bluuebunny/crossref_metadata_2025_split huggingface dataset:
LGG-14. MULTI-OMIC ANALYSIS OF MAPK ACTIVATION IN PEDIATRIC PILOCYTIC ASTROCYTOMA
Authors: Sigaud Romain , Selt Florian , Hielscher Thomas , Overbeck Nina , Usta Diren , Remke Marc , Picard Daniel , Pfister Stephan M , Jones David T W , Brummer Tilman , Witt Olaf , Milde Till 
Published: December 2020

Abstract
Pilocytic astrocytomas (PA) are low-grade gliomas (pLGG) and are the most frequent childhood brain tumors. They are characterized by oncogene-induced senescence (OIS) initiated and sustained by senescence-associated secretory phenotype (SASP) factors. OIS and SASP in PA are thought to be driven by aberrations of the mitogen-activated protein kinase (MAPK) pathway (e.g. KIAA1549:BRAF fusion, BRAFV600E mutation, for the most common MAPK alterations occuring in PA), leading to its sustained activation. The MAPK pathway cascade is activated in a sequential manner: 1) ERK activation, which phosphorylates downstream partners in both cytoplasm and nucleus. 2) ERK-mediated induction of immediate early genes encoding transcription factors. 3) Induction of MAPK target genes expression. 4) Activation of downstream pathways. Our aim is to unravel the molecular partners involved at each level of the sustained MAPK pathway activation in pLGG with different genetic backgrounds (KIAA1549:BRAF fusion and BRAFV600E mutation), and leading to the induction of OIS and SASP factors expression. pLGG cell lines DKFZ-BT66 (KIAA1549:BRAF) and BT-40 (BRAFV600E) were treated with the MEK inhibitor trametinib at key time points, and gene expression profile analysis was performed, allowing transcriptome analysis at each step of the MAPK cascade. This will be combined with a whole proteomic and phospho-proteomic analysis. Combination of the transcriptome and proteome data layers will allow the identification of a) downstream targetable partners activated by the MAPK pathway involved in PA senescence, b) new putative targets that might bring benefit in combination with MAPK inhibitors.
LGG-15. PEDIATRIC LOW-GRADE GLIOMAS IN SAUDI ARABIA: RETROSPECTIVE ANALYSIS OF CHILDREN WITH LOW-GRADE GLIOMAS TREATED IN KING FAHAD MEDICAL CITY KFMC- SINGLE INSTITUTIONAL EXPERIENCE
Authors: Alammar Fahad , Alharpi Musa , Ahmad Maqsood , Al-Banyan Ayman , Alotaibi Fahad E , Shakweer Wafa Al , Abedalthagafi Malak , Mobark Nahla Ali 
Published: December 2020

Abstract
Pediatric Low-grade gliomas (PLGGs) are extremely heterogeneous tumors and account for approximately 35% of childhood brain tumors. This retrospective study on 55 newly diagnosed children (&lt;14 ys) with pathologically confirmed LGG from 2006 to 2016 aimed to review demographic data, clinical and therapeutic aspects and treatment outcome of PLGGs in children in Saudi Arabia. RESULTS: 33 (60.0%) males,22 (40.0%) females, median age at diagnosis 68 months. Pilocytic astrocytoma was the most common pathological diagnosis 42 (76.4%) location of tumor was Infratentorial in 30 patients (54.0%) and Supratentorial in 24 patients (43.2%), 19 patients (34.6%) had total surgical excision, 10 (18.2%) subtotal resection, 20 (36.4%) partial excision and 6 (10.9%) had biopsy only; After initial Surgery 30 patients (54.5%) required adjuvant chemotherapy of whom 14 patients (46.7%) experienced a treatment failure event, 25 patients (45.5%) who were initially observed post surgery 6 patients (24%) of them had relapse /progression and required further therapy. Only 2 patients (3.6%) received radiotherapy due to uncontrolled progression first line chemotherapy carboplatin and vincristine (CV) regimen was tolerated, Carboplatin allergic reactions developed in 21.1% of patients. Median follow-up of 6.49 years, the median time of relapse/ progression was 2.85 years The 5-year overall survival (OS) rates and progression free survival for all patients were 92.2 %, and 63.3% respectively. This study was to document the outcome of pediatric LGG in Saudi Arabia and to serve as a guideline for the future management with incorporation of molecular studies on pediatric LGGs which may help improve the outcome for Saudi children with LGG.
LGG-19. SPINAL LOW-GRADE GLIOMAS IN CANADIAN CHILDREN: A MULTI-CENTRE RETROSPECTIVE REVIEW
Authors: Coltin Hallie , Benipal Savvy , Rassekh S Rod , Nobre Liana Figueiredo , Bennett Julie , Tabori Uri , Wilson Bev , Mehta Vivek , Beaudoin Wendy , Zelcer Shayna , Cheng Sylvia , Hukin Juliette , Hawkins Cynthia , Bouffet Eric , Johnston Donna 
Published: December 2020

Abstract

PURPOSE
Primary spinal low-grade gliomas (LGGs) are rare, can be difficult to treat, and can result in significant morbidity. The management of pediatric spinal LGGs remains controversial.

METHODS
A national multi-centre retrospective review of spinal LGGs diagnosed in children less than 18 years of age between 1990–2015 was undertaken to examine the clinical features, pathological subtypes, and treatment outcomes.

RESULTS
Forty-three patients from five institutions were included. The median age of diagnosis was 5.2 years. All patients were symptomatic at diagnosis. Forty-four percent of patients were diagnosed at least 6 months after symptoms developed. Two patients had metastatic disease at diagnosis. The most common histology was pilocytic astrocytoma (48.8%). Molecular information was available for 15/43 patients: 6 patients had BRAF fusions and 4 patients had BRAF V600E mutations. Gross-total resection was achievable in only 6 patients. Twenty-seven patients were treated with surgery-only and the others received chemotherapy and/or focal radiation. Eleven patients were irradiated. No patients were registered in clinical trials for first-line therapy. Twenty-three patients experienced relapse or progression. Patients were followed for a median of 8.3 years (range, 0.5–20.4 years). Five-year progression-free survival (PFS) and overall survival (OS) rates were 48.3% (95% CI, 32.3% to 62.5%) and 89.7% (95% CI, 74.6% to 96.1%) respectively.

CONCLUSION
There is significant heterogeneity in surgical outcomes and treatment modalities of pediatric spinal LGGs. The PFS and OS rates remain suboptimal, likely due to tumor location. The low clinical trial enrollment rate highlights the paucity of available trials for spinal LGGs.
LGG-20. CLINICAL FEATURES AND TREATMENT RESULTS FOR PEDIATRIC OPTICO-HYPOTHALAMIC ASTROCYTOMA
Authors: Yoshimoto Koji , Hata Nobuhiro , Higa Nayuta , Yonezawa Hajime , Uchida Hiroyuki , Oyoshi Tatsuki , Mizoguchi Masahiro 
Published: December 2020

Abstract
Current consensus for the treatment of optico-hypothalamic astrocytoma (OHA) is a chemotherapy-first policy, limiting the role of surgery for histopathological diagnosis and partial decompression. However, a subgroup of OHA patients show resistance to chemotherapy and have a worse prognosis. In this study, we retrospectively analyzed our clinical experiences of the treatment of patients with OHA in two university hospitals. We have extracted and analyzed the medical charts of 15 pediatric OHA patients treated in two university hospitals since 1990. NF-1-associated OHA patients were excluded. Patient ages ranged from 10 months to 21 years (median 7 years). Out of 15 cases, 12 patients had a tumor larger than 3 cm and classified as Dodge 3. The final histopathological diagnosis was pilocytic astrocytoma in 13 cases. Three patients with tumors classified as Dodge 1 or 2 show good prognosis only by biopsy or partial resection. However, regarding Dodge 3 tumor, patient prognosis is worse regardless of chemotherapy and radiotherapy. After the initial surgery, chemotherapy was administered in 11 cases and radiotherapy in 5 cases. Multiple surgeries are needed for tumor control in 7 patients. Four patients died of tumor progression or treatment-associated complications. When the initial tumor is large enough to cause neurological deterioration, a chemotherapeutic tumor suppressive effect might be limited in a subset of large OHA cases. Therefore, it is important to consider the proper timing of safe surgical decompression in the early phase when a large tumor does not respond to chemotherapy.
LGG-21. MR-GUIDED LASER INTERSTITIAL THERMAL THERAPY FOR UNRESECTABLE AND SYMPTOMATIC PEDIATRIC LOW GRADE GLIOMA
Authors: Kram David , Benjamin-Eze Jessica , Strowd Roy , Tatter Stephen 
Published: December 2020

Abstract

BACKGROUND
Pediatric low-grade gliomas (LGG) not amenable to resection, while often indolent, represent a significant source of cancer-related morbidity and an unmet therapeutic need. Standardly, these patients are treated with sequential lines of chemotherapy, while delaying as long as possible radiation. Magnetic resonance-guided laser interstitial therapy (LITT) is a minimally invasive procedure that utilizes real-time MR thermography to ablate brain lesions.

METHODS
A 15-year-old girl was diagnosed with a suprasellar, hypothalamic LGG, BRAF V600E mutation positive. The tumor was unresectable, and due to progressive vision loss and headaches, the patient underwent treatment. Despite sequential trials of thioguanine/procarbazine/lomustine/vincristine, carboplatin/vincristine, dabrafenib, and combination dabrafenib/trametinib, the patient continued to experience debilitating headaches, malnutrition, school absenteeism, and overall poor quality-of-life. Using real-time, sequential MRI-thermometry and the Neuroblate cooled directional laser catheter, the bulk of the enhancing tumor was heated to a killing temperature.

RESULTS
At 1-year post LITT, the patient’s symptoms were dramatically improved, including greatly improved headaches, malnutrition, school absenteeism, and overall quality of life. LITT was generally well tolerated, though the patient had slight progressive left homonymous hemianopia, thought secondary to LITT impact on the optic tracts. The tumor progressively shrank over the year post-LITT to a peak of 42% volume reduction.

CONCLUSION
We report a case of a pediatric patient with an unresectable low grade glioma who underwent LITT with excellent clinical and radiographic effects. LITT should be considered for children with unresectable and morbid LGGs that fail to respond to more conventional therapies.
LGG-33. ISOMORPHIC DIFFUSE GLIOMA HAS RECURRENT GENE FUSIONS OF MYBL1 OR MYB AND CAN BE DISTINGUISHED FROM OTHER MYB/MYBL1 ALTERED GLIOMAS BASED ON A DISTINCT MORPHOLOGY AND DNA METHYLATION PROFILE
Authors: Wefers Annika K , Stichel Damian , Schrimpf Daniel , Sahm Felix , von Deimling Andreas , Blumcke Ingmar , Jones David T W , Capper David 
Published: December 2020

Abstract
Isomorphic diffuse glioma (IDG) was first described in 2004 as an epilepsy-associated supratentorial diffuse glioma with low cellularity, low proliferation and very monomorphic tumour cells. Most patients had seizures since childhood but were operated on as adults. To study the position of these lesions among brain tumours we histologically, molecularly and clinically analysed 26 histologically typical IDGs. Tumour cells were GFAP-positive, MAP2-, OLIG2- and CD34-negative and the nuclear ATRX-expression was retained. Proliferation was very low. Sequencing of 24 cases revealed an IDH-wildtype status. Cluster analyses of DNA methylation data showed that IDG has a DNA methylation profile distinct from those of different glial/glio-neuronal brain tumours and normal hemispheric tissue. About half of IDGs had copy number alterations of MYBL1 or MYB (13/25) and half of the cases analysed by RNA-sequencing had gene fusions of MYBL1 or MYB with various gene partners (11/22), often associated with an increased RNA-expression of the respective MYB-family gene. Integrating all data available, 77% of IDGs had either MYBL1 (54%) or MYB (23%) alterations. All patients had a good outcome and most were seizure-free after surgery. In summary, we show that isomorphic diffuse glioma is a distinct benign tumour in the family of MYB/MYBL1-altered gliomas. DNA methylation analysis is very helpful for their identification. More recent analyses of a large cohort of MYB/MYBL1-altered brain tumours suggest the presence of a third methylation group that primarily contains paediatric cases and seems to be distinct from IDG and angiocentric gliomas. Further histological, molecular and clinical analyses are ongoing.
LGG-34. CLINICAL AND MOLECULAR CHARACTERIZATION OF A MULTI-INSTITUTIONAL COHORT OF PEDIATRIC SPINAL CORD LOW-GRADE GLIOMAS
Authors: Grob Sydney , Nobre Lianna , Davies Kurtis , Ryall Scott , Aisner Dara , Hoffman Lindsey , Zahedi Shadi , Morin Andrew , Nellan Anandani , Green Adam , Foreman Nicholas , Vibhakar Rajeev , Hankinson Todd , Handler Michael , Hawkins Cynthia , Tabori Uri , Kleinschmidt-DeMasters B K , Levy Jean Mulcahy 
Published: December 2020

Abstract

BACKGROUND
The MAPK/ERK pathway is involved in cell growth and proliferation, and mutations in the BRAF paralog of this pathway have made it an oncogene of interest in pediatric cancer. Previous studies have identified that BRAF mutations as well as BRAF-KIAA1549 fusions are common in intracranial low-grade gliomas (LGGs). Fewer studies have tested for the presence of these genetic aberrations in spinal LGGs. The aim of this study was to better understand the prevalence of BRAF and other genetic aberrations in spinal LGG.

METHODS
We analyzed 46 spinal LGGs from children age 1–25 years from two institutions, Children’s Hospital Colorado (CHCO) and The Hospital for Sick Children (Sick Kids) for the presence of BRAF fusions or mutations. Data was correlated with clinical information. A 67 gene panel additionally screened for other possible genetic abnormalities of interest in the patient cohort from CHCO. In the Sick Kids cohort, BRAFV600E was tested for by ddPCR and IHC while BRAF fusions where detected by FISH, RT-PCR or Nanostring platform.

RESULTS
Of the 31 patient samples who underwent fusion analysis, 13 (42%) harbored the BRAF-KIAA1549 fusion. Overall survival (OS) for patients confirmed positive for BRAF-KIAA1549 was 100% compared to 76% for fusion negative patients. Other mutations of interest were also identified in this patient cohort including BRAFV600E, STK11, PTPN11, H3F3A, APC, TP53, PIK3CA (polymorphism), FGFR1, and CDKN2A deletion.

CONCLUSION
BRAF-KIAA1549 was seen in higher frequency than BRAFV600E or other genetic aberrations in pediatric spinal LGGs and trends towards longer OS although not statistically significant.
LGG-36. DESMOPLASTIC INFANTILE GANGLIOGLIOMA (DIG) WITH A PPP1CB-ALK FUSION IN A 6-YEAR-OLD GIRL
Authors: McDonald William , Nagib Mahmoud , Jenkins Robert , Ida Cristiane , Halling Kevin , Skrypek Mary , Bendel Anne 
Published: December 2020

Abstract
Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are benign glioneuronal tumors that typically occur in infants, involve the superficial cerebral cortex, and have an excellent prognosis. DIA/DIG are a distinct molecular entity based on DNA methylation profiling. BRAF600 mutations are frequently reported in DIG/DIA. A recent comprehensive genetic analysis of infantile hemispheric gliomas identified 2 unique groups: group 1 harbored alterations in the receptor tyrosine kinase (RTK) genes ALK, ROS1, NTRK, and MET and group 2 harbored alterations in the RAS/MAPK pathway. We report a case of a 6.5-year-old girl who presented with seizures and right homonymous hemianopia. MRI of her brain demonstrated a large cystic/solid left hemispheric mass with remodelling of the overlying skull, consistent with a long-standing process. She underwent a gross total resection (GTR) and pathology demonstrated a DIG with a PPP1CB-ALK gene fusion (exon 5 to exon 20) identified by RNA sequencing. She remains disease free 12 months following GTR. A literature review identified 4 reported cases of pediatric brain tumors with PPP1CB-ALK gene fusions including: a 3-month-old with a hemispheric high-grade glioma which recurred 4 years later and pathology showed mature ganglioglioma, with both tumors showing the identical PPP1CB-ALK gene fusion; a 10-month-old infant with a hemispheric low-grade glioma; an infant with a “congenital” hemispheric high-grade glioma; and a child with an astrocytoma with no further clinical data. PPP1CB-ALK gene fusion appears to be a rare oncogenic driver in gliomas of infancy, including DIG.
LGG-40. NATURAL COURSE AND MANAGEMENT OF SMALL ASYMPTOMATIC LESION SUSPECTED OF LOW-GRADE GLIOMA IN CHILDREN
Authors: Muroi Ai , Tsurubuchi Takao , Kohzuki Hidehiro , Suzuki Ryoko , Fukushima Hiroko , Yamaki Yuni , Ishikawa Eiichi , Matsumura Akira 
Published: December 2020

Abstract

OBJECTIVE
The natural course of incidentally discovered small intracranial lesions has not been well discussed. Surgical intervention, including resection and biopsy, could be achieved if the lesion is growing. We present 13 cases with incidentally found, small non-enhancing lesions without related symptoms.

METHODS
We retrospectively reviewed a series of 13 children with T1 hypointense and T2 hyperintense intracranial lesions less than 20 mm in diameter without enhancement. We excluded the patients with NF-1 or Tuberous sclerosis.

RESULTS
Most patients underwent MRI for headache unrelated to the lesions. All cases were located supratentorially. The median age of the patients at the initial examination was 8.9 years (range, 2.2–14.6). Of these children, 2 patients (15.3%) underwent surgery because of progression on follow-up MR images. The pathological diagnosis was compatible with diffuse astrocytoma. Patients were followed for a median of 55 months (range, 11–87) and the overall survival rate was 100%. No patient experienced increase in size after 3 years of follow-up.

CONCLUSIONS
In most patients with small intracranial lesions, the lesions remained stable and conservative management was appropriate. However, in a few cases, the lesions changed in size or quality and surgical intervention was necessary. Long-term follow-up at least 3 years is mandatory.
LGG-46. MOLECULAR CHARACTERIZATION OF HEMISPHERIC LOW-GRADE GLIOMAS IN CHILDREN
Authors: Mišove Adéla , Krsková Lenka , Sumerauer David , Zámečník Josef , Váňová Kateřina , Starý Jan , Perníková Ivana , Vícha Aleš , Libý Petr , Tichý Michal , Táborský Jakub , Kynčl Martin , Zápotocký Michal 
Published: December 2020

Abstract

BACKGROUND
Heterogeneous pathology in hemispheric low-grade gliomas (hemLGG) stress the importance of molecular testing in terms of prognosis prediction and targeted therapy options.

METHODS
Demographic data was collected and targeted genomic approach was employed in the single institutional study. RT-PCR was used to screen for KIAA1549-BRAF fusion and FGFR1 tyrosine-kinase domain duplication (FGFR1-ITD). Direct sequencing evaluated point mutations (BRAF ex15 and ex11, FGFR1 ex12 and ex14). Samples with no detected alteration were subjected to panel RNA-sequencing (FusionPlex Archer Diagnostics).

RESULTS
Within 2000–2019 were diagnosed 76 patients with hemLGG (median age 11.1y, range 0.0y–18.5y) comprising predominantly of ganglioglioma, dysembryoplastic neuroepithelial tumors, and diffuse astrocytoma. 40 % of hemLGG were characterized by BRAF alterations with over 2/3 of those cases harboring BRAF point mutations (two BRAFex11, 12 BRAFV600E). Notably, BRAF fusions were uncommon and detected only in six patients (two KIAA-BRAF fusion, two minor oncogenic BRAF variants, two non-KIAA BRAF fusion). 25 % of alterations were found in genes for receptor tyrosine kinases, consisting of seven patients with FGFR1-ITD, three FGFR2/3 fusions, two FGFR1 mutations, two ALK fusions, and one ROS fusion. Out of MAP kinase pathway, the most frequent alteration was IDH1 mutations (n=9). Two angiocentric gliomas were characterized by MYB-QKI fusion.

CONCLUSION
Targeted sequencing combined with RNA-sequencing is feasible to establish molecular diagnosis in majority of cases and reveal new and rare alterations. Significant prevalence of non-BRAF alterations explains heterogeneity among hemLGG.
LGG-57. SIGNALLING MECHANISMS IN PAEDIATRIC LOW-GRADE GLIOMA
Authors: Patel Ankit , Jones Tania , Woodward Lewis , Dokal Arran , Rajeeve Vinothini , Cutillas Pedro , Stone Thomas , Jacques Thomas , Sheer Denise 
Published: December 2020

Abstract
Paediatric low-grade gliomas (pLGGs) constitute the largest group of childhood CNS tumours. They often cause significant disability and morbidity, despite their indolent growth and the good survival rate of patients. The most common genetic alterations in these tumours, KIAA1549:BRAF fusion and BRAFV600E mutation, lead to abnormal activation of MAPK signalling. The central role of this pathway in pLGG development is emphasized by the occasional presence of other MAPK-activating alterations such as RTK mutations. It is not known how these different aberrations can induce the variety of clinical phenotypes seen in pLGG. Here, we compared pilocytic astrocytomas (PAs) containing the KIAA1549:BRAF fusion with glioneuronal tumours (GNTs) containing the BRAFV600E mutation, to identify differentially activated downstream targets of the MAPK pathway. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used as a multi-proteomic approach. Kinase Set Enrichment Analysis (KSEA) using PhosphositePlus and NetworkIN was used to determine relative enrichment of kinase activity in the tumours compared to healthy control brain tissue. Significant similarities and differences were found in the two tumour types. For example, more robust MAPK activation was found in the GNTs than in PAs. However, while PI3K/AKT1/mTOR signalling was active in both PAs and GNTs, there was statistically higher activation in the PAs. In both tumour types, there was significant reduction in casein kinase 2 activity, which likely affects nuclear translocation of ERK and, in turn, alters the range of its phosphorylated substrates. We will present these data together with transcriptomics to further characterise the downstream targets of these genetic alterations.
LINC-01. COMPLIANCE TO FOLLOW UP IN PEDIATRIC PATIENTS WHO HAVE RECEIVED CRANIOSPINAL IRRADIATION
Authors: Pyone Khin , Tun Thwe , Win Yin , Thinn Aye , Win Khin , Hnin Tint , Khaing Aye 
Published: December 2020

Abstract

OBJECTIVE
Attendance to follow-up after completion of cancer treatment is understudied area. Pediatric cancer patients have sequelae of illness or treatment. Many have no symptom immediately after completion of treatment. Long term follow-up is important to access disease control, early diagnosis of recurrence, second cancer and treatment-related morbidities. Purpose of this study was to evaluate the compliance to follow-up in pediatric patients treated with craniospinal irradiation (CSI).

METHODS
This was retrospective review of follow-up in pediatric neuro-oncology patients who received (CSI) from January 2017 to June 2018 in the Radiotherapy Department of Yangon General Hospital, Myanmar. RESULT: Twenty-three patients received CSI; majority (43%) were medulloblastoma. Median age was 7.5 years (3–17 years). Only seven patients (30.4%) were attended to follow-up more than 6 months after completion of treatment. More than two-thirds of patients (n=16,69.6%) were lost to follow-up. Patients in active follow-up were diagnosed and treated at earlier age below 10years (n=5,21.7%). Demographically, 5 patients (22%) were living in the region around tertiary hospital. Sixteen patients (69.6%) from rural area had limited transportation and difficulty for accommodation in which they were treated. In socioeconomic points, 18 parents (78.2%) had poor education and financial status, lack of understanding about disease, treatment, long-term effects and follow-up.

CONCLUSION
Although this was limited data in CSI patients only, loss to follow-up after 6 months was high. We need to evaluate in all pediatric cancer patients and collaborate to provide financial support, childcare centres for lodging, transportation and health education to promote compliance to follow-up.