bluuebunny/crossref_metadata_2025_split huggingface dataset:
LGG-03. Pediatric spinal deformities concomitant with spinal cord pilocytic astrocytoma
Authors: Kapitancuke Monika , Rutkauskaite Vilma , Zagorskis Rimantas , Bernotavicius Giedrius , Lapteva Ona , Rascon Jelena 
Published: June 2022

Abstract
INTRODUCTION: Childhood spinal cord tumours may lead to spinal deformity. Rapid scoliosis progression, a left thoracic curve and early onset scoliosis are associated with an increased risk of intraspinal anomalies, therefore magnetic resonance imaging (MRI) should be performed. CASE PRESENTATION: A 1-year-old girl presented with progressive early onset scoliosis. MRI of the spine showed diffuse intramedullary lesion at vertebral level T5 – T11 and abnormal curvature of the thoracic spine to the right – 39-degree Cobb angle, after a few moths – 71-degree. Blood and cerebrospinal fluid examination ruled out a neuroinfection and autoimmune diseases. Histology revealed BRAF V600E-mutant pilocytic astrocytoma (PA) (IDH non-mutant), DNA methylation profiling – PA, MGMT promoter methylation – not detected, SNP-A karyotyping – normal. Treatment with weekly vinblastin was started due to non-operable tumour and progressive scoliosis. Spinal deformity was managed using serial casting with only mild correction of curvature. In the second case report, a 14-year-old boy either presented with progressive scoliosis. Spine x-ray showed abnormal curvature of the thoracic spine to the left - 89-degree Cobb angle and after a few years - 120-degree. MRI of the spine detected intramedullary tumour masses located at vertebral level T3-T5. Surgical resection revealed BRAF V600E-mutant PA (IDH, ATRX, TERT non-mutant), DNA methylation profiling – PA, MGMT promoter status – not methylated, SNP-A karyotyping – non-specific trisomy of chromosome 5. The patient was followed-up by routine spine MRI. However, after 8 months new spinal cord masses appeared. It was decided to correct scoliosis only after the total tumour removal. CONCLUSIONS: Intramedullary spinal tumours are overall rare in the pediatric population. Of these, PA accounts for the majority, however treatment remains challenging. BRAF V600E mutation has relatively high frequency in PA. This mutation identification opens more treatment options such as targeted therapy with BRAF V600E and MEK inhibitors for progressive disease.
LGG-04. Clinical and molecular characterization of metastatic pediatric low grade gliomas
Authors: Lindsay Holly , Stuckert Austin , Chintagumpala Murali , Su Jack , Baxter Patricia , Okcu M Fatih , Malbari Fatema , Rednam Surya , Reuther Jacquelyn , Fisher Kevin , Scollon Sarah , Plon Sharon , Roy Angshumoy , Parsons D Will , Lin Frank 
Published: June 2022

Abstract
BACKGROUND: Despite being the most common central nervous system tumor in children, ≤5% of pediatric low grade gliomas (pLGG) present with metastases. Due to their rarity, there is a paucity of clinical and molecular data in metastatic pLGGs. To address the need, we analyzed a cohort of 22 patients with pLGG followed at Texas Children’s Hospital who presented with metastatic disease. RESULTS: The predominant histology was pilocytic astrocytoma (16/22, 73%); average age at diagnosis was 4 years 11 months. The most common sites of primary disease were optic pathway/chiasm (7/22, 32%) and suprasellar (5/22, 23%). Metastatic disease was most commonly noted in the leptomeninges (12/22, 55%). 16/22 patients (73%) were treated with up-front medical therapy following tumor biopsy/resection, the majority with carboplatin-based therapy; the remaining 6 patients received only surgery up-front. Only 2/22 patients (9%) did not progress after their initial treatment with an average follow-up of 42 months. 14 patients (14/22, 64%) had continued disease progression after at least 2 therapeutic interventions; however, only 3 patients (3/22, 14%) eventually received craniospinal radiation. 10 patients (10/22, 45%) received treatment with an agent targeting the mitogen-activated protein kinase (MAPK) pathway. 20/22 patients (91%) were alive at last follow-up (average 72 months). 4/21 patients (19%) harbored a BRAF V600E mutation while 7/20 (35%) had a BRAF::KIAA1549 duplication/fusion. 8/20 patients (40%) were wildtype for both analyzed molecular alterations in BRAF. 8 patients had germline whole exome sequencing performed and all were negative for pathogenic/likely-pathogenic variants related to their clinical phenotype. Methylation analyses are pending on patients with available tumor tissue. CONCLUSION: In our cohort of patients with metastatic pLGG, most tumors progressed despite numerous therapeutic regimens, but the overall survival was &gt;90%. 40% of patients were wild type for the 2 most common MAPK alterations seen in pLGG.
LGG-15. Late mortality and morbidity of adult survivors of childhood glioma treated across three decades: a report from the Childhood Cancer Survivor Study
Authors: de Blank Peter M K , Lange Katharine R , Xing Mengqi , Salehabadi Sedigheh Mirzaei , Srivatava Deokumar , Brinkman Tara M , Ness Kirsten K , Oeffinger Kevin C , Neglia Joseph , Krull Kevin R , Yasui Yutaka , Nathan Paul , Howell Rebecca , Turcotte Lucie , Leisenring Wendy , Armstrong Gregory T , Bowers Daniel C , Okcu M Fatih 
Published: June 2022

Abstract
PURPOSE: Pediatric low-grade glioma therapy has evolved to delay or eliminate radiation. The impact of therapy changes on long-term outcomes remains unknown. METHODS: Cumulative incidence of late mortality (death &gt;5 years from diagnosis), subsequent neoplasms (SNs), and chronic health conditions (CHCs, CTCAE grading criteria) were evaluated in the Childhood Cancer Survivor Study among 5-year survivors of glioma diagnosed 1970-1999. Outcomes were evaluated by diagnosis decade and by treatment exposures received ≤5 years following diagnosis (surgery-only, chemotherapy ± surgery, and cranial radiation ± surgery or chemotherapy). Relative risk (RRs) with 95%CIs estimated long-term outcomes using multivariable piecewise exponential models. RESULTS: Among 2,684 eligible survivors (age at diagnosis (median [range]), 7 years [0-20 years]; time from diagnosis, 24 years [5-48 years]), exposure to cranial radiation decreased [51% (1970s), 45% (1980s), 25% (1990s)] along with late tumor recurrence (&gt;5 & ≤15 years from diagnosis) [9.8% (1970s), 8.8% (1980s), 5.0% (1990s)]. The 15-year cumulative incidence of late mortality was 10.3% (1970s), 6.5% (1980s), and 6.0% (1990s) (p&lt;0.001, comparison of cumulative incidence curves). The 15-year cumulative incidence of grade 3-5 CHCs was 19.7% (1970s), 17.8% (1980s), and 14.2% (1990s) (p&lt;0.0001). A reduction in SN incidence was not observed. In multivariable analyses excluding treatment exposure, later diagnosis (1990s vs. 1970s) was associated with lower risk of late mortality, grade 3-5 CHCs and SNs. Inclusion of treatment exposure in the model attenuated the effect of diagnosis decade. Radiation or chemotherapy exposure increased risk compared to surgery alone for late mortality (radiation RR 4.95, 95%CI 3.79-6.47; chemotherapy RR 2.88, 95%CI 1.85-4.48), CHCs (radiation RR 4.02, 95%CI 3.28-4.94; chemotherapy RR 1.66, 95%CI 1.13-2.45), and SNs (radiation RR 4.02, 95%CI 3.06-6.13, chemotherapy RR 2.08, 95%CI 1.03-4.23)). CONCLUSION: Late mortality and CHCs decreased in childhood glioma survivors diagnosed from 1970-1999 largely due to therapy changes, particularly avoidance of cranial radiation, without increased late recurrence.
LGG-33. A 40-year cohort study of evolving hypothalamic dysfunction in 90 infants and young children (&lt;3y) with optic pathway gliomas
Authors: Picariello Stefania , Cerbone Manuela , D'Arco Felice , Gan Hoong-Wei , O’Hare Patricia , Aquilina Kristian , Opocher Enrico , Hargrave Darren , Spoudeas Helen Alexandra 
Published: June 2022

Abstract
BACKGROUND: Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. METHODS: We aimed to assess presenting disease, tumour location and treatment factors implicated in the evolution of neuroendocrine, metabolic and neuro-behavioural morbidity in children diagnosed before their 3rd birthday and followed over four decades (1981- 2020). RESULTS: Ninety infants/young children followed-up for 9.5 years (range 0.5-25.0) were included in the study. Fifty-two (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) had hypothalamic involvement (H+) and lower endocrine event free survival (EEFS) rates. Median time to first endocrine event was 3.4 years, with EEFS declining up to 13.6 years after diagnosis. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs 46%, p=0.001), H+ (OR 6.1 95% CI 1.7 – 21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7 – 158.6, p=0.017) and surgery (OR 4.8 95% CI 1.3- 17.2, p=0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and clustered with the endocrinopathies. Posterior pituitary disorders were recorded in 15 subjects (16.7%), only after surgery and/or as a consequence of hydrocephalus in those with suprasellar tumours and hypothalamic disease. Neuro-behavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1 – 5.9, p=0.043) and radiotherapy (OR 23.1 C.I. 2.9 – 182, p=0.003). CONCLUSIONS: Very young children with OPHG carry a high risk of endo-metabolic and neuro-behavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in a complex hierarchical pattern overtime whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies.
LGG-36. Analysis of BRAF-related mutations in pediatric low-grade glioma
Authors: Li Shaoqun , Lai Mingyao , Cai Linbo 
Published: June 2022

Abstract
BACKGROUND: Most pediatric low-grade gliomas (pLGGs) are driven by a single genetic event resulting in up-regulation of the RAS/MAPK pathway. BRAF-related mutations are the most freauent molecular alteration in the pathway. To explore BRAF-related mutations in pediatric low-grade glioma is helpful for clinical practice. METHODS: In this study, patients with low-grade glioma aged ≤18 years in Guangdong Sanjiu Brain Hospital were enrolled. All patients accepted the tests of BRAF-related mutations with tumor tissue by next-generation sequencing (NGS). Results: A total of 26 patients diagnosed low-grade glioma and underwent NGS detection were included in this study. The male to female ratio was 6:7, and the median age was 9.5 years. 8 patients had tumors located in the cerebral hemisphere, 6 in the third or fourth ventricle, 5 in the cerebellum, 4 in the optic pathway, and 3 in the brain stem. A total of 14 patients took BRAF-related mutations, such as BRAF-KIAA1549 fusion, BRAF p.V600E mutation and other fusion. BRAF-KIAA1549 fusion was detected in 7 patients with pilocytic astrocytoma or pilomyxoid astrocytoma. BRAF p.V600E mutation was detected in 6 patients, two of whom were pleomorphic xanthoastrocytoma. A rare genetic fusion, BCAS1-BRAF fusion, was detected in 1 patient who had brain stem ganglioglioma. Among the 26 patients, 2 patients without BRAF-related mutations had typical multiple cafe-au-lait macules and were diagnosed as NF1-pLGG. These patients were treated with surgery, radiation, chemotherapy and targeted therapy. Only 2 patients received targeted therapy by Trametinib, Vimofinib and Everolimus after progression of the tumor. However, due to the severity of the disease, they eventually died. CONCLUSIONS: More than half of pLGG patients have BRAF-related mutations, which have the opportunity for targeted therapy. However, the optimal timing of targeted therapy still needs further exploration.
LGG-39. Ascites in a medullary and leptomeningeal ganglioglioma patient following cisplatin treatment necessitating cessation of therapy and conversion to VA shunt
Authors: Cantor Evan , Ogle Andrea , Meyer Ashley , Shatara Margaret , Brossier Nicole M , Abdelbaki Mohamed S , Strahle Jennifer , Cluster Andrew 
Published: June 2022

Abstract
INTRODUCTION: Ganglioglioma is a low grade neoplasm consisting of dysplastic neuronal and neoplastic glial cells and accounts for 5% of pediatric CNS tumors. Management often includes CNS diversion. There have been case reports in which platinum containing chemotherapy has been thought to contribute to CSF malabsorption leading to ascites. CASE: A 13 month old male developed progressive macrocephaly, developmental delay, chronic emesis, and intermittent bilateral cranial nerve VI palsy over the 5 months prior to presentation. MRI brain/spine was significant for an enhancing nodule in the left posterior lateral medulla, nodular thickening and enhancement along the brainstem down to the conus medullaris and in the tentorium, with associated hydrocephalus. Biopsy of the medullary nodule and of the enhancement were consistent with ganglioglioma with BRAF-KIAA1549 fusion, equivocal MYCN amplification, and no BRAF V600E mutation. A ventriculo-peritoneal shunt was placed at the time of biopsy. Therapy was initiated with vincristine (1.5 mg/m2) and carboplatin (175 mg/m2.) Following the 12 week induction phase of therapy, he developed increasing diarrhea, emesis, and abdominal ascites. Peritoneal fluid analysis had no malignant cells and low protein compared to CSF. Ascites was responsive to drainage but would rapidly re-accumulate. Ultimately the patient’s chemotherapy was discontinued after 2 maintenance cycles due to continued symptoms. Acetazolamide was trialed but discontinued due to side effects, so its efficacy could not be determined. He underwent shunt externalization followed by venticulo-atrial (VA) shunt re-internalization. He has not had ascites since that time, at 4 months from surgery. His CNS disease burden has been stable at 6 months off therapy. DISCUSSION: Ascites was most likely due to CSF malabsorption in the abdomen with a possible contribution from platinum containing chemotherapy and less likely secondary to malignant peritoneal cells. Resolution since VA shunt internalization makes alternate explanations less likely.
LGG-40. Growth hormone replacement in children on therapy with Vemurafenib for Low Grade Glioma
Authors: Verrico Antonio , Crocco Marco , Casalini Emilio , Ramaglia Antonia , Rossi Andrea , Iurilli Valentina , Piccolo Gianluca , Milanaccio Claudia , Garrè Maria Luisa , Iorgi Natascia Di 
Published: June 2022

Abstract
BRAF inhibitors (iBRAF) are a therapeutical option for pediatric Low-Grade-Gliomas (pLGG), but their chronic use may be needed to prevent tumor regrowth. Growth hormone (GH) replacement in children with GH deficiency (GHD) and on oncological treatment is under debate. We report on our experience of recombinant human GH (rhGH) replacement in two children (1 Female, 1 Male) which started Vemurafenib therapy, at 5 (F) and 9,25 (M) years of age, for recurrent/progressive chiasmatic-hypothalamic pLGG, with partial response (RANO criteria) and subsequent stable disease. A diagnosis of GHD was established at 9,2 (F) and 11,2 (M) years of age (GH peaks to stimulation tests &lt;3mcg/L), 4,2 (F) and 1,9 (M) years after Vemurafenib start. Both patients were treated with GnRH analogues for precocious puberty. rhGH dose was titrated to 0.020 mg/kg/day during follow-up based on IGF-1 levels &lt; +2 SDS. Height remained stable in both (F: -3,4SDS; M: 0SDS), with a mean growth velocity after 2 years around 6 cm/yr. BMI increased in the F (1,59 to 1,78 SDS) and decreased in the M (2,66 to 2,56 SDS); Dual-X-ray absorbiometry confirmed high fat mass at T0 (F:54,6%; M:48%) and at T24 (F:49,2%; M:48,1%). Lipid profile improved in both patients (F: Triglycerides 175 to 152 mg/dl, LDL 195 to 155 mg/dl; M: Triglycerides 138 to 118 mg/dl, LDL 147 to 147 mg/dl, at T0 and T24, respectively), while baseline blood glucose increased (F: 83 to 96 mg/dl; M 82 to 91 mg/dl). Residual tumor was stable in both patients. CONCLUSIONS: In 2 GHD patients due to pLGG and treated with Vemurafenib, two-years of low-dose rhGH showed beneficial effects on height stabilization and on lipid profile, and a different impact on body composition parameters; rhGH was safe and not associated with residual tumor growth.
LGG-43. Reduction in the cerebrospinal fluid protein level after bevacizumab treatment in patients with optic pathway low-grade gliomas
Authors: Dassi Natália , Cappellano Andrea , Costa Marcos , Watanabe Rodrigo , Soares Carolina , Silva Frederico , Almeida Daniela , Dastoli Patricia , Nicacio Jardel , Cavalheiro Sérgio , Saba Nasjla 
Published: June 2022

Abstract
Cases Presentations: Case 1: A 1-year-old boy with suprasellar pilocytic astrocytoma with previous history of shunting disfunction, treatment according vinblastine protocol due to anaphylactic reaction with carboplatin presented with ascites and necessity of ventricular-atrial shunt. Due to high protein cerebrospinal fluid (CSF) level (551mg/dl) he was submitted to external ventricular drainage and bevacizumab 10mg/kg was associated to his oncology treatment. After three cycles of bevacizumab, the patients’ CSF protein levels decreased dramatically 178 mg/dL, allowing the shunt procedure without complications and shorter hospital stay. Case 2: A ten-year-old boy with suprasellar pilocytic astrocytoma treated with three lines of chemotherapy showed tumor progression one year after the end of carboplatin-vincristine protocol and shunting disfunction. External ventricular drainage was performed, and the CSF showed 590mg/dl protein level. He was treated with vinblastine 6mg/m2 weekly and bevacizumab 10mg/kg each 14 days. After two cycles of bevacizumab, the protein level was 191mg/dl allowing another V-P shunt procedure. Discussion: Optic pathway gliomas frequently cause elevated cerebrospinal fluid protein concentrations leading to shunts occlusions and failures, necessity of external ventricular drainage and longtime hospitalization, implicating risk of serious infections. Bevacizumab is a monoclonal antibody with immunomodulatory and anti-vascular endothelial growth factor (VEGF) activities that has been used in combination with other chemotherapeutic agents such as irinotecan and vinblastine to treat low-grade gliomas and has been reported to decrease the CSF protein concentration.Final Comments: Bevacizumab treatment in patients with gliomas and high CSF protein levels seems effective in decreasing protein leakage from the vessels to the ventricles, thereby improving the scope for successful shunt placement.
LGG-48. The influence of different FGFR1 alterations on pediatric low-grade glioma tumor biology and targeted therapy response
Authors: Morin Eric , DiGiacomo Jeromy , Novikov Dana , Malinowski Seth , Chow Kin-Hoe , Jones David , Alexandrescu Sanda , Ligon Keith , Bandopadhayay Pratiti 
Published: June 2022

Abstract
Pediatric low-grade gliomas (pLGGs) have excellent survival, however, with current standard of care, most patients suffer lifelong severe sequalae. pLGGs are almost exclusively driven by single activating mutations in the MAPK pathway. Clinical trials with small molecule inhibitors in BRAF-altered pLGGs are showing promising results in early clinical trials, and similar efforts are now underway for FGFR1-altered tumors, however the underlying biology and treatment response has not been thoroughly explored in a pre-clinical setting. To explore the genetic landscape of FGFR altered gliomas we assembled a cohort of 87 patients with FGFR1-4 altered gliomas across Dana-Farber Cancer Institute, Boston Children’s Hospital and Brigham and Women’s Hospital. Within this cohort we observed that pLGGs harboring FGFR1 kinase hotspot mutations (FGFR1-N546K or -K656E) frequently harbored a second alteration associated with activation of the MAPK or mTOR pathways, most commonly in the phosphatase PTPN11, NF1 or within the FGFR1 gene itself. Additionally, we observed two previously described structural variants of FGFR1, an FGFR1 internal kinase tandem duplication (FGFR-ITD) and a fusion with TACC1 (FGFR1:TACC1). The relative impact of the different FGFR1 alterations on oncogenicity, therapeutic response and resistance has not been previously explored. To address this, we have established mouse neural stem cell models overexpressing the structural variants and hot spot mutant FGFR1 alone or in combination with a second alteration. Immunoblotting revealed that the addition of a second alteration attenuated phosphorylation of ERK, AKT and S6 and influenced cell proliferation both in normal growth conditions and in absence of growth factor. Treatment with inhibitors of FGFR (Infigratinib) and MEK (Trametinib) revealed variable sensitivity both targeted therapies, suggesting that treatment of FGFR1 driven pLGG might require tailoring to the specific FGFR1 alteration.
MEDB-58. Risk factors and risk prediction models for medulloblastoma recurrence
Authors: Li Juan , Lai Mingyao , Cai Linbo 
Published: June 2022

Abstract
BACKGROUND: There is a clear need for systematic appraisal of models/factors predicting medulloblastoma recurrence because clinical decisions about adjuvant treatment are taken on the basis of such variables. METHODS： A total of 273 patients diagnosed with medulloblastoma were retrospectively analyzed. The pre-rediotherapy neutrophile-lymphocyte ratio (NLR) was calculated, and other clinical characteristics were collected such as genetic type , whether with dissemination, degree with excision. The Kaplan-Meier method was used for survival analysis. Cox regression models was used to identify independent prognostic factors. R software was used to develop a nomogram with all the independent prognostic factors included. The prognostic predictive ability of the nomogram was evaluated by Concordance-index (C-index), area under the curve (AUC), and calibration curve. RESULTS: The median median progression-free survival time was 63.8 months in overall cohort. Univariate and multivariate cox hazards regression analysis identified independent prognostic factors associated with the PFS of patients with medulloblastoma to include age, residual tumor volume ＞1.5cm3 after excision, NLR ＞4.5, whether with dissemination before RT, and whether the genetic type is group 3,which were integrated to establish a nomogram. The C-indexes of nomogram were 0.696 and 0.676 in the training and validation cohort, respectively. The AUC of predicting 3-years PFS showed satisfactory accuracy as well (Training cohort: AUC=0.696; Validation cohort: AUC=0.676). The calibration curve showed agreement between the ideal and predicted values. Kaplan-Meier curves based on the PFS showed significant differences between nomogram predictive low-, and high groups (P &lt; 0.001). CONCLUSIONS: We found that pre-treatment NLR was an independent prognostic factor for recurrence or metastasis of medulloblastoma after treatment. In combination with NRL and clinical factors, nomogram has a good prediction of PFS in patients with medulloblastoma after radiotherapy. It has the potential to facilitate more precise risk stratification to guide personalized treatment of medulloblastoma.