bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPCT-08. ACTIVITY OF LAROTRECTINIB IN PEDIATRIC TROPOMYOSIN RECEPTOR KINASE (TRK) FUSION CANCER PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Goto Hiroaki , Geoerger Birgit , DuBois Steven G , Grilley-Olson Juneko E , van Tilburg Cornelis M , Schulte Johannes , Kang Hyoung Jin , Tahara Makoto , Boni Valentina , Perreault Sebastien , Capra Michael , Reeves John A , Brega Nicoletta , Childs Barrett H , Laetsch Theodore W , Ziegler David S , Doz François 
Published: December 2020

Abstract

BACKGROUND
TRK fusions are oncogenic drivers in a variety of tumors, many involving the CNS. Larotrectinib, a selective FDA- and EMA-approved TRK inhibitor, demonstrated a 79% objective response rate (ORR) and a 35.2-month median duration of response (DoR) in adult and pediatric patients with various non-CNS solid tumors harboring NTRK gene fusions. We report the clinical activity of larotrectinib in pediatric patients with primary TRK fusion CNS tumors.

METHODS
Patients aged &lt;18 years with primary CNS tumors harboring an NTRK gene fusion detected by local molecular testing who were treated with larotrectinib in two clinical trials (NCT02637687, NCT02576431) were identified. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was investigator assessed (RANO).

RESULTS
As of February 2019, 14 pediatric patients with primary TRK fusion CNS tumors were identified. Gene fusions involved NTRK2 (n=10), NTRK1 (n=2), and NTRK3 (n=2). Median age was 7.0 years (range 1.3–16.7). ORR was 45% (95% CI 17–77%) among 11 evaluable patients. Two patients had complete responses (pending confirmation), three had confirmed partial responses, and six had stable disease. 24-week disease control rate was 73%. DoR ranged from 2.6+ to 5.5+ months and progression-free survival ranged from 0.03+ to 13.9+ months. Duration of treatment ranged from 0.03+ to 16.6+ months. Treatment-emergent adverse events were mainly grade 1–2.

CONCLUSIONS
Larotrectinib resulted in objective responses and durable disease control in pediatric patients with primary TRK fusion CNS tumors. These results support expanded testing for NTRK gene fusions in patients with CNS tumors.
EPCT-18. PHASE 0/I STUDY OF GM-CSF AND INTRATHECAL TRASTUZUMAB IN CHILDREN WITH RECURRENT POSTERIOR FOSSA EPENDYMOMA
Authors: Dorris Kathleen , Widener Melissa , Amani Vladimir , Donson Andrew , Schissel Debra , Carson Jessica , Mettetal Ashley , Ramirez Dominique , Gustafson Daniel , Hankinson Todd , Handler Michael , Macy Margaret , Foreman Nicholas 
Published: December 2020

Abstract

BACKGROUND
Posterior fossa ependymoma (PF EPN) is a pediatric central nervous system malignancy that has a poor outcome to standard therapeutic approaches. The majority of PF EPN tumors have increased HER2 expression. Trastuzumab is a monoclonal antibody that targets HER2, and sargramostim (GM-CSF) stimulates hematopoietic progenitor cell proliferation. The combination of trastuzumab and GM-CSF has been shown to trigger antibody-dependent cell cytotoxicity in vitro in PF EPN cell lines.

METHODS
Children aged 1–21 years with relapsed PF EPN and no ventriculoperitoneal shunt or CSF obstruction are eligible for the Phase 0/I institutional trial at Children’s Hospital Colorado. Stratum 1 involves IT trastuzumab and subcutaneous (subQ) GM-CSF prior to standard-of-care surgical resection. Stratum 2 involves a 3 + 3 phase I design with serial IT trastuzumab doses, each preceded by three days of GM-CSF, to establish the MTD for IT trastuzumab.

RESULTS
Trastuzumab was detected in a sufficient number of tumors after presurgical IT delivery in Stratum 1 to open Stratum 2. Four patients (75% female) have been enrolled in Stratum 2 at trastuzumab Dose Level 1. Median age at enrollment is 9.8 years (range, 3.5–20.2 years). Preliminary CSF pharmacokinetic analysis demonstrated detectable trastuzumab up to 14 days after IT doses. No dose-limiting toxicities have occurred. Two patients progressed on therapy (median, 4 cycles). One patient is progression-free at 18 months off therapy. One patient remains on study therapy.

CONCLUSIONS
IT trastuzumab penetrates PF EPN tumor tissue. Stratum 2 remains open to accrual at Dose Level 2.
EPEN-09. IMPACT OF MOLECULAR SUBGROUP ON OUTCOME FOR INFANTS &lt;12 MONTHS WITH INTRACRANIAL EPENDYMOMA - GERMAN EXPERIENCE FROM HIT2000, INTERIM-2000-REGISTRY AND I-HIT-MED REGISTRY
Authors: Obrecht Denise , Mynarek Martin , von Hoff Katja , Witt Hendrik , Pajtler Kristian W , Juhnke B Ole , Warmuth-Metz Monika , Bison Brigitte , Kortmann Rolf-Dieter , Timmermann Beate , Pfister Stefan M , Sahm Felix , Sturm Dominik , von Deimling Andreas , Schüller Ulrich , Pietsch Torsten , Benesch Martin , Gerber Nicolas U , Rutkowski Stefan 
Published: December 2020

Abstract

BACKGROUND
For infant ependymoma (EP), decision for radiotherapy during first-line therapy is a dilemma. We analyzed therapy outcomes of EP patients younger than 12 months at diagnosis according to molecular subgroup.

PATIENTS AND METHODS
Between 2001 and 2017, 30 patients with histological diagnosis of intracranial EP &lt;12 months at diagnosis with DNA-methylation profiling available were registered in HIT-MED-studies/-registries.

RESULTS
In 3/30, DNA methylation-based CNS tumor classification suggested a diagnosis other than EP or could not be assigned to a reference class. Of the remaining 27 tumors, 16 were classified as PF-A, 8 as RELA-fusion positive and 3 as YAP-fusion positive. Median age at diagnosis was 0.73 (0.30–0.99) years. After a median follow-up time of 5.36 (0.20–12.90) years, 59.3% experienced progressive disease (PD). 5y-PFS and -OS for the whole cohort were 38.2% and 73.1%. RELA- and YAP-fusion positive EP had significantly better OS than PF-A (5y-OS for PF-A: 55.9%; RELA 100%; YAP 100%; p=0.023). PFS was not significantly different. All but one patient with relapsed PF-A died despite multimodal salvage strategies. In contrast, patients with relapsing RELA- and YAP-fusion positive EP (n=5), survived with a combination of re-surgery and first or second local radiotherapy.

CONCLUSION
In this cohort of infants &lt;12 months, patients with PF-A had a significantly inferior OS compared to patients with RELA- and YAP-fusion positive EP. Salvage therapy was ineffective for patients with PF-A, whereas patients with can RELA- and YAP-fusion positive EP can be long-term survivors after PD. Therefore, subgroups-specific therapy should be discussed.
EPEN-14. GENERATION OF A C11orf95-RELA FUSION TARGETING ANTIBODY AS A DIAGNOSTIC TOOL FOR SUPRATENTORIAL EPENDYMOMA
Authors: Ruff Lisa , Chan Denice Y , Jenkinson Lesley , Haynes Stuart , Austin Mark , Holt Sarah , Groves Maria , Gilbertson Richard J 
Published: December 2020

Abstract
Ependymomas account for 10% of paediatric brain tumours and arise in the ventricular walls of the central nervous system. Ependymomas were previously classified as one tumour type and all patients received similar treatment. However, recent genomic studies have identified nine different molecular subgroups of the disease, including one supratentorial subtype characterized by a novel fusion gene C11ORF95-RELA. When introduced into neural stem cells, this fusion is a potent driver of tumorigenesis and its presence in patient samples has previously also been shown to negatively correlate with overall survival. Accurate diagnosis of this subgroup is currently limited to sophisticated approaches such as break-apart FISH or RNA sequencing. Here, we report the generation of a C11ORF95-RELA Fusion-specific antibody that can be used for routine immunohistochemistry (IHC). Candidate antibodies were first selected using phage display and favourable leads were subjected to affinity maturation using ribosome display after a screening process involving immunoblotting and IHC. Further IHC-based screening of affinity-matured candidates using fusion-positive and -negative mouse tissue as well as human fusion-negative ependymoma tumour tissue produced one lead antibody. The antibody detects fusion-specific nuclear staining pattern on fusion-positive tissue and does not react with fusion-negative tissues. This candidate antibody is currently being tested on human fusion-positive ependymoma tissue. This accurate diagnostic tool holds great promise to transform the management of patients with supratentorial ependymoma.
EPEN-37. TREATMENT OUTCOME OF RECURRENT EPENDYMOMA IN CHILDREN IN NORTHERN EGYPT
Authors: Fadel Shady , Abdelaziz Zeyad , Kerim Amr Abdel , Abbassy Mahmoud , Samy Samer , Elsaba Basma 
Published: December 2020

Abstract

INTRODUCTION
1/3 of Ependymoma patients will develop recurrence with only 25% are long term survivors. Treatment is usually between surgery, radiotherapy or combinations.

PATIENTS AND METHODS
Retrospective review of children with recurrent Ependymoma in northwest of Egypt between 2005 and 2019 in Alexandria School of medicine records.

RESULTS
27 patients were identified 19 of them after 2010. The median age is 9.7 years (1.5–19), with 16 males and 11 females. Pathology were 11 grade II Ependymoma and 16 anaplastic Ependymoma. 16 had gross residual disease after 1st surgery and 22 received radiotherapy initially at median dose of 53.5 Gy, 4 patients received suboptimal radiotherapy. The initial site was14 supratentorial tumors and 13 infratentorial. Median time to recurrence is 27.6 months(3–84), and recurrences were 17 local and 9 CSF disseminated, and one patient had recurrence at the scar with lung metastasis. At a median follow up of 56.6 months 14(51.8%) are still alive. Treatment was surgery only in 6(4 alive) radiotherapy alone in 2(1alive), combined in 15(9 alive) and 4 patients received neither. The best outcome were in patients with late local relapse treated with complete resection and CSI after 2010. Radiotherapy dose was between 54 to 57.3 Gy and one patient developed reirradiation injury at brain stem. 5 of the 14 living patients is having toxicity in form of hearing aids (4) and low TSH(1).

CONCLUSION
Aggressive treatment of recurrent Ependymoma with surgery and radiotherapy is feasible and about half of the patients are salvageable.
EPEN-38. EZH2 INHIBITORY PROTEIN (EZHIP/Cxorf67) EXPRESSION IS HIGHLY CONCORDANT WITH H3K27me3 LOSS AND IS A PROMISING SURROGATE MARKER FOR POSTERIOR FOSSA TYPE A EPENDYMOMAS
Authors: Nambirajan Aruna , Rajeshwari Madhu , Boorgula Meher , Doddamani Ramesh , Singh Manmohan , Garg Ajay , Suri Vaishali , Sarkar Chitra , Sharma Mehar 
Published: December 2020

Abstract

BACKGROUND
Gene expression and DNA methylation have identified 2 distinct clinicopathological subgroups among the WHO Grade II/III posterior fossa (PF) ependymomas (EPN), of which the PF-A molecular subgroup associates with poor outcome.

OBJECTIVE
To analyse the utility of immunohistochemistry for H3K27me3, Tenascin C, EZHIP (Cxorf67), EZH2 and fluorescence-in-situ-hybridisation for chromosome 1q21 locus gain in the prognostic stratification of PF-EPNs.

METHODS
All PF Grade II/III tumors were retrieved (2009–2019). Immunohistochemistry for H3K27me3, H3K27M-mutation-specific antibody, EZH2, EZHIP, Tenascin-C and fluorescence in-situ hybridisation for 1q21 locus was performed and compared with outcome.

RESULTS
71 PF-EPNs were included. H3K27me3 loss (PF-A) was seen in 65% (46/71) of cases, of which majority were positive for EZHIP (73%, 24/33) and Tenascin C (65%, 28/43). Minority showed chromosome 1q gain (19%, 8/42). An EZHIP negative PF-A tumor was immunopositive for H3K27M-mutant staining, while all others were negative. PF-A EPNs occurred at a median age of 4.5 years (range 1–53), were predominantly grade III (Grade III:II – 1.6:1), and 50% (10/20) of patients on follow-up experienced tumor progression. EPNs with retained H3K27me3 (PF-B) did not show EZHIP expression (0/20) or 1q gain; however, tenascin C expression was seen in 47% (8/25) of them. They occurred predominantly in adults, showed Grade II preponderance and only 2/11 patients on follow-up experienced progression. EZH2 expression did not correlate with H3K27me3 loss but positively correlated with EZHIP expression (p=0.015).

CONCLUSION
H3K27me3 is a reliable surrogate for prognostic classification of PF-EPNs. EZHIP expression is highly concordant with H3K27me3 loss and is a valuable adjunct.
EPEN-50. THE MANAGEMENT AND TREATMENT OF PEDIATRIC SPINAL CORD EPENDYMOMA: RESULTS FROM A COLLABORATIVE INTERNATIONAL MULTI-INSTITUTIONAL REVIEW
Authors: Lucas John , Kumirova Ella , Tsang Derek , Vinitsky Anna , Chiang Jason , Hazrati Lili-Naz , Lane Shelby , Agbahiwe Harold , Upadhyay Santhosh , Tinkle Christopher , Konovalov Dmitry , El-Ayadi Moatasem , Maher Eslam , Emtsova Victoria , Nechesnyuk Alexey , Sarhan Nasim , Loginova Anna , Hsu Chih-Yang , Ladra Matthew , Terezakis Stephanie , Boop Frederick , Klimo Paul , Ahmed Soha , Laperriere Normand , Ramaswamy Vijay , Merchant Thomas 
Published: December 2020

Abstract

PURPOSE
Pediatric Spinal cord ependymoma (SCE) is rare, and the management is often heterogeneous across centers. We evaluated the impact of clinical, pathologic, and treatment-related factors on outcomes in a multi-institutional, international cohort.

METHODS
SCE patients age &lt;21 years were reviewed across 5 institutions. We utilized nonparametric descriptive statistics, survival, and recursive partitioning analysis (RPA) to examine patient, tumor, histopathologic and treatment characteristics, failure pattern, and cause of death.

RESULTS
125 patients were identified, 18 (14.4%) with metastases. Initial surgery was GTR, and STR in 44, 56% of patients respectively. Histology was grade 1, 2, and 3 in 55, 17.7 and 23.2% respectively. 55 patients with initial GTR were observed (52.7%) or irradiated (43.6%); 60 patients had STR and were observed (40%) or irradiated (60%). The 7-year event-free (EFS) and overall survival (OS) was 60% (95% CI 51.5–71.4) and 79% (95% CI 71.1–87.8) respectively. STR and metastasis increased the hazard for death [HR 1.87, 95% CI 1.02–3.57, p=0.05 (vs. GTR)] and [HR 2.28, 95% CI 1.1–5.2, p=0.048 (vs. localized)] respectively. Across 43 failures, local failure predominated (48.8%). Distant and combined failure occurred in 30.2 and 13.9% respectively. Adjuvant RT offered a 20% absolute improvement (vs. observation) in EFS at 5 years regardless of extent of resection. RPA identified thoracic (vs. non-thoracic), grade (1 & 3 vs. 2), STR (vs. GTR) and metastases as determinants of inferior EFS.

CONCLUSIONS
Tumor and treatment-related factors are predictive of EFS. OS is favorable despite diverse schema and frequent distant failures.
EPID-03. COMPARISON OF SURVIVAL IN ADULT AND PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA: A 2018 SEER BASED ANALYSIS
Authors: Moisander-Joyce Hanna M , Sinha Anoushka , Fernandez-Ledon Shannon , Lee Davon T , Hatano Satoki , Kahn Justine , Garvin James H , Zacharoulis Stergios , Gartrell-Corrado Robyn D 
Published: December 2020

Abstract
Medulloblastoma (MB) is the most common high-grade primary brain malignancy in children and accounts for 1% of adult brain tumors. Previous studies have compared survival in pediatric and adult MB from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) database finding no difference. However, diagnostic subgroup analyses are limited. We examined survival in children (age 0–19) and adults (20–79) coded as MB in the 2018 SEER database (2000–2016), using Kaplan Meier analysis, log-rank test and Cox proportional hazard ratios (HR) with 95% confidence intervals (CI).). MB in SEER-18 is defined as ICD-O-3 histology codes 9470–9474 (n=1,728). ICD 9473, supratentorial PNET (sPNET, n=97) is biologically distinct so was analyzed separately. 5-year survival for MB, excluding sPNET, was similar in children (n = 1,091, 75.3%) and adults (n= 488, 79.1%) (HR=0.97, CI: 0.79 – 1.17, p=0.50). Subtype analyses showed no survival difference comparing adults and children with desmoplastic nodular MB (n=222, p=0.09), large cell MB (n=73, p=0.46), or MB NOS (n=1330, p=0.10). In contrast, children with sPNET had improved survival (n=65, 72.3%) compared to adults (n=29, 51.7%) (HR = 2.0, CI: 1.10 – 3.92; p=0.02,). In conclusion, 2018 SEER data for MB continue to show no survival difference between adults and children, suggesting adult patients could appropriately be entered on pediatric MB treatment protocols. Further analyses of the 2018 data are ongoing adjusting for sex, race, and treatment. Comparison of adults and children with MB and sPNET will be re-evaluated using the new 2016 World Health Organization classification.
EPID-05. EVALUATION OF THE INCIDENCE OF CENTRAL NERVOUS SYSTEM TUMORS IN A CHILDHOOD CANCER TREATMENT CENTER AND THE CREATION OF A SPECIFIC GROUP
Authors: Azambuja Alessandra , Barreto Juliana , Cristofani Lilian Maria , Sanders Felipe , Baraldi Helena , Weltman Eduardo , Lucato Leandro , Paes Vitor , Frassetto Fernando , Petitto Carlo , Rosemberg Sergio , Matushita Hamilton , Odone Vicente 
Published: December 2020

Abstract
Central Nervous System Tumors (CNST) are the main solid neoplasm of childhood, representing 20% diagnosis. Based on this information, a search was carried out at a reference treatment center for childhood cancer in the state of Sao Paulo, belonging to University of Sao Paulo- ITACI/HCFMUSP, and at between 2017 and 2019, 352 new patients, 116 of which were neoplasm of CNS (32.9%). Aiming at an incidence of new cases, in 2019, an institutional group was created, with a team composed of Pediatric Oncologists, Neurosurgeons, Radiologists, Radiotherapists and Pathologists. In this first year, 31,8% of the 132 new patients were diagnosed with CNS tumor. According to WHO 2016, 15 patients were classified as a group that includes Diffuse Astrocytomas, Oligodendrioglial Tumors and Other Astrocytic Tumors. Among the other patients, 14.2% were Medulloblastomas, 4.7% Embryonic Tumors and 2.3% ART / RT. Patients diagnosed with diffuse brainstem glioma accounted for 11.9% of the total. The institution had a diagnosis of Angiocentric Glioma, Craniopharyngioma, Plexiform Neurofibroma and Anaplastic Ependymoma. Neuronal-glial tumors accounted for 9.5% of cases. Choroid plexus tumors represents 5%. Among them, 4.72% had metastatic tumors: Neuroblastoma and Ewing’s Sarcoma. Of the total of 42 patients, there were 5 deaths, 4 due to disease progression and one due to clinical complications. With the group, the discussions were carried out, allowing us to analyze that the presence of the Radiotherapy, Neurosurgery and Pathology team from the first moment, optimized the beginning of treatment and increased the patients’ survival.
EPID-07. A GLOBAL PERSPECTIVE ON THE BURDEN OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS
Authors: Moreira Daniel , Qaddoumi Ibrahim , Bhakta Nickhill , Gajjar Amar , Rodriguez-Galindo Carlos 
Published: December 2020

Abstract
Although approximately 90% of pediatric cancer cases exist in low- and middle-income countries, the magnitude of the global burden of pediatric central nervous system (CNS) tumors remains poorly quantified. METHODS: Data from International Incidence of Childhood Cancer-3 and CONCORD-3, which include observed incidence and survival from population-based cancer registries (PBCR), and from GLOBOCAN 2018 and Global Burden of Disease 2016, which produce burden estimates from observed and modelled data, were used to analyze epidemiologic characteristics and correlations for CNS tumors globally. Data from The World Bank were used for national macroeconomic variables. RESULTS: The majority of countries are not covered by PBCR, with information on incidence and survival available for 37% and 27% of countries, respectively. Survival data is not available for any low-income country. The incidence of CNS tumors varies markedly, from 0.4 to 49 x106 person-years, the greatest variability in pediatric cancer subgroups. Modelled data suggests that approximately 40,000 incident cases and 19,000 deaths occur from CNS tumors worldwide. When country-level data are segregated based on World Bank groups, a difference in incidence and survival exists (p&lt;0.05). A higher national health expenditure correlates with both an increased incidence and survival of CNS tumors, while the inverse is true for under-5 mortality (p&lt;0.05). CONCLUSIONS: Scarce facts are available, but this analysis establishes a link between national income and epidemiologic parameters for CNS tumors. In this context, carefully designed initiatives, focusing on a health-systems approach are critical to meet the global challenge of pediatric CNS tumors.
EPID-09. THE INCIDENCE OF PRIMARY BRAIN TUMORS IN CHILDREN IN JAPAN BASED ON 2016 NATIONAL CANCER REGISTRY IN JAPAN
Authors: Watanabe Yuko , Narita Yoshitaka , Kayama Takamasa 
Published: December 2020

Abstract
The national cancer registries began in January 2016 and the actual number of cancer patients in 2016 including primary brain tumors in Japan was released as a preliminary report in January 2019. According to the report, 667 incidence of pediatric brain tumors were reported in aged 0–14 years (boy: 382; girl: 285), of them 537 patients underwent surgery, chemotherapy, or radiation therapy (diagnosis: 516, undiagnosed: 21), and 130 patients were followed up without any treatments. The breakdown of tumor types was 279 Neuroepithelial tumors, 73 Embryonal tumors (61 Medulloblastomas), and 63 Germ Cell Tumors (GCTs). The crude rate per 100,000 population in 2016 was 4.23 for all pediatric brain tumors, 1.77 for Neuroepithelial tumor, 0.39 for Medulloblastoma, and 0.40 for GCTs. In comparison, the United States CBTRUS2019 (2012–2016) reported that the age-adjusted incidence rates per 100,000 population in the United States was 5.74 for all pediatric brain tumors, 4.15 for Neuroepithelial tumors, 0.48 for Medulloblastoma, and 0.22 for GCTs. The age-adjusted incidence in Japan based on the US population in 2000 was 4.21 for all pediatric brain tumors, Neuroepithelial tumor 1.77, Medulloblastoma 0.39, and GCTs 0.39, suggesting that the incidence of Neuroepithelial tumor and Medulloblastoma is lower whereas that of GCTs is approximately twice comparing to the US. By taking advantage of the national cancer registry data, which was publicly opened to researchers in 2019, we report the incidence of primary brain tumors and its comparison worldwide based on the re-classification criteria of primary brain tumors including benign tumor.