bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-37. SINGLE-CELL SYSTEMS NEUROIMMUNOLOGY REVEALS IMMUNOSUPPRESSIVE CORRELATES WITH VENTRICULAR STEM CELL NICHE CONTACT IN HUMAN GLIOBLASTOMA
Authors: Bartkowiak Todd , Barone Sierra , Greenplate Allison , Sinnaeve Justine , Leelatian Nalin , Mistry Akshitkumar , Roe Caroline , Mobley Bret , Chambless Lola , Thompson Reid , Weaver Kyle , Ihrie Rebecca , Irish Jonathan 
Published: November 2019

Abstract
Glioblastomas make up more than 60% of adult primary brain tumors and carry a median survival of less than 15 months despite aggressive standard therapy. Immunotherapy, which is now standard of care for many solid tumors, offers an appealing therapeutic approach that may improve outcomes for glioblastoma patients. Predictive features in glioblastomas that may inform responsiveness to different immunotherapeutic modalities, however, are still lacking. Recent studies have demonstrated that patients whose tumors show radiographic contact with the lateral ventricles, and thus the stem cell niche of the ventricular-subventricular zone (V-SVZ), have reduced survival outcomes compared to patients whose tumors do not contact the V-SVZ. We therefore hypothesized that tumor contact with the V-SVZ engenders a unique, immunosuppressive microenvironment that promotes tumor growth by suppressing anti-tumor immunity. Glioblastoma tumors, obtained in accordance with the Declaration of Helsinki and with institutional IRB approval (#131870, #030372, #181970), were disaggregated into single-cell suspensions and multi-dimensional single-cell mass cytometry was performed to interrogate >30 immune parameters in thirteen immune populations infiltrating human glioblastomas. Using advanced computational dimensionality-reduction tools (Citrus, t-SNE, FlowSOM, and MEM), we identified distinctions among the abundance and phenotypes of tumor-infiltrating immune cells. Firstly, on the basis of tumor contact with the V-SVZ, Citrus identified differential abundance of five T and myeloid cell subsets among glioblastomas. Secondly, differential expression of five functional immune markers was observed in seven distinct immune cell subsets infiltrating glioblastoma tumors. Further, both immune abundance and marker expression correlated with patient outcome. Manual gating analysis and parallel computational pipelines confirmed that comparable cell subsets could be identified with traditional approaches and unsupervised algorithmic analysis. These results provide key insights into the immune microenvironment of glioblastomas. In addition, several clinically actionable immunotherapeutic targets were uncovered that may be used to optimize treatment strategies for glioblastomas based on V-SVZ contact status.
IMMU-47. RNA-NANOPARTICLE VACCINES ARE SAFE AND IMMUNOLOGICALLY ACTIVE IN CLIENT-OWNED CANINES WITH TERMINAL GLIOMAS
Authors: Carrera-Justiz Sheila , Stover Brian , Milner Rowan , Weidert Frances , Huang Jianping , Mitchell Duane , Mendez-Gomez Hector , Sayour Elias 
Published: November 2019

Abstract

BACKGROUND
The lack of appropriate preclinical murine glioblastoma models limits comprehensive toxicity/efficacy evaluation of investigational agents. To overcome this challenge, we evaluated the safety and activity of a new immunotherapeutic technology that we have pioneered (composed of tumor mRNA complexed into a custom lipid-nanoparticle formulation) in client-owned canines (pet dogs) diagnosed with malignant gliomas. OBJECTIVE/

METHODS
Canine malignant gliomas were biopsied for generation of personalized tumor mRNA loaded into our custom lipid-nanoparticle (NP) vector. The patients received RNA-NPs intravenously beginning two weeks after their biopsy once weekly (x3) and no other anti-tumor therapeutic interventions.

RESULTS
Within a few hours after administration, tumor specific RNA-NPs elicited margination of peripheral blood mononuclear cells, which increased in the subsequent days/weeks post-treatment; suggesting that RNA-NPs mediate lymphoid honing of immune cell populations before egress. RNA-NPs also elicited increased: 1) serum interferon-α that spiked at 2 hours; 2) CD80 and MHCII on CD11c+ cells (demonstrating activation of peripheral DCs); and 3) interferon-γ + T-cells (i.e. activated T-cells). After receiving weekly RNA-NPs (×3), the canines had a steady course. Aside from low-grade fevers on the vaccination days, personalized tumor RNA-NPs (1x) were well tolerated with stable blood counts, chemistries, and renal/liver function tests. All patients assessed developed immunologic response with pseudoprogression or stable/smaller tumors by MRI. Although we have treated a small cohort, we have observed improvement in median/overall survival in all canine patients with terminal gliomas receiving RNA-NPs (compared with historical controls).

CONCLUSION
RNA-NPs were feasible, safe and immunologically active in client-owned canines with terminal gliomas. We have not appreciated significant toxicities in canines that would preclude investigation in humans at 1x dosing. Although these results need to be validated in larger canine data sets, these results suggest safety and activity of tumor specific RNA-NPs in canines with terminal gliomas.
IMMU-49. THE SELECTIVE ENRICHMENT OF T CELLS TARGETING UNKNOWN BRAIN CANCER ANTIGENS VIA TROGOCYTOSIS
Authors: Moore Ginger , Divita Bayli , Flores Catherine , Mitchell Duane 
Published: November 2019

Abstract

INTRODUCTION
Trogocytosis is the exchange of membrane components from one cell to another. During T cell activation, dendritic cell (DC) and T cell membranes become anchored around the TCR/MHC complex and their costimulatory molecules. Part of the DC membrane is pulled away, taken in, and educates the T cell to recognize foreign antigens. We have utilized this phenomenon to isolate and expand a select population of T cells that have undergone this interaction. HYPOTHESIS: (1) By selecting for cells that have undergone trogocytosis, we are enriching for a tumor-specific population of T cells and can improve anti-tumor responses in the setting of adoptive cellular transfer (ACT). (2) This approach represents a reliable method to detect tumor-specific antigens across numerous types of brain cancers.

METHODS
Murine DCs are pulsed with KR158B glioma RNA and then stained with a proliferation dye such as Cell Trace Violet. These cells are co-cultured overnight with CD3+ splenocytes of vaccinated mice and IL-2. The cells are then sorted into T cells that have undergone trogocytosis (CD3+ CTV+) and those that have not (CD3+CTV-) and placed back into co-culture with fresh dendritic cells for expansion of tumor-specific T cells and/or restimulation assay. Additionally, T cells are spectratyped and phenotyped by flow cytometry.

RESULTS
Cells that had undergone trogocytosis (CD3+CTV+) demonstrated superior IFNγ secretion and enriched for CD4+ and CD8+ central memory and effector subsets compared to cells that had not undergone trogocytosis (CD3+CTV-). Spectratyping analysis revealed CD3+CTV+ cells enriched for Vβ 5.1/5.2 and Vβ 6, two families we have determined to be crucial for anti-tumor efficacy.

CONCLUSIONS
This method of selection and enrichment of tumor-specific T cells has promising implications for the enhancement of ACT. This method can be used to elucidate tumor-specific antigens that are unique to an individual’s cancer fingerprint.
INNV-09. CLINICAL EFFICACY OF TUMOR TREATING FIELDS FOR NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Liu Yang , Strawderman Myla , Warren Kwanza , Richardson Margie , Serventi Jennifer , Mohile Nimish , Milano Michael , Walter Kevin 
Published: November 2019

Abstract
Recent clinical trials demonstrated that adding tumor treating fields (TTF) to radiotherapy and temozolomide chemotherapy (the Stupp protocol) increased survival for glioblastoma (GBM) patients. However, data is lacking on the magnitude of this survival effect when the regimen is used outside of a clinical trial as part of routine clinical practice. In the present study, we retrospectively identified adult patients with newly diagnosed GBM (n = 240) treated with the Stupp protocol at our institution from January 2005 to July 2017. We grouped patients into two time periods for comparison: 2005–2013 (group 1, Stupp protocol) and 2014–2017 (group 2, TTF+ Stupp protocol). Thirty-six percent (37/104) of patients in group 2 received TTF in conjunction with the Stupp protocol. Within group 2, the 37-patients who received TTF + Stupp had increased 6-month and 1-year survival rates compared to the 67-patients who received Stupp alone (97.1% vs. 75.7%, p = 0.006; 67.6% vs. 53.7%, p = 0.170, respectively). The improvement of survival rate at 6-month was further confirmed by a modified Poisson model (RR: 1.23, p = 0.010) adjusting for sex, age, performance status and extent of resection. However, we did not observe improvements in overall survival (OS) with a Cox model with TTF treatment modeled as a time-dependent covariate (HR = 0.87, p = 0.599). Furthermore, we did not find that the addition of TTF as a treatment option in our center significantly improved OS for patients in group 2 when compared to those in group 1 (429.0 vs. 395.0 days, p = 0.138). Therefore, while adding TTF to the Stupp protocol appeared to benefit patients with newly diagnosed GBM, this effect may be largely due to selection bias. Comprehensive studies including large number of patients as well as longer follow-up time are needed to validate our results.
INNV-10. SAFETY OF APIXABAN FOR VENOUS THROMBOEMBOLISM PREVENTION IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Thomas Alissa , Wright Heather , Walker Hannah , Prasad Prachi , Chan Kelly , Tipirneni Eswar , Goodwin Andrew , Holmes Chris 
Published: November 2019

Abstract
Venous thromboembolism (VTE) impacts an estimated one in every three patients with malignant glioma (MG), resulting in increased morbidity and mortality. Despite the high prevalence and serious consequences of VTE, there is no outpatient standard of care prevention strategy. There have been three prospective clinical trials of VTE prophylaxis in patients with newly diagnosed MG, all of which used an injectable low molecular weight heparin (LMWH) product. We performed an open-label safety study of apixaban, a direct oral anticoagulant (DOAC), for VTE prevention in patients with newly diagnosed MG. All patients had surgery or biopsy two to twenty-one days prior to enrollment in the study. Patients were treated with apixaban 2.5 mg twice daily for up to 6 months. Peak and trough apixaban concentrations were measured at the beginning and end of treatment. Thirteen patients consented to the study and ten enrolled (2 screen-fail, 1 withdrawal). The patients have completed a mean of 4.5 cycles of apixaban (range 2 to 6, with 2 patients still undergoing treatment). There were no bleeding events while receiving apixaban. There were no hematologic or non-hematologic treatment-related adverse events. There were no VTE events observed in patients receiving apixaban. Two patients who came off treatment early due to disease progression developed VTEs after stopping prophylactic apixaban. Quality of life analysis is ongoing. In this pilot study we found that prophylactic dosing of 2.5 mg twice daily of apixaban was safe in the post-operative period for patients with newly diagnosed MG. Our preliminary results suggest that this may be a safe and effective prevention strategy for VTE prophylaxis in this high risk group of patients.
INNV-17. INNOVATIVE EDUCATIONAL APPROACHES TO ENHANCE PATIENT AND CAREGIVER UNDERSTANDING OF TTFIELDS FOR GLIOBLASTOMA
Authors: Shackelford Melissa , Frongillo Peggy , Certo Jeanine 
Published: November 2019

Abstract

INTRODUCTION
The most common, aggressive malignant brain tumor is Glioblastoma (GBM) with patient median survival of 15–21 months. Patients with GBM face devastation of diagnosis, disease-burden, and hardship of seeking accurate information regarding treatment options. Evolving technology-enhanced methods of learning challenge traditional ways patients with cancer are educated and create an educational paradigm shift. The device manufacturer of Tumor Treating Fields (TTFields)) has developed innovative supplementary educational platforms to compliment healthcare provider (HCP) education of patients-caregivers with GBM treated with TTFields. This report aimed to evaluate these supplementary educational platforms.

METHODS
Emerging technology methods were employed to address patient-caregiver frequently asked questions, which included queries regarding treatment overview, mechanism of action, treatment initiation, and management to potentially ease the emotional burden of patients-caregivers seeking TTFields information. The TTFields educational platforms included incorporation of Web program, Buddy Program, Open-House Program (live and webinar), Chalk-Talk Video, and Facebook.

RESULTS
Educational platforms connecting potential and current TTFields patients-caregivers via live/webinar Open-House events ensured patient support. The phone-based Buddy Program allowed for direct 1:1 discussions between potential and current TTFields patients-caregivers. Patient-caregiver surveys revealed 100% would recommend the program to others (n=91); 98% were satisfied with the call experience (n=90); 76% felt the most valuable takeaway was speaking to someone who understands their situation (n=82). Of ambassadors, 98% felt they helped address registrants’ concerns (n=150). A dedicated TTFields Facebook page and first-ever, industry-led Facebook Live event (national broadcast; patients-caregivers discussed unique issues) were launched. Additionally, vignettes (eg, videos, written stories) were shared through a dedicated patient-caregiver website and YouTube channel.

CONCLUSIONS
In an ever-growing information age, it is important that HCPs become aware of innovative ways to reach and provide education for patients with brain cancer. Emerging technology utilization may improve GBM supportive care, by improving communication channels and potentially easing burden.
INNV-19. SURVEYING BIAS IN NEURO-ONCOLOGY AND SOCIETY FOR NEURO ONCOLOGY (SNO) MEMBERS: GENDER AND BEYOND
Authors: Kumthekar Priya , Brastianos Priscilla , Dunbar Erin , Peters Katherine , Porter Alyx 
Published: November 2019

Abstract

BACKGROUND
The face of neuro-oncology providers has evolved over the century. We sought to evaluate if its culture has evolved concurrently. Women in NeuroOncology (“WiN.”) is a SNO subcomittee that identifies the needs of women in neuro-oncology and promotes advancement of the careers of women in neuro-oncology. We created this survey to examine bias within our field with the goal to implement future change.

METHODS
Following IRB approval, we surveyed both male and female SNO members and analyzed de-identified responses.

RESULTS
Of the 206 respondents, 25% identified as male, 84.9% were in academics, 73.7% were primarily research focused (69% clinical), and 59% were medical neuro-oncology focused. The majority of respondents were 36–45 years old (47%), followed by 46–55 (32%), and 21% aged 56+. 69.8% self-identified as white, followed by 22% Asian, 7.8% Latin, and 2.9% Black. The majority reported general professional bias at least “not infrequently”, with 11.7% reporting it “very commonly.” 59.9% reported “not being invited to participate and or being considered for an opportunity”, followed by 46.1% “being minimized, teased or disrespected”, 44.3% “being passed over for professional opportunities”, and 41.9% salary disparity. Furthermore, of those reporting general professional bias, 42.9% reported a lack of effective mentorship and 94% reported some frequency of burnout, with 34% “commonly, very commonly”, followed by 28.3% “not infrequently.” Notably, although only 25% of responders were men, 82.4% of total respondents reported some frequency of gender bias in the workplace, with “not infrequently” being the most commonly reported (48%).

CONCLUSIONS
In this survey, we identified SNO members who have experienced bias. Based on quantitative and qualitative responses, many reported bias manifesting as missing academic opportunities, salary disparity, burnout, and lack of mentorship. As we cultivate the next generation, we will use these results to engage those in leadership to promote unbiased equality.
INNV-20. A SYSTEMATIC REVIEW OF TUMOR TREATING FIELDS THERAPY FOR PRIMARY FOR RECURRENT AND GLIOBLASTOMA
Authors: Shah Pavan , White Taija , Price Carrie , Mukherjee Debraj 
Published: November 2019

Abstract

BACKGROUND
Glioblastoma is an aggressive primary central nervous system malignancy with poor prognosis and limited treatment options. Tumor treating fields (TTFs) are a novel treatment modality utilizing alternating electric fields that have demonstrated promise in randomized clinical trials for primary and recurrent glioblastomas. In addition to these studies, a multitude of smaller investigations have been performed examining their efficacy in a variety of combination therapies. This systematic review of available literature aims to summarize and evaluate the efficacy and safety of TTFs for primary and recurrent glioblastoma patients.

METHODS
A systematic review of the literature was performed according to PRISMA guidelines from database inception through 2/27/2019. Databases queried include PubMed, Embase, Cochrane, Scopus, Web of Science, and ClinicalTrials.gov. 856 unique studies were initially identified in this search, 9 of which met final inclusion criteria. 2 authors independently performed the screening and data extraction of the studies.

RESULTS
Excluding historical controls, 1569 patients were identified in these studies, 1191 of which received TTFs therapy. TTFs were evaluated in single-arm clinical trials (n = 2), randomized clinical trials (n = 2), and retrospective studies (n = 5). These 9 studies are presented based on treatments provided, baseline patient characteristics, and patient outcomes. No adverse events appear to be associated with TTFs other than adverse skin reactions. Given the heterogeneity in the presented studies, a quantitative meta-analysis was not performed.

CONCLUSIONS
TTFs are a novel treatment modality that have demonstrated safety and efficacy in a number of settings and study designs. However, further investigation is needed to continue characterizing treatment outcomes and assessing TTFs interactions with various drug regimens.
INNV-26. IN VITRO CHEMO RESISTANCE PROFILES OF CIRCULATING GLIAL CELLS REPLICATE CHEMO CHARACTERISTICS OF TUMOR TISSUE
Authors: Akolkar Dadasaheb , Patil Sanket , Mhase Vishakha , Devhare Pradip , Fulmali Pooja , Patil Revati , Srinivasan Ajay , Datta Vineet , Schuster Stefan , Bhatia Jatinder , Datar Rajan 
Published: November 2019

Abstract
Survival of high-grade glioma patients remains dismal due to onset of resistance to even the limited systemic treatment option currently available. Except for indirect prediction of alkylating agent Temozolomide response through MGMT promotor methylation and NTRK fusions for larotrectinib, there are no biomarkers available for drug response prediction. Cell based, in vitro chemosensitivity assays can interrogate the efficacy of an array of cytotoxic drugs. However, the unavailability of live tumor cells for such assays pose challenges in clinical practice. Repeat biopsies are neither advisable nor feasible. Access to Circulating Glial Cells (CGCs) can provide real time insight into the chemo dynamics of the tumor. In this study, we show for the first time that CGCs can be harvested from peripheral blood of glioma patients for chemo response and resistance profiles (CRR) of cytotoxic drugs. CGCs were harvested from 15 ml of peripheral blood from high grade GBM patients (n=9) out of whom cells derived from surgically excised tumor tissue were also available for comparison in 2 patients. CellWizard™ process was adopted for enrichment of CGCs which is based upon epigenetically active media with paradoxical chemo-toxicity that selectively induces lethality in normal cells. This paradoxical cytotoxicity of the medium leads to selective elimination of most leukocytes thus facilitating a label free negative enrichment of CGCs. In vitro chemo sensitivity assay performed on live CGCs and cell death events were determined to evaluate response to different class of chemotherapy drugs. Evaluation of drug response showed very high concordance between tumor derived cells and CGCs in both patients where live tissue was available. In 7 patients where CGCs alone could be evaluated, the response showed replication between in vitro profile compared to treatment antecedents in 5 patients. 2 patients were treatment naïve and the response reflected high sensitivity to Temozolomide.
MNGI-06. EFFICACY OF 177LU-DOTATATE THERAPY IN RECURRENT ANAPLASTIC MENINGIOMA
Authors: Kizilbash Sani , Johnson Derek 
Published: November 2019

Abstract

BACKGROUND
177Lu-Dotatate (177Lu-DOTA0-Tyr3-Octreotate) is a beta-particle emitting somatostatin analog recently FDA approved for the treatment of somastatin receptor-positive gastroenteropancreatic neuroendocrine tumors. Somatostatin receptors are highly expressed in almost all meningiomas, therefore 177Lu-Dotatate may be a reasonable treatment strategy for this disease. Furthermore, the short path length of the beta particle should allow for treatment of previously radiated patients with low risk of cerebral radiation necrosis. CASE STUDY: A 61 year-old male presented with a history of atypical meningioma (WHO grade II), recurrent as anaplastic meningioma (WHO grade III). His previous treatments included multiple surgical resections, fractionated radiation therapy, stereotactic radiosurgery, everolimus/octreotide LAR, bevacizumab and hydroxyurea. MRI imaging revealed rapid volumetric progression over the prior nine months with a near tripling in size from 29.9 cm3 to 80.4 cm3. In-111 octreotide confirmed the presence of somatostatin receptors within the tumor. 177Lu-Dotatate was administered intravenously at a dose of 200 millicuries per dose, every eight weeks for four cycles. Treatment was tolerated very well, with no significant adverse events. Tumor volume initially increased to 98.3 cm3 after cycle 1 of treatment, and subsequently decreased to 91.2 cm3 after cycle 2. Eight months after treatment onset, the tumor volume remained stable (93.4 cm3).

CONCLUSION
177Lu-Dotatate may be a safe and effective strategy for the treatment of somastatin receptor-positive meningioma. The transient increase in tumor volume after the first dose in this case may have represented delayed treatment effect or pseudoprogression. A phase II clinical trial is currently being activated to determine the progression-free survival associated with 177Lu-Dotatate in patients with recurrent meningioma.