bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETMR-05. SINGLE-CELL RNA-SEQ OF ETMR REVEALS CELL PROGRAMS OF DEVELOPMENTAL HIERARCHY AND CELLULAR DIVERSITY IN THE TUMOR MICROENVIRONMENT
Authors: de Faria Flavia W , Interlandi Marta , Moreno Natalia , Graf Monika , Melcher Viktoria , Albert Thomas K , Kerl Kornelius 
Published: December 2020

Abstract
Embryonal tumors with multilayered rosettes (ETMR) are deadly brain malignancies affecting young children. No standard treatment is available and the median survival is less than 12 months. Molecularly, the disease is characterized by the miRNA C19MC cluster amplification, with the expression of multiples miRNAs related to a stem cell program. The discoveries on the purely molecular mechanisms of the disease did not help to create a bridge for new treatment strategies so far and the cellular diversity of ETMR remains poorly understood. In this study, we used single-cell RNA sequencing of murine and human tumors to describe ETMR cellular heterogeneity. Our findings support that intra-tumoral heterogeneity is mainly characterized by 4 cellular programs defining a developmental hierarchy related to different metabolic states: 1) Early quiescent NSC-like cells supported by fatty-acid oxidation 2) Late NSC and NP-like proliferative cells fueled by glycolytic metabolism; 3) Post-mitotic neuroblast-like cells, relying on oxidative-phosphorylation; 4) NSC-like proliferative cells, with metabolic plasticity and capable of performing the three types of metabolism. Tumor-specific ligand-receptor interaction analysis revealed that ETMR exchange with microglia and vascular mural cells (MC) signals related to extracellular matrix (ECM) organization (Cxcl12-CxCr4), stem cell signaling (BMPs-BMP receptors), anti-apoptosis and survival (Ntf3-Ntrk), not seen in the control brain. In addition, the vascular MC showed a cancer-associated fibroblast (CAF) phenotype, with potential prognostic implications, as previously demonstrated for other tumors. This study provides new findings to build up a more robust understanding of ETMR biology and opens space for further studies in the field.
ETMR-07. ETANTR: A RARE TUMOR IN A RESOURCE-LIMITED SETTING
Authors: Hoveyan Julieta , Avagyan Manushak , Avagyan Anna , Papyan Ruzanna , Iskanyan Samvel , Danielyan Samvel , Hovhannisyan Garik , Khachatryan Parandzem , Tamamyan Gevorg , Bardakhchyan Samvel 
Published: December 2020

Abstract

INTRODUCTION
Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare aggressive brain tumor with low survival rates. There are about 80 cases reported in literature since 2000 when it was first described. There is no standard treatment scheme for ETANTR yet. CASE REPORT: A 2 years old boy presented with a month-long of headache and inability to hold his head. CT scan and MRI revealed a large mass in the right frontal lobe with midline shift. Subtotal tumor resection was done. Histological and immunohistochemical analyses was consistent with ETANTR in one laboratory and PNET in another. The second opinion suggested by the Center of Pediatric Oncology, Hematology and Immunology in Moscow the diagnosis ETANTR was confirmed. Taking into account certain similarities with medulloblastoma was decided to provide treatment according to HIT-2014 protocol. Control MRI done after 2 cycles of Block SKK Carboplatin/Etoposide found tumor progression and for that reason patient underwent second surgical resection. Considering the age of the child radiation therapy was not expedient and the decision was to continue treatment with HIT 2014 intensified regimen, which includes Cisplatin, Vincristine, Etoposide, Cyclophosphamide and intravenous High dose Methotrexate with intrathecal Methotrexate. Aiming to evaluate the effectiveness of treatment we are planning to perform MRI after this 2nd cycle of intensified regimen.

DISCUSSION
There are difficulties in diagnosis of rare types of cancers in Armenia. Since there is no approved treatment for ETANTR, there is a need for ongoing research to improve its prognosis.
ETMR-08. INTERNATIONAL CONSENSUS PROTOCOL FOR EMBRYONAL TUMOR WITH MULTILAYER ROSETTES
Authors: Hanson Derek , Andre Nicolas , Chi Susan , Filbin Mariella , Fisher Michael , Hoffman Lindsey , Khatib Ziad , Kool Marcel , Narendran Aru , Pizer Barry , Slavc Irene , Vogel Timothy , Ziegler David , Kieran Mark 
Published: December 2020

Abstract
Embryonal tumors with multilayer rosettes (ETMR) are rare and highly-aggressive central nervous system (CNS) neoplasms which occur primarily in young children and carry a dismal prognosis. To date, no large clinical investigations have been conducted to determine the optimal therapy for ETMR. Data from retrospective case series suggest that our most aggressive standard therapies are not sufficient for cure in the majority of cases. New treatment approaches incorporating pre-clinical data and the known biology of ETMR are therefore urgently needed. A German drug screen using the patient-derived ETMR BT183 cell line and its xenograft revealed anti-tumor activity of topotecan, doxorubicin, and actinomycin D; three agents used infrequently for treating infant CNS tumors. Additional results from a small series of ETMR patients suggest that optimization of induction chemotherapy using these active agents may improve response and survival outcomes. In 2019, an international panel of pediatric neuro-oncology experts convened to advance therapy for ETMR. A consensus protocol was developed incorporating maximal safe surgical resection, induction chemotherapy with active pre-clinical agents, intrathecal chemotherapy, radiotherapy, and high-dose chemotherapy. This international consensus protocol represents the first prospective clinical investigation specific to ETMR and will be available through a treatment registry globally and as a clinical trial at select centers. The study aims to improve survival by providing aggressive, optimized therapy for ETMR and will serve as a platform to explore new biologically-promising agents. The investigation will also provide valuable prospective outcome data and correlative biological studies to serve as baseline comparators for future clinical trials.
ETMR-17. SINGLE-CELL TRANSCRIPTOME ANALYSIS OF ETMR PATIENT SAMPLES
Authors: Hovestadt Volker , Shaw McKenzie L , Beck Alexander , Lambo Sander , Hack Olivia A , Gojo Johannes , Madlener Sibylle , Mayr Lisa , Haberler Christine , Czech Thomas , Hanson Derek R , Koschmann Carl , Jabado Nada , Huang Annie A , Slavc Irene , Pfister Stefan M , Alexandrescu Sanda , Bernstein Bradley E , Kool Marcel , Filbin Mariella G 
Published: December 2020

Abstract
Brain tumors are comprised of cells with heterogeneous genetic and transcriptional states, resulting in substantial phenotypic diversity. This diversity is particularly evident in embryonal tumor with multilayered rosettes (ETMR), which shows a striking bi-phasic pattern for which it is named. A better understanding of its underlying molecular makeup is urgently needed to develop more effective therapeutic strategies that eliminate all malignant cell types underlying ETMR initiation, maintenance, progression, and relapse. Furthermore, the cellular origin of ETMR is currently poorly understood. We used plate-based single-cell RNA sequencing to assess the intratumoral heterogeneity in 6 fresh and 4 snap-frozen surgical biopsies, following a workflow that we have previously established to study pediatric high grade gliomas, medulloblastomas, and ependymomas. Computational analyses conducted on &gt;4,000 single cells identified cellular hierarchies ranging from a proliferative, undifferentiated cell population to more differentiated, predominantly neural-like progeny in all samples. Patient-derived cell line and xenograft models partially recapitulated this hierarchy. We further integrated transcriptional programs identified in single cells with available datasets of the developing normal brain, as well as with programs identified in other pediatric brain tumor entities, to inform both putative cellular origins and ETMR-specific oncogenic pathways. These timely results provide unparalleled insights into the molecular underpinnings of the phenotypic heterogeneity observed in ETMR. Analyses aimed at further integrating malignant cell type abundances with genetic alterations and clinical annotations, and therapeutical targeting of malignant cell populations using in-vitro models are currently ongoing.
ETMR-19. SINGLE CELL ANALYSES OF ETMRs REVEAL THAT C19MC+ POPULATION DRIVES CELL CYCLE PROGRESSION AND STEM CELL MAINTENANCE
Authors: Mumal Iqra , Xu Liming , Yao Fupan , Suwal Tannu , Fan Xiaolian , Lu Mei , Huang Annie 
Published: December 2020

Abstract
Embryonal tumors with multilayered rosettes (ETMRs) are highly fatal diseases characterized by recurrent amplification of C19MC, an oncogenic miRNA cluster. While C19MC was discovered as a major driver of ETMRs, its direct role in ETMRs remains unknown. As ETMRs exhibit significant heterogeneity in C19MC expression, we employed single cell transcriptomics to investigate features of C19MC+ population. We conducted single-nuclei RNAseq of 23,269 cells from 6 primary and 2 matched recurrent ETMRs. We also conducted single-cell RNAseq of human neural stem cells (hNSC-5miR) and ETMR cell line (A664-5miR) with stable expression of 5 C19MC miRNAs. Bulk RNAseq (n=27), H3K27Ac ChiP-seq (n=5) and ATAC-seq (n=5) corroborated scRNAseq data and identified core transcription factors (TFs) of C19MC+ population. C19MC+ population (24%) mapped to neuro-epithelial cells and exhibited signatures of cell cycle and stem cell maintenance, consistent with bulk-RNAseq data. The C19MC+ population overlaps with MKI67+ cycling (57%) and PROM1+ stem cell population (56%). Interestingly, interrogation of hNSC-5mir and A664-5miR showed a larger MKI67+/PROM1+ population compared to controls. Likewise, hNSC-5miR/A664-5miR in vitro and in vivo experiments showed increased proliferation/stemness. C19MC+ population is characterized by SHH, WNT, mTOR, Hippo and IGF-signalling and driven by MEIS1, SOX11, ZNF521, RFX4 and NR2F2 TFs. Recurrent ETMRs exhibit a persistent but smaller C19MC+ population. Intriguingly, recurrent tumors were more quiescent with a smaller proliferative population. C19MC is directly involved in driving cell cycle and stemness in ETMRs. Cellular and molecular features of primary and recurrent ETMRs were remarkably different, suggesting that C19MC plays a different role upon recurrence.
GCT-02. THE LONG-TERM OUTCOMES AND SEQUELAE ANALYSIS OF INTRACRANIAL GERMINOMA FROM 187 PATIENTS IN THE SINGLE INSTITUTE: NECESSITY FOR THE ADAPTATION OF RADIOTHERAPY DOSE AND VOLUME
Authors: Lee Joo Ho , Kim Il Han , Eom Keun-Yong , Kim Seung Ki , Wang Kyu-Chang , Kim Tae Min , Heo Dae Seog , Kang Hyoung Jin , Shin Hee Young 
Published: December 2020

Abstract

PURPOSE
We aimed to refine the radiotherapy (RT) volume and dose determinant for disease failures and long-term sequelae in the intracranial germinoma.

METHODS
The main treatment for intracranial germinoma was craniospinal RT only (n=51) during 1981–1992 and RT with upfront chemotherapy (CRT) (n=152) during 1992–2015 in Seoul National University Hospital. All 187 cases were confirmed histologically. RT fields included craniospinal, whole-ventricle (WV), whole-brain (WB), and focal radiotherapy. RT dose was dependent on the M status and combination of chemotherapy. The median follow-up duration was 115 months (range, 3–358).

RESULTS
The 10-year overall and recurrence-free survival was 94.5% and 91.4%. The complete response rate after chemotherapy was 62.6%. For the patients with complete response, WV RT 16–20 Gy, and focal boost of 25–36 Gy after upfront chemotherapy showed no in-field recurrence. The causes of death were progression (n=3), 2nd malignancy (n=6), treatment-related complications (n=7), and others (n=8). For non-sellar tumors, the rate of hormonal replacement treatment was significantly related to WB RT and WB/WV RT dose ≥ 30 Gy (p=.030, and .026). After a latency of the median 20 years, ten patients (5.3%) developed 2nd malignancy. WB RT and WB/WV dose ≥ 30 Gy were significantly correlated with the 2nd malignancy (p=.024, and .004). The rate of severe neurocognitive dysfunction was significantly associated with WB/WV dose ≥ 30 Gy (p=.027).

CONCLUSION: CONCLUSION
RT with or without upfront chemotherapy exhibits the excellent control rate of disease. However, the intensity and volume of RT are critical for managing treatment toxicities. Adaptation and further de-intensification of RT should be followed.
GCT-09. HEALTH AND SOCIAL ISSUES IN THE LONG-TERM GERM-CELL TUMOR SURVIVORS
Authors: Matsutani Tomoo , Horiguchi Kentaro , Ikegami Shiro , Hirono Seiichiro , Murai Hisayuki , Saeki Naokatsu , Iwadate Yasuo 
Published: December 2020

Abstract
Germ cell tumor (GCT) is a rare juvenile CNS tumor that is more frequent in eastern Asia. Most survivors require continuous medical care for hormone replacement, maintenance of shunting devices, and late radiation-induced effects. In the present study, we retrospectively analyzed medical records of long-term GCT survivors, and make the health and social issues clear. Ninety-two GCT patients were treated in our institute from 1982 to 2018, and 81 patients, of which medical records are available, are included. The median follow-up period is 12.2 years, and 47 patients (58.1%) are followed for more than ten years. The overall survival rate is gradually decreasing more than ten years follow-up, such as 10-, 15- and 25-years survival are 92.3, 87.7, and 73.3%, respectively. In the long-term follow-up, eight subsequent malignancy and seven cerebrovascular events are recorded. These events occurred 20 years or more after the treatments, and six CNS malignancies were observed in survivors irradiated with 50Gy or more. As social issues, forty-two of 50 adult survivors had been employed after the treatments, but only thirty-four (70.8%) are still working. Of note, only nine (18.8% of adults) survivors got married. All four married women require any hormone replacement, while only one of 4 men requires the replacement. Long-term follow-up of GCT survivors revealed subsequent malignancy and social problems. A recent attempt to decrease the dose of irradiation might overcome some issues. As a conclusion, GCT survivors require a supporting program for not only health but also social issues.
GCT-12. INTRACRANIAL GROWING TERATOMA SYNDROME: CLINICAL IMPLICATION FROM SINGLE UNIVERSITY EXPERIENCES
Authors: Kim Chae-Yong , Kwon Ji-Yeon , Go Kyeong-O , Hwang Kihwan , Han Jung Ho , Choi Hyoung Soo , Kim You Jung , Choi Byung Se , Kim In Ah , Choe Gheeyoung , Kim Seung-Ki , Phi Ji Hoon , Wang Kyu-Chang , Cho Byung-Kyu 
Published: December 2020

Abstract
In general, intracranial germ cell tumors (GCT) are sensitive to chemotherapy, radiation therapy, and have favorable outcomes. However, a rare chemotherapeutic retro conversion phenomenon, known as intracranial growing teratoma syndrome (iGTS), shown a poorer prognosis. We analyze the diagnostic characteristics and the result of treatment response for the patients with iGTS treated in our institutes (SNUH and SNUBH, from 1997 to 2019). The electronic medical records and PACS were used for reviewing the clinical information, follow-up MRI images, tumor markers (alpha-fetoprotein, human chorionic gonadotropin, in serum or cerebrospinal fluids), and pathological findings. Out of 328 intracranial GCT patients, seventeen were finally identified as iGTS. Sixteen out of 17 patients were non-germinomatous GCTs, and 1 were germinomas. Initial pathology was common in order of immature teratoma (26.7%), other than immature teratoma (11.5%), and germinoma (0.5%). All of the tumors showed typical ‘honeycomb appearance’ in their follow-up MRI images. Sixteen out of 17 tumors were surgically resected as 2nd look surgery. Among them, 13 tumors were gross totally resected. Twelve were alive without evidence of recurrences during follow-up periods, and the other was dead from the progression of the disease. Among the other than the gross total resection group (n=4), two patients were dead, one recurred the tumor, and the other is following up with stable disease after adjuvant radiation therapy. Early detection and total resection of the tumor as possible might be meaningful for favor prognosis, especially in non-germinomatous GCTs patients.
GCT-24. RELAPSE PATTERN AND QUALITY OF LIFE IN PATIENTS WITH LOCALIZED GERMINOMA ORIGINATING FROM BASAL GANGLIA REGION
Authors: Li Bo 
Published: December 2020

Abstract

BACKGROUND
The optimal radiation field in localized basal ganglia (BG) germinoma was not well defined, mostly due to unknown relapse patterns. In our institute, both focal radiotherapy (FR) and craniospinal irradiation (CSI) plus boost were considered in this population until whole-brain radiotherapy (WBRT) plus boost became an option in 2008. Thus, a retrospective study was conducted to address the issue. Furthermore, the health-related quality of life (HRQOL) was also evaluated.

METHODS
Patients who were diagnosed as localized BG germinoma between 2000 and 2017 were studied. HRQOL was evaluated by PedsQL 4.0 (≤15 years) and SF-36 (&gt;15 years) questionnaires based on the age at last follow-up.

RESULTS
Among 161 patients included, 35 patients received FR, 109 patients received WBRT plus boost, and 17 patients received CSI plus boost. After a median follow-up of 83 months (range, 13 to 214 months), 15 patients relapsed in FR group, 4 in WBRT group and 0 in CSI group. The 5-year DFS was 74.3%, 97.2%, and 100%, respectively (p&lt;0.001). Among 15 patients who relapsed after FR, 14 had positive radiological findings, in which 6 (42.8%) had lesions documented at the periventricular area, and 7 (50.0%) in the frontal lobe. HRQOL data were available in 69 patients, which generally scored low. In 38 patients evaluated by SF-36, those receiving CSI had significantly lower mental component scores than those receiving WBRT (p=0.027) or FR (p=0.011).

CONCLUSIONS
Patients with localized BG germinoma present a unique relapse pattern. WBRT, which covers at-risk areas, showed both better disease control and HRQOL.
GCT-26. PROGNOSTIC FACTORS IN PATIENTS WITH BASAL GANGLIA GERM-CELL TUMORS: A RETROSPECTIVE ANALYSIS OF THE SINGLE CHINESE INSTITUTE EXPERIENCE FROM 2009 TO 2019
Authors: Hu Qingjun , Li Juan , Lai Mingyao , Zhou Cheng , Zhou Zhaoming , Shan Changguo , Hong Weiping , Zhang Yangqiong , Wang Lichao , Cai Linbo 
Published: December 2020

Abstract

OBJECTIVE
To evaluate the clinical factors related to the prognosis of basal ganglia germ cell tumors.

METHODS
A retrospective analysis of 52 cases of the basal ganglia germ cell tumors treated from January 2009 to January 2019 in the department of oncology of Guangdong Sanjiu Brain Hospital. The median age: 12 years (range: 5–32), The median course of disease: 11.7 months (range: 1–54). Thirteen cases were diagnosed by biopsy and 39 cases were diagnosed by elevated tumor markers. There were 31 patients (59.6%) diagnosed with germinomas and 21 patients (40.4%) with non-germ germ cell tumors. Univariate and multivariate survival analysis was performed.

RESULTS
To October 15, 2019, the median follow-up time was 30.4 months (range 2–124 months). The 5-year survival rate was 85%, and the 5-year progression-free survival rate was 84%. Multivariate analysis found whether serum AFP was greater than 100mIU / ml, (with HR: 11.441,95% CI: 2.09–47.66, P = 0.005),the degree of surgical resection(with HR 5.323 (1.19–23.812), P = 0.029), PD as the effect of radiotherapy (HR: 16.53, (1.19–23.81), P = 0.001) were independent prognostic factor affecting survival.

CONCLUSION
The pathological type, degree of surgical resection, and response to initial treatment can all affect survival.
GCT-35. SALVAGE CRANIOSPINAL IRRADIATION FOR RECURRENT GERMINOMAS
Authors: Kanamori Masayuki , Saito Ryuta , Sonoda Yukihiko , Kumabe Toshihiro , Tominaga Teiji 
Published: December 2020

Abstract

BACKGROUND
The treatment strategies for recurrence has not been established.

PURPOSE
To clarify the tumor control and complications of salvage craniospinal irradiation (CSI) for recurrent germinoma.

METHODS
We retrospectively reviewed the medical record. Among 153 germinomas treated in Tohoku University Hospital since 1983, 22 had recurrence of germinoma. At first recurrence, 7 cases received CSI, whereas 15 cases did chemotherapy and/or radiation therapy other than craniospinal field (non- CSI). CSI was performed at 24 Gy/ 12 fractions or 30 Gy/ 25 fractions.

RESULTS
CSI had statistically significant better recurrence-free survival rate after recurrence than non-CSI (100% vs 33%, p&lt;0.001: log-rank test). In addition, tumor control was obtained in all of four cases with the failure after non- CSI treatments for recurrence. The late complications of these 11 cases were examined. The local dose before CSI was 24- 50 Gy, and the median interval from last irradiation to CSI was 33 months. Median follow- up period after CSI was 126 months. Three patients developed newly developed visual or cognitive deficits. These patients received high-dose irradiation at initial treatment or multiple treatment before CSI. There were no late complications in the cases which had prior chemotherapy and 24 Gy of irradiation to whole ventricle only before CSI.

CONCLUSION
Low dose CSI for the first recurrence of germinoma is effective and safe in the cases treated by chemotherapy and low dose irradiation to whole ventricle only.
GCT-36. TREATMENT RESULTS AND RADIATION-INDUCED TUMORS IN CASES OF CENTRAL NERVOUS SYSTEM GERM CELL TUMOR: A LONG-TERM FOLLOW-UP STUDY IN KUMAMOTO PREFECTURE
Authors: Yamamoto Takahiro , Makino Keishi , Nakamura Hideo , Kuroda Jun-ichiro , Itoyama Takashi , Takezaki Tatsuya , Ota Kazutaka , Shinojima Naoki , Mukasa Akitake 
Published: December 2020

Abstract

INTRODUCTION
Central nervous system germ cell tumor (GCT) is one of the pediatric brain tumors. Although there have been epidemiological studies in the past, long-term prognosis and the late effects remained unclear. In this study, we examined GCT over the past 41 years in Kumamoto prefecture.

METHODS
Epidemiological features and complications with radiation-induced tumors were searched in patients diagnosed with GCT in the 41-year period from 1977 to 2018.

RESULTS
There were 93 patients diagnosed with GCT. These cases were divided into 14-year periods before and after incorporation of chemotherapy into the treatment, and the results for germinomas were compared. An improvement in the 10-year survival rate from 12 of 23 cases (52.2%) between 1977 and 1991 to 19 of 28 cases (67.9%) between 1992 and 2006 was observed. The 10-year survival rate for germinoma cases that received medical treatment during a more recent 5-year period between 2004 and 2009 increased to over 90%. However, 10.3% of all long-term survivors of GCT developed radiation-induced glioblastoma. The examination results showed that regardless of the tumor type, patients who received a high dose of radiation during their initial treatment developed the complication of radiation-induced glioblastoma within 10 to 25 years after their initial treatment.

CONCLUSION
This study suggests that the long-term survival rates for GCT are improving but the rate of radiation-induced glioblastoma in these cases are too high to be ignored. Long-term follow-up of at least 10 years is essential to effectively evaluate the details of treatment for pediatric brain tumors.