute febrile illness. MRI revealed a normal pituitary and an intraventricular mass without hydrocephalus. She underwent gross total resection of the mass, later determined to be a choroid plexus papilloma. The patient’s galactorrhea resolved abruptly following resection. Because of her galactorrhea, our patient underwent neuroimaging revealing an incidental mass without associated hydrocephalus. To our knowledge, precocious puberty and hyperprolactinemia have not been described in neoplasms distant from the pituitary. Thus, these lesions should be recognized as a potential etiology of precocious puberty and hyperprolactinemia.
RARE-51. MOLECULAR INSIGHTS INTO MALIGNANT PROGRESSION OF CHOROID PLEXUS PAPILLOMA (CPP)
Authors: Yankelevich Maxim , Finlay Jonathan L , Gorsi Hamza , Kupsky William , Boue Daniel R , Koschmann Carl J , Kumar Chandan , Mody Rajen 
Published: December 2020

Abstract
Malignant transformation of CPP is rare and the mechanisms remain elusive. We report a case of progression of papilloma into carcinoma where we performed molecular sequencing of both samples. A boy was found to have a brain mass soon after birth. The gross total resection (GTR) was diagnostic of CPP. Six years later he developed a recurrent mass that demonstrated progression to a choroid plexus carcinoma (CPC). The patient received chemotherapy according to a “HeadStartII” protocol. He is 2.5 years off therapy and disease-free. A sequencing study consisting of 1700 genes and tumor transcriptome was done. The analysis of both samples revealed a germline variant of TP53(R248W) with LOH and an allele frequency of 39% in the germline sample, suggesting a mosaicism. Analysis of both samples identified extensive aneuploidy and similar pattern of gains in chromosomes 7/8/12/20/21/X. Copy number aberrations newly acquired in the carcinoma included copy gain of chromosomes 5q/12/15q/20, and copy loss of chromosomes 5q/13/22. The papilloma was found to harbor 3 somatic mutations with 4% to 21% allelic fractions, all lost in the carcinoma. These mutations were of unknown significance and with too low allelic fractions to be responsible for the transformation. More pertinently, chromosomal aneuploidy was significant with additional losses in the carcinoma. This resulted in the losses of two critical tumor suppressor genes, RB and BRCA2, playing a possible role in the observed transformation. The “HeadStart” experience suggested that the prognosis of TP53 mutant CPC may be improved in the absence of radiation therapy.
RARE-53. PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE DIFFERENTIATION (PPTID) AND DICER1 SYNDROME: A CASE REPORT
Authors: Toll Stephanie , Gupte Avanti , Sood Sandeep , Kupsky William , Altinok Deniz , Miller Steven , Bhambhani Kanta 
Published: December 2020

Abstract

BACKGROUND
DICER1 syndrome is a rare inherited tumor predisposition syndrome linked to an increased risk of several malignancies. Affected individuals most commonly develop pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors. Brain tumors in these patients are rare, however; the increased frequency of pineoblastoma in this population has been established. Traditionally, pineal parenchymal tumors of intermediate differentiation (PPTIDs) have not been associated with DICER1 syndrome, with research suggesting alternative mutations driving tumorigenesis. These tumors are pathologically and clinically diverse, with long-term surveillance based on therapeutic interventions. Here we describe a case of a germline DICER1 mutation in a patient with a PPTID, suggesting that this mutation is not limited to pineoblastoma as previously reported. CASE: We describe a 19 year-old female with a WHO grade III PPTID treated with multimodal therapy including surgery, craniospinal irradiation (CSI) and chemotherapy. She was noted to have a thyroid mass at diagnosis and was subsequently diagnosed with a benign thyroid nodule, followed most recently by a cataract with pathology concerning for medulloepithelioma of the ciliary body. Due to the known association between medulloepithelioma and DICER1 syndrome, targeted germline sequencing was obtained and confirmed a pathogenic heterozygous mutation.

CONCLUSION
To our knowledge this is the first report of a PPTID in a patient with DICER1 syndrome. This association highlights the clinical implications of molecular evaluation in pediatric brain tumors, for both immediate therapeutic decisions and long-term surveillance.
RARE-54. MOLECULAR ANALYSIS OF ROSETTE-FORMING GLIONEURONAL TUMOR AT MIDBRAIN; REPORT OF TWO CASES
Authors: Handa Hajime 
Published: December 2020

Abstract
Rosette-forming glioneuronal tumor (RGNT) is a tumor that primarily arises at posterior fossa. We experienced two rare cases of RGNT located at midbrain and investigated their molecular features. Case 1 is a 23-year-old female, and Case 2 is an 18-year-old male. Both cases were surgically removed by the occipital transtentorial approach. Histological analysis demonstrated a biphasic pattern of neurocytic and glial components. The former consisted of neurocytic rosettes and perivascular pseudorosettes, and the latter was GFAP positive, corresponding to the diagnosis of RGNT. Both cases have an excellent clinical course without receiving chemotherapy or radiation therapy. Small residual tumors of both cases shrunk and maintained for 27 and 12 months, respectively. Case 1 underwent DNA methylation array and a subsequent DNA methylation-based classifier, indicating that the case matched RGNT with a 0.99 calibrated score. Also, we identified FGFR1 K656 mutation. Pyrosequence analysis of other genes such as IDH1 R132, IDH2 R172, BRAF T599, BRAF V600, H3F3A K27, H3F3A G34, HIST1H3B K27, TERT C228, FGFR1 N546 had no mutations. RT-PCR of KIAA1549-BRAF fusion was not detected. DNA methylation status of Case 2 is under investigation. Pyorosequence analysis identified TERT C228 mutation but did not identify other mutations such as FGFR1 N546 and K656. Midbrain RGNT corresponds to the histological and molecular features of RGNT. RGNT needs to be differentially diagnosed in the case of a midbrain tumor.
RARE-59. CARDIAC REMODELING IN PATIENTS WITH CHILDHOOD-ONSET CRANIOPHARYNGIOMA – RESULTS OF HIT-ENDO AND KRANIOPHARYNGEOM 2000/2007
Authors: Sowithayasakul Panjarat , Buschmann Leona Katharin , Boekhoff Svenja , Müller Hermann L 
Published: December 2020

Abstract

BACKGROUND
Hypothalamic obesity caused by childhood–onset craniopharyngioma results in long–term cardiovascular morbidity. Knowledge about clinical markers and risk factors is rare.

PATIENTS AND METHODS
A cross–sectional study on transthoracic echocardiographic parameters was performed to determine the associations with clinical and anthropometric parameters in 36 patients with childhood-onset adamantinomatous craniopharyngioma.

RESULTS
Body mass index (BMI) correlated with the thickness of interventricular septum in diastole (IVSd) (r=0.604, p&lt;0.001) and left ventricular diastolic posterior wall in diastole (LVPWd) (r=0.460, p=0.011). Due to wide range of disease duration, 17 pediatric and 19 adult patients were analyzed separately. In the adult subgroup (age at study ≥18 years), BMI correlated with IVSd (r=0.707, p=0.003), LVPWd (r=0.592, p=0.020) and left ventricular internal diameter in diastole (LVIDd) (r=0.571, p=0.026). In the pediatric subgroup (age at study &lt;18 years), no correlation between cardiac parameters and BMI was observed. Only LVIDd correlated with disease duration (r=0.645, p&lt;0.001). All cardiac functions were within the normal range, indicating no association with severe functional impairments.

CONCLUSIONS
Cardiac remodeling in patients with childhood-onset craniopharyngioma correlates with the degree of hypothalamic obesity and disease duration. However, echocardiography has limited sensitivity in craniopharyngioma patients with obesity, so cardiac magnetic resonance imaging (MRI) should be considered as an alternative diagnostic approach for patients with craniopharyngioma and hypothalamic obesity.
RONC-02. MEASURING THE EFFECT OF CLINICALLY-RELEVANT RADIOTHERAPY PROTOCOLS ON THE JUVENILE MOUSE BRAIN
Authors: Buck Jessica , Somers Kale , Whitehouse Jacqueline , Howlett Meegan , Hii Hilary , Strowger Brooke , Ebert Martin , Mehnert Andrew , Gottardo Nick , Endersby Raelene 
Published: December 2020

Abstract
Treatment for medulloblastoma involves craniospinal irradiation which is associated with devastating late effects. Clinical trials that simply reduce radiotherapy dosage have resulted in inferior survival rates, whereas new chemo/radiotherapy combinations that improve survival have been identified using preclinical models. However, the potential late effects of novel treatments are currently understudied and the assessment of radiation-induced late effects in mice remains challenging. Here, we aimed to measure the effect of multifractionated radiotherapy on the juvenile mouse brain as a baseline measure for future studies. NOD/Rag1-/- mice received either 8Gy whole-brain radiotherapy (WBRT) using an X-RAD SmART preclinical platform, 18Gy fractionated WBRT (9x2Gy doses), single, or multiple sham treatments beginning at postnatal day (P)16. Mice were aged to adulthood (&gt;P63), then high resolution anatomical brain scans were obtained on a Bruker 9.4T MRI to measure the effects of WBRT on whole brain and specific regional area volumes. A single 8Gy dose (n=10) markedly reduced brain volume by 8.5% compared to single-sham controls (n=11, p&lt;0.0001), whereas fractionated 18Gy treatment (n=7) did not cause significant differences in brain volume compared to multi-sham controls (n=4, p&gt;0.99). Current analyses are focused on measuring treatment effects on specific areas of the brain, as well as other anatomical differences using a range of MRI techniques. These results will serve as a valuable tool to measure potential treatment-associated effects caused by novel chemo/radiotherapy combinations on the developing brain. This will enable future studies to assess the potential safety of novel treatment to inform clinical decision making.