bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETMR-13. Embryonal Tumor with Multilayered Rosettes in an Infant: Case Report
Authors: Yu Llarx Saundt , Palabyab Eric Paolo , Baticulon Ronnie 
Published: June 2022

Abstract
Embryonal tumor with multilayered rosettes (ETMR) is a highly malignant tumor (WHO grade 4) seen predominantly in infants. It includes morphologically distinct embryonal tumors namely, embryonal tumor with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma. The presence of multilayered rosettes and C19MC amplification at chromosome 19q13.42 confirms the diagnosis. The median overall survival is less than a year and the prognosis is generally poor. We report the case of a 1-year-old girl who presented with vomiting, lethargy, and increasing head circumference over a period of six months. On admission, she was drowsy and irritable. Verbal output was limited to moans and motor response was localizing. She was macrocephalic with a head circumference of 51 cm. MRI showed a large 5 x 5 x 6.5cm contrast-enhancing cerebellar vermian tumor with obstructive hydrocephalus. There was no evidence of leptomeningeal disease or spinal metastasis at this time. She underwent a right frontal ventriculoperitoneal shunt insertion, followed by suboccipital craniotomy and subtotal tumor resection one week later. Her shunt was ligated two days after tumor excision, due to development of bilateral subdural hygromas. The patient regained full consciousness, but still had spastic lower extremities and inability to swallow at the time of discharge. Histopathology and immunostains were consistent with an embryonal tumor, possibly ETMR, and the patient was for advised chemotherapy. Before initation of chemotherapy, the patient was admitted in another instution because of alteration in sensorium. Repeat imaging showed progression of the patient’s subdural hygromas, requiring insertion of a subduroperitoneal shunt. The patient died seven weeks after tumor resection due to progression of her tumor residual. Management options for ETMR are limited, especially in low- and middle-income countries. International linkages may help facilitate the accurate diagnosis and early treatment of these patients with rare but aggressive brain tumors.
ETMR-15. Central Nervous System Embryonal Tumor with EWSR1 translocation: Evolving changes in histology, sequencing, and epigenetics at relapse in 2 patients and potential treatment implications
Authors: Littrell Mary , Bielamowicz Kevin , Gokden Murat , Jayappa Sateesh , Albert Gregory 
Published: June 2022

Abstract
INTRODUCTION: Histologically diagnosed embryonal tumors (ET) of the central nervous system (CNS) in the pediatric population represent a group of aggressive malignancies with historically poor prognoses. Immunohistochemistry (IHC) and cytogenetics refined tumor classification and improved treatment strategies. Modern advancements in molecular methods including methylation profiling provide further delineation of distinct ET subclasses. CASE DESCRIPTION: We present two cases with initial diagnosis of a CNS embryonal tumor with EWSR1 rearrangement. Relapsed tissue in both cases displayed acquisition of INI-1 loss consistent with atypical teratoid/rhabdoid tumor (AT/RT). The first case presented at 14 months of age with vomiting and altered mental status. Imaging revealed right frontal lobe hemorrhagic mass with signs of increased intracranial pressure; pathology returned as a CNS embryonal tumor with EWSR1-PLAGL1 translocation. Patient ultimately experienced multiple relapses with tumor sample each with INI-1 loss. The second case presented at 11 months of age with new onset seizures and was found to have right frontal tumor; pathology returned as CNS embryonal tumor with EWSR1-PLAGL1 translocation. Patient experienced recurrence in original tumor bed and pathology was consistent with malignant recurrence with INI-1 loss. Methylation profiling for diagnostic samples in both patients was consistent with ET not otherwise specified, while methylation profiling of relapsed tissue in both cases was consistent with AT/RT. EWSR1 translocation was persistent from diagnostic to relapsed samples. CONCLUSION/DISCUSSION: These cases illustrate the need for ongoing analysis in patients with CNS primitive neuroectodermal tumors and EWSR1 rearrangements, and the unique role of molecular studies in relapsed tissue. The emergence of treatment resistance in a subpopulation of cells more consistent with AT/RT suggests these patients could benefit from upfront and experimental treatment approaches for AT/RT.
GCT-01. Pediatric intracranial germ cell tumors and primary polyuria-polydipsia syndrome: a 13-year single institutional experience
Authors: Pavone Rossana , Fonte Carla , Ricci Franco , Varriale Gaia , Enrico Giorgia , Censullo Maria Luigia , Gori Carlotta Gemma , Guidi Milena , Buccoliero Anna Maria , Caporalini Chiara , Genitori Lorenzo , Sardi Iacopo 
Published: June 2022

Abstract
Intracranial germ cell tumors (IGCTs) represent about 4% of all childhood brain tumors. They are common in both the pineal and pituitary regions and sometimes they can be bifocal. Suprasellar and bifocal IGCTs usually present stereotypical symptoms, including primary polyuria-polydipsia syndrome (PPS). Consolidated IGCTs’ therapy is based on the International Society of Pediatric Oncologic (SIOP) CNS GCT II protocol consisting of primary pre-radiation chemotherapy combining etoposide, carboplatin and/or cisplatin and ifosfamide. PPS management in these patients requires monitoring of electrolytes and fluids during chemotherapy, especially for cisplatin and/or ifosfamide-based cycles, for which hyperhydratation is required. We report the results of our single-center cohort of patients with IGCTs treated between 2008 and 2021, focusing on the clinical presentation, treatment and long-term follow-up. Thirty-one patients were analyzed (median age=13 years, 87% male). Twelve children (39%) presented a PPS and needed desmopressin treatment, maintained at long-term follow-up data update in all. Over these PPS patients, 6 had bifocal germinomas, 4 suprasellar germinomas, 1 metastatic germinoma and 1 non-germinomatous IGCT. Eleven PPS children (92%) received cisplatin and/or ifosfamide-based chemotherapy: all of them had optimal biochemical urine and blood investigations before, during and after chemotherapy. None of them presented serious complications during treatment. After a median follow-up of 5 years, two patients (6.5%) died (1 IGCT-related, 1 non-cancer related) and one had a second malignancy (parotid gland mucoepidermoid carcinoma, 6 years after IGCT diagnosis). Childhood IGCTs have an excellent prognosis, but present a significant risk of long-lasting severe endocrine sequelae which may be worsened by the primary oncological strategy, requiring careful management of complications related to fluid and electrolytes disturbances. In order to avoid post-treatment pituitary insufficiency, guidelines for diabetes insipidus management when cisplatin and/or ifosfamide-based protocols are used should be established and all patients should receive meticulous endocrine follow-up.
GCT-10. Successful Salvage of Relapsed intracranial Non-Germinaoteous Germ Cell Tumors NGGCTs in a Child With Renal Insufficiency with Novel platinum-Free chemotherapy Regimen
Authors: Mobark Nahla Ali , Alharbi Musa , Ballourah Walid , AlSultan Abdulrahman , Manjomi Fahad Al , Alotabi Fahad , Balbaid Ali Abdullah O , Rayis Mohammed , AlNaqib Zaid G , Aljabarat Wael abdel Rahman , Finlay Jonathan L 
Published: June 2022

Abstract
The Outcome for relapsed NGGCT is poor. Salvage therapy usually consist of reinduction platinum-based chemotherapy regimen followed by high-dose-chemotherapy and autologous-stem-cell-rescue (HDC/AuSCR) and re-irradiation with no consensus on optimal management and usually associated with remarkable toxicity. We present a 12-year-old boy diagnosed with a localized pineal Non-Germinaoteous Germ Cell Tumors NGGCTs of mixed origin with elevated AFP he had ETV and biopsy started on COG ACNS0122 protocol after receiving first cycle (carbo/Etoposide) he developed acute renal failure investigation showed small dysplastic kidney to avoid nephrotoxicity of platinum agents chemotherapy changed to VBE (Vinblastine, Bleomycin and Etoposide) post 3rd cycle MRI showed increase in size of the pineal mass with normal tumor markers representing Growing Teratoma Syndrome He had total surgical resection of the tumor Pathology showed predominant teratoma component He received radiation therapy CSI then another 3 cycles of VBE 4 months following treatment completion he presented with elevated AFB and new right anterior temporal lesion Spinal MRI and CSF were negative. He had 2 cycles of Salvage Non-nephrotoxic 4-drug regimens GEMPIV Gemcitabine 800 mg/m2 days 1 and 14. Paclitaxel 80 mg/m2 days 1 and14, Irinotecan 50 mg/m2 daily for 5 days Vinblastine 6 mg/m2 weekly days 1,8,14 MRI after 2 cycles showed remission with undetectable AFP then 2 consolidation cycles of etoposide and thiotepa (HDC/AuSCR) The 3rd consolidation cycles were cancelled due to hematological toxicity During treatment phases chemotherapy was well tolerated doses were adjusted according to his GFR with renal conservative and supportive therapy.post (HDC/AuSCR) he experienced delayed hematological recovery with persistent thrombocytopenia responded to Eltrombopag then he had focal Temporal lobe irradiation Currently patients in remission with chronic stage 3 renal Insufficiency Conclusions: this case showed that relapsed intracranial NGGCT can be successfully salvaged without platinum-based chemotherapy in patients with renal insufficiency.
GCT-11. 24 Gy whole ventricular radiotherapy alone is sufficient for disease control in localised germinoma in CR after initial chemotherapy – final of the SIOP CNS GCT II study
Authors: Calaminus Gabriele , Bison Brigitte , Conter Cecile Faure , Frappaz Didier , Peyrl Andreas , Gerber Nicolas U , Müller Jans-Enno , Ajithkumar Thankamma , Morana Giovanni , Cross Justin , Pietsch Torsten , Smith Colin , Solem Kristin , Devenney Irenne , Garre Maria Luisa , Brisse Herve , Zimmermann Martin , Kortmann Rolf-Dieter , Alapetite Claire , Nicholson James 
Published: June 2022

Abstract
SIOP CNS GCT II aimed to establish if 24 Gy Whole Ventricular Radiotherapy (WVRT) in localised germinoma is sufficient for tumour control. After central review of radiological response after ‘CarboPEI’ chemotherapy, patients in complete remission (CR) were consolidated with 24 Gy WVRT. Between 2/2012 and 7/2018, 194 patients from 8 European countries with histologically-confirmed fully-staged localised germinoma were registered, of whom 167 were protocol pts. CR after chemotherapy was achieved in 65 patients, Of the 102 patients not in CR after chemotherapy 91 had partial remission (PR), 8 stable disease (SD), 3 progressive disease (PD). All 65 patients in CR received 24 Gy WVRT alone; two of these relapsed, both locally, 7 and 12 months after diagnosis. Of the 102 non-CR patients after chemotherapy, 91 with PR and 8 with SD received 24 Gy WVRT and 16 Gy boost, of which five relapsed (four local, one distant) 2 -7 years from diagnosis. One additional patient who remained in CR died of infection in CR, 4 years after Dx. In three patients with PD all received 24 Gy ventricular irradiation with varying tumour boosts. 16-30 Gy, no relapses occurred. Median follow-up of the whole group was 4,2 years. 4- years event-free survival (EFS) for patients in CR treated with WVRT only (n=65) was 97% (standard error 2%). 4-years EFS for patients with non-CR ( WVRT 24 Gy and 16 Gy to 30 Gy tumour boost) (n=102) was 95% (standard error 2%). Localised germinoma in CR after chemotherapy had an excellent outcome with 24 Gy WVRT alone. 24 Gy WVRT is therefore considered the standard consolidation treatment in this group and should be used as the standard for further treatment studies in localised germinoma evaluating the recent international consensus on radiological response criteria ( Lancet Oncology accepted).
GCT-13. KRAS MUTATION IN PEDIATRIC INTRACRANIAL GERM CELL TUMORS
Authors: Khaiman Chusana , Techavichit Piti , Teerapakpinyo Chinachote , Shuangshoti Shanop 
Published: June 2022

Abstract
BACKGROUND: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations were reported in patients diagnosed with IGCTs. OBJECTIVES: To describe clinicopathologic, molecular features of KRAS mutation and treatment outcome of children diagnosed with IGCTs. METHODS: A retrospective review in patients diagnosed with IGCTs at Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2019. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue for the molecular study. Identifies mutations in codon 12,13 and 61 of the KRAS gene was performed by using the real-time PCR technique of the Cobas® test and pyrosequencing method. RESULTS: Eighteen patients were diagnosed with IGCTs (11 males and seven females). Age ranged from 5 to 14 years (median 10.5 years). The diagnosis was germinoma and non-germinomatous IGCTs in 9 patients each. Elevated markers were revealed in approximately 25% of patients. Four patients (2 patients with germinoma and 2 with non-germinomatous IGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was given in 16 patients and craniospinal radiation (CSI) was given only in leptomeningeal metastasis. With the median follow-up of 26 months, overall survival is 88.9% in germinomas and 37% in non-germinomatous IGCTs. Mutation of the KRAS gene was detected by pyrosequencing technique in one patient. The mutation located at codon 61, frequency 38.3% units, nucleotide substitution CAA &gt; CTA and amino acid substitution was Q61L. The patient who carries mutant gene was diagnosed germinomatous germinoma with CSF metastasis and eventually died from treatment-related toxicity. CONCLUSIONS: Our study revealed treatment outcomes of IGCTs in Thai children. We describe KRAS codon 61 mutation in metastasis germinoma patients with poor outcome, support KRAS codon 61 mutation (Q61L) may have a clinical correlation in IGCTs.
GCT-20. Multi-Institutional Analysis of Pediatric Relapsed/Refractory Central Nervous System Germ Cell Tumors
Authors: Nagabushan Sumanth , Dhall Girish , Abdelbaki Mohamed 
Published: June 2022

Abstract
Central nervous system (CNS) germ cell tumors (GCTs) constitute ~ 4% of primary pediatric brain tumors in the United States. While multimodality therapy approaches have ensured &gt;80% survival benefit, these patients still experience relapses, with no established standard of care. Their rarity limits knowledge of their outcomes and associations with location, metastatic status, impact of surgery, serum, and cerebrospinal fluid (CSF) biomarkers, to only a few smaller trials and case series.This international multi-institutional retrospective study for relapsed/refractory germinomas and NGGCTs, will evaluate the association between different treatment modalities and 5-year OS and EFS; patterns of relapse, including along biopsy tracts; and potentially identify predictors of recurrence. De-identified patient data at primary and relapse time points will be collected focusing on treatment approaches such as surgery, conventional/high dose chemotherapy, photon/proton radiation therapy; timing and site of relapse; imaging characteristics and serum/CSF biomarkers (BHCG/AFP). Our collaborators include multiple sites across North America, Australia, Europe, Africa, South America, the Middle east, India, Singapore, and Malaysia. 6 recurrent intracranial germinomas on the CBTN (Children’s Brain Tumor Consortium) database were assessed, demonstrating a male gender preponderance (4) and recurring in the suprasellar region (3), frontal lobe (2) and spinal cord (1). 2 underwent gross total resection while 1 had biopsy only. Conventional or high-dose chemotherapy was administered in 5, while 2 received craniospinal and 1 proton radiation. 4 patients are alive. Median OS was 738 days and EFS 1093 days. However, biomarker (AFP/BHCG) data was unavailable. Updated results will be presented at the conference. With global partnership and contribution, we anticipate this study to help bridge existing gaps in our knowledge of this rare patient cohort and establish a consensus standard of care, through prospective clinical trials in the future. We acknowledge the CBTN for kindly providing data access.
GCT-22. OUTCOMES OF CHILDREN WITH LOCALIZED AND METASTATIC GERMINOMA TREATED WITH CHEMOTHERAPY FOLLOWED BY RADIATION THERAPY WITHOUT PRIMARY TUMOR BOOST
Authors: Bajin Inci Yaman , Foo Jen Chun , Bouffet Eric , Ertl-Wagner Birgit , Tsang Derek , Laperriere Norman , Dirks Peter , Drake James , Bartels Ute 
Published: June 2022

Abstract
BACKGROUND: Response-based radiation therapy has been the approach for germinoma after chemotherapy. However, the presence of residual lesions at the end of chemotherapy did not demonstrate a negative impact on progression-free survival (PFS). Similarly, resection of residual tumors after chemotherapy did not show a survival benefit. AIM: Our study objective was to determine long-term outcomes of a cohort who received chemotherapy and radiation therapy without primary tumor boost even in the absence of complete response to chemotherapy. METHOD: This retrospective study analyzed the outcome of germinoma patients diagnosed and treated at a tertiary care center from January 2006 to December 2021. RESULTS: Twenty-nine children (14 male; median age 12.8 years) were identified. Median follow-up was 63 months (range 9-187 months). Twenty children had localized disease and tumor location was suprasellar (n= 9), pineal (n= 10), and bifocal (n= 1) while 9 children had metastatic disease at presentation. All patients completed multi-agent chemotherapy followed by either whole ventricular (WVI) (23.4 Gy) (n = 23), whole brain (WBI) (23.4 Gy) (n = 5) or craniospinal radiation (CSI) (23.4 Gy) (n= 1). Two children, who had localized disease at presentation and received WVI after chemotherapy, relapsed 9 months and 32 months after completion of treatment respectively. None of them had local relapses. Location of relapse was distant, outside (n= 1) and inside (n= 1) the radiation field. Five-year PFS was 93% and overall survival (OS) was 100%. CONCLUSION: In this limited experience, excellent 5-year PFS and OS rates were achieved with chemotherapy followed by radiation therapy delivered without primary tumor boost. This study also demonstrated the absence of local relapse despite omitting primary tumor boost in patients with localized and metastatic germinoma.
HGG-03. PEDIATRIC BITHALAMIC GLIOMA H3K27M NEGATIVE AND EGFR POSITIVE: A DISTINCT ENTITY WITH POTENTIAL SENSIBILITY TO EGFR INHIBITORS
Authors: Hernandez Marta Cortes , Schiaffino Guiomar Gutierrez , Almeida Silvia Torrejon , MoroñO Sara Iglesias , Lara Bernardo Weil , Leon Maria Isabel Martinez , Alvarez Martina 
Published: June 2022

Abstract
INTRODUCTION: Brain tumors are the most common solid tumors of childhood and optimal therapeutic strategies for many subtypes remain unknown. Bithalamic gliomas, in contrast with unilateral, have frequent mutations in the EGFR oncogene and only rare Histone H3 mutation. These EGFR mutations are small inframe insertions within exon 20 or missense mutations within exon 7 and occur in absence of gene amplification. CASE REPORT: A previously healthy 10-years-old boy with adequate neuropsychomotor development was admitted with a 5-day-long headache. A brain magnetic resonance imaging (MRI) showed an expansive midline lesion with thalamic extension. The tumor showed no diffusion restriction or contrast enhancement. An endoscopic septostomy and biopsy were performed.The histopahotology showed a diffused astrocytoma grade II. The immunohistochemistry was negative for IDH1 and 2, BRAF mutation, P53 and H3K27M. Next generation sequencing (NGS) ruled out histone H3K27M mutation and showed EGFR mutation in exon 7. The patient experimented clinical and radiological disease progression in a few weeks, confirming the high grade glioma despite the histopahological diagnosis.He received radiotherapy (Total dose 54Gy) and after radiation he started target therapy with Osimertinib, a third generation tirosin kinase inhibitor. As a toxiticy, he experienced neutropenia Grade 2. Disease evaluation performed after 2 cycles showed stable disease. DISCUSSION: Our case report represents a distintc molecular class of pediatric-type bithalamic glioma characterized by EGFR alteration and absence of H3K27M mutation. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.
HGG-13. Combined CDK inhibition and arginine-deprivation as targeted therapy for arginine-auxotrophic glioblastoma multiforme cells
Authors: Riess Christin , del Moral Katharina , Fiebig Adina , Kaps Philipp , Linke Charlotte , Hinz Burkhard , Rupprecht Anne , Frank Markus , Fiedler Tomas , Koczan Dirk , Troschke-Meurer Sascha , Lode Holger N , Engel Nadja , Classen Carl Friedrich , Maletzki Claudia 
Published: June 2022

Abstract
INTRODUCTION/BACKGROUND: Glioblastoma multiforme show constitutive activation of cyclin-dependent kinases (CDKs) or arginine auxotrophy. This renders tumor cells vulnerable towards arginine-depleting substances, such as arginine deiminase from Streptococcus pyogenes (SpyADI). Previously, we confirmed the susceptibility of patient-derived GBM cells towards administration of SpyADI as well as CDK inhibitors (CDKis). To improve effects, we applied a sequential (SEQ) CDKi/SpyADI approach to examine mechanistic insights and drug susceptibility. MATERIALS AND METHODS: Three arginine-auxotrophic patient-derived GBM lines with different molecular characteristics were cultured in 2D and 3D (spheres and glioma stem-like cells (GSC)) and effects of this combined CDKi/SpyADI approach were analyzed. This included viability staining via Calcein AM in 2D and 3D-Glo in 3D culture and cell death analysis via flow cytometry. Therapy-induced morphological changes were identified with transmission electron microscopy (TEM). Besides, 3D-invasiveness, cellular stress, and DNA damage responses were measured. RESULTS: All SEQ-CDKi/SpyADI combinations yielded synergistic antitumoral effects, characterized by impaired cell proliferation, invasiveness, and viability. Notably, this SEQ-CDKi/SpyADI approach was most effective in 3D models. Mitochondrial impairment was demonstrated by increasing mitochondrial membrane potential and decreasing oxygen consumption rate along with extracellular acidification rate after abemaciclib/SpyADI monotherapy or its combination regimens. TEM confirmed damaged mitochondria and endoplasmic reticulum together with increased vacuolization under CDKi mono- and SEQ- CDKi/SpyADI combination therapy. SEQ-abemaciclib/SpyADI treatment suppressed the DSB repair system via NHEJ and HR, whereas SEQ-dinaciclib/SpyADI treatment increased γ-H2AX accumulation and induced Rad51/Ku80. The latter combination also activated the stress sensor GADD45 and β-catenin antagonist AXIN2. CONCLUSION: This study highlights the antitumoral potential of a combined SpyADI/CDKi approach. We show that sequential application of these substances has complex effects on mitochondrial dysfunction, invasiveness, and DNA-damage response. This provides a good starting point for further proof-of-concept studies to move forward with this strategy.