Abstracts i53 NEURO-ONCOLOGY • JUNE 2022 target genes. To map PB subgroups to their putative developmental beginnings, we created a single-cell transcriptional atlas of the murine pineal gland across 11 developmental stages (E11-P21). Trajectory inference within the developing pineal gland revealed a differentiation continuum of early, mid, and mature alpha-/beta pinealocytes. Cross-species correlation and deconvolution identi- fed signifcant associations between multiple PB subgroups and specifc differ- entiation states of the pinealocyte lineage, suggestive of developmental origins. Characterization of pinealocyte development informed generation of biologic- ally faithful disease models, including a novel genetically engineered mouse model of the PB-RB subgroup. PB-Rb1 mouse tumors were histologically and molecularly validated for their fdelity to human tumor counterparts, exhib- iting up-regulation of key pinealocyte lineage markers that are diagnostic in patients. Finally, high-throughput drug screening identifed several promising pharmacological candidates that may attenuate consequences of Rb1 def- ciency in affected children. 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 Mary Littrell, MD, Kevin Bielamowicz, MD, Murat Gokden, MD, Sateesh Jayappa, MD, Gregory Albert, MD; University of Arkansas for Medical Sciences, Little Rock, AR, USA INTRODUCTION: Histologically diagnosed embryonal tumors (ET) of the central nervous system (CNS) in the pediatric population represent a group of ag- gressive malignancies with historically poor prognoses. Immunohistochemistry (IHC) and cytogenetics refned tumor classifcation and improved treatment strategies. Modern advancements in molecular methods including methylation profling provide further delineation of distinct ET subclasses. CASE DESCRIP- TION: 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 frst 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; path- ology returned as CNS embryonal tumor with EWSR1-PLAGL1 translocation. Patient experienced recurrence in original tumor bed and pathology was con- sistent with malignant recurrence with INI-1 loss. Methylation profling for diag- nostic samples in both patients was consistent with ET not otherwise specifed, while methylation profling of relapsed tissue in both cases was consistent with AT/RT. EWSR1 translocation was persistent from diagnostic to relapsed sam- ples. 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 beneft from upfront and experimental treatment approaches for AT/RT. ETMR-16. EMBRYONAL TUMORS WITH MULTI-LAYERED ROSETTES: A CASE SERIES IN TREATMENT FOR NEWLY DIAGNOSED CHILDREN Hung Tran 1 , Ashley Margol 2 , Jennifer Cotter 2 , Linda Szymanski 2 , Katrina O’Halloran 2 , Benita Tamrazi 2 , George Michaiel 2 , Eisha Christian 1 , Darian Esfahani 1 , Tom Belle Davidson 2 ; 1 Kaiser Permanente, Los Angeles, CA, USA. 2 CHLA, Los Angeles, CA, USA BACKGROUND: Embryonal tumors with multi-layered rosettes (ETMRs) are rare pediatric brain tumors with poorly defned prognostic features, standard of care treatments or outcome data. Recent data suggest that high- dose chemotherapy and radiotherapy is correlated with improved survival compared to chemotherapy alone. CASE DESCRIPTIONS: Four patients with newly diagnosed ETMRs were treated with 2 cycles of induction chemo- therapy per PBTC-026 using isotretinoin, vorinostat, vincristine, cisplatin, etoposide, cyclophosphamide with added intrathecal topotecan. Second look surgery was performed if not in complete remission (CR). Consolidation was with three cycles of marrow-ablative chemotherapy (carboplatin and thiotepa) with autologous hematopoietic cell rescue followed by focal irradiation and 12 cycles of maintenance chemotherapy with intrathecal topotecan, vorinostat and isotretinoin. Patient 1 was a 3-year-old female with right parietal tumor, lo- calized, and achieved gross total resection (GTR). Patient 2 was an 11-month- old male with posterior fossa tumor, localized, and achieved subtotal resection. Patient 3 was a 9-month-old female with posterior fossa tumor with near GTR, and metastasis to T12/L1 and L3/L4. [DTB1] [HNT2] Patient 4 was a 34-month-old male with a right frontal lobe tumor, localized and achieved GTR. Patient 1 is now 18 months from diagnosis and in CR. Patient 2 had second look surgery both after induction and consolidation but suffered neuro- logic injury to the brainstem which led family to decline further therapy. He is currently 14 months from diagnosis with stable residual disease. Patient 3 had local disease recurrence following radiation therapy at 10 months post diagnosis[DTB3] [HNT4] , prior to maintenance. Patient 4 remains in CR at 13 months from diagnosis, currently in maintenance with vorinostat and isotretinoin but declined intrathecal topotecan. CONCLUSION: This case series adds to current knowledge of intensive multi-modal therapy for newly diagnosed ETMR. Further study to defne standard optimal treatments in this high-risk group of patients is warranted. GERM CELL TUMORS GCT-01. PEDIATRIC INTRACRANIAL GERM CELL TUMORS AND PRIMARY POLYURIA-POLYDIPSIA SYNDROME: A 13-YEAR SINGLE INSTITUTIONAL EXPERIENCE Rossana Pavone 1 , Carla Fonte 1 , Franco Ricci 2 , Gaia Varriale 2 , Giorgia Enrico 1 , Maria Luigia Censullo 1 , Carlotta Gemma Gori 1 , Milena Guidi 1 , Anna Maria Buccoliero 3 , Chiara Caporalini 3 , Lorenzo Genitori 4 , Iacopo Sardi 1 ; 1 Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children's Hospital, Florence, Italy. 2 Auxo- endocrinology Unit, Meyer Children's Hospital, Florence, Italy. 3 Pathology Unit, Meyer Children's Hospital, Florence, Italy. 4 Neurosurgery Unit, Meyer Children's Hospital, Florence, Italy 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 fuids during chemotherapy, especially for cisplatin and/or ifosfamide-based cycles, for which hyperhydratation is re- quired. We report the results of our single-center cohort of patients with IGCTs treated between 2008 and 2021, focusing on the clinical presenta- tion, 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 pre- sented 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 prog- nosis, but present a signifcant risk of long-lasting severe endocrine sequelae which may be worsened by the primary oncological strategy, requiring careful management of complications related to fuid and electrolytes dis- turbances. In order to avoid post-treatment pituitary insuffciency, guidelines for diabetes insipidus management when cisplatin and/or ifosfamide-based protocols are used should be established and all patients should receive me- ticulous endocrine follow-up. GCT-02. IMAGING RESPONSE ASSESSMENT FOR CENTRAL NERVOUS SYSTEM GERM CELL TUMOURS: CONSENSUS RECOMMENDATIONS FROM THE EUROPEAN SOCIETY FOR PAEDIATRIC ONCOLOGY BRAIN TUMOUR GROUP (SIOPE-BTG) AND NORTH AMERICAN CHILDREN’S ONCOLOGY GROUP (COG) Giovanni Morana 1 , Dennis Shaw 2 , Shannon MacDonald 3 , Claire Alapetite 4 , Thankamma Ajithkumar 5 , Aashim Bhatia 6 , Hervé Brisse 4 , Camilo Jaimes 7 , Thomas Czech 8 , Girish Dhall 9 , Jason Fangusaro 10 , Cecile Faure-Conter 11 , Maryam Fouladi 12 , Darren Hargrave 13 , Julie Harreld 14 , Dipayan Mitra 15 , James Nicholson 5,16 , Mark Souweidane 17 , Beate Timmermann 18 , Gabriele Calaminus 19 , Ute Bartels 20 , Brigitte Bison 21 , Matthew Murray 5,16 ; 1 University of Turin, Turin, Italy. 2 Seattle Children’s Hospital and University of Washington, Seattle, WA, USA. 3 Massachusetts General Hospital, Boston, MA, USA. 4 Institut Curie, Paris, France. 5 Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 6 Children's Hospital of Philadelphia, Philadelphia, PA, USA. 7 Boston Children’s Hospital and Dana-Farber/Harvard Cancer Center, Boston, MA, USA. 8 Medical University of Vienna / Vienna General Hospital, Vienna, Austria. 9 University of Alabama of Birmingham, Alabama, USA. 10 Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA. 11 Institute of Paediatric Hematology and Oncology, Lyon, France. 12 Nationwide Children’s Hospital, Colombus, Ohio, USA. 13 Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 14 Dartmouth-Hitchcock Medical Center, Norris Downloaded from https://academic.oup.com/neuro-oncology/article/24/Supplement_1/i53/6600611 by guest on 31 January 2024