bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPID-10. EPIDEMIOLOGY STUDY OF UNCOMMON CHILDHOOD BRAIN TUMOURS IN ASIAN CHILDREN
Authors: Chan Godfrey Chi-Fung , Liu Anthony Pak-Yin , Shing Matthew Ming-Kong , Ku Dennis Tak-Noi 
Published: December 2020

Abstract
Our local registry identified 656 brain tumours from Jan 1999 to Dec 2018, (incidence: 29.8/yr/million). Other from Glioma, Medulloblastoma/PNET, Germ Cell tumours, Ependymoma, the remaining rarer tumours accounted for 18% (n=118). The 7 more common groups are: craniopharyngioma(n=28); ATRT(n=18); choroid plexus papilloma/CA(n=12); Ganglioglioma(n=11); ETMR(n=7); DNET(n=7); meningioma(n=6). Their respective incidences are 1.27; 0.81; 0.55; 0.5; 0.32; 0.32 0.27/yr/million. For craniopharyngioma, M:F=15:13 and median age was 7.4yrs (2mons-16.5yrs). 12/28 children had surgery alone and 13/28 had focal RT post-surgery with better outcome. 3 underwent intra-cystic interferon-beta also stable. For ATRT, M:F=7:8 and median age was 2.3yrs (4mos-14.2yrs). 2 had metastatic disease and 7/18 patients remained alive. For choroid plexus tumours, there were 7 papilloma, 2 atypia and 3 carcinoma. M:F=5:6 and median age was 1.5yrs (4mos-14yrs). All papilloma, 1/2 atypia and 1/3 carcinoma survived. For ganglioglioma, M:F=7:4 with median age of 5.5yrs (5mos-13.2yrs). They commonly presented with seizure and only one died (brainstem primary). The ETMR includes ependymoblastoma and medulloepithelioma, they had quite different clinical characteristics and outcome. 6/7 DNET had convulsion and M:F=6:1. Median age was 11.5yrs (2.66-14yrs). They all survived even if incompletely resected. For meningioma, 1/6 had germline mutation of NF-2 gene. M:F=3:3 and onset was &gt;8yrs except the NF-2 patient. All survived but the NF-2 had multiple recurrences. 4 patients developed secondary meningioma due to irradiation but they were &gt;18yrs so excluded. In summary, rarer forms of childhood brain tumours only accounted for &lt;20% of all brain tumours and they had diverse presenting features and outcome.
EPID-16. INTEGRATION OF EHR AND CANCER REGISTRY DATA TO CONSTRUCT A PEDIATRIC NEURO-ONCOLOGY SURVIVORSHIP COHORT AND IMPROVE LONG-TERM FOLLOW-UP CARE
Authors: Noyd David , Howell Claire , Oeffinger Kevin , Landi Daniel , Schroeder Kristin 
Published: December 2020

Abstract

BACKGROUND
Pediatric neuro-oncology (PNO) survivors suffer long-term physical and neurocognitive morbidity. Comprehensive care addressing late effects of brain tumors and treatment in these patients is important. Clinical guidelines offer a framework for evaluating late effects, yet lack of extended follow-up is a significant barrier. The electronic health record (EHR) allows novel and impactful opportunities to construct, maintain, and leverage survivorship cohorts for health care delivery and as a platform for research.

METHODS
This survivorship cohort includes all PNO cases ≤18-years-old reported to the state-mandated cancer registry by our institution. Data mining of the EHR for exposures, demographic, and clinical data identified patients with lack of extended follow-up (&gt;1000 days since last visit). Explanatory variables included age, race/ethnicity, and language. Primary outcome included date of last clinic visit.

RESULTS
Between January 1, 2013 and December 31, 2018, there were 324 PNO patients reported to our institutional registry with ongoing analysis to identify the specific survivorship cohort. Thirty patients died with an overall mortality of 9.3%. Two-hundred-and-sixteen patients were seen in PNO clinic, of which 18.5%% (n=40) did not receive extended follow-up. Patients without extended follow-up were an average of 3.5 years older up (p&lt;0.01); however, there was no significant difference in preferred language (p=0.97) or race/ethnicity (p=0.57).

CONCLUSION
Integration of EHR and cancer registry data represents a feasible, timely, and novel approach to construct a PNO survivorship cohort to identify and re-engage patients without extended follow-up. Future applications include analysis of exposures and complications during therapy on late effects outcomes.
EPID-18. TRENDS IN INCIDENCE AND SURVIVAL OF MALIGNANT PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS IN THE NETHERLANDS
Authors: Hoogendijk Raoull , van der Lugt Jasper , van Vuurden Dannis , Hoving Eelco , Kremer Leontien , Wesseling Pieter , Karim-Kos Henrike 
Published: December 2020

Abstract

BACKGROUND
Variation in survival of pediatric central nervous system (CNS) tumors is large between countries. Within Europe, the Netherlands had one of the worst reported survival rates of malignant CNS (mCNS) tumors during 2000–2007.

METHODS
Using the Netherlands Cancer Registry, we evaluated trends in incidence and survival of pediatric mCNS tumors (behavior /3, 5th digit in the morphology code) diagnosed between 1990–2017.

RESULTS
839 newly-diagnosed mCNS tumor patients &lt;18 years were registered between 1990–2017. Incidence of mCNS tumors remained stable (average incidence rate, 21.6 per million person-years). However, an increased incidence of malignant gliomas, NOS was found (Estimated Annual Percentage Change (EAPC) 11.6% p&lt;0.001). This appears to be related to a registration shift between 1990–1999 and 2000–2009 as brainstem tumors increased (+25%, n=79) for astrocytomas and other gliomas but decreased (-31%, n=32) for unspecified intracranial and intraspinal neoplasms. Overall, 5-year observed survival (5Y-OS) of mCNS tumors increased from 51% in 1990–1999 to 61% in 2010–2017 (P-for-trend&lt;0.001). This increase was not constant over time, as 5Y-OS for the period 2000–2009 was 47%. The only significant decrease in survival was found for malignant astrocytomas and other gliomas with a 5Y-OS of 56% in 1990–1999 decreasing to 48% in 2010–2017 (P-for-trend&lt;0.001).

CONCLUSION
Between 1990–2017 incidence of mCNS tumors in the Netherlands remained stable and survival increased. However, a decrease in survival was seen for malignant astrocytomas and other gliomas, which is partially explained by the registration shift of brainstem tumors. The impact of this shift on survival for all mCNS tumors is subject to further research.
ETMR-03. THE ROLE OF FOXR2 IN PEDIATRIC BRAIN CANCER
Authors: Schmitt-Hoffner Felix , van Rijn Sjoerd , Hübner Jens-Martin , Lambo Sander , Mauermann Monika , Mack Norman , Schwalm Benjamin , Pfister Stefan , Kool Marcel 
Published: December 2020

Abstract
Forkhead Box R2 (FOXR2) is a transcription factor of the Forkhead Box family that has been correlated with tumorigenesis, aberrant cell growth or tumor progression. Expression of FOXR2 in pediatric brain tumors is, besides in subsets of medullo-, pineo- and glioblastoma, primarily present in CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2), a novel entity that we in 2016 identified from the former class of primitive neuroectodermal tumors of the central nervous system (CNS-PNET). Analyzing CNS-NB-FOXR2 tumors we found that FOXR2 mRNA is expressed in an anti-correlative manner compared to the proto-oncogenes MYC and MYCN. With immunoprecipitation analyses we show that FOXR2 binds to MYC and MYCN and is thereby stabilizing these proteins. These observations on the interaction and the anti-correlative manner suggest that FOXR2 and MYC(N) may drive tumor formation in a molecularly similar fashion. To investigate this further we stably expressed FOXR2, MYCN and MYC and a combination of FOXR2 with MYC(N) in human neural stem cells (hNSC) and injected these in the striatum of NSG mice. We could show that hNSC itself do not from a tumor, whereas the expression of FOXR2 and/or MYC(N) in hNSC results in tumorigenesis. Tumors expressing both, FOXR2 and MYC(N) were growing faster than tumors with FOXR2 alone. In addition, tumors are currently being analyzed by ChIP-sequencing for FOXR2, MYC, and MYCN, to better understand the mechanisms how FOXR2 drives tumor formation compared to its interaction partners MYC and MYCN.
ETMR-10. EARLY FOCAL RADIOTHERAPY AND TEMOZOLOMIDE FOLLOWING COMPLETE RESECTION APPEAR SUPERIOR TO INTENSIVE CHEMOTHERAPY AND DELAYED RADIOTHERAPY IN CHILDREN WITH EMBRYONAL TUMORS WITH MULTILAYERED ROSETTES (ETMR)
Authors: Mayr Lisa , Gojo Johannes , Peyrl Andreas , Azizi Amedeo , Dieckmann Karin , Haberler Christine , Czech Thomas , Slavc Irene 
Published: December 2020

Abstract

BACKGROUND
Embryonal tumor with multilayered rosettes (ETMR) is a rare, aggressive embryonal central nervous system tumor characterized by LIN28A expression and alterations in the C19MC locus. ETMRs predominantly occur in young children, have a dismal prognosis, and no definitive treatment guidelines have been established. We report on our experience in nine consecutive patients.

METHODS
Between 2006 and 2017, nine patients were diagnosed with ETMR. Median age was 25 months (5–38), seven were treated for primary diagnosis, two referred with progressing tumors, seven diagnosed prospectively, two retrospectively, five were located supratentorially, three pineal, one in the brainstem.

RESULTS
Seven patients had a gross total resection, one a partial resection and one a biopsy at initial diagnosis, followed by second resections at progression. Six patients were treated with intensive chemotherapy regimens including high-dose chemotherapy in three patients and all recurred after a median of 6 months (range 2–11) and all except one patient who died after high-dose chemotherapy, succumbed to their disease after a median of 13 months (range 7–28). Two patients were treated with gross total tumor resection, early focal radiotherapy and concomitant temozolomide followed by temozolomide and intrathecal therapy for one year and both are in continuous complete remission 51 and 46 months after diagnosis.

CONCLUSION
Gross total resection followed by early focal radiotherapy, temozolomide, and intrathecal chemotherapy seem to be superior to intensive chemotherapy including high-dose chemotherapy. Steady progression was observed in both patients with initial biopsy and PR only despite intensive therapy. Radiotherapy at recurrence/progression was not successful.
ETMR-12. EMBRYONAL TUMOR WITH MULTILAYERED ROSETTES: A SINGLE CENTER EXPERIENCE
Authors: Yoshimura Sodai , Sugawa Masahiro , Fukuoka Kohei , Mori Makiko , Arakawa Yuki , Kobayashi Masao , Tanami Yutaka , Nakazawa Atsuko , Koh Katsuyoshi , Kurihara Jun 
Published: December 2020

Abstract

BACKGROUND
Embryonal tumor with multilayered rosettes (ETMR) is a rare, highly malignant tumor of the central nervous system and is usually diagnosed in children aged &lt;2 years. Currently, because no defined treatment strategy has been reported, treatment regimens are often extrapolated from other embryonal tumors. Therefore, data collection of ETMR cases is important for further understanding EMTR. Here, we present our experience with four patients with ETMR.

MATERIAL AND METHODS
Patients with a pathological diagnosis of ETMR from 1999 to 2016 at Saitama Children’s Medical Center were included. Their clinical data were retrospectively analyzed.

RESULTS
This study included four cases of ETMR (one male and three females). The mean age at diagnosis was 29.5 (range, 15–37) months. Presenting symptoms included seizure, hemiparesis, vomiting, and headache. The mean maximal tumor diameter was 42.5 mm. The tumor locations included frontal lobe, temporal lobe, occipital lobe, cerebellum, and brainstem. Gross total resection was achieved in two cases. Fluorescence in situ hybridization analysis demonstrated amplification of 19q13.42 chromosome region in all cases, and diffuse positive expression was observed in the immunohistochemical staining for LIN28A. Systemic postoperative chemotherapy was administered to all patients. Three patients received intrathecal therapy and three were irradiated. The mean overall survival and progression-free survival were 45.3 and 42 months, respectively. Two patients who underwent gross total resection are alive without recurrence.

CONCLUSION
Complete surgical resection may be an important prognostic factor in patients with ETMR. Further prospective studies are needed to confirm these results.
ETMR-15. USE OF HIGH-DOSE CHEMOTHERAPY FOR TWO CHILDREN WITH EMBRYONAL TUMOR WITH MULTILAYERED ROSETTES
Authors: Kusano Shimpei , Fujimura Junya , Fujiwara Megumi , Yaguchi Akinori , Ishibashi Takeshi , Tomita Osamu , Tamaichi Hiroyuki , Kondo Akihide , Shimizu Toshiaki 
Published: December 2020

Abstract
Embryonal tumor with multilayered rosettes (ETMR) is new entity defined in the 4th revised edition of the WHO classification of tumors of the central nervous system. Although radical resection, radiotherapy, and multiagent chemotherapy are considered to be necessary for ETMR, the efficacy of chemotherapy for ETMR in Japan has not been established. Here, we report different clinical courses for two children with localized ETMR treated with the St. Jude medulloblastoma-96 (SJMB96) regimen, which consists of four cycles of high-dose chemotherapy with autologous peripheral blood stem cell transplantation. For both children, the diagnosis of ETMR, C19MC-altered was confirmed after gross total tumor resection. Multiagent chemotherapy was administered following cranio-spinal irradiation with local boost. One month after completion of the treatment, one patient experienced local recurrence but has been in remission for over 2 years after tumor resection and stereotactic irradiation with a CyberKnife and treatment every three weeks with bevacizumab. The other patient also experienced local recurrence after the third cycle of chemotherapy and several times thereafter. Although she again underwent tumor resection and local irradiation, her tumor grew larger and invaded. Because her prognosis was very poor, her parents choose only palliative care. Based on our experience, we believe that continuous chemotherapy at conventional doses is preferred over intensive-dose chemotherapy such as SJMB96. However, the number of reports on chemotherapy for ETMR is still small, and a prospective multicenter trial is needed to establish effective chemotherapy for ETMR.
GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
Authors: Takami Hirokazu , Ichimura Koichi , Fukuoka Kohei , Mukasa Akitake , Saito Nobuhito , Narita Yoshitaka , Shibui Soichiro , Nakazato Yoichi , Nishikawa Ryo , Matsutani Masao 
Published: December 2020

Abstract

BACKGROUND
We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.

METHODS
Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews.

RESULTS
All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.

CONCLUSIONS
These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
GCT-45. YOLK SAC TUMOR IN THE CEREBELLAR VERMIS - A CASE REPORT
Authors: Otake Saori , Matsutani Tomoo , Watanabe Yousuke , Numata Osamu , Ando Ryo , Ochiai Hidemasa , Junichiro Ikeda , Iwadate Yasuo 
Published: December 2020

Abstract
Yolk sac tumor (YST) is a non-germinomatous malignant germ cell tumor in a young child. It usually arises along a midline axis, mostly pineal region or suprasellar compartment, and it is exceedingly rare to locate in a cerebellar vermis. In the present report, we describe a case of a pure YST located in the cerebellar vermis and review the previous literature. A three-year-old boy visited a local clinic for gait disturbance and frequent vomiting. Gadolinium-enhanced magnetic resonance imaging (MRI) showed a homogeneously-enhanced mass with a cystic component in his cerebellar vermis, and it resulted in hydrocephalus. By its location and his age, our pre-operative diagnosis was a medulloblastoma, and we performed a total resection of the tumor with ventricular drainage. Unexpectedly, the histological investigation revealed it to be a YST. We confirmed that the serum levels of α-fetoprotein (AFP) had elevated at 3176.4 ng/ml in his preserved sample, obtained before the surgery, and it was consistent with the pathological diagnosis. He is receiving chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by radiation therapy. In this case, pre-operative MRI revealed that the tumor did not grow into the IVth ventricle in spite of midline location, which was not typical for medulloblastoma. Of note, serum AFP levels had increased, and they might contribute to a precise pre-operative diagnosis and be able to propose an alternative treatment plan, such as neoadjuvant chemotherapy to reduce surgical risk. As a conclusion, a YST should be considered even if it locates in a cerebellar vermis.
GCT-48. OUTCOME OF CNS MALIGNANT NON-GERMINOMATOUS GERM CELL TUMORS (GCT) WITH AFP &gt; 1000 ng/ml AT DIAGNOSIS TREATED ACCORDING TO SIOP CNS GCT 96
Authors: Calaminus Gabriele , Frappaz Didier , Kortmann Rolf-Dieter , Ajithkumar Thankamma , Pietsch Torsten , Vasiljevic Alexandre , Ricardi Umberto , Faure-Conter Cecile , Timmermann Beate , Alapetite Claire , Murray Matthew J , Garre Maria Luisa , Nicholson James C 
Published: December 2020

Abstract
Analysis of CNS MMGCT with AFP &gt;1000 ng/ml (serum and/or CSF) at diagnosis, treated on trial in SIOP-CNS-GCT-96, revealed an inferior prognosis (32% 5-year progression-free survival) compared with AFP &lt;1000 ng/ml (76%). As this patient group is small, to evaluate a bigger cohort, we revisited all patients treated according to SIOP-CNS-GCT-96, who were registered in the database until July 2015. Between October 1996 and July 2015, 373 patients with CNS MMGCT were registered. 48 patients (13%) presented with an AFP &gt;1000 ng/ml at diagnosis. 41 patients were evaluable with a median observation time of 2.4 years; 6/41 received chemotherapy alone. Primary site, histological components (if available), metastatic status and outcome were evaluated. Primary site was pineal in 29/41, suprasellar in 6/41, bifocal 1/41 and other in 5/41 patients. 10/41 patients were metastatic at diagnosis. Four to five courses of standard PEI and radiotherapy (RT) or 2 standard and two intensified PEI (as for SIOP CNS GCT II) were administered in 32 patients. Two received less then 4x PEI and RT, 6 patients &lt;6 years were treated with PEI (either standard or intensified) alone. 16/34 patients with PEI and RT are alive in CR; 2/6 patients without RT survived. Overall, 18/40 (45%) survived. 10–15% of CNS MGGCT are high-risk patients by diagnostic AFP, with the pineal as the main tumour site. Outcome of &lt;50% survival is unsatisfactory. Further research, international cooperation and common data analysis is needed to identify additional risk factors and develop alternative treatment strategies.
GCT-53. CASE OF INTRACRANIAL GROWING TERATOMA SYNDROME WITH DIFFICULTY IN TIMING OF RESECTION
Authors: Yoshitake Hidenobu , Nakamura Hideo , Hamamoto Yuta , Otsu Yusuke , Kikuchi Jin , Koga Motohisa , Kajiwara Soushou , Nagata Yui , Matsumoto Yoshihisa , Hashikawa Takuro , Sakai Hideki , Komaki Satoru , Takeshige Nobuyuki , Miyagi Naohisa , Nakagawa Setsuko , Takahashi Kenji , Sugita Yasuo , Morioka Motohiro 
Published: December 2020

Abstract

BACKGROUND
Intracranial Growing teratoma syndrome(iGTS) is a phenomenon in which a tumor with a teratoma component grows during treatment, and its pathological tissue is often a mature teratoma. Here we report a case of iGTS in which the timing of surgery was determined by tumor markers and changes in tumor size on MRI images. CASE-REPORT: 11-year-old boy with a short stature. He developed a headache and we found a pineal gland tumor on MRI. Due to obstructive hydrocephalus, an endoscopic third ventriculostomy and biopsy were performed. The pathological diagnosis was mature teratoma, but AFP was elevated at 104.2 ng/mL. Considering NGGCT, we started chemoradiation immediately. Despite the declining AFP, it gradually increased, at which point we suspected iGTS. Resection was considered, but at some point tumor growth had stopped, so radiation therapy and a second course of ICE therapy preceded the resection. Thereafter, the tumor was completely removed, and a third course of ICE therapy was performed.

DISCUSSION
The onset mechanism of iGTS has not been elucidated, and its prediction is difficult. Early resection of the tumor is required, but discontinuation of radiation therapy and side effects of chemotherapy also need to be considered. In our case, resection was performed after normalization of AFP and recovery of myelosuppression. The patient followed an uneventful course, but the timing of resection was controversial.

CONCLUSION
We experienced a case of iGTS in NGGCT, a mixed tumor with mature teratoma. The optimal timing of the resection was discussed and literature was reviewed.
GCT-55. INTRACRANIAL GERMINOMA ORIGINATING FROM ATYPICAL LOCATION WITH SUBCLINICAL ADH INSUFFICIENCY
Authors: Kuranari Yuki , Miwa Tomoru , Kono Maya , Kanazawa Tokunori , Yoshida Kazunari 
Published: December 2020

Abstract

INTRODUCTION
Intracranial germinomas are rare tumors which usually develop in the midline structures and affect in 90% of cases the pineal gland and suprasellar regions. Sometimes they involve basal ganglia, septum pellucidum, and other regions. We report a very unusual presentation of an intracranial germinoma originating from the lateral ventricle.

METHODS
A 10-year-old boy presented with a 1-year history of polydipsia and polyuria. During the hypertonic saline test, a low ADH was detected and established the diagnosis of subclinical ADH insufficiency. MRI showed a heterogeneously enhancing periventricular lesion in the lateral ventricle, but no other abnormal findings, including hypophyseal stalk. Initially, the correlation of imaging findings and clinical symptoms were not clear. With suspected subependymoma, tumor removal was performed by small craniotomy. Since the intra-operative pathological diagnosis was germinoma, we performed only partial removal of the tumor. After establishing the histological diagnosis of germinoma, the patient received chemotherapy using carboplatin and etoposide, followed by radiation therapy. MRI showed no recurrence for five years after treatment. RESULTS/

CONCLUSION
Our case presents two atypical features. First, intracranial germinoma originating from the lateral ventricle is quite rare. Though the cases with intracranial germinoma originating from septum pellucidum and corpus callosum have been reported, this case is even different. Second, imaging findings did not match clinical symptoms. The cause of subclinical ADH deficiency may be the occult hypophyseal germinoma. In conclusion, we report a 10-year-old case with a very unusual presentation of an intracranial germinoma originating from the lateral ventricle.