bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-19. HDAC INHIBITORS SENSITIZE MYC-AMPLIFIED MEDULLOBLASTOMA TO IMMUNOTHERAPY BY ACTIVATING THE NF-kB PATHWAYS
Authors: Marquardt Viktoria , Theruvath Johanna , Pauck David , Picard Daniel , Reifenberger Guido , Borkhardt Arndt , Cheshier Samuel , Kurz Thomas , Remke Marc , Mitra Siddhartha 
Published: December 2020

Abstract
Medulloblastoma is the most common malignant brain tumor in childhood and comprises four distinct molecular subgroups with further layers of intertumoral heterogeneity. Amplification of the oncogene MYC drives tumorigenesis and constitutes a hallmark feature underlying Group 3 biology. Employing our in-house drug screening pipeline, we evaluated a library of epigenetic inhibitors (n=78) in various brain tumor cell lines followed by a secondary HDACi library (n=20) screen, we identified the clinically established, class I selective HDACi CI-994 as the compound with the most preferential antitumoral effect in MYC-driven medulloblastoma. We confirmed that the inhibitor response was in part MYC-dependent as our lentiviral-based MYC-overexpression model showed higher sensitivity towards CI-994 treatment as compared to the isogenic control with low endogenous MYC expression. CI-994 showed significant antitumoral effects at the primary site and at the metastatic compartment in two orthotopic mouse models of MYC-driven medulloblastoma. RNA sequencing profiling of tumor cells treated with CI-994 at IC50 revealed an up-regulation of multiple innate inflammatory pathways like NFκB, TLR4, Interferon-gamma, and TGFbeta. Flow cytometry analysis revealed an increased surface expression of MHC-I. We combined CI-994 with an anti-body against the innate checkpoint CD47 which acts as a “don’t eat me” signal previously shown by us to have significant anti-tumor activity against MYC-driven MB. Combining CI-994 with anti-CD47 shows a significant increase in macrophage-mediated phagocytosis of tumor cells and a significant increase in the survival of tumor-bearing mice.
LGG-18. EVEROLIMUS TREATMENT IN PEDIATRIC PATIENTS AFFECTED BY LOW-GRADE GLIOMAS (pLGG) NON-TSC, BRAF v600-WT
Authors: Cacchione Antonella , Miele Evelina , Lodi Maria Chiara , Carai Andrea , Colafati Giovanna Stefania , Camassei Francesca Diomedi , Locatelli Franco , Mastronuzzi Angela 
Published: December 2020

Abstract

BACKGROUND
MAPK pathway is the hallmark of pediatric low grade gliomas (pLGGs); hyperactivation of mTOR (mammalian target of rapamycin) might be a suitable biomarker for therapeutic response. We investigated the feasibility of Everolimus, mTOR inhibitor, in patients affected by pLGGs.

METHODS
Patients 1 to 18 years old, diagnosed with pLGG, with a positive tumor biopsy for mTOR/phospho-mTOR and radiological and / or clinical disease progression, treated at Bambino Gesù Children’s Hospital in Rome were evaluated. Tumor DNA methylation analysis was performed in 10 cases. Exclusion criteria included: Tuberous Sclerosis patients, Sub Ependymal Giant Astrocytoma. Everolimus was administered orally at a dose of 2.5 mg or 5 mg daily based on body weight. Patients were evaluated with brain MRI every 4, 8 and 12 months after treatment start and every six months thereafter.

RESULTS
16 patients were enrolled from September 2014 and 2019. The median age was 7.5 years old. All patients had at least one adverse event. Events rated as severe (grade 3/4) were reported in 6 patients. Stomatitis was the most frequent adverse event. One patient discontinued treatment due to grade 4 toxicity (ulcerative stomatitis and fatigue). The median duration of treatment was 21 months (4–57 months). Brain MRI evaluations have showed disease stability in 11 patients, partial response in 2 patients and disease progression in 3 patients.

CONCLUSIONS
Everolimus has proven to be well tolerated and effective treatment in terms of disease stability in patients with pLGGs. It’s also an excellent example of chemo-free personalized approach.
LGG-32. CLINICAL OUTCOME OF PEDIATRIC GLIOMAS IN SINGLE INSTITUTION
Authors: Uchida Hiroyuki , Higa Nayuta , Yonezawa Hajime , Oyoshi Tatsuki , Yoshimoto Koji 
Published: December 2020

Abstract
Gliomas in children are rarer than in adult, then treatment strategies might vary from facility to facility. We report clinical features and outcome of pediatric glioma in our institution. Twenty-nine patients diagnosed with glioma, exclude ependymoma, 14 boys and 15 girls, among 98 pediatric brain tumor patients treated at Kagoshima University Hospital since 2006 were reviewed histopathology, extent of resection, adjuvant therapy and outcome, etc. Mean age at surgery was 10.4 (S.D. 5.6) years. Median follow-up period was 19.1 months. Histopathological diagnosis comprised 8 pilocytic astrocytoma, 3 ganglioglioma, 2 subependymal giant cell astrocytoma, 5 WHO grade Ⅱ astrocytoma, 8 glioblastoma, and desmoplastic infantile astrocytoma, anaplastic astrocytoma and astroblastoma were one case each. Tumor resection was performed in 24 cases, and 5 cases underwent biopsy. Chemotherapy was performed in 15 cases and irradiation was performed in 9 cases. Out of 5 WHO grade Ⅱ astrocytoma cases, 2 cases underwent biopsy following chemotherapy, 1 case underwent biopsy only and other 1 case underwent total resection. The four cases show long survival ranged from 71 to 136 months without irradiation. All of eight glioblastoma cases show poor prognosis ranged from 8.6 to 26.7 months regardless of chemo-radiotherapy. In management for pediatric brain tumor patients, irradiation is often laid over until recurrence. In WHO grade Ⅱ astrocytoma, the treatment strategy might be reasonable using appropriate chemotherapy even though biopsy cases.
LGG-47. SYSTEMIC THERAPY OF ROSETTE-FORMING GLIONEURONAL TUMOR OF THE FOURTH VENTRICLE INAN ADOLESCENT
Authors: McNall-Knapp Rene , Gross Naina , Zaky Wafik , Cornwell Benjamin , Gavula Theresa , Bavle Abhishek 
Published: December 2020

Abstract
An 11 y.o. female presented to a GI specialist with complaints of morning vomiting and periumbilical abdominal pain for several months. Had progressing symptoms with GI work-up for ~1 year. She developed diplopia and worsening headaches. Imaging revealed a T2/FLAIR hyperintense mass in the 4th ventricle with heterogeneous enhancement and obstructive hydrocephalus. Three T2 bright, non-enhancing, subcentimeter masses identified in the right cerebellum. Due to poor differentiation between tumor and normal tissue at brainstem, only partial resection (PR) was feasible. Pathology initially called pilocytic astrocytoma (PA). All symptoms resolved after PR. Slow progression in the tumor and “satellite” lesions noted over two years. Second opinion and molecular typing reclassified the tumor as rosette-forming glioneuronal tumor (RFGNT) with a mutation in PIK3CA. Therapy started with vinblastine and carboplatin with stable disease x 7 months, discontinued due to allergic reaction to carboplatin. Initiated therapy with everolimus, an mTOR inhibitor. The tumor’s characteristics on imaging changed with initial growth and increase in peripheral enhancement in one satellite and the primary tumor. Nevertheless, we persevered. When comparing pre-treatment MRI to most recent 7 months later, there has been an overall decrease in volume of expansile heterogenous tumor along the margins of the fourth ventricle. The degree of peripheral enhancement associated with the mass has increased. RFGNT is a rare tumor included in WHO classification since 2007. Ellezam et al identified recurrent PIK3CA mutations. To our knowledge, this is the only report of treatment targeting the mutation. We report a radiographic response despite initial growth.
LGG-50. INTEGRATED MOLECULAR AND CLINICAL ANALYSIS OF 1,000 PEDIATRIC LOW-GRADE GLIOMAS UNCOVERS NOVEL SUBGROUPS FOR CLINICAL RISK STRATIFICATION
Authors: Tabori Uri , Ryall Scott , Zapotocky Michal , Bennett Julie , Nobre Liana , Ellison David , Santi Mariarita , Karajannis Matthias , Hawkins Cynthia 
Published: December 2020

Abstract
Pediatric low-grade gliomas (pLGG) are primarily driven by genetic alterations in the RAS/MAPK pathway, most commonly involving BRAF of NF1. Despite their molecular convergence, pLGG often show unexplained variability in their clinical outcome. To address this, we molecularly characterized a cohort of &gt;1,000 clinically annotated pLGG. 84% of cases harbored a detectable driver mutation. The remaining 16% of patients nonetheless showed RAS/MAPK pathway up-regulation at the RNA level. The clinical presentation and outcome of pLGG appeared highly variable and linked to the alteration type: re-arrangement or SNV. Re-arrangement-driven tumors were diagnosed at a younger age (6.6 versus 10.9 years, p&lt;0.0001), enriched for WHO grade I histology (88% versus 66%, p&lt;0.0001), infrequently progressed (27% versus 46%, p&lt;0.0001), and rarely resulted in death (3 versus 13%, p&lt;0.0001) as compared to SNV-driven tumors. These included the rarest molecular drivers of pLGG, for which we now have the clinicopathologic features of including MYB, MYBL1, FGFR2 fusions, FGFR1-TACC1, FGFR1 SNVs, IDH1 p.R132H, and H3.3 p.K27M. Utilizing this information, we suggest novel risk categories of pLGG that effectively predicted patient outcome. Low-risk tumors progressed infrequently and rarely succumbed to their disease (10-year PFS of 71% and OS of 98%). Intermediate-risk pLGG had a 10-year PFS and OS of 35% and 90%, respectively. High risk pLGG almost invariably progressed (10-year PFS of 0%) and these patients often succumbed to their disease (10-year OS of 41%). These data highlight the biological and clinical differences between pLGG subtypes and offers molecular based risk stratification to these cancers.
LGG-51. BRAF ALTERATIONS IN PEDIATRIC LOW-GRADE GLIOMAS: RESULTS FROM A BRAZILIAN COHORT
Authors: Restine Felipe , Sakamoto Luis Henrique , Real Juliana Monte , Pereira Gregorio , Fernandes Jennifer Marx , Aguiar Simone dos Santos , Epelman Sidnei 
Published: December 2020

Abstract

BACKGROUND
Pediatric low grade gliomas (PLGG) are the most common central nervous system neoplasms in children. These are driven almost exclusively by alterations in the RAS/MAPK pathway. Specifically, alterations in the BRAF gene have emerged as an important target for therapy. This study aimed to identify the frequency of BRAF alterations in a Brazilian cohort of PLGGs.

RESULTS
Forty-one patients diagnosed between 2001 and 2017 had enough FFPE tissue available for analysis. Real-time PCR test (n=35) was used to assess for BRAFV600E mutations, while BRAF fusions were detected by break-apart fluorescence in situ hybridization (n=30). The histologic distribution was as follows: 73% pilocytic astrocytoma, 12% ganglioglioma, 3% diffuse astrocytoma, 5% pleomorphic xanthoastrocytomas (PXA) and 7% NOS (n = 41). BRAF fusions were present in 21 patients (51%): 17 pilocytic astrocytomas, 2 xanthoastrocytoma, 1 pilomyxoid astrocytoma and 1 diffuse astrocytoma. BRAFV600E was detected in 4 cases (10%): 2 pilocytic astrocytomas, 1 ganglioglioma and 1 PXA. As expected, BRAF translocations were more frequent in pilocytic astrocytomas (p&lt;0.001). From 22 patients treated in our institution, 59% were male with a mean age of 9.7 years, 50% occurred in the posterior fossa and 77% treated by surgery only. One patient relapsed and died from disease (BRAF V600E positive) (follow-up median=44.7 months). These are the first results using a CLIA method showing the frequency of BRAF abnormalities in a Brazilian population. Although preliminary, BRAF alterations are present in 61% of the cases emphasizing the importance of incorporating this analysis in the current work-up guidelines.
LGG-53. PNOC001 (NCT01734512): A PHASE II STUDY OF EVEROLIMUS FOR RECURRENT OR PROGRESSIVE PEDIATRIC LOW-GRADE GLIOMAS (pLGG)
Authors: Mueller Sabine , Aboian Mariam , Nazemi Kellie , Gauvain Karen , Yoon Janet , Minturn Jane , Leary Sarah , AbdelBaki Mohamed S , Goldman Stewart , Elster Jennifer , Resnick Adam , Molinaro Annette M , Phillips Joanna , Prados Michael , Haas-Kogan Daphne 
Published: December 2020

Abstract

OBJECTIVE
To estimate the 6-month Progression Free Survival (PFS6) associated with everolimus for progressive/recurrent pLGGs and to determine if activated PI3K/Akt/mTOR pathway as measured by positive phosphorylated-ribosomal protein S6 (p-RPS6) status was associated with response. METHOD: Patients 3–21 years of age with recurrent or progressive pLGG were enrolled. Everolimus was administered orally at 5 mg/m2 daily. Tissue availability for molecular analysis was mandatory. Immunohistochemistry (IHC) for p-RPS6 was performed centrally. An adaptive Simon two-stage design was employed based on p-RPS6 status. Based on results of the first stage, enrollment in the second stage was either limited to pathway activated patients or open to all subjects.

RESULTS
From December 2012 to July 2019 a total of 65 subjects enrolled [median age 9 years (range 3–19); 43% female]. As of December 15, 2019 median number of treatment cycle is 8 (range 1–24); 7 patients remain on treatment. Toxicity profile is similar to published reports with rash and elevated lipid profiles as most common adverse events. PFS6 for the entire cohort is 63%; PFS6 is 64% for the activated and 61% for the non-activated patients. Central imaging review (n=52) revealed 1 partial response, 1 complete response, 33 stable disease, and 17 progressive disease at the end of study treatment. Initial molecular analysis identified BRAF alterations in 35/65 patients.

CONCLUSION
Everolimus is well tolerated and active in a subset of pLGGs. Ongoing analyses will assess predictive biomarkers of response and will be reported at the meeting.
LINC-02. IMPLEMENTATION OF AN INTEGRATED NEURO-ONCOLOGY SERVICE: CLINICIANS’ PERSPECTIVE ON CONDUCT OF NEURO-ONCOLOGY MULTIDISCIPLINARY TEAM MEETING FROM A SINGLE-INSTITUTION IN MALAYSIA
Authors: Foo Jen Chun , Vida Jawin , Hany Ariffin , Loh Pei Yuin , Sutharsan Sockalingam , Dharmendra Ganesan , Chandran Thambinayagam Hari , Revathi Rajagopal 
Published: December 2020

Abstract

INTRODUCTION
Multidisciplinary Team (MDT) meetings are essential in the management of complex cancer cases. There are limited data regarding clinicians’ perception on conduct of neuro-oncology MDT meetings and its impact on clinical management. In University Malaya Medical Centre (UMMC), weekly neuro-oncology MDT meeting was established since 2013 to discuss adult and paediatric complex central nervous system tumour cases.

OBJECTIVE
To determine clinicians’ perception and level of satisfaction of neuro-oncology MDT meeting.

METHODOLOGY
Web-based questionnaire was distributed via e-mail to all neuro-oncology MDT clinicians at UMMC in April 2019.

RESULT
Eighteen out of 20 clinicians responded to the survey. Respondents were: neurosurgeons (n=5), adult oncologists (n=4), paediatric oncologists (n=3), radiologists (n=2), radiation oncologists (n=2) and pathologists (n=2). Majority of clinicians (65%) agreed at current weekly MDT meeting with maximum length of one hour duration and 75% of them suggested to discuss 5 to 10 cases during each meeting. Almost all of them (94.4%) preferred e-mail as method of communication to disseminate information before and after the meetings. MDT members expected 100% attendance from neurosurgeons. Fourteen (70%) clinicians agreed that patients/ parents/ carers do not receive copy of MDT meeting plans and only seven (35%) clinicians document MDT meeting plans in patients’ medical record. Overall, all clinicians felt that MDT meeting improved decision-making process, enhanced continuity of coordinated care and promoted good communication among team members.

CONCLUSION
The structure and logistics of neuro-oncology MDT meeting in UMMC are generally agreed upon. However, documentation of post-meeting plan and notification to patients need uniformity.
LINC-12. COMBINED ADULT AND PAEDIATRIC NEURO-ONCOLOGY LONG-TERM SURVIVOR CLINIC EXPERIENCE FROM A TERTIARY CANCER CENTRE IN A LOW-MIDDLE-INCOME COUNTRY
Authors: Krishnatry Rahul , Prasad Maya , Chinnaswamy Girish , Chaterjee Abhisheik , Goda Jayant , Sridhar Epari , Moiyadi Aliasgar , Shetty Prakash , Saha Arushi , Singh Vikas , Golambade Nayana , Gupta Tejpal 
Published: December 2020

Abstract
NeuroOncology survivor clinics (NOS) is uncommon in low-middle-income countries. We started combined (paediatric and adult) NOS clinic in our tertiary a cancer centre (Jan-2017) and review here the demographic, clinical-pathological and treatment spectrum for our paediatric (0-18years) and adult (&gt;18years) survivors (&gt;5years since their initial diagnosis) till date. Of total 312 patients registered, 198 (63.5%) were adults while 114 (36.5%) were paediatric at-diagnosis with median age (IQR) at presentation: 34 (23–41) and 9(6 – 13) years respectively. In both groups, only 33% were females. The median (IQR) time since diagnosis was 9 (9–14) and 8 (6–12) years respectively with 60% of paediatric turning into adult survivors. The commonest paediatric tumours were glioma (52, 45.6%), embryonal (34, 29.8%), and ependymoma (12, 10.5%) versus gliomas (114, 57.6%) and benign tumours (42, 21.2%) in adults. The low-grade-glioma comprised 90.4% of all pediatric gliomas and intermediate-grade (90%) in adults. The primary treatment consisted of radiotherapy and chemotherapy in 95% and 43% versus 99% and 36% in adults versus paediatric patients respectively. Temozolomide and multi-drug combinations were the commonest chemotherapy used in adults and paediatrics respectively. Relapse and retreatments were seen in 16.6 and 14% of adults and paediatric patients. There were two deaths each in each group since registration (median 12 months). Although the baseline diagnosis/treatment characteristics are different, survivors of both group had a similar number of retreatments and deaths. Combined survivor clinics may present an interesting and unique opportunity to learn and provide challenging service in this part of the world.
LINC-16. MEDULLOBLASTOMA IN A BOY WITH RUBINSTEIN-TAYBI SYNDROME: A CASE REPORT
Authors: del Campo Regina M Navarro-Martin , Soto-Mancilla Juan Luis , Arredondo-Navarro Luis A , Orozco-Alvarado Ana L , Sanchez-Zubieta Fernando A 
Published: December 2020

Abstract

BACKGROUND
Rubinstein–Taybi syndrome (RTS) is characterized by multiple congenital anomalies and associated with mutations in CREBBP (70%) and EP300 (5–10%). Previous reports have suggested an increased incidence of benign and possibly also malignant tumors, but the correlation remains unclear. Here we present a case of a patient with RTS and medulloblastoma. CLINICAL CASE: A 5-year-old male presented with increased intracranial pressure. An MRI revealed a 4.2 x 4.7 cm mass in the midline of cerebellum arising from the floor of 4th ventricle. The patient underwent a complete resection and pathology revealed medulloblastoma, classic histology. Staging established no disseminated disease. At diagnosis, a peculiar phenotype consisting in mild mental retardation, microcephaly, down-slanting palpebral fissures, broad nasal bridge, highly arched palate, mild micrognathia, screwdriver incisors and wide thumbs and toes was noted. Clinical genetics evaluation was consistent with RTS. Karyotype was performed and normal. Further genetics testing was not done. Treatment consisted in 8 cycles of chemotherapy and craniospinal radiation (2300 cGy to spine, 5500 cGy Total). At the end of treatment, there was no evidence of disease. He was under surveillance for 33 months free of disease, but relapsed with a supratentorial meningeal disease that ultimately resulted in death.

CONCLUSION
This report highlights the fact that pediatric medulloblastoma can be associated to RTS, in this case associated to classical histology and recurrent disease.
LINC-19. CURRENT SITUATION OF PEDIATRIC TUMORS OF CENTRAL NERVOUS SYSTEM IN CHINA - THE FIRST CNOG NATIONAL WIDE REPORT
Authors: Ma Jie ,   CNOG (Children’s Neuro-Oncology Group) in China
Published: December 2020

Abstract
Tumors of Central Nervous System (CNS) are most seen solid tumor in childhood. Accounting approximate 25–30% of pediatric neoplasms, treatments on these tumors are complicated as they occur in different age ranges, have various types according to classification system and contain different characteristic molecular profiles. There are huge gaps of medical services for children with CNS tumors in different regions in China, which is blamed to limited medical resources and lack of epidemiology data for Chinese population. After the establishment of CNOG (Children’s Neuro-Oncology Group) in China in 2017, national wide registry (CNOG-MC001) was conducted to collect data on the basic information about pediatric tumors of CNS. Results of 4059 cases from 37 centers providing medical services for pediatric CNS tumors in 25 provinces from 6 greater administrative areas in China showed distinct tumor ratio, compared to worldwide data by WHO classification. The mean of age was 8.01 ± 4.73, with a male vs. female ratio as 1.48 to 1. Embryonal tumor, astrocytic & oligodendroglial tumors, and other astrocytic tumors were three most common tumor types in CNS of children. The lost follow-up rate was surprisingly high as 53.07%. In all, this is the first national wide registry for pediatric CNS tumor in China and the results attracted public and government’s attentions for further epidemic investigations.
LINC-23. PRE-OPERATIVE AND POST-OPERATIVE INTERVENTIONS REDUCE RATES OF VENTRICULITIS IN PEDIATRIC BRAIN TUMOR PATIENTS: A PILOT STUDY
Authors: San Laura Melissa Stephanie Diamante - , Pedro Marciel , Alcasabas Ana Patricia , Lukban Marissa , Khu Kathleen , Legaspi Gerardo , Qaddoumi Ibrahim , Moreira Daniel 
Published: December 2020

Abstract

BACKGROUND
The Philippine General Hospital, a public national referral center, sees 60–80 pediatric brain tumor cases per year. Historically, the rate of post-operative ventriculitis has been high, resulting in treatment delays and poor outcomes. Starting in July 2019, as a means to decrease infections, patients were provided standardized bathing and wound care kits and caregivers were trained to follow a bathing and wound care protocol.

METHODS
This quality improvement study included patients younger than 18 years who underwent craniotomy at PGH were enrolled. The type of surgery, length of surgery, existence of post-operative CNS infection, length of stay and total cost of care was collected. The outcome of these interventions are analyzed 6 months after implementation.

RESULTS
Thirty-two 32 patients were included, with mean age of 7 years (1–16). The surgeries performed were: tumor resection (n=20), ventriculo-peritoneal shunt insertion (VPS) (n=3), endoscopic third ventriculostomy (n=3), resection with tube ventriculostomy (n=3), Ommaya reservoir placement (n=2), and resection with shunt (n=1). Median surgery time was 4 hours (1–10). Three patients (9.4%) developed ventriculitis. No surgical site infections occurred. Compared to historical controls, a lower rate of infections was noted (9.4% vs. 15.5%, runchart analysis). Patients without post-operative infections had a shorter length of stay (median 14 vs 48 days, p&lt;0.05) and a lower cost of care (median $1098 vs. $2425 USD, p&lt;0.05).

CONCLUSION
Implementation of simple hygiene interventions effectively lowered post-operative CNS infections and hospital costs in a public hospital setting. Incorporation of these into standard clinical practices is urgently needed.