bluuebunny/crossref_metadata_2025 huggingface dataset:
QOL-25. MICROSTRUCTURAL BRAIN CHANGES ASSOCIATED WITH NEUROCOGNITIVE AND FUNCTIONAL OUTCOMES OF INTRACRANIAL GERM CELL TUMUOR SURVIVORS – A DIFFUSIONAL KURTOSIS IMAGING STUDY
Authors: Tso Wan-Yee Winnie , Hui Sai Kam , Lee Tatia Mei Chun , Liu Anthony Pak Yin , Ip Patrick , Cheng Kevin , Fong Daniel , Chang Dorita , Ho Frederick K W , Yip Ka Man , Ku Dennis , Cheuk Daniel K L , Luk Chung Wing , Shing Ming Kong , Leung L K , Khong Pek Lan , Chan Godfrey Chi Fung
Published: December 2020

BACKGROUND

Childhood intracranial germ cell tumour (iGCT) survivors are prone to radiotherapy-related neurotoxicity which can lead to neurocognitive dysfunction. Diffusion kurtosis imaging (DKI) is a MRI technique that quantifies microstructural changes in the grey and white matter of the brain. This study aims to investigate the associations between MR-DKI metrics, the cognitive and functional outcomes of childhood iGCT survivors.

METHOD

20 childhood iGCT survivors who had received cranial radiotherapy were recruited. DKI parameters were determined for iGCT survivors and 18 control subjects. Neurocognitive assessment using the Hong Kong Wechsler Intelligence Scales for Children (HKWISC)/ Wechsler Adult Intelligence Scale – Revised (WAIS-R) and functional assessment using the Lansky/ Karnofsky performance scales were performed for GCT survivors.

RESULTS

There were significant negative correlation between the IQ scores and the mean diffusivity (MD) in multiple white matter regions of iGCT survivors including: anterior limb of internal capsule, superior fronto-occipital fasciculus, anterior corona radiata, uncinate fasciculus, cingulum and hippocampus. Mean kurtosis (MK) values of the superior fronto-occipital fasciculus were positively correlated with IQ scores. For grey matter, the MD of the olfactory, insula, caudate, heschl gyrus, parahippocampal gyrus, hippocampus, anterior cingulum, frontal inferior operculum, middle and superior temporal gyrus, middle and superior frontal orbital gyri, cuneus and precentral gyrus were negatively correlated with IQ scores. Most of the microstructural changes with associated functional impairment were white matter regions.

CONCLUSION

Our study identified vulnerable brain regions with significant white and grey matter microstructural changes that were associated with impaired cognitive function or deficits in physical functioning.
QOL-43. ENDOCRINE AND METABOLIC CHANGES IN CHILDREN TREATED FOR MEDULLOBLASTOMA
Authors: Kalinin Alexey , Strebkova Natalia , Zheludkova Olga
Published: December 2020

We examined 63 patients (40 males/23 females) after complex treatment of medulloblastoma. Patients had a median age (range) of 11.3 (5.5 ÷ 17.9) years. The median time after the end of treatment was 3.7 (1.5 ÷ 11.6) years. Endocrine disorders were detected with the following frequency: growth hormone deficiency - 98.41% (62 of 63 patients), thyroid hormone deficiency – 69.8% (44/63), adrenal hormone deficiency - 17.4% (11/63). Three cases (4.7%) of premature sexual development were also detected. Lipids levels, beta-cell function and insulin resistance (IR) during 2-h oral glucose tolerance test were evaluated. A mono frequent bioelectrical impedanciometer was used to measure body composition. Overweight (SDS BMI> 1) was observed only in 16 patients (3 girls and 13 boys), obesity (SDS BMI> 2) in 1 boy. Dyslipidemia was found in 34 patients (54%). All patients underwent oral glucose tolerance test. Insulin resistance (ISI Matsuda <2.5 and/or HOMA-IR> 3.2) was detected in 7 patients (11/1%), impaired glucose tolerance (120 min glucose ≥7.8 mmol / l) was observed in 2 patients with IR and in 2 patients without IR. At the same time, IR and impaired glucose tolerance were encountered in only 5 children with overweight and no one with obesity. All patients with impaired glucose tolerance had normal values of fasting glucose (4.3 ÷ 5.04 mmol / l) and HbA1c (4.8 ÷ 5.8%). A bioelectrical impedanciometer was used to measure body composition in 49 cases, the percentage of adipose tissue was increased in 14 patients (28%) with normal BMI.
QOL-56. THE RELAPSED AND OR PROGRESSED BRAIN TUMOURS IN CHILDREN: RHC, GLASGOW EXPERIENCE
Authors: Sastry Jairam , Mang Paul Van Siang Liang , Murpy Dermot , Ronghe Milind , McIntosh Diana
Published: December 2020

INTRODUCTION

The outcome for children with relapsed or progressed brain tumours is poor. The aim of this project was to identify total number of children who have relapsed or progressed with Brain tumour and to determine the types of tumours, treatment offered and assess outcome.

METHODS

This is a retrospective study of all patients treated for relapsed or progressed brain tumours between 2007 and 2017 at the Royal Hospital for children. Patients were identified using the unit database. Clinical data included demographics, histologic diagnosis, treatment characteristics and outcome which was obtained from electronic records.

RESULTS

46 children were included (22M:24F). The median age of diagnosis was 5 years. There were 16 histological subtypes of brain tumours: pilocytic astrocytoma (n=12, 26%), optic pathway glioma (n=4,7%), medulloblastoma (n=8, 17%), ependymoma (n=4, 9%), high grade glioma (n=3, 7%, DIPG (n=2, 4%) and others 13(32.2%). 28(61%) had relapsed at a median time of 18 months. Tumour progression occurred in 18(31%) at a median time of 21.5 months. Post-relapse or progression therapy included surgery (14, 30%), chemotherapy (17, 40%) and radiotherapy (5, 10.9%). 50% of the patients remain alive with 17(37%) being stable and 6(13%) with progression of disease. 50% had died of disease progression.

CONCLUSIONS

The relapse and or progression was seen 61% of patients. The commonest tumours in this cohort were pilocytic astrocytoma and medulloblastoma. Chemotherapy was the most used regimen followed by surgery and radiotherapy. Primary dissemination at the time of diagnosis was associated with poor prognosis.
QOL-59. CEREBELLAR MUTISM SYNDROME AND THE SURGICAL RISK FACTORS: A PROSPECTIVE MULTICENTRE STUDY OF 500 PATIENTS UNDERGOING TUMOUR SURGERY IN THE POSTERIOR FOSSA
Authors: Grønbæk Jonathan Kjær , Wibroe Morten , Toescu Sebastian , Grillner Pernilla , Mallucci Conor , Molinari Emanuela , Solem Kristin , Westerholm-Ormio Mia , Kiudeliene Rosita , Mudra Katalin , Hauser Peter , van Baarsen Kirsten , Hoving Eelco , Zipfel Julian , Nysom Karsten , Schmiegelow Kjeld , Sehested Astrid , Juhler Marianne , Mathiasen René
Published: December 2020

OBJECTIVE

Cerebellar mutism syndrome (CMS) is a severe neurological complication of tumour surgery in the posterior fossa in childhood. The incidence is reported between 8 and 39%, where CMS sets in within days of surgery and resolves within months, yet long-term sequelae are seen in most patients. This prospective cohort study investigates the course of CMS and the surgical cause of the syndrome. POPULATION AND

METHODS

We included 500 children with a tumour in the posterior fossa with planned surgery or open biopsy. Enrolment was conducted between 2014 and 2020 in 26 centres in ten European countries. Speech, neurological symptoms and surgical procedure were registered in predefined standardized forms pre-operatively and at three post-operative follow-ups within one year. PRELIMINARY

RESULTS

A total of 426 children underwent primary surgery and were eligible for analyses. CMS occurred in 56 patients (13.1%) one day (median; IQR: 0–2 days) after surgery and resolved within 38 days (median; IQR: 4–52 days). Another 58 patients (13.6%) had less severe speech impairment. Mutism was associated with lower age (OR: 0.91 [95%CI: 0.85;0.98, p=0.014]), medulloblastoma (OR: 2.5 [95%CI: 1.4;4.7, p=0.0036]) and ATRT (OR: 12.9 [95%CI: 3.4;51.9, p=0.00018]) and tumour location in the fourth ventricle (OR: 4.0 [95%CI: 2.3;7.2, p<0.0001]). Preliminary multivariate analyses revealed no significant association between mutism and surgical access.

CONCLUSION

CMS is a common complication predominantly seen in younger children after tumour surgery for a medulloblastoma or ATRT in the fourth ventricle. The incidence is not related to the surgical access in this study population.
RARE-06. OPTIMIZATION OF PROTON RADIATION THERAPY FOR GIANT CRANIOPHARYNGIOMAS
Authors: Flores Valerie Cruz , Stapleton Stacie , Tuite Gerald , Ramakrishna Naren
Published: December 2020

Craniopharyngiomas are benign intracranial tumors located in the sellar and suprasellar region. Their size and extent of invasion into surrounding structures vary considerably. While the majority of craniopharyngiomas on presentation are between 1–3 cm without hypothalamic invasion, a significant proportion of patients present with ‘giant’ craniopharyngiomas of >4cm in dimension with large cystic extension through the 3rd ventricle. These tumors pose a challenge both for surgical resection as well as for radiation therapy. Proton beam therapy (PBT) has become the preferred standard of care after subtotal resection of pediatric craniopharyngiomas. In the setting of giant craniopharyngioma, the use of proton therapy allows a reduction of dose to surrounding normal brain, but changes in cyst volume can result in either under-coverage of tumor or excess dose to surrounding brain, an effect further magnified by the sharp gradients associated with proton dose distributions. In this case report we describe the proton treatment planning and intra-treatment monitoring of two patients with giant craniopharyngiomas with largest pre-operative of dimension 6cm, and 9cm, respectively, and 6cm and 5.5cm, respectively, pre-radiation. Both patients had drains inserted to Ommaya reservoirs. We performed surveillance imaging during RT utilizing spiral computer tomography (CT) on a weekly basis and reconstructed the treatment dose on the surveillance CTs to ensure target coverage and normal tissue sparing. We compared the dosimetry in these cases for PBT versus intensity-modulated radiation therapy, characterized the cyst evolution during treatment in 3 dimensions, and define an optimized protocol for treatment planning and intra-treatment monitoring.
RARE-10. ADAMANTINOMATOUS CRANIOPHARYNGIOMA RESIDES OUTSIDE THE BLOOD BRAIN BARRIER
Authors: Prince Eric , Vijmasi Trinka , McWilliams Jennifer , Hengartner Astrid , Staulcup Susan , Foreman Nicholas , Jordan Kimberly , Dorris Kathleen , Hoffman Lindsey , Hankinson Todd
Published: December 2020

BACKGROUND

Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. Genetically engineered mouse models of ACP demonstrate that perturbation of the fetal anterior pituitary can generate tumors analogous to ACP. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control, with the most common agent being the humanized monoclonal antibody, tocilizumab. This agent demonstrated poor blood-brain barrier (BBB) penetration in primates. We present findings from two children enrolled on a phase 0 clinical trial (NCT03970226) of a single dose of preoperative intravenous tocilizumab prior to resection of newly diagnosed ACP.

METHODS

Blood samples were obtained at multiple timepoints. Serum was isolated via ficoll separation. Tumor tissue and cyst fluid were obtained 4–6 hours following the single IV dose of tocilizumab. Tissue was snap-frozen. Tumor was homogenized in RIPA buffer. Free tocilizumab in serum, cyst fluid, and tumor tissue was measured using enzyme-linked immunosorbent assay (ELISA) against a standard curve.

RESULTS

Both patients in this trial demonstrated clinically relevant levels of tocilizumab (≥ 4µg/mL) in serum, cyst fluid, and tumor tissue, compared to undetectable levels in control samples.

CONCLUSION

ACP resides outside BBB protection. In addition to demonstrating the feasibility of systemic delivery of tocilizumab, these findings indicate that other large molecules, including those known to have poor BBB penetration, may be systemically delivered as part of an antitumor regimen in the treatment of ACP.
RARE-15. EARLY PSEUDOPROGRESSION POST-RADIATION IN PAEDIATRIC HIGH-GRADE GLIOMA PATIENTS WITH CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY: TWO CASE REPORTS FROM A SINGLE CENTRE
Authors: Teng Ay-Jiuan , Gilmartin Breege , Campbell Marty , Bhatia Kanika , Wheeler Greg , Sullivan Michael , Hansford Jordan , Khuong-Quang Dong-Anh
Published: December 2020

BACKGROUND

Constitutional Mismatch Repair Deficiency (CMMRD) is a cancer predisposition syndrome caused by biallelic mutations in the mismatch repair pathway, and high-grade glioma (HGG) constitute the most prevalent brain tumours. Pseudoprogression alludes to radiological changes that mimic tumour progression, but are in fact due to other causes such as therapy related inflammation. It can occur as early as three months post treatment. To our knowledge, its characteristics in CMMRD patients has not been reported.

METHODS

We retrospectively identified seven patients with CMMRD and history of HGG at The Royal Children’s Hospital, Melbourne from 2005 to 2019. Our objective was to review the characteristics of pseudoprogression in this cohort.

RESULTS

Out of the seven patients, two with constitutional loss of PMS2 demonstrated evidence of pseudoprogression. Patient 1 presented at 16 years old with a cerebellar anaplastic astrocytoma. She developed clinical and radiological progression within two weeks of starting radiotherapy, persisting up to four months after completion. However, six months post radiation she improved without intervention and the tumour remains stable five years post therapy. Patient 2 presented at 17 years old with a midbrain anaplastic astrocytoma, and showed signs of progression four weeks after completion of radiotherapy. She was then treated with Bevacizumab, an anti-VEGFA antibody with remarkable response. She subsequently received Nivolumab, a checkpoint inhibitor with ongoing stable disease for four months.

CONCLUSION

Our findings showed that pseudoprogression can occur early in the treatment course in CMMRD patients. Identification of this entity is important for appropriate clinical management.
RARE-20. MALIGNANT PERIPHERAL NERVE SHEATH TUMOR OF A CRANIAL NERVE IN AN INFANT WITH NEUROCUTANEOUS MELANOSIS
Authors: Carter Lacey , Gross Naina , McNall-Knapp Rene , Peterson ,and Jo Elle
Published: December 2020

At one month of age, a female presented with a giant congenital nevus along lower back and thighs and hydrocephalus. A ventriculoperitoneal shunt was placed. An MRI was done at six months, initially reported as normal. At eleven months of age, five months after original MRI, patient presented with dysconjugate gaze and lethargy. MRI showed new 3.8 x 3.7 x 3.4 cm right cerebellopontine angle mass extending into Meckel’s cave and foramen ovale along with leptomeningeal disease extending from the mass along the entire length of the spinal cord. Retrospective review of prior MRI revealed subtle leptomeningeal enhancement concerning for neurocutaneous melanosis (NCM). Given the leptomeningeal disease, family elected for open biopsy and debulking of lesion instead of aggressive resection. Histologically, the mass showed hypercellular spindle cell neoplasm with mitotic activity and necrosis mixed with remnants of normal cranial nerve. GFAP was negative, excluding a glioma. HMB-45, MITF, panmelanoma, and Melan-A were negative, excluding melanoma. A negative myogenin stain ruled out ectomesenchymoma. S-100 protein and SOX-10 positivity with variable loss of staining for trimethylation of histone H3 K27 were indicative of malignant peripheral nerve sheath tumor (MPNST). Given the course of the mass, trigeminal nerve MPNST was presumed. Given the poor prognosis of intracranial MPNST and NCM, family elected to forgo treatment and was discharged with hospice. She died 25 days after surgery. Cranial nerve MPNST is rare. MPNST in patients with NCM has not previously been reported to our knowledge.
RARE-25. RETINAL ASTROCYTOMA mTOR INHIBITOR THERAPY IN TUBEROUS SCLEROSIS MOSAICISM
Authors: Evans Naomi , Paton Katherine , Gill Harinder Kaur , Hukin Juliette
Published: December 2020

INTRODUCTION

Everolimus is an inhibitor of mTORC1 (mammalian target of rapamycin complex 1), it is Health Canada and FDA approved for SEGA and renal angiomyolipoma in the setting of tuberous sclerosis complex (TSC). There is little data available in regards to this treatment of TSC associated retinal astrocytoma (RA). Although the behaviour of RA is often indolent or slowly progressive, aggressive behaviour with retinal detachment and neovascular glaucoma requiring enucleation has been reported in several patients. Definite TSC diagnosis is established when either two major features or one major and two minor features are present. Probable TSC diagnosis is established when one major plus one minor feature is present.

METHODS

We report a child with probable TSC mosaicism, with negative serum NGS for TSC but RA and retinal achromic patch on the left. A left retinal peripapillary astrocytoma around optic nerve and very close to fovea was noted. There was concern that if it grew or there were to be any leakage it would cause visual impairment. This lead to therapy with everolimus 4.5 mg/m2/d aiming for level between 5 and 10 mcg/L.

RESULTS

This boy has had a gradual reduction of the RA over the last 29 months, with healthy retina in the region no longer occupied by the lesion and preserved vision. He has tolerated therapy well with occasional mouth ulcers.

CONCLUSION

mTORC1 inhibition is effective therapy to preserve vision in the setting of retinal astrocytoma and tuberous sclerosis mosaicism.
RARE-33. GIANT CELL TUMOR OF THE SKULL BASE WITH A HISTORY OF A SUCCESSFUL RESPONSE TO DENOSUMAB AND LATER DEVELOPING A SECOND TUMOR
Authors: Avagyan Manushak , Tamamyan Gevorg , Danielyan Samvel , Harutyunyan Martin , Karapetyan Nune , Karamyan Nerses , Vardevanyan Hovhannes , Mkhitaryan Armen , Bardakhchyan Samvel
Published: December 2020

BACKGROUND

Giant cell tumor of bone(GCTB) is a rare neoplasm with unpredictable behavior, possible malignant transformations, and/or lung metastases. Surgery is usually the treatment of choice. In unresectable or metastatic cases, treatment with denosumab is a new treatment option. CASE PRESENTATION: A 14-years-old female presented with cachexia, dysphagia, diplopia, discoordination, strabismus, and multiple cranial nerve palsies in 10.2015. MRI revealed intra-extracranial mass arising from C2 vertebrae, compressing the medulla oblongata and the left cerebellar hemisphere, invading to the sphenoid bone and nasopharynges. Biopsy showed a GCTB. Surgical resection was done, which was incomplete because of tumor location (cranial nerve and vertebral artery involvement). Then local radiation therapy was performed 50.4Gy. During RT patient’s condition declined and MRI showed disease progression. Treatment with denosumab 120mg q4w was initiated in 03.2016, which yielded successful results. Disease was under control for three years until 03.2019. Then she returned with clinical symptoms of diplopia and severe headache. MRI showed local tumor progression. Repeated biopsy revealed undifferentiated pleomorphic sarcoma, which could be either a malignant transformation of GCTB or a new tumor. The patient later underwent two cycles of chemotherapy with Ifosfamide/Doxorubicin. MRI after 2nd cycle showed marked tumor progression. The patient didn’t receive any further treatment because of cachexia and died due to disease progression in 12.2019.

CONCLUSION

To our knowledge, this is the youngest patient ever reported with a skull base tumor with such a clinical development, successful and long-time remission with denosumab and with such a chemotherapy-resistant malignant transformation or second cancer.
RARE-41. SECOND MALIGNANCIES FOLLOWING TREATMENT FOR PRIMARY CENTRAL NERVOUS SYSTEM TUMORS IN PEDIATRIC PATIENTS: A SINGLE-INSTITUTIONAL RETROSPECTIVE REVIEW
Authors: Pytel Nicholas , Dedekam Erik , Salamat M Shahriar , Puccetti Diane
Published: December 2020

Second malignant neoplasms following treatment for primary central nervous system (CNS) tumors in children are rare occurrences but may often have dire consequences, particularly, if thought to be induced by prior therapies. The authors retrospectively reviewed pediatric patients with primary CNS malignancies from the University of Wisconsin over the last 25 years (1994 – 2019) with any secondary malignant neoplasm and determined seven patients met criteria. Treatment modalities were reviewed with all patients receiving surgery, chemotherapy, and radiotherapy for treatment of their first malignancy. The second neoplasms found included 4 high-grade gliomas, 1 meningioma, 1 thyroid carcinoma, and 1 myelodysplastic syndrome. The median latency time between diagnoses was 9 years (range 4 -17 years). The outcomes varied according to histopathology of the second neoplasm with the high-grade glioma patients all deceased from progressive disease. The high-grade gliomas were thought to have been induced by prior radiation in most cases. The remaining patients are still alive, at the time of this writing, and in follow up after treatment for their second neoplasm. Thus, long-term follow up is essential for children treated for a primary CNS tumor given the variety of second neoplasms that could arise with differential consequences. In addition to our single institutional outcomes, we will also present an updated review of the literature of pediatric patients with primary CNS tumors and second malignancies.
RARE-43. FAVORABLE OUTCOME OF A YOUNG GIRL WITH RECURRENT METASTATIC PINEOBLASTOMA ASSOCIATED WITH A DICER1 MUTATION
Authors: Rossi Adam , Verona Gregory , Ritter Ann , Richard Hope , Sisler India , Wang Zhihong
Published: December 2020

Pineoblastomas have been thought to portend a poor prognosis, especially in younger children or those with metastases. Long term survivors after relapse, especially for those with metastatic disease are rare. We report a young girl with a DICER1 mutation who survived recurrent metastatic pineoblastoma. She was initially diagnosed at the age of 3 with a localized pineoblastoma, underwent gross total surgical resection, and received high dose chemotherapy with autologous stem cell transplant per COG ACNS0334 without radiation therapy. 16 months after completion of treatment, she relapsed at primary site with widespread spinal metastasis. She then received cranial spinal radiation of 3600Gy with proton beam, with boost to primary to 5580Gy, followed by chemotherapy with Temozolomide, Irinotecan and Avastin per COG ACNS0821. She is now 3 years and 3 months from completion of treatment, is doing well clinically with stable imaging findings. No particular alteration was identified from the tumor molecular testing of her initial pineoblastoma. Of note, she was diagnosed with pleuropulmonary blastoma soon after her initial diagnosis of pineoblastoma, and was found to have a DICER1 mutation (c.2062C>T; pR688*) thought to be a nonsense mutation. While radiation therapy following recurrence is known to improve the outcome, more recent studies suggest that tumors lacking the molecular features of high grade glioma also has a positive impact on prognosis. In addition, we speculate that DICER1 mutations might increase sensitivity of cancer cells to some chemotherapy through modulating gene expression and /or interfering with DNA repair mechanisms, therefore, affecting treatment outcome.
RARE-45. SARCOMAS INVOLVING THE CENTRAL NERVOUS SYSTEM AT INITIAL PRESENTATION IN CHILDREN AND YOUNG ADULTS: A CASE SERIES
Authors: Liu Yen-Lin , Chen Shu-Mei , Lee Hsin-Lun , Huang Jia-Hui , Chen Shu-Huey , Kao Yu-Chien , Chang Hsi , Tsai Min-Lan , Tseng Sung-Hui , Hsieh Kevin L C , Chang Chia-Yau , Wang Jinn-Li , Miser James S , Wong Tai-Tong
Published: December 2020

Sarcomas of bone, soft tissue, or neural origin may occasionally invade the central nervous system (CNS), causing diagnostic and therapeutic challenges. We aim to investigate the clinical features of sarcomas involving the CNS at initial presentation. During 2015/01–2019/12, nine consecutive patients (4 Males and 5 Females) younger than 30 years of age treated at a University Healthcare System in Northern Taiwan were included. The median age was 8.7 years (range, 2–24 years); diagnoses were Ewing Sarcoma with EWSR1 rearrangements (n=4), CIC-NUTM1 Sarcoma (n=1), Osteosarcoma (n=2), Malignant Peripheral Nerve Sheath Tumor (MPNST; n=1), and extramedullary myeloid sarcoma (n=1). The tumors originated from the skull (n=1), dura (n=1), vertebra (n=4), spinal canal (n=1), or extra-CNS sites (n=2). Four patients had metastases (1 Ewing sarcoma, 2 osteosarcoma, and 1 extramedullary myeloid sarcoma). The main symptom at diagnosis was facial/eye pain (n=2), back pain (n=3), arm weakness (n=1), or gait disturbance (n=3). Upfront neurosurgical decompression (n=7) or urgent radiotherapy (n=1) was performed in most patients. At a median follow-up duration of 20.1 months, the overall survival rate was 70%. All patients with Ewing sarcoma (n=4) and CIC-NUTM1 sarcoma (n=1) achieved Complete Response after surgery, interval-compressed chemotherapy, radiotherapy, and adjuvant chemotherapy. Patients with stage IV osteosarcoma (n=2) had Partial Response; the patients with MPNST and extraskeletal myeloid sarcoma died of Progressive Disease at 18 and 3 months after diagnosis, respectively. We conclude that timely decompression, early diagnosis, and histology-driven multimodality treatment are effective strategies in managing sarcomas involving the CNS.
RARE-47. DIFFUSE LEPTOMENINGEAL DISSEMINATED GLIONEURONAL TUMOR: CASE-SERIES
Authors: Sanders Felipe Hada , Matushita Hamilton , Azambuja Alessandra , Frasseto Fernando , Rosemberg Sergio , Odone Vicente , Teixeira Manoel Jacobsen
Published: December 2020

Diffuse leptomeningeal disseminated glioneuronal tumor (DL-GNT) is a rare brain tumor that presents as a plaque-like subarachnoid tumor, commonly involving the basal cisterns and interhemispheric fissure of children but lacking intraparenchymal tumor. Here we report two cases focusing on clinicopathologic features. In all patients, radiography revealed characteristic leptomeningeal thickening and enhancement with minor superficial parenchymal lesions. The broadcast of the knowledge about this type of disease is important to increase awareness on this subject.
RARE-58. CONGENITAL METASTATIC CHORDOMA OF THE CLIVUS
Authors: Grajowska Wieslawa , Stepaniuk Maria , Trubicka Joanna , Wójcicka-Kowalczyk Katarzyna , Krych Piotr , Dembowska-Baginska Bozenna , Perek-Polnik Marta
Published: December 2020

Chordomas are rare midline axial skeletal neoplasms that typically present in adults. They are infrequent in childhood with typical localization in the spheno-occipital skull base. They are derived from remnants of the embryonic notochord. We present the case of 4 months old girl, who was born with „blueberry muffin” syndrome and was first negatively diagnosed for neuroblastoma and leukemia (two negative skin biopsies were performed) was admitted with axial laxity. In imaging testes there was a tumor of the scull base, metastases in the lungs and kidneys (that were not seen at previous assessments) and a small lesion in the heart. The third biopsy of skin lesion was performed and pathological examination revealed a neoplasm composed of cords, clusters, and chains of multivacuolated cells embedded within a myxoid matrix and separated by fibrous septa. No atypical and dedifferentiated features were present. Mitotic activity was not observed. Neoplastic cells showed the typical cytoplasmic immunostaining for EMA, S100 and cytokeratin AE1/AE3, strong nuclear brachyury expression, and retention of nuclear INI-1 expression. The diagnosis of chordoma was established. Neoplastic tissue and blood samples were obtained for molecular analysis using next generation sequencing, including germline mutations assessment (are ongoing). Chemotherapy as for soft tissue sarcomas was undertaken. Currently a patient is on treatment with improvement of neurological status.
RONC-08. SURVIVAL IMPACT OF POSTOPERATIVE RADIOTHERAPY TIMING IN PEDIATRIC AND YOUNG ADULT EPENDYMOMA
Authors: Shah Sunny , Mallory Chase , Gates Kevin , Rubens Muni , Maher Ossama , Niazi Toba , Khatib Ziad , Appel Haley , Kotecha Rupesh , Mehta Minesh , Hall Matthew
Published: December 2020

INTRODUCTION

Postoperative radiotherapy is commonly given for WHO Grade 2–3 intracranial ependymoma. Clinicians generally aim to begin radiotherapy ≤5 weeks following surgery, but the optimal timing remains uncertain.

METHODS

The National Cancer Database was queried for patients (age ≤39 years) with localized WHO Grade 2–3 intracranial ependymoma treated with surgery and postoperative radiotherapy. Multivariable logistic regression was used to identify factors associated with delayed postoperative radiotherapy, defined as starting >8 weeks after surgery. Overall survival (OS) curves were plotted based on radiotherapy timing (≤5 weeks, 5–8 weeks, and >8 weeks after surgery) and compared by log-rank test. Multivariate analysis (MVA) was used to identify factors associated with OS.

RESULTS

In the final analytic set of 1,043 patients, age ≥21 years (OR 2.07, 95% CI 1.56–2.74) and WHO Grade 2 tumors (OR 1.41, 95% CI 1.08–1.85) were significantly associated with delayed time to adjuvant radiotherapy. No difference in 3-year OS was observed in patients who initiated radiotherapy ≤5 weeks, 5–8 weeks, and >8 weeks after surgery (89.8% vs. 89.1% vs. 88.4%; p= 0.796). On MVA, anaplastic histology (HR 2.414, 95% CI 1.784–3.268, p<0.001) and subtotal resection (HR 2.398, 95% CI 1.519–3.788, p<0.001) were significantly associated with reduced OS. Timing of radiotherapy, total radiotherapy dose, age, insurance status, and other factors were not significant.

CONCLUSION

Delayed postoperative radiotherapy was not associated with inferior survival in patients with intracranial ependymoma, suggesting delayed radiotherapy initiation may be considered in patients requiring longer postoperative recovery or referral to an appropriate radiotherapy center.
RONC-26. A CASE OF RADIATION NECROSIS OF THE CEREBELLUM 16 YEARS AFTER CHEMORADIOTHERAPY FOR MEDULLOBLASTOMA
Authors: Miyata Mayuko , Nonaka Masahiro , Asai Akio
Published: December 2020

BACKGROUND

If new lesions are observed during follow-up of the malignant tumor after treatment, it is difficult to distinguish whether the tumor is a recurrent lesion, secondary cancer, or radiation necrosis of the brain. We have encountered a patient with symptomatic radiation necrosis of the cerebellum 16 years after treatment of medulloblastoma. CASE PRESENTATION: A 24-year-old man who had received a tumor resection and chemoradiotherapy for cerebellar medulloblastoma at the age of 8 presented with dizziness. For the past 16 years, there was no recurrence of the tumor. He subsequently underwent MRI scan, and T1-Gd image showed enhanced lesion in the right cerebellar peduncle. Cerebrospinal fluid cytology analysis was negative for tumor. We suspected tumor reccurence or secondary cancer, and performed lesion biopsy. The result of the pathological examination was radiation necrosis of the cerebellum. DISCUSSION: The interval of radiation necrosis of the brain and radiotherapy can vary from months to more than 10 years. So, whenever a new lesion is identified, radiation brain necrosis must be envisioned. According to guidelines in Japan, there is no absolute examination for discriminating tumor recurrence from radiation brain necrosis and diagnosis by biopsy may be required.

CONCLUSION

We experienced a case of symptomatic radiation necrosis of the cerebellum 16 years after treatment. In patients showing new lesion after long periods of time, the possibility of radiation necrosis to be considered.
SURG-03. IMMERSIVE VIRTUAL REALITY APPLICATIONS IN NEUROSURGICAL ONCOLOGY
Authors: Carai Andrea , Mastronuzzi Angela , Colafati Giovanna Stefania , Voicu Paul , Onorini Nicola , Carboni Alessia , Del Baldo Giada , Herur-Raman Aalap Jamadagni , De Benedictis Alessandro , Marras Carlo Efisio
Published: December 2020

Tridimensional (3D) rendering of volumetric neuroimaging is increasingly been used to assist surgical management of brain tumors. New technologies allowing immersive virtual reality (VR) visualization of obtained models offer the opportunity to appreciate neuroanatomical details and spatial relationship between the tumor and normal neuroanatomical structures to a level never seen before. We present our preliminary experience with the Surgical Theatre, a commercially available 3D VR system, in 60 consecutive neurosurgical oncology cases. 3D models were developed from volumetric CT scans and MR standard and advanced sequences. The system allows the loading of 6 different layers at the same time, with the possibility to modulate opacity and threshold in real time. Use of the 3D VR was used during preoperative planning allowing a better definition of surgical strategy. A tailored craniotomy and brain dissection can be simulated in advanced and precisely performed in the OR, connecting the system to intraoperative neuronavigation. Smaller blood vessels are generally not included in the 3D rendering, however, real-time intraoperative threshold modulation of the 3D model assisted in their identification improving surgical confidence and safety during the procedure. VR was also used offline, both before and after surgery, in the setting of case discussion within the neurosurgical team and during MDT discussion. Finally, 3D VR was used during informed consent, improving communication with families and young patients. 3D VR allows to tailor surgical strategies to the single patient, contributing to procedural safety and efficacy and to the global improvement of neurosurgical oncology care.
SURG-24. NOVEL MALLEABLE FORCIPES FOR ENDOSCOPIC ASSISTED TECHNIQUE IN PEDIATRIC BRAIN TUMORS
Authors: Nakahara Yukiko , Ito Hiroshi , Yoshioka Fumitaka , Inoue Kohei , Ogata Atsushi , Masuoka Jun , Abe Tatsuya
Published: December 2020

Recent advances in optical devices and surgical instruments have been applied to neurosurgery. Even with modifications, one of the most serious risks is injury of neuronal and vascular structure caused by operation of surgical instruments in a narrow surgical field. Fixed instruments are not practical for pediatric brain tumor surgeries because the length of the curved or angled tip portion is limited because of the narrow entrance. We developed a novel malleable forceps to resolve the difficulties related to microsurgical procedures. The malleable forceps has two shafts with a sharp cup at the tip. The entire forceps was made of stainless steel, with a silver and nickel alloy inserted between 10 and 40 mm from the tip. In the alloy part, the surgeon can flex the forceps freely using a special cylinder. The special cylinder is useful to prevent from slipping of the cups of tip. The maximum angle that can be bent is 70 degrees vertically. We also developed a monoshaft malleable forceps. We used these flexible forcipes in the case of various pediatric brain tumors including craniopharyngioma. We performed tumor resection by anterior interhemispheric trans-lamina terminalis approach. After procedure of tumor resection using microscope, endoscope inserted around the pituitary stalk. The piece of calcified tumor could be easily removed without any complications. These forcipes can be deformed to an appropriate angle and can be applied to various cases, especially pediatric brain tumors.
SWK-02. WEAVING COMFORT AND SUPPORT FOR CHILDREN WITH BRAIN TUMORS AND THEIR FAMILIES IN AN OUTPATIENT CLINIC
Authors: Hawks Ria , Bloom Jane , Packard Maurine , Lugo Sonia , Ulysses Nadine , Zacharoulis Stergios
Published: December 2020

Parents of children diagnosed with brain tumors report high levels of stress at diagnosis and feelings of “being lost” on transition to outpatient follow-up care (Jackson AC, et al, 2007). Ssori is a Japanese form of free-style weaving that encourages people facing life-limiting challenges to discover inner strengths. We report our experience with Saori weaving with brain tumor patients and their families in a pediatric oncology outpatient clinic at a major university medical center. During 2019, we offered weaving sessions twice a week. We had a total of 151 encounters with hematology/oncology patients (age 5–18 years), siblings, or parents. Among these patients there were 20 with primary brain tumor diagnoses. Weaving was offered in the art therapy area of the clinic. After creating a fabric, the weavers had the opportunity to have their work sewn into functional objects, such as pillows, bags, purses, or healing pouches filled with beans that can be heated or cooled for comfort. Brain tumor patients readily engaged in weaving, despite various degrees of neurologic disability including hemiparesis or low vision. In the words of an 8 y/o weaver. “This is so cool. Daddy, can we always come when the weavers are here, so I can weave?” And from a mother: “This is great. She’s focused and busy!” Case studies, including a presentation of Legacy work, will be reported. In conclusion, Saori weaving can be an impactful intervention for childhood brain tumor patients and their families in an outpatient clinic setting.
SWK-03. CAREGIVER EXPERIENCES FOR PEDIATRIC BRAIN TUMOR PATIENTS AND THEIR FAMILIES AT A DEDICATED MEDICAL SPECIALTY CAMP
Authors: Brownfield Ryan , Galantowicz Barb , Russell Claire , Chabot Jennifer , Coven Scott
Published: December 2020

BACKGROUND

Medical specialty camps have provided children with unique psychosocial experiences; however, dedicated pediatric brain tumor camps are rare in the United States, except in limited locations. This study aimed to glean caregiver perceptions from a dedicated family brain tumor camp, and to learn about the family experience with navigating a neuro-oncology diagnosis. DESIGN: Flying Horse Farms is a non-profit organization located in Mt. Gilead, Ohio and a member of the SeriousFun Children’s Network, a global community of camps and programs serving children with serious illnesses and their families, at no cost. The institutional review board at Ohio University approved this project at Flying Horse Farms in September 2017. Consent from caregivers was obtained prior to participation in the study, which provided the opportunity to complete three separate phases: a pre-camp survey, attend a semi-structured interview during the weekend, and complete a post-camp survey.

RESULTS

11 families were present for the weekend, and 10 families consented to participate in all three phases. For 6 families, this was their first experience at Flying Horse Farms. For 9 of the 10 families, the camp met their expectations. Additionally, 9 out of 10 families reported they would be interested in attending a diagnosis specific camp again in the future.

CONCLUSIONS

This work demonstrates the feasibility of conducting research at a medical specialty camp without restricting the camp experience. Better understanding of the attendee’s attitudes toward camp may enhance the experience and the neuro-oncology journey in the future.
SWK-07. A MULTINATIONAL SURVEY OF PAEDIATRIC NEURO-ONCOLOGY SERVICES: A EUROPEAN RESEARCH NETWORK (ERN) PAEDCAN PROJECT
Authors: Cooper Katherine , Pizer Barry , Lane Steven , Rutkowski Stefan
Published: December 2020

BACKGROUND

Brain tumours are clinically and biologically highly diverse and account for 25% of paediatric neoplasms. They carry the highest mortality and morbidity of tumour groups. Their management presents significant challenges with performing modern diagnostic assessments, applying multimodal treatment and establishing interdisciplinary cooperation. Outcomes across Europe differ significantly with varying 5year survival reports of 42–79%. This SIOP-Europe PaedCan survey assessed the structures and facilities for individual states and highlight areas for cooperation and support. DESIGN: An online questionnaire was sent to SIOP-Europe Brain Tumour Group members. This had 55 questions assessing pathology, staging, surgery, radiotherapy and paediatric oncology infrastructure. For analysis of the data we divided countries into lower and higher economic status according to GDP (World Bank 2019) with a cut off of $30,100.

RESULTS

There were 388 respondents from 44 countries in 181 different institutions. In the lower GDP group we noted decreased access to biological characterisation of tumours and interdisciplinary tumour boards. In this group of nations, patients were less likely to have treatment by a paediatric specialist neurosurgeon, paediatric neuro-oncologist, neuroradiologist, and paediatric radiation oncologist. There was also less availability to perform early MRI (ventilated) and less access to proton beam therapy. This study supports the aim of the ERN to produce a roadmap document with specific standards and publish guidelines for all relevant diagnostic and therapeutic components of care. The ERN also aims to identify a network of institutions to provide patient advice and training to equalise treatment and outcomes for all children across Europe.
TBIO-01. SEX DIFFERENCES IN REDOX STATE UNDERLIE GLUTAMINE DEPENDENCY IN MALE GLIOBLASTOMA
Authors: Sponagel Jasmin , Zhang Shanshan , Chinnaiyan Prakash , Rubin Joshua , Ippolito Joseph
Published: December 2020

Glioblastoma (GBM) is an aggressive brain tumor in children and adults. It occurs more commonly in males, but female patients survive significantly longer. Understanding the molecular mechanisms that underlie those sex differences could support novel treatment strategies. In this regard, we found that male and female GBM patient samples differ in their metabolite abundance and that males exhibit a significantly higher abundance of amino acid metabolites. We confirmed those findings in a murine model of GBM, which has previously yielded important insights into sexual dimorphism in GBM. Furthermore, we found that male GBM cell cultures are significantly more sensitive to amino acid deprivation, which was almost entirely driven by amino acids involved in the synthesis of the antioxidant glutathione. Glutaminase 1 (GLS1) mediates the conversion from glutamine to glutamate, a crucial component of glutathione. We found that male GBM cells exhibited higher levels of GLS1, suggesting they are more dependent on glutamate. Indeed, we found that male GBM cells are more sensitive to pharmacological GLS1 inhibition with the clinical inhibitor CB-839. This correlated with significantly increased reactive oxygen species (ROS) in males compared to females. We further confirmed sex differences in redox state through pharmacological depletion of glutathione that resulted in a significant increase in ROS and cell death in male GBM. Together, these data indicate that male GBM cells are more dependent on glutamine to regulate ROS levels. This reveals novel sex-specific metabolic targets for GBM and underlines the importance of considering sex in metabolic targeting approaches.
TBIO-02. IMMUNE PROFILING OF RARE EMBRYONAL BRAIN TUMORS REVEAL EVIDENCE OF DYSREGULATED INTERFERON SIGNALLING AS A POTENTIAL DETERMINANT OF IMMUNOLOGICAL HETEROGENEITY
Authors: Popovski Dean , Yao Fupan , Bondoc Andrew , Al-Karmi Salma , Ho Ben , Lindsay Holly , Li Xiao-Nan , Rutka James , Huang Annie
Published: December 2020

Embryonal brain tumors (EBTs) remain the most common malignant pediatric brain tumors. Despite recent advances and improved understanding of the molecular biology of EBTs, clinical outcomes remain poor for rare EBTs. Previous large-scale genomic studies of rare EBTs have shed light on distinct genomic, transcriptomic and epigenomic profiles. Interestingly, these studies have revealed prominent tumor heterogeneity that provides opportunity to develop novel treatment strategies to improve patient outcomes. To examine the tumor microenvironment and identify tumor- specific biological dependencies, we performed deconvolution analysis of bulk gene expression (171 RNA-seq, 236 microarrays) and 586 methylation arrays, which revealed significant intra and inter-tumoral heterogeneity and implicated interferon (IFN)-mediated signalling as a determinant of a distinct immunological profile in rare EBTs. To further elucidate the importance of IFN signalling, we performed scRNA-seq on 20 primary samples, which provided evidence of a spectrum of IFN-immunological responses that vary from immunosuppressive to immunologically exhaustive that occur in a host dependent manner. To further validate our findings, we utilised a genetically engineered murine model of Atypical Teratoid Rhabdoid Tumor and primary xenografts in humanised mice to corroborate our in-silico profiles in vivo. Through amalgamation of our in-silico data with our in vivo data, we have identified evidence that dysregulated IFN responses represent a core element of the immunological heterogeneity present within subsets of rare EBTs. An improved understanding of the immune milieu in rare EBTs will provide avenues to develop specific onco-immune targets to address this clinical need.
TBIO-09. IN SILICO ANALYSIS IDENTIFIES A PUTATIVE CELL-OF-ORIGIN FOR BRAF FUSION-POSITIVE CEREBELLAR PILOCYTIC ASTROCYTOMA
Authors: Younes Subhi Talal
Published: December 2020

Childhood cancers are increasingly recognized as disorders of cellular development. This study sought to identify the cellular and developmental origins of cerebellar pilocytic astrocytoma, the most common brain tumor of childhood. By leveraging publicly available gene expression data from such tumors and controlling for driver mutations, a set of eight known neuro-developmental genes were identified as being upregulated in cerebellar pilocytic astrocytoma. Mapping those genes onto mouse neuro-developmental atlases identified significant overlap in their expression within the ventricular zone of the cerebellar anlage. Further analysis with a single cell RNA-sequencing atlas of the developing mouse cerebellum defined this overlap as occurring in ventricular zone progenitor cells at the division point between GABA-ergic neuronal and glial lineages, a developmental trajectory which closely mirrors that previously described to occur within pilocytic astrocytoma cells. Furthermore, ventricular zone progenitor cells and their progeny exhibited evidence of MAPK pathway activation, the paradigmatic oncogenic cascade known to be active in cerebellar pilocytic astrocytoma. Gene expression from developing human brain atlases recapitulated the same anatomic localizations and developmental trajectories as those found in mice. Taken together, these data suggest this population of ventricular zone progenitor cells as the cell-of-origin for BRAF fusion-positive cerebellar pilocytic astrocytoma.
TBIO-21. Lnc-TALC PROMOTES O6-METHYLGUANINE-DNA METHYLTRANSFERASE EXPRESSION VIA REGULATING THE C-MET PATHWAY BY COMPETITIVELY BINDING WITH miR-20b-3p
Authors: Wu Pengfei , Cai Jinquan , Chen Qun
Published: December 2020

Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules implicated in diverse biological processes, including therapeutic resistance. However, the mechanisms underlying lncRNA-mediated temozolomide (TMZ) resistance in glioblastoma (GBM) remain largely unknown. To illustrate the role of lncRNA in TMZ resistance, we induce TMZ resistant GBM cells, perform a lncRNA microarray of the parental and TMZ-resistant cells, and find an unreported lncRNA in GBM, lnc-TALC (temozolomide-associated lncRNA in glioblastoma recurrence), correlated with TMZ resistance via competitively binding miR-20b-3p to facilitate c-Met expression. A phosphorylated AKT/FOXO3 axis regulated lnc-TALC expression in TMZ-resistant GBM cells. Furthermore, lnc-TALC increased MGMT expression by mediating the acetylation of H3K9, H3K27 and H3K36 in MGMT promoter regions through the c-Met/Stat3/p300 axis. In clinical patients, lnc-TALC is required for TMZ resistance and GBM recurrence. Our results reveal that lnc-TALC in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.