bluuebunny/crossref_metadata_2025_split huggingface dataset:
RONC-05. PRESERVING VISION IN OPTIC PATHWAY GLIOMA AMONG PATIENTS WITHOUT NEUROFIBROMATOSIS TYPE 1
Authors: Hanania Alexander , Paulino Arnold , Ludmir Ethan , Shah Veeral , McGovern Susan , Grosshans David , Okcu Fatih , Baxter Patricia , Su Jack , Chintagumpala Murali 
Published: December 2020

Abstract

PURPOSE
Sporadic optic pathway/hypothalamic gliomas (OP/HGs) represent a unique entity within pediatric low-grade glioma. Despite favorable survival, the location makes treatment difficult and local progression debilitating. We conducted longitudinal assessment of visual acuity (VA) among patients treated in the modern era with chemotherapy (CT) or early radiotherapy (RT).

METHODS
Clinical characteristics were abstracted for patients treated over a 15-year period (2000–2015) at a single institution. Comprehensive ophthalmologic data taken at three to six-month intervals was examined with age-appropriate VA metrics converted to LogMAR scale. Kaplan-Meir “blindness-free survival” (BFS) curves were calculated as time to bilateral functional blindness (i.e. LogMAR ≥ 0.8 in both eyes), stratified by treatment and compared using log-rank test.

RESULTS
Thirty-six patients with median follow-up of 7.6 years (range: 2–17) were identified. Median age at diagnosis was 2.5 years (IQR: &lt;1–5). Early RT was administered as initial therapy (n=6) or first-line salvage (n=5) in a total of eleven patients (31%) at a mean age of 12 years (range: 6–17). Twenty-five patients (69%) were maintained primarily on CT with a mean age at initiation of 2.4 years (range &lt;1–8). Of these, five patients received RT after ≥2 systemic therapy regimens. In terms of visual preservation, five/eight-year BFS rates were 84%/59% and 100%/100%, for CT and early RT, respectively (p=0.046).

CONCLUSIONS
In a contemporary cohort, early RT, defined as initial or 1st line salvage therapy for OP/HGs manifested in superior VA. Children undergoing CT are at highest risk of functional blindness following five years of treatment.
RONC-20. RECURRENT HIGH-GRADE ASTROBLASTOMA TREATED WITH STEREOTACTIC RADIOTHERAPY
Authors: Nishimoto Shota , Kawanishi Yu , Fujita Shohei , Yawata Toshio , Ueba Tetsuya 
Published: December 2020

Abstract

INTRODUCTION
Astroblastoma is a rare, mostly supratentorial glial tumor, occurring predominantly in children and young adults. However, treatment strategies have not yet been established for this rare disease.

CASE PRESENTATION
A 6-year-old male presented with headache and nausea. CT and MR imaging revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MR imaging 13 months after surgery suggested local recurrence and enlargement was found 3 months later. Stereotactic radiotherapy (SRT) was performed. MR imaging after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However, 11C-methionine PET revealed radiation necrosis. The last follow-up MR imaging 15 months after SRT showed no further recurrence.

CONCLUSION
Astroblastoma is rare, so no optimal management is known. SRT may be effective to treat recurrent astroblastomas. 11C-methionine PET/CT is useful for the differentiation from radiation necrosis.
RONC-21. IDENTIFICATION OF EPIGENETIC DRUGS AS RADIOSENSITIZERS IN PEDIATRIC HIGH-GRADE GLIOMAS
Authors: Metselaar Dennis , ter Huizen Giovanna , Meel Michaël Hananja , Goulding Joshua , Waranecki Piotr , Carcaboso Angel Montero , Kaspers Gertjan , Hulleman Esther 
Published: December 2020

Abstract
Pediatric high-grade gliomas (pHGG) are malignant brain tumors with a high mortality rate. Radiotherapy (RT) is one of the cornerstones of current pHGG treatment, while the efficacy of chemotherapeutics remains inferior. The use of chemotherapeutics that specifically sensitize tumor cells to irradiation are poorly understood, but may help to increase the effect of RT in pHGG treatment. Since recent studies revealed pHGG to be epigenetically dysregulated, we tested 148 epigenetic drugs on eight primary pHGG models in the presence and absence of RT, to assess their radiosensitizing potential. Based on synergy scores, we found 22 compounds that resulted in enhanced cytotoxicity in the presence of RT. The effect of these compounds on pHGG was further investigated by tracking spheroid growth microscopically for 30 days, identifying four molecules that stopped spheroid-expansion solely in combination with RT (p=&lt;0.001, multilevel regression). Parallel cell-viability assays reported identical results. Furthermore, tumor migration in 3D matrigel growth assays, using non-toxic doses of the four identified compounds, revealed that two compounds (the selective HDAC-inhibitors; chidamide and entinostat) stop the infiltrative growth characteristics of pHGG cells, exclusively in combination with RT. RNA-Seq data showed that entinostat and chidamide inhibit DNA-repair pathways like the Fanconi anemia cascade and homologous recombination. Since we anticipate that entinostat- or chidamide-induced radiosensitization can be enhanced by blocking kinase-driven escape mechanisms, we are currently conducting a kinome-wide CRISPR/Cas9 knockout screen in three primary pHGG models to develop combinational therapies. These results highlight entinostat and chidamide as potential radiosensitizers in pHGG treatment.
RONC-23. NOVEL APPROACH TO REDUCE ACUTE ESOPHAGEAL TOXICITY IN CRANIO-SPINAL IRRADIATION USING INTENSITY MODULATED PROTON THERAPY
Authors: Nakra Vineet , Chilukuri Srinivas , Gaikwad Utpal , MP Noufal , Patro Kartikeshwar , T Rajesh , Shamurailatpam Dayananda , Sunder Sham , Burela Nagarjuna , T Rishan , Tonse Raees , K Muthiah , Jalali Rakesh , A Manikandan , Krishnan Ganapathy 
Published: December 2020

Abstract

INTRODUCTION
We present our experience of a novel approach using intensity modulated proton therapy(IMPT) for cranio-spinal irradiation(CSI) leading to reduced acute esophageal toxicity and reduced treatment interruptions. MATERIAL AND

METHODS
Seven children younger than 12 years old treated consecutively with CSI using IMPT were included in this study. Three among 7 children received concurrent chemotherapy(CCT). Entire vertebral body(VB) was part of target volume in all patients. The IMPT plan was generated using 3 fields with single field optimisation technique. Last 5 patients were treated using dose gradient(DG) (98-93%) deliberately created in anterior most 3-5mm of VB. Initial 2 patients were treated with intention of covering entire VB with 98% isodose. Monte Carlo algorithm was used for dose calculations and optimisation, and robustness assessed for 3mm setup and 3.5% range uncertainty.

RESULTS
The CSI dose ranged from 21.6GyE to 35GyE. In patients without DG, maximum and mean dose to esophagus(36.67GyE vs. 25.45GyE, 31.53GyE vs. 20.41GyE), midline mucosa(28.95GyE vs. 25.31GyE, 21.8GyE vs. 14.61GyE) and bowel bag(32.9GyE vs. 24.27GyE, 3.59GyE vs. 3.21GyE) were higher compared to patients with DG. Both patients where DG was not created, developed grade 2 esophageal toxicities requiring supportive care and treatment interruptions(4 and 2days). All 5 patients with DG did not develop significant esophageal toxicity and had no interruptions.

CONCLUSION
Creating a dose gradient over anterior VB using IMPT reduces dose to esophagus and midline mucosa leading to lower acute esophageal toxicity which potentially avoids treatment interruptions during CSI.
SURG-06. AWAKE CRANIOTOMY FOR BRAIN TUMOR IN PEDIATRIC PATIENTS
Authors: Almeida Carlos , Antoniazzi Alessandra Levy , Mançano Bruna Minniti , Matsushita Marcus , Bacci Rachel Eggers , Basso Danielli , Lourenço Lucas Dias 
Published: December 2020

Abstract

BACKGROUND
The challenge of surgery in neurooncology is to achieve the maximum extent of resection while preserving eloquent functions. Intra-operative cortical mapping during resection of a brain tumor allows direct stimulation in eloquent areas with a reduction in postoperative deficits. This procedure has been performed in adults and children down to the age of 11 years. There are only two cases reported on the literature of an 8-year-old and 9-year-old child submitted to an awake craniotomy for brain tumor resection. Pediatric patients are prone to more risks than adults because they become easily agitated after pain sensation. Extensive preparation for the procedure is essential for pediatric patients in order to avoid a lack of cooperation. CASE PRESENTATION: Two patients, with 9-year-old presented with seizures due to a tumor in the left temporoparietal region. In order to identify language and motor–controlling areas during resection, we proposed an awake craniotomy. Because of their ages, they were prepared by a multidisciplinary team. The children’s cooperation during the mapping procedure and tumor resection were exceptional. Postoperative cranial MRI confirmed partial resection of the lesion, whose remnant was located in the left motor area. No seizures occurred during the postoperative period, and both were discharged without a neurological disability on the fifth day after the surgery. Histology revealed a dysembryoplastic neuroepithelial tumor (WHO grade I).

CONCLUSION
Brain mapping during resection of a tumor in an awake pediatric patient is feasible and can be safely performed even in patients under 11-year-old.
SURG-14. ENDOSCOPIC SURGERY FOR PEDIATRIC INTRAVENTRICULAR TUMOR WITHOUT HYDROCEPHALUS: INDICATION, SURGICAL TECHNIQUE, AVOIDANCE OF COMPLICATION, AND ITS PROSPECT
Authors: Takayanagi Shunsaku , Takami Hirokazu , Tanaka Shota , Shin Masahiro , Saito Nobuhito 
Published: December 2020

Abstract

INTRODUCTION
Neuroendoscopic surgery is useful for intraventricular tumors accompanied by ventriculomegaly. However, it is often challenging for cases with small ventricles. Our institution is actively performing surgeries for pediatric intraventricular tumors without frank ventriculomegaly.

METHODS
Seven cases of intraventricular tumors without ventriculomegaly (5 cases of subependymal giant cell astrocytoma (SEGA) and 2 cases of germ cell tumors (GCTs)) were analyzed. The age ranged between 3 and 14 years (median 5 years). The sizes of SEGA were between 10-27mm, and all the tumors showed an enlargement around the foramen of Monro, which was the indication for surgery. Biopsy and third ventriculostomy were performed for GCTs. For resection, after making a small craniotomy of 2 x 3 cm, ellipse-cone-like sheath with a diameter of 12mm or 17mm was inserted through it to the lateral ventricle, which enabled a wide surgical view. Under a rigid endoscope of 4mm diameter, 2 types of surgical instruments were employed, making the microsurgical procedure like under a microscope, with a wider view, possible. For the cases of tumor resection, septostomy and placement of a drain in the ventricle were performed at the end of surgery.

RESULTS
The lesions were safely approached in all the cases. For resection, endoscopic microsurgery was possible, and tumor was totally removed in all the cases. No postoperative complication was observed in any of them.

CONCLUSIONS
Our experience shows that tumor resection can be safely achieved with the aid of endoscope even for cases without ventriculomegaly.
SURG-17. CLINICAL CHARACTERISTICS AND OUTCOMES OF EPILEPSY-RELATED BRAIN TUMOR IN CHILDREN
Authors: Usami Kenichi , Terashima Keita , Abe Yuichi , Kiyotani Chikako , Ogiwara Hideki 
Published: December 2020

Abstract

OBJECTIVE
Epilepsy is one of the earliest symptoms in pediatric brain tumor. Gross total resection (GTR) of the tumor does not necessarily achieve seizure free, therefore it is controversial whether surrounding epileptic foci should be resected at the initial surgery. The aims of this study are to report clinical characteristics and outcome of pediatric epilepsy-related brain tumor (ERBT) and to discuss treatment strategy.

METHODS
Subjects were children less than 18 years old who underwent surgery for ERBT. Patients in whom epilepsy had been controlled before surgery were excluded. Data were collected from medical record and retrospectively reviewed.

RESULTS
Twenty-one children (8 boys and 13 girls) were analyzed in this study. The mean age at surgery was 6.8 years. Tumor was astrocytic tumor in 10, gangliogioma in 4 and dysembryoplastic neuroepithelial tumor in 3. Intracranial subdural electrodes were placed prior to tumor resection in 5 cases. GTR was achieved in 14 (67%). Seizure free was achieved in 15 (71.4%). GTR was significantly associated with seizure free (p=0.002).

CONCLUSION
In most of ERBT, seizure free can be achieved by lesionectomy alone. However, the resection of surrounding epileptic foci is required in some cases. Detailed examinations to detect the epileptic foci should be performed in ERBT, particularly in case of drug-resistant intractable epilepsy.
SURG-19. COMPLETE RESOLUTION OF ADHD AFTER GROSS TOTAL RESECTION OF DYSEMBRYIOPLASTIC NEUROEPITHELIAL TUMOR
Authors: Navarro Luis Angel Arredondo , del Campo Regina Malinali Navarro Martín , Oliva Lorelay Livier Gutiérrez , Mancilla Juan Luis Soto , Carnalla Maria De Lourdes De La Mora , Ibarra Daniel Perez-Rulfo , Zubieta Fernando Sánchez 
Published: December 2020

Abstract
A 3-year-old boy with a history of attention-deficit/hyperactivity disorder (ADHD) presented a single focal tonic seizure. A thorough physical examination revealed no neurological deficit. A contrast enhanced MRI showed an isointense lesion in the anterior part of the cingulate gyrus extending through the left frontal lobe. After initial evaluation, the parents refused surgical treatment and a close follow up was then considered. At the age of five, the ADHD become more evident and the patient was started on methylphenidate. Poor clinical response was seen with the initiation of stimulant. The boy presented a second generalized seizure and the parents agreed surgical management. An interhemispheric approach was then performed and a gross total resection was achieved. The histopathological diagnosis corresponded to a dysembryoplastic neuroepithelial tumor (DNET). Four years after the resection, the patient is seizure free and the ADHD has also resolved without the need of medication. The disappearance of seizures is common after surgical resection of DNET tumors, but this case establishes an association with ADHD.
SWK-10. TELEHEALTH IN OUTPATIENT PEDIATRIC NEURO-ONCOLOGY CARE
Authors: Raber Shannon , Hoffman Carly , Yarbrough Carol , Branagan Linda , Penumarthy Neela , Manning Jami , Reddy Alyssa , Banerjee Anuradha , Kline Cassie , Mueller Sabine 
Published: December 2020

Abstract

BACKGROUND
Telehealth is an emerging modality that can include patient evaluation, review of test results, and clinical decision-making. Access to care and quality of life are challenges for patients with pediatric brain tumors and their families. Herein we describe the introduction of video visits within our outpatient services led by nurse practitioners and nurse coordinators.

METHODS
The pediatric neuro-oncology program at University of California, San Francisco - Benioff Children’s Hospital (UCSF) established a robust telehealth practice to improve access to care for children and young adults with brain and spine tumors. Our nursing team identifies appropriate time points to offer video visits in lieu of in-person visits. Families are guided to connect through secure video conferencing. Data was collected retrospectively through electronic medical record schedules, billing records, and UCSF patient satisfaction surveys.

RESULTS
Since 2015 we have utilized telehealth for over 400 encounters. The service was limited to patients located in California. Introduction of telehealth resulted in savings of 2300 hours of travel by car, over $22,000 in gas, and over 127,000 miles traveled. Surveys indicate patient satisfaction is equal to or better than in-person experiences. Anecdotally, this service allows for face-to-face contact with patients who have significant barriers to travel. Challenges have included technology platforms, native language, provider and patient acceptance, and billing.

CONCLUSION
Overall, telehealth is feasible as a tool to deliver outpatient care in pediatric neuro-oncology. Implementation of video visits in clinical practice increases access to neuro-oncologic care and improves quality of life for patients and families.
SWK-12. PEDIATRIC NEURO-ONCOLOGY PARENT PERSPECTIVE ON ASPECTS OF SOCIAL AND EMOTIONAL SUPPORT FOR ONLINE APPLICATION
Authors: Koch Kendra , Fettig Tatum , Slining Meghan 
Published: December 2020

Abstract
Addressing family needs for social/emotional support is part of the duty of oncology care teams. This research presents a (2020) scoping review and a (2019) focus group initiated to explore pediatric neuro-oncology parent experience of social/emotional support in conjunction with developing an online peer application to address family needs. Currently, the value of online support is in the forefront of clinical conversation. The focus group queried eight parents whose children were under neuro-oncology treatment in the Northwest USA. Thematic findings include—parents want supportive peers who have (1) a personal and deep understanding of parenting a child with serious illness (they “get it”); (2) particular characteristics and skills that promote and sustain relationships, including—(a) good social skills, (b) ability to engage in “balanced” (cancer/non-cancer) conversations, (c) individual similarities (beliefs, age of children, cancer diagnosis/treatment), (d) logistic commonalities (location, availability), (e) pro-social personal characteristics (i.e. sense of humor, emotional/social flexibility), and an (f) ability to navigate and maintain social/emotional boundaries. Parents also initiated discussion about “the burden of supportive relationships” and supporting families doing “normal” activities without worrying about treatment side effects and contagions. The literature review supports finding (1) above; reveals the paucity of evidence-based supports available to this population; underscores the critical need for practitioners and researchers to develop more evidence-based supports and interventions for families of children experiencing cancer; and supports practitioners’ consistently assessing parent and sibling social and emotional needs and then consistently referring or intervening when needs are identified.
TBIO-06. BDNF-TRKB SIGNALING REGULATES NEURON-GLIOMA SYNAPTOGENESIS AND PROMOTES TUMOR PROGRESSION
Authors: Taylor Kathryn , Zhang Helena , Hui Alexa , Gillespie Shawn , Monje Michelle 
Published: December 2020

Abstract
Pediatric high-grade gliomas (pHGG) are a devastating group of diseases that urgently require novel therapeutic options. We have previously demonstrated that pHGGs hijack mechanisms of brain development and plasticity to their advantage. Here, we investigated the role of microenvironmental BDNF on pediatric gliomas, independent of the NTRK fusion events commonly identified in infant HGG. Genetic deletion or pharmacological blockade of NTRK2 (TrkB), in patient-derived pediatric glioma increases survival in multiple DIPG and pGBM patient-derived orthotopic xenograft models. Unlike the paracrine BDNF-TrkB signaling observed between subpopulations of adult HGG malignant cells, pediatric glioma express TrkB, but not BDNF ligand. BDNF is secreted by normal brain cells in response to neuronal activity and conditioned medium experiments from cortical slices of mice indicates the brain microenvironment as the chief source of BDNF ligand. Addition of recombinant BDNF protein increases pediatric glioma cell proliferation and activates the canonical downstream MAPK signaling pathway, an effect that is blocked by genetic or pharmacological TrkB inhibition in pHGG. However, the glioma growth-promoting effects of BDNF in vivo cannot be explained by stimulation of MAPK signaling alone. We therefore examined the effects of BDNF signaling on neuron-to-glioma synapse formation, a newly recognized microenvironmental interaction important for pediatric glioma progression. We find that BDNF-TrkB signaling promotes neuron-to-glioma synaptogenesis in neuron-glioma co-culture. We are presently exploring the role for BDNF-TrkB signaling in glioma synaptic plasticity and function. Funding: Abbie’s Army Foundation
TBIO-07. SINGLE-CELL TRANSCRIPTOMIC PROFILE REVEALS MACROPHAGE HETEROGENEITY IN SONIC-HEDGEHOG MEDULLOBLASTOMA AND THEIR DISTINCT RESPONSES TO DIFFERENT TREATMENT MODALITIES
Authors: Dang Mai , Haldar Malay 
Published: December 2020

Abstract
Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment. Pro-inflammatory macrophages can suppress while anti-inflammatory macrophages can promote tumor growth. Despite their abundance in many tumors, the origins and diversity of TAMs are not well understood, especially in pediatric brain tumors. Using single-cell RNA sequencing in a genetically engineered mouse model (Ptch+/-:p53-/-) of SHH-MB, we identified the dual microglia and monocytic origin of macrophage and their transcriptomic heterogeneity. We demonstrate differential recruitment and function of macrophages under distinct modalities of tumor therapy of molecular targeted hedgehog inhibition versus radiation. We additionally identify a monocytic macrophage population recruited post-radiation that is immune suppressive, suggesting a mechanism for radiation treatment failure. These insights uncover potential strategies for immunomodulation as adjunctive therapy for radiation.
TBIO-27. RASOPATHIES AND BRAIN TUMOROGENESIS: ARE SOS1 MUTATIONS ARE CONCERNED?
Authors: Abdelmoula Nouha Bouayed , Louati Rim , Abdelmoula Balkiss , Aloulou Samir 
Published: December 2020

Abstract
Germ line gain-of-function mutations in several members of the RAS/MAPK pathway, including PTPN11 are associated with signalopathies named Rasopathies and known as Noonan syndrome and closely related conditions. Patients harboring Rasopathies are at increased risk of myeloproliferative diseases and solid tumors, such as neuroblastoma. Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, represent the second most frequent genetic defect in Rasopathies. However, SOS1 mutations are rare in human malignancies and patients with germline SOS1 mutations may not be at increased risk of developing cancer. Here, we report a SOS1 variant found to segregate in a Tunisian pedigree with many members affected by brain tumors as well as epileptic disorder. During our genetic counselling for congenital heart diseases, a 9-year-old female born at Sfax from a consanguineous couple and having pulmonic valvular stenosis, has been investigated at the molecular level. Screening of mutations in the entire coding sequence of PTPN11, Braf and SOS1, was conducted using HRM analysis and bidirectional sequencing. Heterozygous single nucleotide substitution of SOS1 gene: c.1655 G&gt;A was confirmed. This mutation affected the PH-REM linker domain with substitution of residue Arg552 to Lys: p.Arg552Lys. This mutation accounts for one-third of all mutations reported in SOS1 during Rasopathies. Although no other molecular exploration was done, family history revealed other affected children by neurodevelopmental and epileptic conditions as well as recurrent brain malignancies in the paternal family. Two aunts developed blindness and then died subsequently to tumor progression.