bluuebunny/crossref_metadata_2025_split huggingface dataset:
RARE-21. CLINICAL CHARACTERISTICS OF GLIOSARCOMA AND OUTCOME FROM STANDARDIZED TREATMENT RELATIVE TO CONVENTIONAL GLIOBLASTOMA
Authors: Frandsen Simone , Broholm Helle , Larsen Vibeke A , Grunnet Kirsten , Møller Søren , Skovgaard Poulsen Hans , Regner Michaelsen Signe 
Published: November 2019

Abstract

INTRODUCTION
Gliosarcoma (GS) is a rare histopathologic variant of glioblastoma (GBM) characterized by a biphasic growth pattern consisting of both glial and sarcomatous components. Reports regarding its relative prognosis compared to conventional GBM are conflicting and although GS is treated as conventional GBM, supporting evidence is lacking. The aim of this study was to characterize demographic trends, clinical outcomes and prognostic variables of GS patients receiving standardized therapy and compare these to conventional GBM.

METHODS
680 GBM patients, treated with maximal safe resection followed by Stupp’s regimen (radiotherapy with concomitant and adjuvant temozolomide) at a single institution, were retrospective reevaluated by reviewing histopathological records and tumor tissue for identification of GS patients. Clinicohistopathological characteristics obtained via assessment of medical records and imaging analysis were compared between the GS and GBM cohorts. Kaplan-Meier survival estimates were compared with log-rank testing, while cox-regression modeling tested for prognostic factors in GS patients.

RESULTS
The cohort revealed 26 primary gliosarcoma (PGS) patients (3.8 %) and 7 secondary gliosarcoma (SGS) patients (1.0 %). Compared to conventional GBM tumors, PGS tumors were significantly more often located in the temporal lobe (53.8 %, p = 0.006) and MGMT-unmethylated (73.9 %, p = 0.009). No significant differences were found between PGS and conventional GBM in progression-free-survival (6.8 and 7.6 months respectively, p = 0.105) and in overall survival (13.4 and 15.7 months respectively, p = 0.201). Also, survival from recurrence was not significant different between PGS, SGS and GBM (5.8, 8.6 and 7.4 months respectively, p = 0.694). MGMT status was the only factor prognostic for PGS survival (p = 0.022).

CONCLUSION
Despite tumor difference between GS and GBM, the patients present similar survival outcome from standardized treatment. This support continues practice of radiation and temozolomide for GS patients.
RARE-24. GROWTH PATTERN ANALYSES OF HEMANGIOBLASTOMA IN SPORADIC AND VHL CASES
Authors: Takami Hirokazu , Burns Terry , Parney Ian 
Published: November 2019

Abstract
Central nervous system hemangioblastoma (CNS HGB) is a rare neoplasm. Sporadic and von-Hippel Lindau (VHL)-associated forms exist. Predicting tumor growth is difficult, making the indication for intervention challenging. A retrospective analysis of consecutive, neurosurgically managed CNS HGB at Mayo Clinic spanning 1988–2018 was performed to clarify their characteristics. 117 sporadic and 67 VHL HGBs were reviewed. 9 sporadic lesions (8 cases) and 80 VHL lesions (35 cases) had tumor size data at ≥4 follow-up time-points beyond 1 year. The median follow-up was 8.0 years. No statistical difference existed between sporadic and VHL lesions regarding growth speed or growth latency (period of time without growth). Symptomatic lesions showed faster growth than asymptomatic lesions (2.79 vs 0.59 cm3/month, p=0.005). Solid and cystic portions often showed different growth patterns in cases harboring both (66.7%). Cyst growth was faster than solid portions (1.22 vs 1.05cm3/month, p=0.009) and growth latency was longer in the latter (15.2 vs 18.5%, p=0.25). Lesions’ growth were classified as linear (7), exponential (49), cubic (regressed to cubic function curve, 7), saltatory (19) and no-growth (7) patterns. Growth latency often existed in growing lesions (27-out-of-64 linear/exponential/cubic lesions, 57.8%), being average 8.3% of follow-up time. Contrarily, although saltatory lesions grew slower than exponential lesions (p=0.03), their overall growth speed was comparable to linear/cubic lesions (0.67cm3/month), and 9-out-of-19 showed growth surges at their ends. Growth speed at each follow-up roughly depended on the tumor size in cubic regression (R2=0.52). However, whereas total 18/821 time-point lesions showed rapid growth (≥1cm3/m, 2.2%), relatively small lesions (≤2cm3) also occasionally showed rapid growth (5/687, 0.73%). Not all large (>5cm3) lesions grew rapidly (8/62, 12.9%). These results revealed while symptomatic/large/cystic lesions tend to grow more rapidly, HGB behavior is difficult to predict, which stresses the importance of careful follow-up.
RARE-30. PEDIATRIC GLIOBLASTOMA IN THE POST-TEMOZOLOMIDE ERA: OUTCOMES AND CHARACTERISTICS
Authors: Chandra Ankush , Oh Taemin , Wadhwa Harsh , Shah Sumedh , Gupta Nalin , McDermott Mike , Berger Mitchel , Aghi Manish 
Published: November 2019

Abstract

INTRODUCTION
Glioblastoma (GBM) is the most common brain tumor, however, is a rare occurrence in children and is poorly characterized. We evaluated the characteristics and outcomes of pediatric GBM (pGBM).

METHODS
Retrospective analysis of pediatric (age< 18) patients diagnosed with GBM undergoing first glioblastoma resection at our brain tumor center (2005- 2016).

RESULTS
From 1457 GBM patients, we identified twenty-four (1.65%) pGBMs (Median Age=9 years, Females=45.8%). Median overall survival (OS) was 32.1 months, while the median progression-free survival was 11.5 months. The commonest symptoms at presentation were headaches (54.2%,n=13) and motor symptoms (50%,n=12). Mean tumor diameter was 4.5 cm and 25% of the cohort underwent gross total resection (GTR) of their tumor. Univariate analysis revealed median OS significantly associated with tumor extent of resection (GTR=56.4 months; STR/Biopsy=13.7 months, p=0.001), age at surgery (>10 years=43.9 months, < 10 years= 17.2 months, p=0.01), tumor size (> 4cm= 9.1 months, < 4cm=56.9 months, p=0.01),motor symptoms at presentation (present=14.9 months, absent=41.04 months, p=0.02) and infratentorial tumors (infratentorial=17.4 vs supratentorial=53.4 months, p=0.02). Multivariate analysis revealed GTR (HR 0.2[95% CI 0.07–0.72]; p=0.03), Age >10 years (HR 0.6[95% CI 0.02–0.64]; p=0.002), tumor >4 cm (HR 2.89[95% CI 1.88–4.11]; p=0.001) and EGFR amplification (HR 3.48[95% CI 0.82–17.4]; p=0.005) to be independent predictors of OS. Comparing patients under and over 10 years, we found that older patients had smaller tumors at presentation (4.9 vs 3.6 cms, p=0.03), greater rates of preoperative temozolomide (n=1,7.7% vs n=6, 54.5%) and bevacizumab (n=1,7.7% vs n=4, 36.4%) treatment, and lower rates of EGFR amplification (66.7% vs 11.1%) that could explain survival disparities between groups.

CONCLUSION
Motor symptoms, larger tumors at presentation and tumor EGFR amplification may be indictive of poorer outcomes in pGBM. However, maximal tumor resection, aggressive chemoradiation and tumor presentation at age >10 years may confer better prognosis in these patients.
RARE-31. TREATMENT OUTCOME OF CHILDREN WITH PLEOMORPHIC XANTHOASTROCYTOMA: RETROSPECTIVE ANALYSIS – A SINGLE INSTITUTION EXPERIENCE
Authors: Maher Ossama , Niazi Toba , Khatib Ziad , Ragheb John 
Published: November 2019

Abstract

BACKGROUND
Pleomorphic xanthoastrocytoma (PXA) and anaplastic pleomorphic xanthoastrocytoma (APXA) are two types of rare astrocytomas in pediatrics. There is limited literature reporting their outcomes.

METHODS
A retrospective analysis of pediatric patients with diagnosis of PXA and APXA treated at Nicklaus Children’s Hospital was conducted using descriptive measures.

RESULTS
A chart review of patients with brain tumors from 2001 to 2019 revealed that 13 patients (median age 6 years, range 2–17 years) were diagnosed with non-metastatic PXA (n=12) and APXA (n=1). Six patients (46%) were male. Clinical presentation included seizures (n=8), headaches (n=2) cranial nerve palsies (n=2). Diagnostic imaging showed tumor in the temporal lobe (n=5), parietal lobe (n=2), temporoparietal lobe (n=2), frontal lobe (n=1), occipital lobe (n=1), others (n=2). BRAF V600E mutation were identified in three of five analyzed tumors including PXA (n=4) and APXA (n=1). Surgical intervention consisted of gross total resection (n=8) and near/subtotal resection (n=5). Ten patients (76%) required a second surgery (median 2; range 1–4) due to local recurrence. The median time to recurrence was 3 years (range 6 months - 7 years). Three patients (23%) had malignant transformation of PXA, which occurred three to eight years from the initial surgery; one of them also had extensive spinal metastasis. Focal radiation was given to six patients (46%) due to multiple recurrence (n=2), malignant transformation (n=3), APXA (n=1). At a median follow up of 8 years (range 3 to 20 years), eight patients remain alive, three patients had lost to follow up, two patients died from progressive disease. Long-term sequelae varied as follows; seizures (n=5), motor weakness (n=4), cranial nerve palsies (n=2), and learning disability (n=1).

CONCLUSION
PXA is associated with high local recurrence rate and uncommonly malignant transformation to APXA in pediatrics, which requires close follow-up due to unpredictable biological behavior of these tumors.
RARE-34. TUMOR IMMUNITY AND EXTRACRANIAL METASTASES, AND MECHANISM OF PD-L1 EXPRESSION IN INTRACRANIAL SOLITARY FIBROUS TUMOR/HEMANGIOPERICYTOMA
Authors: Kamamoto Dai , Ohara Kentaro , Kitamura Yohei , Yoshida Kazunari , Sasaki Hikaru 
Published: November 2019

Abstract
Intracranial solitary fibrous tumor (SFT) /hemangiopericytoma (HPC) are rare, however, these tumors are often associated with aggressive clinical course with recurrence and/or extracranial metastasis. PD-1, PD-L1 play important roles as immune-checkpoint mediators within tumor microenvironment, and the antibodies to these molecules are now approved for the treatment of various kinds of cancers. Some mechanisms of activation of PD-L1 are reported, including cytokines or chemokines from immune cells in tumor microenvironment, and genetic mutations such as translocation, or amplification. We have investigated the expression of PD-1, PD-L1, and tumor infiltrating lymphocytes (TIL) in 16 cases of SFT/HPC by immunohistochemistry. Kaplan-Meier method and log-rank/Wilcoxon tests were used to analyze the relationship between their expression with overall survival (OS), progression free survival (PFS), metastasis free survival (MFS), and time to treatment failure (TTF; metastasis or death). Additionally, we have analyzed amplification of PD-L1 gene by FISH, translocation between promotor region of CIITA and PD-L1 by PCR, and mutation in 3’-UTR by immunohistochemistry with antibody recognizes C-terminus (clone; SP-142) of PD-L1. PD-L1 was expressed in most of tumor cells. The intensity of PD-L1 expression was negatively associated with MFS (p=0.04), and diffuse pattern of PD-L1 expression showed trends towards shorter TTF compared with partial expression (p=0.08). Notably, with the combination analysis of PD-L1 and CD8(+) TIL, the diffuse PD-L1 expression with less CD8(+) was significantly associated with shorter TTF (p=0.005). However, there was no significant relevance between the expression of those immune-checkpoint molecules and OS or PFS. Although neither amplification of PD-L1 gene, 9p24.1, nor translocation between CITTA and PD-L1 were observed, difference in immunohistochemistry with two different anti-bodies was observed. In intracranial SFTs/HPCs, tumor immunity mechanism associated with PD-1/PD-L1 may play an important role in their extracranial metastases, and mutation in 3’-UTR may be a cause of PD-L1 activation in SFT/HPC.
RARE-38. CNS LYMPHOMA INVOLVING HYPOTHALAMIC-PITUITARY AXIS
Authors: Shin Dong-Won , Jun Yoo Hee , Hoon Kim Jeong 
Published: November 2019

Abstract

BACKGROUND
It is rare for CNS lymphoma which involves the hypothalamic-pituitary axis. It could result in misdiagnoses such as pituitary adenoma, craniopharyngioma, or glioma. We report clinical findings of eight cases of either primary or secondary lymphoma involving the hypothalamic-pituitary axis(H-P axis).

METHODS
We retrospectively reviewed 488 patients who were diagnosed as CNS lymphoma from 2000 to 2017 in our institute. There were eight patients (8/488, 1.6%) who had H-P axis involvement in radiographic findings while six patients received chemotherapy. We analyzed patient characteristics, pathologies, clinical features, laboratory findings, imaging, and treatment outcome.

RESULTS
The mean age was 48-year-old (range 18~80) and male to female ratio was 5:3. We performed endonasal TSA for four patients, endoscopic biopsy for two patients, and stereotactic biopsy for two patients. There were six patients of diffuse large B-cell lymphoma and two patients of MALT lymphoma. Seven patients were PCNSL and one patient was metastasized lymphoma. All patients had hormone imbalance whereas three patients had visual disturbance and one patient had diabetes insipidus. Initial serum LDH was 337±167IU/L(range 169~567 except one patient). MRI finding was different from the usual pattern which was low SI in T1 and high SI with perilesional edema in T2, on the other hands, our patients group revealed that five patients(62.5%) had iso SI in both T1 and T2, and only two patients(25%) showed perilesional edema in T2. Median OS and PFS of six patients who received chemotherapy were 34.8 months(range 0.9~93.7) and 33.0 months(range 0.9~93.4), respectively. Two patients(25%) died in 26 days and 51 days after diagnosis because of pneumonia and cardiac arrest, respectively. And one patient lost to follow up after diagnosis.

CONCLUSION
CNS lymphoma involving H-P axis is rare, however, we need to understand its unique characteristic.
RARE-41. GLIOBLASTOMA MULTIFORME AND OTHER CNS TUMORS IN HEREDITARY MISMATCH REPAIR DEFICIENCIES
Authors: Dishion Evan , Korson Clayton , Groh Darren 
Published: November 2019

Abstract

BACKGROUND
Lynch syndrome (LS) and constitutional mismatch repair deficiency syndrome (CMMRD) are caused by germline mutations in mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6, and PMS2. LS patients have an inherited mono-allelic MMR defect, whereas CMMRD patients have a bi-allelic defect. MMR is critical to maintaining genomic integrity during DNA replication and these germline defects are known to produce microsatellite instability (MSI). Both LS and CMMRD have reported cases of increased primary brain cancer, namely glioblastoma multiforme (GBM). Given the shared pathophysiology of these syndromes, the large number of cases and registry studies published, and recent treatments of CNS tumors in CMMRD, a literature review has been conducted. OBJECTIVES: Review the pathophysiology of germline MMR deficiency and how it relates to brain tumor formation. Review the risk of developing primary CNS tumors with various MMR defects. Review the current management of CNS tumors in LS and CMMRD.

METHODS
Literature review of the most recent understanding of pathophysiology, all literature on CNS tumors in LS and CMMRD, and the current management of GBM including recent literature on CMMRD.

RESULTS
The lifetime risk of developing a primary malignant brain tumor or other CNS tumor in the United States has been calculated at 0.62%. Based on registry data, current estimates of the lifetime risk of developing a primary CNS tumor in LS is between 1–8.7%. Of the 146 genetically confirmed cases of CMMRD, 58 cases of high-grade gliomas were identified (including GBM). Most patients with CMMRD carry homozygous germline mutations in PMS2 (approximately 60%). Although primary CNS tumors appears to be a less common extra-colonic manifestation in LS, it is relatively common amongst CMMRD patients. Acknowledgement: Henry Lynch
RARE-48. GROWING KNOWLEDGE AND EMERGING QUESTIONS RELATED TO POT-1 GERMLINE MUTATIONS AND ASSOCIATED MALIGNANCIES: A CASE REPORT
Authors: Ruiz Amber , Eastman Boryana , Halasz Lia , Jarvik Gail , Brown Lauren , Graber Jerome 
Published: November 2019

Abstract
Protection of telomeres 1 (POT1) is a member of a family of genes responsible for maintenance of telomere integrity. Germline mutations of the POT1 gene have been associated with tumorigenesis of multiple tissue types, conferring an increased risk of development of malignancies such as melanoma, chronic lymphocytic leukemia, gliomas, and cardiac sarcomas. We present the case of a 28 year old male who first presented at the age of 15 with personality changes. Several years later, he was found to have a left frontal, IDH mutated, WHO grade III anaplastic astrocytoma. Following successful treatment with gross total resection, radiation therapy, and adjuvant chemotherapy, the patient represented with an MRI showing enhancement concerning for osteomyelitis and possible tumor recurrence. Pathology of the dura was consistent with myxofibrosarcoma. Staging PET scan at that time revealed multiple hypermetabolic lung lesions found to be Lanagerhans cell histiocytosis. Given the patient’s complex oncological history, genetic testing was performed. He was found to carry a heterozygous mutation of the POT1 gene. This case raises the suspicion for a broader POT1-associated cancer predisposition than previously described in the literature. Moreover, this prompts further questioning of an association between POT1 mutations and IDH status in related gliomas. Patients with POT1 mutations might also be at increased risk of secondary malignancies after radiation exposure, which may require closer observation after treatment.
STEM-01. CHARACTERIZATION OF ORTHOTOPIC GLIOBLASTOMA MODEL FOR THE GENE-AND CELL THERAPY
Authors: Han Ji-Hun , Chang Da-Young , Lee Young-Joon , Suh-Kim Haeyoung , Kim Sung-Soo 
Published: November 2019

Abstract
Intrinsic heterogeneous and infiltrative nature of glioblastoma cells to the adjacent normal brain parenchyma are the main obstacles to the treatment of glioblastoma multiforme (GBM). The infiltrative nature of GBM increases following various treatments, which often leads to tumor recurrence. U87 cell line, a commonly used as a GBM cell line till recently, has appeared inappropriate for GBM model. Thus, we established an orthotopic GBM model using another cell line, LN229. Here, we discuss the infiltrative nature of LN229 in the mouse brain and their interaction with adjacent brain microenvironment. We also show that the LN229-driven brain tumor model is appropriate for the study of mesenchymal stem cell-mediated gene therapy using deliver a bacterial suicide gene, cytosine deaminase (CD).
STEM-03. CONSUMPTION OF A HIGH-FAT DIET INHIBITS THE TUMOR SUPPRESSIVE ACTIVITY OF HYDROGEN SULFIDE, DRIVING CANCER STEM CELL ENRICHMENT AND DISEASE AGGRESSION IN GLIOBLASTOMA
Authors: Silver Daniel , Roversi Gustavo , Bithi Nazmin , Troike Katie , Neumann Chase , Mark Brown J , Hine Christopher , Lathia Justin 
Published: November 2019

Abstract
Glioblastoma (GBM) remains among the deadliest of human malignancies. Effective disease management is lacking due in part to the emergence of the cancer stem cell (CSC) phenotype. The tumor cell extrinsic, environmental, and lifestyle factors that result in CSC enrichment are not well understood. Alongside other pathological features, the CSC state endows populations of tumor cells with a fluid metabolic profile that enables utilization of multiple nutrition sources. Therefore, to test the impact of diet on CSC enrichment, we interrogated disease progression in tumor-bearing mice fed either a high-fat diet (HFD), similar to the Western Pattern diet or a control low-fat diet. Compared to controls, HFD-consumption resulted in the presentation of a hyper-aggressive disease phenotype with truncated survival and tumors markedly enriched in tumor-initiating SOX2+ CSCs. To understand the underlying mechanism driving this finding, we examined tumors for the diet-regulated metabolite hydrogen sulfide (H2S). H2S is an endogenously produced bio-active gasotransmitter similar to nitric oxide. It functions principally through protein S-sulfhydration to regulate a variety of cellular programs including mitochondrial function, stress signaling and metabolism. While there is exceedingly limited information on H2S and GBM, its HFD-driven suppression has been reported in other organ systems. We discovered a significant reduction in H2S synthesis resulting from HFD-consumption in the brain of the mouse and a striking decrease in protein S-sulfhydration in human GBM tumor tissue when compared to non-cancerous control brain tissue. We demonstrated that chemical inhibition of H2S synthesis resulted in increased tumor cell viability whereas exposure to chemical H2S donors led to pronounced cell death of cultured mouse and human GBM cells. These data demonstrate for the first time, that H2S serves as a tumor suppressor for GBM. Moreover, the diet-driven suppression of H2S helps explain the hyper-aggressive in vivo phenotype that presents in response to HFD-consumption.
STEM-04. NICARDIPINE SENSITIZES APOPTOSIS OF GLIOMA STEM CELLS INDUCED BY TEMOZOLOMIDE THROUGH INHIBITING AUTOPHAGY
Authors: Dong Jun , Shi Jia 
Published: November 2019

Abstract

BACKGROUND
Glioma stem cells (GSCs) play an important role in tumor progression and recurrence. Currently, treatments of glioma are limited mainly due to strong tolerance of GSCs against conventional chemotherapeutic drugs such as temozolomide. Nicardipine, a calcium antagonist, is commonly used in the therapy of hypertension, which is recently repurposed in the comprehensive strategies against gliomas in our previous studies. Here, we explored the cytotoxic sensitization effect of nicardipine combining temozolomide and the underlying mechanisms.

METHODS
Two human glioma stem cell lines were applied and treated with nicardipine, temozolomide, and combination of both, respectively. Cell viability was detected by CCK-8, cell apoptosis was analyzed by flow cytometry, and immunoblot was used to detect autophagic-releated proteins including p62, LC3 and mTOR. The mTOR agonists and inhibitors were applied to further evaluate whether nicardipine inhibits autophagy via mTOR pathway.

RESULTS
GSCs had strong tolerance against temozolomide while nicardipine could significantly inhibit the viaibility of GSCs and promote cell apoptosis when acting together with temozolomide, indicating that nicardipine could sensitize the toxicity of temozolomide. Furthermore, both temozolomide and nicardipine could inhibit autophagy, and the effects of nicardipine was more prominent, suggesting that nicardipine might enhance GSCs apoptosis induced by temozolomide through inhibiting autophagy. Further molecular studies showed that the cytotoxic sensitization effects of nicardipine was induced through activation of the phosphorylation level of mTOR, which was abolished with the treatment of rapamycin, a mTOR inhibitor.

CONCLUSION
Our results suggested that nicardipine could sensitize apoptosis of glioma stem cells induced by temozolomide through inhibiting autophagy, which was mediated by activation of mTOR activity.