bluuebunny/crossref_metadata_2025_split huggingface dataset:
LGG-38. GENETIC ANALYSIS OF NEUROEPITHELIAL TUMORS IN THE PEDIATRIC AND ADOLESCENT AND YOUNG ADULT AGE IN A SINGLE INSTITUTE
Authors: Makino Yasuhide , Kawauchi Takeshi , Arakawa Yoshiki , Shofuda Tomoko , Yoshioka Ema , Tanji Masahiro , Mineharu Yohei , Kanemura Yonehiro , Miyamoto Susumu 
Published: December 2020

Abstract
Molecular diagnosis in brain tumors has been widely spread after the publication of WHO 2016 classification. But it become a major problem that there are some tumors not to be classified on its criteria, especially in pediatric neuroepithelial tumors. To clarify the characteristics of gliomas in pediatric and adolescent and young adult age (AYA), we picked up 131 neuroepithelial tumors under 30-year-old at Kyoto University and analyze their molecular profiles. Hot spot mutations in IDH1/2, H3F3A, HIST1H3B, TERT promoter, and BRAF were analyzed by Sanger sequencing, and 1p/19q codeletion was examined by FISH or MLPA. With the pathohistological diagnosis and genetic information, all tumors were classified based on WHO 2016 classification. The terms “not otherwise specified” (NOS) and “not elsewhere classified” (NEC) were used based on cIMPACT-NOW. There were 25 glioblastomas and 34 pilocytic astrocytomas, which accounted for a larger percentage than in adult tumors. IDH-wild type gliomas accounted for 55% in diffuse astrocytomas and 69% in anaplastic astrocytomas. The percentages of gliomas with NEC were 50% of oligodendrogliomas and 20% in anaplastic oligodendrogliomas, respectively. Most pilocytic astrocytomas were under 20-year-old (27 patients) and located in infratentorial area (21 patients). Based on WHO 2016 classification, not a few neuroepithelial tumors in pediatric and AYA ages could be classified clearly. These tumors had more different genetic abnormalities than those in adult. Therefore, it may be important to evaluate these tumors with comprehensive genetic analysis.
LGG-42. BEVACIZUMAB-ASSOCIATED SECONDARY AMENORRHEA AND PREMATURE OVARIAN FAILURE IN ADOLESCENT FEMALE PATIENTS WITH LOW-GRADE CNS DISEASE
Authors: Zhukova Nataliya , Chan Kiri , Walshe Kathryne , Downie Peter A , Wood Paul 
Published: December 2020

Abstract
Compelling body of evidence exists to use bevacizumab, a humanized monoclonal anti-VEGF antibody, in selected paediatric patients with low-grade CNS tumours. Common toxicities of bevacizumab, hypertension, proteinuria, epistaxis, mucosal perforation, decreased wound healing are well reported. However, the effect of bevacizumab on female ovarian function and long-term fertility is still being documented. Current evidence for bevacizumab-associated decline in ovarian function is largely from breast and colon cancer cohorts where exposure to multimodal chemotherapy confounds causative relationships. Fertility counseling and oocyte cryopreservation is currently offered as standard of care to post-pubertal females at high risk of infertility due to high-dose radiation and chemotherapy. Adolescent females with low-grade CNS tumours on bevacizumab represent a unique population which could potentially be at high risk for infertility. We report 2 cases of adolescent girls treated with bevacizumab as a single agent and in combination with vinblastine for NF2-associated vestibular schwannomas and brainstem glioma respectively. Both patients were post-pubertal with established menstrual cycles and normal baseline FSH/LH/oestradiol/AMH values prior to commencement of therapy. They became amenorrhoeic shortly after starting of therapy with levels of FSH/LH/oestradiol suggestive of premature ovarian failure. One patient has remained asymptomatic, whereas the other has developed profound post-menopausal symptoms interfering with quality of life which necessitated commencement of hormone-replacement therapy. Appropriate pretreatment fertility investigation and consultation should be offered to all post-pubertal females starting on bevacizumab. Further research into the long-term effects of gonadal toxicity in both females and males with drugs inhibiting angiogenesis is needed.
LINC-04. POSSIBLE ROLE OF NEOADJUVANT CHEMOTHERAPY IN METASTATIC PURE GERMINOMA IN LOW AND MIDDLE INCOME COUNTRIES. A PRO POS OF A CASE
Authors: Leal-Cavazos Carlos , Escamilla-Luna Paola , Luna Marissa Fernandez-De , Vidal-Gutierrez Oscar 
Published: December 2020

Abstract

BACKGROUND
CNS germ cell tumors represent about 3–5 % of pediatric brain tumors, 60% are pure germinomas. Germinomas are very sensitive to chemotherapy which has helped to reduce volume and dose of radiotherapy in localized disease while maintaining excellent survival. In metastatic disease the SIOP GCT-96 trial showed no benefit with addition of chemotherapy to craniospinal irradiation alone. Radiotherapy maybe not readily available in Low/Middle Income Countries (LMIC).

METHOD
We describe a patient in which the use of neoadjuvant chemotherapy helped to rescue vision. The patient is a 9 year old female with a 3 months history of morning headaches and vomits. Visual decline was noticed a month before admission when the child had completely loss vision of the right eye and left eye was partially affected. MRI showed a large suprasellar mass with ventricular nodules. Beta-hGC in CSF was mildly elevated. Patient received 2 cycles of carboplatin/etoposide. After first cycle there was a complete vision recovery in both eyes. After the second course the MRI showed complete response in primary and metastatic disease. Patient received CSI (24Gy + 16 Gy Boost) after 2 cycles of chemotherapy. Chemotherapy was very well tolerated without side effects. Patient vision is 20/20 in both eyes without deficit in visual fields.

CONCLUSION
Although the addition of chemotherapy in metastatic germinoma has no clear role in reducing radiotherapy it could possible help selected patients in attempt to rescue vision when radiotherapy is not readily available.
LINC-10. SIOP PODC ADAPTED TREATMENT GUIDELINES FOR CRANIOPHARYNGIOMA IN LOW- AND MIDDLE-INCOME SETTINGS
Authors: amayiri Nisreen , Spitaels Ariane , Zaghloul Mohamed , Figaji Anthony , Cavalheiro Sergio , Muller Hermann L , Elhassan Moawia , Parkes Jeannette , Mushtaq Naureen , El Beltagy Mohamed , Yousef Yacoub , Esiashvili Natia , Sullivan Michael , da Costa Marcos Devanir , Dastoli Patricia , Mubarak Fatima , Bartels Ute , Chamdine Omar , Davidson Alan , Musharbash Awni , Alcasabas Patricia , Bouffet Eric , Bailey Simon 
Published: December 2020

Abstract
Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage and behavioral changes are amongst the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries (LMICs) where resources are variable. We provide a risk-stratified management guideline for children diagnosed with craniopharyngioma in a resource limited setting based on the service levels describing the facilities and personnel required for management as previously specified by the Pediatric Oncology in Developing Countries (PODC) committee of The International Society of Pediatric Oncology (SIOP). A multi-disciplinary group of neurosurgeons, radiation and pediatric oncologists, radiologists, pediatric endocrinologists and an ophthalmologist with experience in managing children with craniopharyngioma in LMIC setting was formed and carried online meetings to form a consensus guideline. The clinical characteristics (including the visual and endocrine presentations), suggestive radiological features as well as potential treatment options including surgery, radiotherapy and intra-cystic therapies were discussed in depth and in relation to available resources. In addition, hormonal management, pre- and post-operative PICU care and expected future complications related to craniopharyngioma and to follow up these children were discussed and documented in the guideline. We believe this guideline is a useful reference for health care providers in LMIC.
LINC-15. OUTCOME OF CHINESE CHILDREN WITH MEDULLOBLASTOMA: A MULTI-CENTER EXPERIENCE WITH RISK-ADAPTED THERAPY
Authors: Sun Xiaofei , Liu Anthony Pak-Yin , Yang Qunying , Wang Jian , Wu Shaoxiong , Zhen Zijun , Wang Jingsheng , Guo Haixia , Jiang Lian , Ma Xiaoli , Weng Wenjun , Yang Lihua , Huang Libin , Li Juan , Chan Godfrey Chi-Fung 
Published: December 2020

Abstract

BACKGROUND
Medulloblastoma is the commonest brain tumor in young children but literature on Chinese is scarce. We hereby present the outcome of children with medulloblastoma managed according to a risk- and age-stratified guideline from ten institutions across China.

METHODS
Patients &lt;18 years of age diagnosed with medulloblastoma between January 2016 and April 2019 were reviewed. Patients ≥3 years, stratified into average-risk (≤1.5cm2 residual tumor, non-metastatic, non-anaplastic histology) and high-risk (others) groups, were treated with risk-adapted craniospinal irradiation (average-risk: 23.4Gy, high-risk: 36Gy), tumor boost, and chemotherapy (lomustine/cisplatin/vincristine). Patients &lt;3 years (considered high-risk, other than patients with localized and desmoplastic/nodular histology) received chemotherapy (cyclophosphamide/vincristine, high-dose methotrexate, carboplatin/etoposide) with/without delayed irradiation.

RESULTS
112 patients were included with a median age at diagnosis of 6.5 years (range: 0.5–16.7). 16 patients (14.3%) had residual tumor &gt;1.5cm2 and 36 (32%) had metastasis. Available data on histological subtype (n=87) were classic in 56 (64%), desmoplastic/nodular or extensive nodularity in 23 (26%), and large cell/anaplastic in 8 (9%). Molecular subgrouping (n=55) assigned tumors as WNT-activated (n=8, 15%), SHH-activated (n=17, 31%), Group 3 (n=12, 22%) and Group 4 (n=18, 33%). Respective 2-year EFS/OS for patients ≥3 and &lt;3 years were 86.0±4.0%/96.4±2.1% and 57.8±12.6%/81.4±9.8% (EFS/OS p&lt;0.001/p=0.009). Significant difference in outcome was also observed between patients with average-risk and high-risk disease (EFS/OS p=0.006/p=0.018).

CONCLUSION
We demonstrated feasibility in protocolizing the inter-disciplinary treatment for medulloblastoma in China. This will serve as a prototype for the standardization of pediatric neuro-oncology care in the country.
LINC-30. A CLINICOPATHOLOGICAL STUDY OF IMMUNOGENICITY AND IMMUNE EVASION MECHANISMS AMONG MOLECULAR SUBGROUPS OF MEDULLOBLASTOMA
Authors: Kaur Kavneet , Suri Vaishali , Sharma Mehar C , Suri Ashish , Sarkar Chitra 
Published: December 2020

Abstract

INTRODUCTION
Medulloblastomas have been well characterised in terms of genomics, epigenomics, transcriptomics and recently proteomics. However, there is limited knowledge regarding immunogenicity, immune-microenvironment and immune evasion mechanisms in different molecular subgroups of medulloblastoma. It is important to analyze these parameters to understand tumor progression, prognostic stratification as well as treatment response to available immunotherapeutic drugs.

MATERIALS AND METHODS
Molecular subgrouping performed by immunohistochemistry(IHC), Nanostring and 850k-methylation array. Immune profile by IHC for CD3, 20, CD8 [tumor infiltrating lymphocytes (TILs)], CD163 [tumor-associated macrophages (TAMs)], and PD-L1 and CTLA-4 [immune checkpoint proteins].

RESULTS
A total of 35 cases were analyzed with age-range from 1 to 54 years (77% pediatric and 23% adult). 82% cases were located in midline, while rest in cerebellar hemispheres. On molecular subgrouping, MBs were subdivided into 8 WNT, 10 SHH, 8 Group 3 and 9 Group 4. Twenty four cases had follow up, 12 with no evidence of disease while 12 with progressive disease or death. PD-L1 expression ranged from 0% to 20% and included 5SHH, 2WNT and 1Group 3. CTLA4 positive lymphocytes ranged from 0 to 33 in 4 cases: 1WNT, 3 SHH, 1Group4. TILs ranged from 0–220/mm2 with a median of 3. TAMs ranged from 0–60/mm2 with a median of 18. Both TILs and TAMs were significantly higher in SHH subgroup.

CONCLUSION
PD-L1 positivity and number of TILs and TAMs were significantly more in SHH-subgroup tumors followed by WNT tumors. CTLA-4 expression did not correlate with subgroups. All parameters showed a positive trend with increasing age.
MBCL-01. METHYLATION PROFILING OF PEDIATRIC MEDULLOBLASTOMA IN SAUDI ARABIA IN A CLINICAL SETTING PERMITS SUB-CLASSIFICATION AND REVEALS NEW OUTCOME PREDICTIONS
Authors: Alharbi Musa , Mobark Nahla , Balbaid Ali Abdullah O , Bashawri Yara , Safieh Leen Abu , Alowayn Albandary , Alaljelaify Rasha , AlSaeed Mariam , Almutairi Amal , Alqubaishi Fatmah , Alsolm Ebtehal , Ahmad Maqsood , Al-Banyan Ayman , Alotabi Fahad E , Snuderl Matija , Abedalthagafi Malak 
Published: December 2020

Abstract
Medulloblastoma (MB) is the most common childhood malignant brain tumor. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3) and Group 4 (G4) WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signalling whilst G3/G4 tumors show recurrent chromosomal alterations. each subgroup has distinct clinical outcomes, the ability to subgroup SA-FPPE samples holds significant prognostic and therapeutic value. We performed the first assessment of MB-DNA methylation patterns in Saudi Arabian SA cohort using archival biopsy materials (FPPE n=49). Of the 41 materials available for methylation assessments, 39 could be classified into the major DNA methylation subgroups (SHH, WNT, G3 and G4). Methylation analysis was able to reclassify tumors that could not be sub-grouped through NGS testing, highlighting its improved accuracy for MB molecular classifications. Independent assessments demonstrate clinical relationships of the subgroups, exemplified by the high survival rates observed for WNT tumors. Surprisingly, the G4 subgroup did not conform to previously identified phenotypes, with a high prevalence in females, high metastatic rates and a large number of tumor-associated deaths. DNA methylation profiling enables the robust sub-classification of four disease sub-groups in SA-MB patients. Moreover, the incorporation of DNA methylation biomarkers can significantly improve current disease-risk stratification schemes, particularly concerning the identification of aggressive G4 tumors. These findings have important implications for future clinical disease management in MB cases across the Arab world.
MBCL-17. METASTATIC MEDULLOBLASTOMA CAN BE CURED WITHOUT EXCISION OF THE PRIMARY TUMOR: A SINGLE CENTER EXPERIENCE
Authors: Dvir Rina , Constantini Shlomi , Roth Jonathan , Rosenfeld-Keidar Hila , Ospovat Inna , Elhasid Ronit 
Published: December 2020

Abstract

INTRODUCTION
Metastatic medulloblastoma is a challenging disease The current clinical approach advocates removal of the primary tumor in the posterior fossa despite evidence of metastatic disease and administer oncologic treatment within several weeks: Infants of 3–4 years are treated by tandem high dose chemotherapy with stem cell support (ACNS0334 protocol), while older children are given radiotherapy and tandem high dose chemotherapy with stem cell support (SJMB03 protocol). We postulate that a resection of the primary tumor is not obligatory, and a biopsy may suffice in order to enable prompt oncological treatment without affecting the long-term survival.

PATIENTS AND METHODS
Between 2010-2019 7 patients with metastatic medulloblastoma (median age 4.5, age 1–10) were treated with biopsy only, five spinal and two from the primary tumor. Six children had a concurrent VP shunt. Four presented with cord compression, and two with neurological deterioration. Four needed emergency radiotherapy. Two infants received protocol ACNS0334, five patients received protocol SJMB03.

RESULTS
Six patients (85%) survived; .3 patients are long term survivors (&gt; 5 years), 2 patients are in remission for 2–3 years, one patient is on active therapy. Only 1 patient died after a late (4 years) metastatic relapse not in the posterior fossa.

CONCLUSIONS
Metastatic medulloblastoma can be cured without excision of the primary tumor and without mutilating surgery. Long term prognosis is probably more attributable to disease subtype and prompt oncologic treatment. This approach merits further studies and may have implications on treatment of non-metastatic tumors.
MBCL-20. DETECTION OF SOMATIC MUTATIONS BY USING RNA-SEQ DATA IN CHILDHOOD MEDULLOBLASTOMA AND ITS POTENTIAL CLINICAL APPLICATION: A COHORT SERIES OF 52 CASES STUDY IN TAIWAN
Authors: Wong Tai-Tong , Wu Kuo-Sheng , Ho Donald Ming-Tak , Lin Shih-Chieh , Huang Wen-Chang , Laing Muh-Lii , Chen Hsin-Hung 
Published: December 2020

Abstract

BACKGROUND
In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). Part of our aim was to explore the clinical application for drug target identification and finding clues to genetic predisposition.

METHODS
In total, 52 frozen tumor tissues of childhood MBs were collected. RNA-Seq and DNA methylation array data were generated. Molecular subgrouping was performed. We selected 51 clinically relevant genes for somatic variant calling using RNA-Seq data. Correlated clinical findings to genetic predisposition were defined. Potential drug targets and genetic predispositions were explored.

RESULTS
Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Potential drug targets were detected in the pathways of DNA damage response. Five patients with relevant clinical findings to genetic predisposition clustered in SHH MBs. The corresponding somatic driver mutations involved TP53, MSH6, PTEN, PTCH1, and TERT promoter (suspicious). For validation, whole exome sequencing (WES) of blood and tumor tissue was used in 10 patients with SHH MBs in the cohort series. This study included the five patients with potential genetic predispositions. Four patients exhibited relevant germline mutations named as TP53, MSH6, PTEN, and SUFU.

CONCLUSION
The findings of this study provide valuable information for personalized care of childhood MB in our cohort series and in Taiwan.
MBCL-34. EFFICACY OF METHOTREXATE (MTX) ACCORDING TO MOLECULAR SUB-TYPE IN YOUNG CHILDREN WITH MEDULLOBLASTOMA (MB): A REPORT FROM CHILDREN’S ONCOLOGY GROUP PHASE III TRIAL ACNS0334
Authors: Mazewski Claire , Kang Guolian , Kellie Stewart , Gossett Jeffrey , Leary Sarah , Li Bryan , Aridgides Paul , Hayes Laura , Reddy Alyssa , Shaw Dennis , Burger Peter , Judkins Alexander , Geyer Jeffrey Russell , Fouladi Maryam , Huang Annie 
Published: December 2020

Abstract
ACNS0334, a Phase 3 trial, compared outcomes of children &lt;36 months treated with intensive chemotherapy +/-high-dose methotrexate. Nodular-desmoplastic M0-stage MB were excluded. Treatment included 3 induction cycles (cyclophosphamide/etoposide/vincristine/cisplatin+/-mtx) and 3 consolidation cycles (carboplatin/thiotepa with stem cell rescue). Radiation (RT) was at physician discretion. Molecular sub-typing was by DNA-methylation. Log-rank testing was used to compare survival differences. Molecular sub-typing of 38 MB identified 11 Sonic Hedgehog (SHH), 25 Group 3 (GP3), 2 Group 4 (GP4). Five-year survival (OS) was 100% for 5 SHH with MTX and 4 SHH without MTX; 80% for 10 GP3 with MTX, 40% for 15 GP3 without MTX (p=0.025). Only 6/14 survivors received RT: 4 for residual following therapy (1 SHH and 3 GP3) and 2 GP3 salvaged after progression. Two GP3 deaths were associated with toxicity; all others were due to disease. Histology among SHH was nodular-desmoplastic (8) or classic (3); GP3 histology was classic (17) or anaplastic (7). Whole-exome sequencing identified 6 somatic PTCH1 and 1 germline SUFU alteration(s) among 9 SHH. Among GP3, no p53 mutations were found; copy-number analysis identified 5/25 with myc-amplification, 5/25 iso17q, 11/25 with 8 loss, 14/25 with loss of 11. Among GP3, 14/19 had no significant germline mutation. ACNS0334 achieved 100% survival for metastatic SHH. Benefit of methotrexate was observed in GP3 MB supporting incorporation of methotrexate into standard therapy for GP3. Upfront central pathology review and molecular sub-typing are critical for future clinical trial risk stratification of young children with embryonal tumors.
MBCL-52. ENDOCRINE PROFILE AFTER MEDULLOBLASTOMA TREATMENT
Authors: Pavon-Mengual Miriam , Curry Helen , Saraff Vrinda , Mohamed Zainaba , Benghiat Helen , Ford Daniel , Peet Andrew , Adamski Jenny , English Martin 
Published: December 2020

Abstract

BACKGROUND
Treatment of medulloblastoma has evolved substantially with more chemotherapy, risk-adapted dosing of radiotherapy (RT) and new RT techniques. We present the endocrine profile for our patients treated over a 20-year period.

METHODS
The charts of patients treated for medulloblastoma between 1/1/00 and 31/12/19 were reviewed. 105 were available. Group 1 received chemotherapy alone, Group 2 received 23.4 Gy whole CNS RT with a posterior fossa (PF) boost to 54 Gy, Group 3 received &gt; 35 Gy whole CNS RT with PF boost to 54–59 Gy, Group 4 received PF RT to 54 Gy. All received chemotherapy according to national guidelines or clinical trials relevant at the time.

RESULTS
Group 1 (M:F 11:6, 7 survivors mean age 2 years range 1–7) had no endocrinopathies. At 5 years from diagnosis Group 2 (M:F 15:13) and Group 3 (M:F 35:14) had the following %

RESULTS
Survival 77:61; Growth Hormone deficiency 92:100; Thyroid deficiency 75:81; ACTH deficiency 42:33. Girls were more likely to need sex hormone replacement than boys. Group 4 (M:F 7:5 mean age 2) were all treated in the first decade. 3 survivors, one GH deficiency, one thyroxine deficiency, one both.

CONCLUSIONS
There is a trend to earlier endocrinopathies in the group 3 vs group 2 patients, but it does not reach statistical significance. Girls are more likely to need sex hormone replacement than boys. This investigation provides a contemporary profile of endocrinopathy after treatment for medulloblastoma that can be used for future comparisons.
MBRS-01. DISSECTING REGULATORS OF THE ABERRANT POST-TRANSCRIPTIONAL LANDSCAPE IN MYC-AMPLIFIED GROUP 3 MEDULLOBLASTOMA
Authors: Kameda-Smith Michelle , Zhu Helen , Luo EnChing , Venugopal Chitra , Xella Agata , Brown Kevin , Fox Raymond , Yee Brian , Xing Sansi , Tan Frederick , Bakhshinyan David , Adile Ashley , Subapanditha Minomi , Picard Daniel , Moffat Jason , Fleming Adam , Hope Kristin , John Provias , Remke Marc , Lu Yu , Reya Tannishitha , Reimand Juri , Wechsler-Reya Robert , Yeo Gene , Singh Sheila 
Published: December 2020

Abstract
Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm, with Group 3 (G3) MB representing the most aggressive subgroup. MYC amplification is an independent poor prognostic factor in G3 MB, however, therapeutic targeting of the MYC pathway remains limited and alternative therapies for G3 MB are urgently needed. Here we show that an RNA-binding protein, Musashi-1 (MSI1) is an essential mediator of G3 MB in both MYC-overexpressing mouse models and patient-derived xenografts. Unbiased integrative multi-omics analysis of MSI1 function in human G3 MB suggests a paradigm shift beyond traditional gene-based profiling of oncogenes. Here we identify MSI1 as an oncogene in G3 MB driving stem cell self-renewal through stabilization of HIPK1 mRNA, a downstream context-specific therapeutic target for drug discovery.