bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATRT-11. Anatomico-biological correlations define a new layer for ATRT molecular subgroups pointing to potential lineages of origin
Authors: Lobon-Iglesias Maria , Andrianteranagna Mamy , Han Zhi-Yan , Masliah-Planchon Julien , Tauziede-Espariat Arnault , Frah Magali , Dufour Christelle , Chauvin Celine , Bouarich Rachida , Manriquez Valeria , Turczinski Sandrina , Delattre Olivier , Baulande Sylvain , Ayrault Olivier , Servant Nicolas , Beccaria Kevin , Dangouloff-Ros Volodia , Bourdeaut Franck 
Published: June 2022

Abstract
Atypical teratoid rhabdoid tumors (ATRT) are divided in three molecular subgroups, the so-called MYC, TYR and SHH subgroups. This heterogeneity suggests some diversity in the cells of origin, which remain hypothetical thus far. A careful radiological review of 55 MRI at diagnosis was performed in parallel with a careful analysis of mouse tumor origin in the Rosa26-CreERT2::Smarcbflox/flox model. Methylation, bulk RNAseq and scRNAseq analyses were integrated to these anatomic information to highlight potential origin for each molecularly and anatomically defined subgroups. We demonstrated that mouse Myc-ATRTs derive from extra-parenchymal meningeal areas, a finding consistant with many human MYC ATRT being clearly of intra-cranial extra-axial origin. Although this finding could point to a neural crest origin, transcriptomic features fail to unravel any lineage-specific signature. We also defined a distinct supra-tentorial SHH ATRT subgroup, characterized both in mouse and Humans by neural features pointing to the ganglionic eminence progenitors as the candidate origin. Finally we identified a distinct infra-tentorial SHH ATRT subgroup, not observed in mice, with hindbrain/midbrain boundary progenitor signature. scRNAseq from human SHH infra-tentorial tumors consistently suggest a dedifferentiation process involving the Notch pathway in the oncogenic transformation of hindbrain/midbrain neural progenitors.
ATRT-14. Malignant rhabdoid tumors of cranial nerves – ATRT or extracranial rhabdoid tumor?
Authors: Gruhle Miriam , Nemes Karolina , Steinbügl Mona , Johann Pascal D , von Luettichau Irene , Steinborn Marc , Tippelt Stephan , Fleischhack Gudrun , Lehrnbecher Thomas , Bens Susanne , Siebert Reiner , Hasselblatt Martin , Vokuhl Christian , Bison Brigitte , Kröncke Thomas , Melchior Patrick , Timmermann Beate , Frühwald Michael C 
Published: June 2022

Abstract
INTRODUCTION: Malignant rhabdoid tumors (MRT) are highly aggressive neoplasias mostly affecting young children. They are classified as rhabdoid tumors of the central nervous system (ATRT, atypical teratoid rhabdoid tumor), rhabdoid tumors of the kidney (RTK) or extracranial rhabdoid tumors arising from any soft tissue outside the central nervous system (eMRT, extracranial extrarenal MRT). We report a series of four MRTs with cranial nerve involvement. METHODS: Patients were identified from a cohort of 132 patients with MRT (2017 – 2021), as part of the European Rhabdoid Registry (EU-RHAB). Diagnosis of MRT was confirmed immunohistochemically with loss of INI1 expression. Details regarding symptoms at first presentation, diagnostic staging, genetic findings, therapy and the course of disease are reported. REPORT OF CASES/RESULTS: The series contains two MRT affecting the trigeminal nerve and two cases with third cranial nerve involvement. They were two female and two male patients with a median age of 4.7 years (1-159 months) at diagnosis. Location of the main tumor mass differed between being located intra- and extracerebrally. Metastases at diagnosis occurred in one patient, a germ-line mutation in SMARCB1 was present in two patients. Two patients received therapy according to EU-RHAB recommendations with an incomplete resection, conventional chemotherapy enhanced by intraventricular methotrexate and radiotherapy. Both patients are currently alive with no signs of progression, one of them bearing a germ-line mutation. Two patients received palliative treatment after surgery due to rapid progression. Median overall survival was 17.3 (1.4-53.1) months. CONCLUSION: MRT of the cranial nerves affect the peripheral nervous system in close proximity to the brain, thus forming a unique sub-entity between ATRT and eMRT. The selected cases provide insight into the particular challenge regarding clear classification, diagnostics and therapy.
ATRT-16. Mechanisms of myeloid cell-induced resistance in AT/RT
Authors: Disch Alina , Melcher Viktoria , Walter Carolin , Interlandi Marta , Moreno Natalia , de Faria Flavia W , Graf Monika , Hasselblatt Martin , Albert Thomas K , Kerl Kornelius 
Published: June 2022

Abstract
INTRODUCTION: Atypical teratoid/rhabdoid tumor (AT/RT) is a primary pediatric tumor entity of the central nervous system showing intra- and intertumoral heterogeneity concerning the molecular landscape and cellular composition. Myeloid cells are considered key orchestrators of the immunological tumor microenvironment (TME) of AT/RT. Tumor-infiltrating CD68+ macrophages favor chemotherapy resistance and recurrence, and are consequently related to a poor patient outcome. METHODS: Using single-cell RNA sequencing (scRNA-seq) of human and murine AT/RT samples, multiplex immunohistochemistry, depletion of myeloid cells in mouse models and advanced cell culture models for myeloid tumor cell communication, we obtained deeper mechanistic insight into these cell-cell interactions. RESULTS: Infiltrating CD68+ macrophages interact with AT/RT tumor cells generating intermediary hybrid-like cells with autonomous communication properties, increasing the cell heterogeneity of AT/RT. By depletion of myeloid cells in AT/RT mouse models followed by scRNA-seq of tumor and non-tumor samples, we demonstrated that tumor formation is hindered. Furthermore, we give mechanistic insights into how myeloid cells contribute to tumorigenesis. IN CONCLUSION: the dynamic and extensive interactions between tumor cells and myeloid cells do not only potentiate cellular heterogeneity but might also induce cellular plasticity associated with the acquisition of resistance to chemotherapy and seem to be essential for AT/RT development.
RARE-02. Craniopharyngiomas diagnosed as incidentalomas - results of KRANIOPHARYNGEOM 2007
Authors: Boekhoff Svenja , Bison Brigitte , Eveslage Maria , Sowithayasakul Panjarat , Müller Hermann L 
Published: June 2022

Abstract
PURPOSE: Childhood-onset craniopharyngiomas (CP) are diagnosed due to clinical symptoms (symCP) or incidentally (incCP). We investigated clinical manifestations and outcome in incCPs and symCPs. METHODS: IncCP were discovered in 4 (3m / 1f) and symCP in 214 (101m / 113f) CP recruited 2007–2014 in KRANIOPHARYNGEOM 2007. Age, sex, height, body mass index (BMI), tumor volume, degree of resection, pre- and postsurgical hypothalamic involvement/lesions, pituitary function and outcome were compared between both subgroups. RESULTS: Reasons for imaging in incCP were cerebral palsy, head trauma, nasal obstruction, and tethered-cord syndrome, whereas headache (44%), visual impairment (25%), and growth retardation (17%) lead to imaging in symCP. Tumor volume at diagnosis was smaller in incCP (median 2.39 cm3; range: 0.14 – 4.10 cm3) when compared with symCP (15.86 cm3; 0.002 – 286.34 cm3). Age, gender, BMI, height, hydrocephalus, tumor location, and hypothalamic involvement at diagnosis of incCP were within the range of these parameters in symCP. Complete resections were achieved more frequently (3/4 patients) in incCP when compared with symCP (20%). Surgical hypothalamic lesions were distributed similar in incCP and symCP. Irradiation was performed only in symCP (33%). No noticeable differences were observed concerning survival rates, endocrine deficiencies, BMI, height, functional capacity and quality of life of the 4 incCP cases when compared with the symCP cohort. CONCLUSIONS: IncCP are rare (1.8%) and characterized by lack of endocrine deficiencies, resulting in normal height and BMI, no hydrocephalus, and smaller tumor volume at diagnosis when compared with symCPs. Outcome of the observed incCP is similar with symCP.
RARE-07. Low resting energy expenditure is associated with clinical and radiological hypothalamic damage in children surviving a suprasellar brain tumor
Authors: van Schaik Jiska , Burghard Marcella , Lequin Maarten , van Maren Emiel , van Dijk Anne , Takken Tim , Rehorst Lineke , Bakker Boudewijn , Meijer Lisethe , Hoving Eelco , van Meeteren Netteke Schouten- , Fiocco Marta , Tissing Wim , van Santen Hanneke 
Published: June 2022

Abstract
INTRODUCTION: Children with suprasellar brain damage are at risk for hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE) contributing to the development of hypothalamic obesity. Decreased REE, however, is not present in all children with hypothalamic damage. Our aim was to assess which children suspect for HD have low REE, and if REE outcome can be associated with clinical severity of HD or with radiological posterior hypothalamic damage. METHODS: A retrospective cohort study was performed evaluating all children diagnosed with brain injury at risk for HD in whom REE measurement was performed. Measured REE (mREE) was compared to predicted REE (pREE) using amongst others the Schofield equation. Low REE was defined as mREE&lt;90% compared to pREE. Radiologic hypothalamic damage was scored using Muller grading score. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage. RESULTS: Sixty-seven children suspected for HD (94% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had mREE &lt;90% compared to the pREE. Children with severe HD symptoms had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD symptoms. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no damage or with anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with DI were significant risk factors for reduced REE. CONCLUSION: Not all children suspect for HD have a low REE. Low REE is associated with clinical and radiological scores for hypothalamic damage. REE measurements in childhood brain tumor survivors may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions.
RARE-14. Newborn with hypothalamic hamartoma and Pallister-Hall syndrome
Authors: Flaßkühler Anna Meera , Friedrich Carsten , Beckhaus Julia , Boekhoff Svenja , Fiedler Kai , Becking Mechthild Schulze , Hitz Marc-Philipp , Gieldon Laura , Spranger Stephanie , Bison Brigitte , Hoppe Florian , Müller Hermann L 
Published: June 2022

Abstract
A female full-term newborn of 41 + 2 weeks gestational age with a respiratory adaptation disorder and hypercapnia was transferred from an external maternity clinic to our pediatric intensive care unit. The child is the second child of healthy, non-consanguineous parents. Multiple dysmorphias were noticed at arrival. We identified a choanal atresia/stenosis on both sides in the respiratory tract, a high palate, a submucous cleft palate, a bifid uvula, a laryngeal cleft and a bronchus suis. The child required intubation and ventilation. In addition, we recognized brachydactyly of the hands and feet. The phalanges were not visibly separable. There was nail hypoplasia and rocker bottom feet on both sides. Furthermore, we saw an anal atresia. In routine laboratory work-up, a hypoglycemia and not measurable low TSH serum concentration was noticed. Extended endocrinological laboratory diagnostics revealed a complete pituitary insufficiency. On cranial MRI, a large, iso- to slightly hyperintense space-occupying mass (3.8x3.7x2.5 cm3), originating from the hypothalamus was observed. The brainstem was displaced posteriorly by the mass. The imaging is consistent with a hypothalamic hamartoma. With regard to the present findings, we assumed an underlying genetic cause of the congenital malformations. As a clinical diagnosis, a Pallister-Hall syndrome was suspected. As described in our case, we saw the characteristic features: dysmorphia of the hands and feet, upper respiratory tract, anal atresia, and hypothalamic hamartomas. The Pallister-Hall syndrome is caused by mutations in the GLI3 gene on the 7p13 chromosome. It is inherited in an autosomal dominant manner and its prevalence is unknown. In our patient, a heterozygous, probably pathogenic variant in the GLI3-Gene was proven by Next Generation Sequencing (NGS).
RARE-15. Astroblastoma, MN1 altered comprises two molecularly and clinically distinct subgroups defined by the fusion partners BEND2 and CXXC5
Authors: Schmitt-Hoffner Felix , Gojo Johannes , Mauermann Monika , von Hoff Katja , Sill Martin , Stichel Damian , Capper David , Tauziede-Espariat Arnault , Varlet Pascale , Aldape Kenneth , Abdullaev Zied , Donson Andrew M , Schüller Ulrich , Snuderl Matija , Brandner Sebastian , Łastowska Maria , Trubicka Joanna , Miele Evelina , van der Lugt Jasper , Bunt Jens , Kramm Christof , Zapotocky Michal , Sahm Felix , Korshunov Andrey , Jäger Natalie , Pfister Stefan M , Kool Marcel 
Published: June 2022

Abstract
In the recent 5th edition of the WHO classification of CNS tumors, ‘Astroblastoma, MN1 altered’ is recognized a distinct brain tumor type, occurring in children and young adults. Due to its rarity and novelty, little is known about clinical and molecular traits. Therefore, we initiated an international effort and collected tissue samples, clinical and molecular data from 176 patients with Astroblastoma, MN1 altered, identified by their distinct DNA methylation profiles. DNA methylation-based t-SNE clustering analyses revealed that Astroblastoma, MN1 altered tumors form one distinct main cluster (n=158) showing MN1:BEND2 and single cases with EWSR1:BEND2 fusions and a further adjacent, but distinct smaller cluster (n=18) mostly defined by MN1:CXXC5 fusions. Both fusion partner-defined groups show a median age of 12 years but distinct copy-number aberrations, characteristically a gain of chromosome 5 in one third of the CXXC5-fused group and a loss of chromosome 16q in one third of BEND2-fused cases. As previously reported, a vast majority of Astroblastoma, MN1 altered patients are female, which we confirm for the BEND2-fused group (85%). The CXXC5-fused group, however, shows 75% male patients. Interestingly, 9/10 tumors of the few male patients observed in the BEND2-fused group were all located infratentorially or in the spinal cord, whereas almost all female cases show a supratentorial location (85/87). Histologically, the BEND2-fused group was primarily reported as Astroblastoma (39%), whereas in the CXXC5-fused cases, 31% CNS-PNET and only 8% Astroblastoma histologies were originally assigned. Preliminary clinical analyses showed that the BEND2-fused group has a relatively good 5/10-year OS of 97%/89%, but a less favorable 5/10-year PFS of 48%/35%, in line with previous studies. Patients showing CXXC5-fused tumors (n=8) indicated 5/10-year OS and PFS rates of 83%/83% and 60%/60%, respectively. Additional survival and molecular analyses are being conducted to further characterize Astroblastoma, MN1 altered tumors and its molecular subgroups.
RARE-17. Multi-institutional craniopharyngioma cohort highlights need for more comprehensive data collection on comorbidities and quality of life
Authors: Marshall Emily , Crowley Julia , McCormack Shana , Rood Brian , Hankinson Todd , Cheng Sylvia , DeCuypere Michael , Lam Sandi , Goldman Stewart , Ballester Lance , Faig Walter , Velasco Ryan , Arya Kamnaa , Storm Phillip Jay B , Resnick Adam , Prados Michael , Mueller Sabine , Malbari Fatema , Kline Cassie 
Published: June 2022

Abstract
BACKGROUND: Pediatric craniopharyngioma is associated with long-term survival, but tumor- and therapy-related complications often negatively impact quality of life (QoL). Standard treatments include resection and radiation, but institutional practices vary and recurrence rates remain high. In this review, we utilized a cohort from the Children’s Brain Tumor Network (CBTN) to evaluate outcomes for craniopharyngioma. METHODS: CBTN provides clinical and genomic data for pediatric patients diagnosed with primary central nervous system tumors across 25+ institutions. We collected data for 124 patients, ages 0-21, diagnosed with craniopharyngioma between 2012-2020. Variables collected included treatment, recurrence/progression, and comorbidities. RESULTS: Excluding patients without confirmed pathologic diagnosis (n=10) or follow-up data (n=39), 75 patients remained. For initial treatment, most (n=46, 61%) received surgery alone (9 partial, 33 near-total resection). Twenty-six (35%) underwent both surgery and radiation, with 9 receiving both therapies upfront and 17 receiving radiation at progression/recurrence. Four (5%) patients received chemotherapy. Over half of the cohort (n=39, 52%) had at least one progression/recurrence, and four died (5%). Significantly higher rates of progression/recurrence (84% vs. 32%, p=4.0e-5) were identified in patients that had surgery and radiation, compared to surgery alone. Time to recurrence, progression, or death was shorter for the surgery and radiation group (HR=4.1, p&lt;1.0e-4), and for those that underwent partial versus near-total resection (HR=2.7, p=0.1.2e-2). Comorbidities were likely underreported, based on low rates of visual (32%), neuroendocrine (27%), and neurologic (28%) deficits at diagnosis, and 29 patients (39%) with unspecified medical history. CONCLUSIONS: CBTN provides a robust repository of information on treatment and survival of craniopharyngioma patients. However, we found a paucity of data on associated comorbidities and QoL outcomes. We advocate that future datasets and clinical trials routinely collect functional outcomes alongside therapy and survival data, particularly in craniopharyngioma where long-term survival is balanced with future QoL.
RARE-25. Primary Intracranial Ewing Sarcoma in a Child: Case Report
Authors: Custodio John Emmanuel , Baticulon Ronnie , Palabyab Eric Paolo , Golidtum Jared Paul 
Published: June 2022

Abstract
Ewing sarcoma is a rare childhood tumor which accounts for 3% of all pediatric malignancies. More so, primary intracranial involvement with meningeal attachment is even rarer, accounting for only 1% of all Ewing sarcoma. We report a case of a 5-year-old boy who presented with headache, vomiting, and left-sided weakness that rapidly progressed over a period of three months. Cranial MRI showed a 7.1 x 6.7 x 8.6 cm multilobulated, heterogeneously enhancing, mixed solid and cystic extra-axial tumor compressing the frontoparietal lobe and causing significant midline shift. It was attached to the falx and infiltrated the middle third of the superior sagittal sinus. We performed a large right frontoparietal craniotomy to excise the tumor. Because of massive bleeding from the tumor, only a subtotal resection was possible. The bone flap was left out. The patient was discharged fully awake but with right hemiplegia on the fourteenth post-op day. Histopathologic examination revealed a spindle cell neoplasm that exhibited diffuse membranous staining for CD99. Fluorescence in-situ hybridization confirmed EWSR1 gene rearrangement, consistent with Ewing sarcoma. Three months after his surgery, the patient subsequently received 56 Gy of radiation therapy. At twelve months post-op, he remains fully awake and is back in school. He has residual left hemiparesis, but with antigravity movement. A multidisciplinary team involving Pediatric Oncology, Pediatric Neurology, Neurosurgery, Pathology, Radiation Oncology, and Rehabilitation Medicine is essential for patients with rare central nervous system tumors, to maximize effective treatment strategies despite limited resources.
RARE-28. The use of subcutaneous interferon in patients with craniopharyngioma: an institutional retrospective review
Authors: Patil Prabhumallikarjun , Gray Rachel , Goldman-Yassen Adam , Aguilera Dolly , Castellino Robert , Janss Anna , Mazewski Claire 
Published: June 2022

Abstract
Current strategies for managing craniopharyngioma result in significant morbidity. Successful treatment with interferon alfa(INFα) after progression is reported in the literature. This retrospective review details our institutional experience with INFα in craniopharyngioma patients. Method: Between 2000-2021, we treated 81 craniopharyngioma patients. Twenty-two patients received 26 treatment courses of subcutaneous INFα. Twenty-three courses were evaluable for response. Results: Ten patients received upfront INFα after cyst decompression +/- ommaya placement. Progression free survival(PFS) ranged between 7-38mo. Three patients continue on treatment (10+, 12+, 14+mo); seven progressed (four on treatment (7, 9, 25, 38mo), three after treatment (13, 19, 32mo)). At progression, three underwent surgery alone, three underwent surgery and radiation, one resumed INFα. Thirteen patients received INFα after progression. Prior to INFα, eight patients had had surgery, five surgery and radiation. Two in each group had INFα, previously. PFS ranged between 5-82+mo. One patient remains on treatment (5+mo); four continue in follow-up without progression (23+,40+,64+,82+mo) with two patients avoiding radiation to date; eight progressed (three on treatment (6-8mo), five after treatment (16,24,26,46,71mo)). At progression, two underwent surgery alone, three underwent surgery and radiation, one received re-irradiation, two resumed INFα. While receiving INFα, two patients experienced serious adverse events (one intra-tumoral hemorrhage (not attributed to INFα), one suicidal ideation). Both recovered. One tolerated retreatment with INFα. Three additional patients stopped INFα for intolerance, but two received INFα at subsequent progression. No other unanticipated side effects were reported. Conclusion: INFα therapy in patients with both newly diagnosed and progressive craniopharyngioma delayed the need for aggressive surgical resection and/or radiotherapy in some cases. In some patients, INFα resulted in prolonged stabilization of disease delaying or avoiding radiation. Overall, INFα side effects were manageable. These results are encouraging regarding INFα therapy for patients with craniopharyngioma and warrant further evaluation with a clinical trial.