bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-29. AIF1 IS A PROGNOSTIC BIOMARKER AND CORRELATED WITH IMMUNE INFILTRATES IN GLIOMAS
Authors: Chai Yi , Liu Wei , Wang Junhua , Hu Libo , Zhang Yuqi 
Published: December 2020

Abstract
Gliomas remain highly variable clinical behaviors, leading to emerging studies to identify prognostic factors. AIF1 (Allograft Inflammatory Factor 1) is critical for promoting both macrophage- and dendritic cells (DCs)-mediated inflammatory response and growth of vascular smooth muscle cells and T-lymphocytes. Through comparative analyses of primary LGG patients from The Cancer Genome Atlas (TCGA) dataset and Chinese Glioma Genome Atlas(CGGA) dataset, we reported that the expression level and methylation level of AIF1 gene vary among glioma patients and AIF1 expression or gene body methylation is significantly associated with glioma patient survival. Cox regression results confirmed that AIF1 played an independent predictor of survival in lower-grade glioma(LGG), with a cox coefficient of 0.251 indicating a worse prognosis. Moreover, AIF1 expression was positively correlated with infiltrating levels of CD4+ T and B cells, macrophages, neutrophils, and DCs in LGG and glioblastoma(GBM). AIF1 expression also showed strong correlations with specific immune cell markers in LGG and GBM. In addition, AIF1 expression potentially contributed to the regulation of glioma-associated macrophages and microglia. In conclusion, our findings suggested that AIF1 was correlated with prognosis and immune infiltrating levels, and it can be used as a prognostic factor in gliomas.
IMMU-30. UPREGULATED T CELL AND INTERFERON-Γ-RELATED GENE EXPRESSION IS ASSOCIATED WITH INCREASED SURVIVAL IN RECURRENT PEDIATRIC HIGH-GRADE GLIOMA
Authors: Davidson Tom , Hugo Willy , Wang Anthony , Kim Jiyoon , Li Gang , Prins Robert 
Published: December 2020

Abstract
Recurrent pediatric high-grade glioma (pHGG) is the leading cause of cancer-related mortality in children. Immunotherapy is a successful treatment approach for a growing number of cancers and is being investigated as a treatment strategy for pHGG. Immunotherapy has shown the most benefit in tumors with increased infiltrating T cells at baseline. Our recently published results revealed that neoadjuvant checkpoint inhibition in recurrent adult glioblastoma was associated with upregulation of a T cell and interferon-γ-related gene expression signature (Tcell-IFNγGES) and was correlated with a significantly extended overall survival (OS). In this study, we examined the immune landscape in recurrent pHGG and the association of Tcell-IFNγGES in the tumor with survival. We analyzed tumor RNAseq data collected at time of recurrence from a historical cohort of 42 pHGG patients from the Children’s Brain Tumor Tissue Consortium. We found a significant transcriptional enrichment of Tcell-IFNγGES in 54% of the tumors. The survival of patients with high Tcell-IFNγGES was observed to be significantly higher than patients with low Tcell-IFNγGES, (log-rank p=0.05). The 3-year OS for patients with low versus high Tcell-IFNγGE was 28.5% (95%, CI:13.7%-59.5%) compared to 50.2% (95%, CI:33.1%-76.1%). When patients were stratified by age, gender and race, low Tcell-IFNγGES was found to be a poor OS prognostic factor (hazard ratio=2.4 (1.14–5.14), p=0.02). This indicates a strong relationship of decreased Tcell-IFNγGES and increased risk of death. Future investigations are necessary to validate these findings, and to explore the value of Tcell-IFNγGES as a predictive biomarker for response to immunotherapy in pHGG.
IMMU-31. PNOC007: H3.3K27M SPECIFIC PEPTIDE VACCINE COMBINED WITH POLY-ICLC FOR THE TREATMENT OF NEWLY DIAGNOSED HLA-A2+ H3.3K27M DIFFUSE MIDLINE GLIOMAS (DMG)
Authors: Mueller Sabine , Taitt Jared , Bonner Erin , Lulla Rishi , Goldman Stewart , Banerjee Anu , Chi Susan , Whipple Nicholas S , Crawford John , Gauvain Karen , Nazemi Kellie , Watchmaker Payal , Nejo Takahide , Okada Kaori , Butterfield Lisa H , Nazarian Javad , Villaneuva-Meyer Javier , Molinaro Annette M , Prados Michael , Okada Hideho 
Published: December 2020

Abstract

OBJECTIVE
To assess safety and efficacy within a multi-center trial the H3.3K27M specific peptide vaccine with poly-ICLC in HLA-A02.01+ patients diagnosed with H3.3K27M+ DMGs.

METHODS
After focal radiation therapy, participants 3–21 years of age were enrolled into two strata. Stratum A: newly diagnosed diffuse intrinsic pontine glioma (DIPG); Stratum B: other DMGs. H3.3K27M vaccine was administered with poly-ICLC IM every 3 weeks for 8 doses followed by every 6 weeks for a total of 96 weeks. Immuno-monitoring of peripheral blood mononuclear cell (PBMC) and imaging occurred every 3 months. Modified iRANO criteria were applied. PBMC samples were evaluated by mass cytometry.

RESULTS
From November 2016 until March 2019, 19 eligible patients (median age 11, range 5–17 yrs; 53 % female) were enrolled in Stratum A and 10 eligible patients (median age 13, range 7–18 yrs; 60 % female) in Stratum B. Treatment was well tolerated (7 grade 3; 0 grade 4 related toxicities). Median number of vaccines per participant was 6 (range 1–11). Overall survival at 12 months was 40% (95% CI 22–73%) for Stratum A and 39% (95% CI 16–93%) for Stratum B. Among the 19 subjects with longitudinal immune cell assessments, 7 exhibited an expansion of K27M-reactive CD8+ effector memory T-cells correlating with prolonged survival (p=0.028).

CONCLUSION
H3.3K27M specific vaccine in combination with poly-ICLC is well tolerated. CyTOF-based immune monitoring of PBMCs facilitates sensitive high-throughput analysis. Further investigation is warranted to determine if this may be predictive of clinical outcomes.
LGG-02. A BRAIN TUMOR DIAGNOSED AFTER TRANSITION TO THE DEPARTMENT OF ADULT NEUROSURGERY FROM THE DEPARTMENT OF PEDIATRICS
Authors: Shibata Yasushi 
Published: December 2020

Abstract
The patient was a 17-year-old boy with a history of 4 non-febrile convulsions at 15 and 16 years of age. He visited the Department of Pediatrics at a pediatric hospital. An electroencephalogram showed right frontal spike discharge. MRI was performed and judged to show no abnormality. The pediatric doctor diagnosed him with epilepsy. At 17 years old, he was referred to our Department of Adult Neurosurgery for transition. Physical and neurological examinations showed no abnormalities. Brain MRI showed right frontal cortical small tumor, with T1 low, T2 high, diffusion-weighted imaging low, and partial contrast enhancement. We diagnosed him with a brain tumor and symptomatic epilepsy. We surgically removed a right frontal cortical tumor. A pathological examination finalized the diagnosis of dysembryoplastic neuroepithelial tumor. MRI confirmed the total removal of the tumor. Anticonvulsant was started before surgery. No epileptic seizure was observed, so the anticonvulsant medication was gradually tapered and stopped at two years after the surgery. No epilepsy nor recurrence has been observed thus far. The problem with the initial management of this case at the Department of Pediatrics in the pediatric hospital was that the brain tumor was missed despite an MRI examination. Had the transition not happened, this brain tumor might not have been diagnosed. A brain tumor is a rare disease, and epilepsy is a common disease. However, in cases of non-febrile convulsion, a brain tumor should be considered. Collaboration within a single department, hospital and local area should be established.
LGG-06. LONG-TERM OUTCOME OF NEWLY DIAGNOSED LOW GRADE GLIOMA
Authors: Sirachainan Nongnuch , Boongerd Attaporn , Pakakasama Samart , Anurathapan Usanarat , Hansasuta Ake , Songdej Duantida , Pongpicha Pongpak , Dhanachai Mantana , Hongeng Suradej 
Published: December 2020

Abstract

INTRODUCTION
Low grade glioma (LGG) is the most common central nervous system (CNS) tumor in children accounted for 30–50%. Regarding benign characteristic of disease, surgical management remains the mainstay of treatment. However, surgical approach is limited in some conditions such as location at brainstem or infiltrative tumor. Chemotherapy and radiation treatments have been included in order to control tumor progression. The 5-years survival rate is approach 90% especially in patients who receive complete resection. However, the outcome of children with LGG in low to middle income is limited. Therefore, the aim of the study was to determine long-term outcome of children with newly diagnosed LGG.

METHODS
A retrospective study enrolled children aged &lt;18 years who were newly diagnosed LGG during January 2006- December 2019. Diagnosis of LGG was confirmed by histological findings of grade I and II according to WHO criteria.

RESULTS
A total of 40 patients, female to male ratio was 1:1.35 and mean (SD) for age was 6.7 (4.0) years. The most common location was optic chiasmatic pathway (42.5%), followed by suprasellar region (25.0%). Sixty percent of patients received at least partial tumor removal. Chemotherapy and radiation had been used in 70% and 10.0% respectively. The 10-year progression free survival was 74.1±11.4% and overall survival was 96.2±3.8%. SUMMARY: Treatment of Pediatric LGG mainly required surgical management, however, chemotherapy and radiation had been used in progressive disease. The outcome was excellent.
LGG-16. PILOMYXOID ASTROCYTOMA OF THE CERVICAL SPINAL CORD IN A 7-YEAR-OLD ARMENIAN BOY: A CASE REPORT
Authors: Avagyan Anna , Sargsyan Lilit , Hoveyan Julia , Iskanyan Samvel , Bardakhchyan Samvel , Danielyan Samvel , Tamamyan Gevorg 
Published: December 2020

Abstract

BACKGROUND
Pilomyxoid astrocytoma (PMA) is a glial tumor that occurs predominantly in the hypothalamic-chiasmatic region and rarely in spinal cord. It has similar features as pilocytic astrocytomas, with some distinct histological characteristics and worse prognosis. The 2007 WHO recognized PMA as a Grade II glioma due to its aggressive behavior and dissemination tendency, but according to 2016 version grading of the pilomyxoid variant is under research. Here we report a case with a rare location, aggressive behavior and rapid progression. CASE PRESENTATION: A 7-year-old boy presented with headache, nausea, vomiting. Imaging revealed an intramedullary tumor extending from C2 to C6 with hydrocephalus. A ventriculo-peritoneal shunt and complete surgical resection were performed with significant improvement in the patient’s condition. Histopathological findings were consistent with pilomyxoid variant of pilocytic astrocytoma, with negative BRAF V600E and MGMT. Three months later, the follow-up imaging revealed disease recurrence with leptomeningeal metastases, for which the patient received standard-dose craniospinal irradiation 35.2 Gy with boosts to tumor bed and metastatic sites 49.6 Gy and 54 Gy respectively. 11 months later tumor progression was revealed with new metastatic lesions in the bones. Patient received 6 cycles of chemotherapy with TMZ and Avastin, but continued to suffer disease progression on therapy and he succumbed to his disease at 24 months from diagnosis.

CONCLUSION
Given the rarity of documented patients with spinal pilomyxoid astrocytoma with rapid progression, as well as the lack of certain WHO classification and treatment guidelines, this case report might be useful for development of more efficient treatment strategies.
LGG-22. EVALUATION OF IMMUNE AND GENOMIC CHARACTERISTICS IN PEDIATRIC OPTIC NERVE GLIOMA (ONG)
Authors: Campbell Ashley A , Silverman Andrew M , Moisander-Joyce Hanna , Wu Cheng-Chia , Mansukhani Mahesh , Zanazzi George , Turk Andrew , Canoll Peter D , Garvin James H , Kazim Michael , Gartrell-Corrado Robyn D 
Published: December 2020

Abstract
Pediatric optic nerve glioma (ONG) is a rare, sight-threatening tumor. We previously reported clinical, radiologic, histopathologic, and molecular characteristics of pediatric ONG patients treated at Columbia University Medical Center between 2000–2017. Here we evaluate this cohort and one additional patient using quantitative multiple immunofluorescence (qmIF) and next generation sequencing (NGS) using the Columbia Combined Cancer Panel (CCCP). For qmIF, 4 micron immuno-blank slides were stained for CD3, CD8, CD68, CD163, HLA-DR, and Olig2. QmIF images were analyzed and data were processed in R studio and compared based on tumor mutation and treatment history. QmIF failed in 1 case and CCCP failed in 2 cases. CCCP confirmed KIAA1549:BRAF fusions in 2 patients, identified NF1 in 2 patients, and demonstrated both a KIAA1549:BRAF fusion and SETD2 mutation in the added case. Qualitative analysis showed immune infiltrate across cases included macrophages (CD68+, 1.6–6.5% of all cells) and T cells (CD3+, 0.4% to 1.5%). Non-cytotoxic T cells (CD3+CD8-) comprised 60.7–100% of the T cell compartment. There was no difference when comparing mutation groups. However, patients who previously received radiation had increased CD3+, specifically CD3+CD8- cells compared to non-irradiated patients (p=0.01 and p&lt;0.01, respectively) while CD3+CD8+ and CD68+ cells were not different between groups (p=0.49 and p=0.27, respectively). In summary, qmIF analysis showed increased tumor infiltration by non-cytotoxic T cells in previously irradiated pediatric ONG patients compared to non-irradiated patients, while there was no difference in macrophages of cytotoxic T cells. This type of analysis may be useful in designing immunotherapeutic strategies for pediatric ONG.
LGG-27. TARGETED THERAPY FOR PEDIATRIC LOW-GRADE GLIOMAS AND PLEXIFORM NEUROFIBROMAS WITH TRAMETINIB
Authors: Nguyen Tiffany , McMahon Kathleen , Hemenway Molly , Levy Jean Mulcahy , Foreman Nicholas , Dorris Kathleen 
Published: December 2020

Abstract

BACKGROUND
Targeted therapy aimed at modulating the RAS/RAF/MEK/ERK pathway is of increasing interest for patients with plexiform neurofibromas and low-grade gliomas. Trametinib is an FDA-approved MEK inhibitor that has little published pediatric experience to date.

METHODS
A retrospective chart review of patients treated with trametinib for low-grade gliomas (LGG) and/or plexiform neurofibromas (PN) between 2015–2018 was conducted at Children’s Hospital Colorado. Data collected included patient demographics, lesion location, Neurofibromatosis type 1 (NF1) status, best response of PN/LGG to trametinib, duration of trametinib therapy, and reported toxicities at least possibly attributed to trametinib.

RESULTS
Thirty (57% male; 73% NF1) patients were identified. Sixteen (53%) patients had PN only, 12 (40%) had LGG only, and two (7%) patients had both PN and LGG. The most common LGG location was the optic pathway/hypothalamus (72%). The most common location of PN was the face (63%). Two-thirds (8/12) of patients with LGG had a BRAF alteration or NF1 mutation. The median age at start of trametinib therapy was 9.9 years (range, 2.0 – 18.8 years). The median duration of trametinib therapy was 0.8 years (range 0.1 – 2.9 years). The most commonly reported adverse event was rash. No patients developed retinal toxicity or cardiotoxicity. Only two (7%) patients discontinued for toxicity and one (3%) for progressive disease.

CONCLUSIONS
Trametinib can be administered without significant toxicity to children with PN or LGG. Clinical benefit is noted in this cohort; however, prospective clinical trials are necessary to characterize efficacy formally.
LGG-29. TREATMENT FOR RECURRENT OPTIC PATHWAY PILOCYTIC ASTROCYTOMA
Authors: Nonaka Masahiro , Miyata Mayuko , Yamamura Natsumi , Asai Akio 
Published: December 2020

Abstract
Chemotherapy after biopsy or partial resection of the tumor is widely accepted as first-line therapy for optic pathway pilocytic astrocytoma. However, there is no standard of care for recurred tumors. We investigated our cases which showed recurrence after initial therapy. Retrospective analysis of four recurrent optic pathway pilocytic astrocytoma cases was performed. All patients underwent partial resection or biopsy of the tumor, and all received carboplatin and etoposide- based chemotherapy as initial treatment. Mean age at first therapy was 2.3 years old, and mean time from initial therapy to recurrence of the tumor was 5.6 years. Two patients were totally blind at the time of recurrence, and other two had partial visual field losses. One patient underwent total resection of the tumor, and other three patients underwent partial resection followed by chemotherapy. Visual function in patients with visual acuity did not deteriorate after removal of the recurrent tumor. There was no recurrence of the tumor who underwent total resection.　All of the three patients who had partial resection followed by chemotherapy recurred. Mean time from first recurrence to second recurrence was 1.8 years. After second recurrence, all patients underwent radiation therapy. One patient died due to malignant transformation of the tumor. For recurrent optic pathway pilocytic astrocytoma, prognosis may be better if total resection of the tumor without deteriorating the vision is possible.
LGG-30. TRAMETINIB-ASSOCIATED HYPONATREMIA IN A CHILD WITH LOW GRADE GLIOMA IS NOT SEEN FOLLOWING TREATMENT WITH ALTERNATIVE MEK INHIBITOR
Authors: Lazow Margot A , Lawson Sarah A , Salloum Ralph , Hummel Trent R , Smiley Natasha Pillay , DeWire-Schottmiller Mariko D , Fouladi Maryam , de Blank Peter M 
Published: December 2020

Abstract
Molecularly targeted therapy with MEK inhibitors is increasingly being incorporated into the treatment of pediatric low-grade gliomas (LGGs). Trametinib is an orally available MEK1/2 inhibitor that has demonstrated tumor control in LGGs with BRAF alterations. Safe expansion of MEK inhibitor therapy within the pediatric patient population demands adequate understanding of and surveillance for potential MEK-inhibitor specific toxicities, especially among young children. Hyponatremia has been reported in adult patients receiving BRAF/MEK inhibitor combination treatment as well as in two pediatric patients with known diabetes insipidus treated with trametinib monotherapy. To our knowledge, single-agent trametinib has not previously been reported to be associated with hyponatremia in children in the absence of an underlying endocrinopathy. We present a case of hyponatremia associated with trametinib use in an infant with progressive LGG without known endocrine dysfunction, which recurred after significant dose reduction. Therapy with an alternative MEK1/2 inhibitor, binimetinib, provided excellent tumor response without hyponatremia. Hyponatremia is a rare but serious side effect of trametinib, even without underlying pituitary dysfunction. Infants and patients lacking the ability to quickly regulate fluid intake in response to osmolality changes are at particular risk of suffering severe consequences from hyponatremia and should be monitored closely with initiation of trametinib. Switching to a different drug within the same class may offer an alternative to significant dose reduction or discontinuation due to this toxicity.
LGG-45. A REPORT OF IDH-MUTANT BRAINSTEM ASTROCYTOMAS IN YOUNG ADULTS
Authors: Chang Ellen , Tamrazi Benita , Cotter Jennifer , Margol Ashley 
Published: December 2020

Abstract
IDH-mutant astrocytomas are well-recognized in the adult population and while increasingly identified, are rare in children and young adults. These tumors typically arise in cortical locations, however cases of these tumors occurring in the brainstem have been reported in the adult literature. Here we present two cases of young adults with IDH-mutant astrocytomas of the brainstem. Patient 1 was initially diagnosed with an infiltrative low grade glioma (LGG) of the brainstem at 19 years of age based on conventional magnetic resonance imaging and magnetic resonance spectroscopy characteristics. She was treated with LGG therapy and had stable disease for over three years. At the time of disease progression she underwent biopsy and pathology was consistent with an anaplastic astrocytoma, IDH1 R132S mutant. Despite treatment she experienced rapid disease progression and died six months later. Patient 2 is a 17-year-old male who underwent up-front biopsy of an infiltrating brainstem lesion; pathology was consistent with diffuse astrocytoma, IDH1 R132H mutant. He was treated with focal irradiation and chemotherapy and continues to have stable disease 26 months post diagnosis. To our knowledge, this is the first report of IDH-mutant astrocytomas occurring the brainstem in young adult patients. Both patients’ tumors harbored accompanying TP53 mutations, but not ATRX mutations. These two cases reveal the importance of obtaining biopsies for brainstem tumors to perform molecular characterization and appropriate prognostication.
LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY
Authors: Robison Nathan , Pauly Jasmine , Malvar Jemily , Gardner Sharon , Allen Jeffrey , MacDonald Tobey , Aguilera Dolly , Baxter Patricia , Bendel Anne , Kilburn Lindsay , Leary Sarah , Bowers Daniel , Dorris Kathleen , Gauvain Karen , Alva Elizabeth , Cohen Kenneth , Nazemi Kellie , Tan Yi Juin , Margol Ashley , Dhall Girish , Rosser Tena , Davidson Tom , Plant Ashley , Ullrich Nicole , Bandopadhayay Pratiti , Agar Nathalie , Ligon Keith , Sposto Richard , Wright Karen , Kieran Mark 
Published: December 2020

Abstract

BACKGROUND
RAS/RAF/MEK/ERK pathway activation is the primary driver for most pediatric low-grade gliomas (LGG). Binimetinib is an orally bioavailable MEK1/2 inhibitor found to have significant central nervous system penetration in a preclinical model.

OBJECTIVE
The primary objective of this multi-institutional open-label phase II study was to assess preliminary efficacy of binimetinib in progressive pediatric LGG. The study included strata for both neurofibromatosis type I (NF1) and non-NF1 associated tumors, as well as a target validation (surgical) stratum. NF1 and surgical strata remain open to enrollment and will be reported separately.

METHODS
Children aged 1–18 years with previously treated recurrent or progressive LGG were eligible. The dose of binimetinib was 32 mg/m2/dose twice daily. Partial and minor responses were defined, respectively, as 50% and 25% decrease in maximal two-dimensional measurements.

RESULTS
Fifty-seven eligible patients without NF1, median age 8 years, were enrolled and began treatment; 26 were female; 28 had documented KIAA1549-BRAF fusion. Eleven patients discontinued drug in the first year due to toxicity, and an additional 27 required dose reduction. The most common drug-attributable grade 3 toxicities included creatine kinase elevation (n=9 patients), rash (n=8), and truncal weakness (n=8). Truncal weakness improved or resolved with dose reduction or cessation. Grade 4 toxicities included creatine kinase elevation (n=2) and transient colitis (n=1). Of 44 patients with preliminary response data available, 22 (50%) showed a minor (n=7) or partial (n=15) response.

CONCLUSION
Binimetinib is active, with manageable toxicities, in children without NF1 with progressive LGG.