bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-31. THE IMPACT OF MOLECULAR PROFILING OF PEDIATRIC CNS TUMORS ON TUMOR DIAGNOSIS AND MANAGEMENT - A SINGLE CENTER EXPERIENCE
Authors: Sabet Kazuhiro , Zwienenberg Marike , Lechpammer Mirna , Jin Lee-Way , Solomon David , Kline Cassie , Antony Reuben 
Published: December 2020

Abstract

BACKGROUND
Next generation sequencing (NGS) plays a role in neuro-oncology research and in clinical diagnosis and management. Here, we describe how NGS for pediatric CNS tumors impacted clinical diagnosis and therapy at a single institution.

METHODS
NGS was performed using the UCSF 500 Gene Panel (targeted sequencing platform covering about 500 cancer associated genes). Patients were selected for NGS based on tumor pathology /need to identify therapeutic targets. We collected data on patient demographics, tumor histology/pathway alterations/therapeutic targets/therapy and used descriptive statistics for data analysis.

RESULTS
Between January 2016 and July 2019, about one-third of patients with CNS tumors seen at our institution (N=29) were interrogated. NGS revealed pathway alterations in 20/29 patients. Treatment recommendations/modifications based on pathway alterations/therapeutic targets impacted the therapy of 18 patients. Patient groups: Medulloblastoma (N=6), alterations in WNT, SHH, and TP53 pathways (Vismodegib recommended for SHH pathway alteration but not used). High-grade glioma (N=4), alterations (with treatment changes) included, NF1(Trametinib, Everolimus); MSH2/MLH1(Nivolumab); CDKN2A/CDKN2B/CDKN2C(Abemaciclib); EGFR (Osimertinib, Afatinib); H3K27M (Panobinostat/ONC201); BRAFV600 (Dabrafenib, Trametinib); ATRT (N=1) SMARCB1; Low Grade Glioma (N=10), BRAFV600(Vemurafenib) /BRAFKIAA1549 fusion (Trametinib)/ PIK3CA; DIPG (N=5), H3K27M/BCOR/ P53/ACVR/PIK3CA (LY3023414, Everolimus)/PDGFR(Dasatinib); Ependymoma (N=3), PFA/PFB/RELA Fusion. Seven patients were treated with targeted therapy + conventional therapy. In 8 patients targeted therapy remains an option but not yet needed.

CONCLUSIONS
NGS of pediatric brain tumors is widely available and contributes to the diagnosis/therapy of pediatric CNS tumors. Optimal chemotherapy/targeted therapy combinations are areas of study.
QOL-19. PARENT-REPORTED COGNITIVE PROBLEMS AND DIRECT ASSESSMENT OF COGNITION IN CHILDREN TREATED FOR A BRAIN TUMOR
Authors: Lemiere Jurgen , Sleurs Charlotte , Van den Wyngaert Linde , Vandenabeele Karen , Vandereydt Josefien , Vercruysse Trui , Jacobs Sandra 
Published: December 2020

Abstract
The Pediatric Perceived Cognitive Function (PedsPCF) item bank is a short parent and self-reported cognitive screening questionnaire developed in the context of pediatric oncology. The PedsPCF demonstrated satisfactory psychometric properties and the scores of the PedsPCF are found to be associated with clinical outcomes. Today little research is available to evaluate whether the PedsPCF is correlated with direct assessments of neurocognitive domains. The aim of the current study is to investigate whether important cognitive domains, such as different aspects of intelligence, memory, visuomotor integration can predict the PedsPCF score. We obtained 100 PedsPCF filled in by parents from children treated for a brain tumor. All these children completed a comprehensive neuropsychological battery. Mean age at diagnosis was 7.47 years and mean age at completion of PedsPCF and testing 13.84. The most common diagnoses were pilocytic astrocytoma (n=43) and medulloblastoma (n=14). A linear regression model with verbal comprehension, perceptual reasoning, processing speed, visuomotor integration as predictors for overall PedsPCF score was significant (p.005), but the overall model fit was limited (adjusted R2: 14%). Visuomotor integration and processing speed were significant predictors (beta = 0.56 and -0.29). Our results are in line with the overall finding that the correlation between questionnaires assessing quality of survival and direct assessments of cognition are low. For clinical practice these results are important as the PedsPCF can’t be used to replace direct cognitive assessments or vice versa.
QOL-20. IMPACT OF RADIATION DOSE AND VOLUME ON MEMORY FUNCTIONING IN CHILDREN WITH MEDULLOBLASTOMA: A REPORT FROM CHILDREN’S ONCOLOGY GROUP (COG) ACNS0331
Authors: Embry Leanne , Colte Paul , Cullen Patsy , Michalski Jeff , Li Yimei , Han Yuanyuan , Hardy Kristina 
Published: December 2020

Abstract

BACKGROUND/OBJECTIVES
We examined longitudinal verbal and visual memory functioning in children treated for medulloblastoma on COG protocol ACNS0331.

METHODS
Children with medulloblastoma participated in neuropsychological testing at three timepoints over a 6-year period. Children aged 3–7 years were randomized to receive craniospinal irradiation (CSI) of either 23.4Gy (standard dose; SDCSI) or 18Gy (lower dose; LDCSI). Children aged 8+ received SDCSI. All children were also randomized to receive either a reduced radiation boost to the involved field (IFRT) or a standard boost to the whole posterior fossa (PFRT). Memory functioning was evaluated an average of 0.67(T1), 2.95(T2), and 4.90(T3) years post-diagnosis.

RESULTS
Of 464 eligible patients enrolled on ACNS0331, 354 (76%; 65.3% male, 83.1% white) completed some neuropsychological testing. Mean age at diagnosis was 9.1 years (range=3–19). Verbal and visual short-term memory and learning were broadly within the average range for the overall sample at all three timepoints. However, a large percentage of children exhibited scores ≥1SD below the mean on tasks of verbal learning both immediately (43.4%) and after a delay (40.7%) at T3. In addition, 58.6% of children randomized to SDCSI exhibited impairment in verbal learning after a delay compared to 34.8% of children randomized to LDSCI, and 35.0% of those aged ≥8 at diagnosis receiving SDCSI.

CONCLUSIONS
Younger children receiving SDCSI have particularly high rates of memory impairment five years after diagnosis of medulloblastoma. Limiting CSI dose and/or volume in young children treated for this diagnosis may improve outcomes for memory functioning.
QOL-25. MICROSTRUCTURAL BRAIN CHANGES ASSOCIATED WITH NEUROCOGNITIVE AND FUNCTIONAL OUTCOMES OF INTRACRANIAL GERM CELL TUMUOR SURVIVORS – A DIFFUSIONAL KURTOSIS IMAGING STUDY
Authors: Tso Wan-Yee Winnie , Hui Sai Kam , Lee Tatia Mei Chun , Liu Anthony Pak Yin , Ip Patrick , Cheng Kevin , Fong Daniel , Chang Dorita , Ho Frederick K W , Yip Ka Man , Ku Dennis , Cheuk Daniel K L , Luk Chung Wing , Shing Ming Kong , Leung L K , Khong Pek Lan , Chan Godfrey Chi Fung 
Published: December 2020

Abstract

BACKGROUND
Childhood intracranial germ cell tumour (iGCT) survivors are prone to radiotherapy-related neurotoxicity which can lead to neurocognitive dysfunction. Diffusion kurtosis imaging (DKI) is a MRI technique that quantifies microstructural changes in the grey and white matter of the brain. This study aims to investigate the associations between MR-DKI metrics, the cognitive and functional outcomes of childhood iGCT survivors.

METHOD
20 childhood iGCT survivors who had received cranial radiotherapy were recruited. DKI parameters were determined for iGCT survivors and 18 control subjects. Neurocognitive assessment using the Hong Kong Wechsler Intelligence Scales for Children (HKWISC)/ Wechsler Adult Intelligence Scale – Revised (WAIS-R) and functional assessment using the Lansky/ Karnofsky performance scales were performed for GCT survivors.

RESULTS
There were significant negative correlation between the IQ scores and the mean diffusivity (MD) in multiple white matter regions of iGCT survivors including: anterior limb of internal capsule, superior fronto-occipital fasciculus, anterior corona radiata, uncinate fasciculus, cingulum and hippocampus. Mean kurtosis (MK) values of the superior fronto-occipital fasciculus were positively correlated with IQ scores. For grey matter, the MD of the olfactory, insula, caudate, heschl gyrus, parahippocampal gyrus, hippocampus, anterior cingulum, frontal inferior operculum, middle and superior temporal gyrus, middle and superior frontal orbital gyri, cuneus and precentral gyrus were negatively correlated with IQ scores. Most of the microstructural changes with associated functional impairment were white matter regions.

CONCLUSION
Our study identified vulnerable brain regions with significant white and grey matter microstructural changes that were associated with impaired cognitive function or deficits in physical functioning.
QOL-43. ENDOCRINE AND METABOLIC CHANGES IN CHILDREN TREATED FOR MEDULLOBLASTOMA
Authors: Kalinin Alexey , Strebkova Natalia , Zheludkova Olga 
Published: December 2020

Abstract
We examined 63 patients (40 males/23 females) after complex treatment of medulloblastoma. Patients had a median age (range) of 11.3 (5.5 ÷ 17.9) years. The median time after the end of treatment was 3.7 (1.5 ÷ 11.6) years. Endocrine disorders were detected with the following frequency: growth hormone deficiency - 98.41% (62 of 63 patients), thyroid hormone deficiency – 69.8% (44/63), adrenal hormone deficiency - 17.4% (11/63). Three cases (4.7%) of premature sexual development were also detected. Lipids levels, beta-cell function and insulin resistance (IR) during 2-h oral glucose tolerance test were evaluated. A mono frequent bioelectrical impedanciometer was used to measure body composition. Overweight (SDS BMI&gt; 1) was observed only in 16 patients (3 girls and 13 boys), obesity (SDS BMI&gt; 2) in 1 boy. Dyslipidemia was found in 34 patients (54%). All patients underwent oral glucose tolerance test. Insulin resistance (ISI Matsuda &lt;2.5 and/or HOMA-IR&gt; 3.2) was detected in 7 patients (11/1%), impaired glucose tolerance (120 min glucose ≥7.8 mmol / l) was observed in 2 patients with IR and in 2 patients without IR. At the same time, IR and impaired glucose tolerance were encountered in only 5 children with overweight and no one with obesity. All patients with impaired glucose tolerance had normal values of fasting glucose (4.3 ÷ 5.04 mmol / l) and HbA1c (4.8 ÷ 5.8%). A bioelectrical impedanciometer was used to measure body composition in 49 cases, the percentage of adipose tissue was increased in 14 patients (28%) with normal BMI.
QOL-56. THE RELAPSED AND OR PROGRESSED BRAIN TUMOURS IN CHILDREN: RHC, GLASGOW EXPERIENCE
Authors: Sastry Jairam , Mang Paul Van Siang Liang , Murpy Dermot , Ronghe Milind , McIntosh Diana 
Published: December 2020

Abstract

INTRODUCTION
The outcome for children with relapsed or progressed brain tumours is poor. The aim of this project was to identify total number of children who have relapsed or progressed with Brain tumour and to determine the types of tumours, treatment offered and assess outcome.

METHODS
This is a retrospective study of all patients treated for relapsed or progressed brain tumours between 2007 and 2017 at the Royal Hospital for children. Patients were identified using the unit database. Clinical data included demographics, histologic diagnosis, treatment characteristics and outcome which was obtained from electronic records.

RESULTS
46 children were included (22M:24F). The median age of diagnosis was 5 years. There were 16 histological subtypes of brain tumours: pilocytic astrocytoma (n=12, 26%), optic pathway glioma (n=4,7%), medulloblastoma (n=8, 17%), ependymoma (n=4, 9%), high grade glioma (n=3, 7%, DIPG (n=2, 4%) and others 13(32.2%). 28(61%) had relapsed at a median time of 18 months. Tumour progression occurred in 18(31%) at a median time of 21.5 months. Post-relapse or progression therapy included surgery (14, 30%), chemotherapy (17, 40%) and radiotherapy (5, 10.9%). 50% of the patients remain alive with 17(37%) being stable and 6(13%) with progression of disease. 50% had died of disease progression.

CONCLUSIONS
The relapse and or progression was seen 61% of patients. The commonest tumours in this cohort were pilocytic astrocytoma and medulloblastoma. Chemotherapy was the most used regimen followed by surgery and radiotherapy. Primary dissemination at the time of diagnosis was associated with poor prognosis.
QOL-59. CEREBELLAR MUTISM SYNDROME AND THE SURGICAL RISK FACTORS: A PROSPECTIVE MULTICENTRE STUDY OF 500 PATIENTS UNDERGOING TUMOUR SURGERY IN THE POSTERIOR FOSSA
Authors: Grønbæk Jonathan Kjær , Wibroe Morten , Toescu Sebastian , Grillner Pernilla , Mallucci Conor , Molinari Emanuela , Solem Kristin , Westerholm-Ormio Mia , Kiudeliene Rosita , Mudra Katalin , Hauser Peter , van Baarsen Kirsten , Hoving Eelco , Zipfel Julian , Nysom Karsten , Schmiegelow Kjeld , Sehested Astrid , Juhler Marianne , Mathiasen René 
Published: December 2020

Abstract

OBJECTIVE
Cerebellar mutism syndrome (CMS) is a severe neurological complication of tumour surgery in the posterior fossa in childhood. The incidence is reported between 8 and 39%, where CMS sets in within days of surgery and resolves within months, yet long-term sequelae are seen in most patients. This prospective cohort study investigates the course of CMS and the surgical cause of the syndrome. POPULATION AND

METHODS
We included 500 children with a tumour in the posterior fossa with planned surgery or open biopsy. Enrolment was conducted between 2014 and 2020 in 26 centres in ten European countries. Speech, neurological symptoms and surgical procedure were registered in predefined standardized forms pre-operatively and at three post-operative follow-ups within one year. PRELIMINARY

RESULTS
A total of 426 children underwent primary surgery and were eligible for analyses. CMS occurred in 56 patients (13.1%) one day (median; IQR: 0–2 days) after surgery and resolved within 38 days (median; IQR: 4–52 days). Another 58 patients (13.6%) had less severe speech impairment. Mutism was associated with lower age (OR: 0.91 [95%CI: 0.85;0.98, p=0.014]), medulloblastoma (OR: 2.5 [95%CI: 1.4;4.7, p=0.0036]) and ATRT (OR: 12.9 [95%CI: 3.4;51.9, p=0.00018]) and tumour location in the fourth ventricle (OR: 4.0 [95%CI: 2.3;7.2, p&lt;0.0001]). Preliminary multivariate analyses revealed no significant association between mutism and surgical access.

CONCLUSION
CMS is a common complication predominantly seen in younger children after tumour surgery for a medulloblastoma or ATRT in the fourth ventricle. The incidence is not related to the surgical access in this study population.
RARE-06. OPTIMIZATION OF PROTON RADIATION THERAPY FOR GIANT CRANIOPHARYNGIOMAS
Authors: Flores Valerie Cruz , Stapleton Stacie , Tuite Gerald , Ramakrishna Naren 
Published: December 2020

Abstract
Craniopharyngiomas are benign intracranial tumors located in the sellar and suprasellar region. Their size and extent of invasion into surrounding structures vary considerably. While the majority of craniopharyngiomas on presentation are between 1–3 cm without hypothalamic invasion, a significant proportion of patients present with ‘giant’ craniopharyngiomas of &gt;4cm in dimension with large cystic extension through the 3rd ventricle. These tumors pose a challenge both for surgical resection as well as for radiation therapy. Proton beam therapy (PBT) has become the preferred standard of care after subtotal resection of pediatric craniopharyngiomas. In the setting of giant craniopharyngioma, the use of proton therapy allows a reduction of dose to surrounding normal brain, but changes in cyst volume can result in either under-coverage of tumor or excess dose to surrounding brain, an effect further magnified by the sharp gradients associated with proton dose distributions. In this case report we describe the proton treatment planning and intra-treatment monitoring of two patients with giant craniopharyngiomas with largest pre-operative of dimension 6cm, and 9cm, respectively, and 6cm and 5.5cm, respectively, pre-radiation. Both patients had drains inserted to Ommaya reservoirs. We performed surveillance imaging during RT utilizing spiral computer tomography (CT) on a weekly basis and reconstructed the treatment dose on the surveillance CTs to ensure target coverage and normal tissue sparing. We compared the dosimetry in these cases for PBT versus intensity-modulated radiation therapy, characterized the cyst evolution during treatment in 3 dimensions, and define an optimized protocol for treatment planning and intra-treatment monitoring.
RARE-10. ADAMANTINOMATOUS CRANIOPHARYNGIOMA RESIDES OUTSIDE THE BLOOD BRAIN BARRIER
Authors: Prince Eric , Vijmasi Trinka , McWilliams Jennifer , Hengartner Astrid , Staulcup Susan , Foreman Nicholas , Jordan Kimberly , Dorris Kathleen , Hoffman Lindsey , Hankinson Todd 
Published: December 2020

Abstract

BACKGROUND
Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. Genetically engineered mouse models of ACP demonstrate that perturbation of the fetal anterior pituitary can generate tumors analogous to ACP. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control, with the most common agent being the humanized monoclonal antibody, tocilizumab. This agent demonstrated poor blood-brain barrier (BBB) penetration in primates. We present findings from two children enrolled on a phase 0 clinical trial (NCT03970226) of a single dose of preoperative intravenous tocilizumab prior to resection of newly diagnosed ACP.

METHODS
Blood samples were obtained at multiple timepoints. Serum was isolated via ficoll separation. Tumor tissue and cyst fluid were obtained 4–6 hours following the single IV dose of tocilizumab. Tissue was snap-frozen. Tumor was homogenized in RIPA buffer. Free tocilizumab in serum, cyst fluid, and tumor tissue was measured using enzyme-linked immunosorbent assay (ELISA) against a standard curve.

RESULTS
Both patients in this trial demonstrated clinically relevant levels of tocilizumab (≥ 4µg/mL) in serum, cyst fluid, and tumor tissue, compared to undetectable levels in control samples.

CONCLUSION
ACP resides outside BBB protection. In addition to demonstrating the feasibility of systemic delivery of tocilizumab, these findings indicate that other large molecules, including those known to have poor BBB penetration, may be systemically delivered as part of an antitumor regimen in the treatment of ACP.
RARE-15. EARLY PSEUDOPROGRESSION POST-RADIATION IN PAEDIATRIC HIGH-GRADE GLIOMA PATIENTS WITH CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY: TWO CASE REPORTS FROM A SINGLE CENTRE
Authors: Teng Ay-Jiuan , Gilmartin Breege , Campbell Marty , Bhatia Kanika , Wheeler Greg , Sullivan Michael , Hansford Jordan , Khuong-Quang Dong-Anh 
Published: December 2020

Abstract

BACKGROUND
Constitutional Mismatch Repair Deficiency (CMMRD) is a cancer predisposition syndrome caused by biallelic mutations in the mismatch repair pathway, and high-grade glioma (HGG) constitute the most prevalent brain tumours. Pseudoprogression alludes to radiological changes that mimic tumour progression, but are in fact due to other causes such as therapy related inflammation. It can occur as early as three months post treatment. To our knowledge, its characteristics in CMMRD patients has not been reported.

METHODS
We retrospectively identified seven patients with CMMRD and history of HGG at The Royal Children’s Hospital, Melbourne from 2005 to 2019. Our objective was to review the characteristics of pseudoprogression in this cohort.

RESULTS
Out of the seven patients, two with constitutional loss of PMS2 demonstrated evidence of pseudoprogression. Patient 1 presented at 16 years old with a cerebellar anaplastic astrocytoma. She developed clinical and radiological progression within two weeks of starting radiotherapy, persisting up to four months after completion. However, six months post radiation she improved without intervention and the tumour remains stable five years post therapy. Patient 2 presented at 17 years old with a midbrain anaplastic astrocytoma, and showed signs of progression four weeks after completion of radiotherapy. She was then treated with Bevacizumab, an anti-VEGFA antibody with remarkable response. She subsequently received Nivolumab, a checkpoint inhibitor with ongoing stable disease for four months.

CONCLUSION
Our findings showed that pseudoprogression can occur early in the treatment course in CMMRD patients. Identification of this entity is important for appropriate clinical management.
RARE-20. MALIGNANT PERIPHERAL NERVE SHEATH TUMOR OF A CRANIAL NERVE IN AN INFANT WITH NEUROCUTANEOUS MELANOSIS
Authors: Carter Lacey , Gross Naina , McNall-Knapp Rene , Peterson ,and Jo Elle 
Published: December 2020

Abstract
At one month of age, a female presented with a giant congenital nevus along lower back and thighs and hydrocephalus. A ventriculoperitoneal shunt was placed. An MRI was done at six months, initially reported as normal. At eleven months of age, five months after original MRI, patient presented with dysconjugate gaze and lethargy. MRI showed new 3.8 x 3.7 x 3.4 cm right cerebellopontine angle mass extending into Meckel’s cave and foramen ovale along with leptomeningeal disease extending from the mass along the entire length of the spinal cord. Retrospective review of prior MRI revealed subtle leptomeningeal enhancement concerning for neurocutaneous melanosis (NCM). Given the leptomeningeal disease, family elected for open biopsy and debulking of lesion instead of aggressive resection. Histologically, the mass showed hypercellular spindle cell neoplasm with mitotic activity and necrosis mixed with remnants of normal cranial nerve. GFAP was negative, excluding a glioma. HMB-45, MITF, panmelanoma, and Melan-A were negative, excluding melanoma. A negative myogenin stain ruled out ectomesenchymoma. S-100 protein and SOX-10 positivity with variable loss of staining for trimethylation of histone H3 K27 were indicative of malignant peripheral nerve sheath tumor (MPNST). Given the course of the mass, trigeminal nerve MPNST was presumed. Given the poor prognosis of intracranial MPNST and NCM, family elected to forgo treatment and was discharged with hospice. She died 25 days after surgery. Cranial nerve MPNST is rare. MPNST in patients with NCM has not previously been reported to our knowledge.
RARE-25. RETINAL ASTROCYTOMA mTOR INHIBITOR THERAPY IN TUBEROUS SCLEROSIS MOSAICISM
Authors: Evans Naomi , Paton Katherine , Gill Harinder Kaur , Hukin Juliette 
Published: December 2020

Abstract

INTRODUCTION
Everolimus is an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), it is Health Canada and FDA approved for SEGA and renal angiomyolipoma in the setting of tuberous sclerosis complex (TSC). There is little data available in regards to this treatment of TSC associated retinal astrocytoma (RA). Although the behaviour of RA is often indolent or slowly progressive, aggressive behaviour with retinal detachment and neovascular glaucoma requiring enucleation has been reported in several patients. Definite TSC diagnosis is established when either two major features or one major and two minor features are present. Probable TSC diagnosis is established when one major plus one minor feature is present.

METHODS
We report a child with probable TSC mosaicism, with negative serum NGS for TSC but RA and retinal achromic patch on the left. A left retinal peripapillary astrocytoma around optic nerve and very close to fovea was noted. There was concern that if it grew or there were to be any leakage it would cause visual impairment. This lead to therapy with everolimus 4.5 mg/m2/d aiming for level between 5 and 10 mcg/L.

RESULTS
This boy has had a gradual reduction of the RA over the last 29 months, with healthy retina in the region no longer occupied by the lesion and preserved vision. He has tolerated therapy well with occasional mouth ulcers.

CONCLUSION
mTORC1 inhibition is effective therapy to preserve vision in the setting of retinal astrocytoma and tuberous sclerosis mosaicism.