bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXTH-04. INTRATHECAL (IT) DELIVERY OF TYPE I POLARIZED DENDRITIC CELL VACCINE (DC1) ERADICATES TUMOR GROWTH IN BREAST CANCER (BC) XENOGRAFT MODEL WITH BRAIN METASTASES (BM) AND LEPTOMENINGEAL DISEASE (LMD)
Authors: Law Vincent , Kodumudi Krithika , Snyder Colin , Czerniecki Brian , Forsyth Peter 
Published: December 2020

Abstract

BACKGROUND
Approx. 5% of BM will also develop LMD. Currently there is no effective treatment for BC-associated BM/LMD. As systemic therapies do not prevent the disease recurrence and eventual death, the better option would be direct-targeted approach. We have shown that there is a loss of the anti-HER2 and anti-HER3 CD4 Th1 immune response in BC patients (pts). In a clinical setting, administration of class II HER2 peptide-pulsed Type I polarized dendritic cell vaccine (HER2-DC1) partially restored anti-HER2 Th1 immune responses with pathologic complete response in HER2+ BC patients. In this study, we examined the IT delivery of HER2/HER3- DC1 in BC-LMD model.

METHODS
Luciferase-labeled HER2+ TUBO BC cell line was injected into the cisterna magna of BALB/c mice to develop BM/LMD. We developed a technique, coined the “Top Hat” (TH) for mouse model that mimics the Ommaya reservoir in BC-pts. The TH essentially allows us to administer IT treatment directly into CSF. BC-BM/LMD bearing mice were given HER2- and Her3 peptide-pulsed Type I polarized DC1 through the TH.

RESULTS AND DISCUSSION
BM/LMD mice were randomized into following groups: 1) systemic Her2-DC1 2) IT Her2-DC1 3) IT Her2-/Her3-DC1. The median survival (MS) of control mice was 10 days and systemically treated mice was 19 days. IT Her2-DC1 animals did significantly better than both control and systemic treated groups (MS: 63 days; p&lt; 0.0001) and overall survival (OS): 44%. Interestingly, mice given IT Her2-/Her3-DC1 had the best OS (78%). Surviving animals were eventually disease free. Mice that had complete tumor regression were immune to subsequent rechallenge with TUBO cells. Immune cell infiltration in the of CSF, spinal cord and tissues of experimental mice are currently ongoing.

CONCLUSIONS
Our preclinical data supports the clinical relevance of using intrathecal delivery of DC1 vaccine as a potential treatment for BM and LMD of BC-pts.
EXTH-28. MOLECULAR CHARACTERIZATION OF HUMAN GLIOMAS AND IDENTIFICATION OF NEOPLASMS RESPONSIBLE FOR NEW BIOPHARMACEUTICALS OBTAINED FROM ANIMAL VENOM: A TRANSLATIONAL APPROACH
Authors: Barreto dos Santos Natalia , da Silva Monize Valeria , de Lima Munhoz Jaqueline , da Rocha-e-Silva Thomaz A A , Sutti Rafael , Verinaud Liana , Araujo João Luiz Vitorino , Raposo Catarina 
Published: December 2020

Abstract
Gliomas correspond to approximately 80% of primary malignant brain tumors in adults. Associate histopathological classification to the identification of the molecular profile of these tumors is a great strategy to predict the tumor’s behavior and its responsiveness to the treatments. Studies have shown the potential of using biopharmaceuticals against cancer. Our research group has recently found two main subfractions isolated from Phoneutria nigriventer spider venom (PnV) (called SF1 and SF11) that can act decreasing the number of migrating cells during transwell assay. Therefore, the present study aimed to characterize, as regards molecular identity, the responsiveness of glioma samples collected from patients to the molecules purified from the PnV, in order to improve diagnostic and prognostic predictions, as well as contribute to the development of new drugs. After consent of the patients, samples of the tumors clinically diagnosed as glioma were collected during the surgical procedure to cultivation, that were performed until 10 passages to establish a lineage before use. To analyze its responsiveness to PnV in a migration assay, cultured human glioblastoma (1-JA63) cells were treated with PnV-isolated (HPLC) subfractions (SF1 and SF11 at 1 µg/ml) for 12 and 48 h (control stayed in IMDM) in a transwell system. SFs (mainly SF1) treatment induced a significant reduction in the number of migrating cells after 48 hours of exposure, in comparison to the control (untreated). Ongoing trials continue the establishment of another tumor samples of gliomas and migration tests with PnV subfractions will be carried out, to compare their effects in relation to other degrees of the disease also correlating the tumor response to the drug with the molecular profile. The results will contribute to the development of a potential individualized therapy also adding information about the correlation between the molecular identity of the tumor and its prognosis.
EXTH-42. SPIDER VENOM COMPONENTS DECREASE GLIOBLASTOMA CELL MIGRATION AND INVASION THROUGH RHOA-ROCK AND NA+/K+-ATPASE β2: POTENTIAL MOLECULAR ENTITIES TO TREAT INVASIVE BRAIN CANCER
Authors: Raposo Catarina , dos Santos Natalia Barreto , Caballero Marcus , Bonfanti Amanda , da Rocha-e-Silva Thomaz A A , Sutti Rafael , Verinaud Liana 
Published: December 2020

Abstract
Glioblastoma (GB) cells have the ability to migrate and infiltrate the normal parenchyma, leading to the formation of recurrent tumors often adjacent to the surgical extraction site. We recently showed that Phoneutria nigriventer spider venom (PnV) has anticancer effects mainly on the migration of human GB cell lines (NG97 and U-251). The present work aimed to investigate the effects of isolated components from the venom on migration, invasiveness, morphology and adhesion of GB cells. The involvement of RhoA-ROCK signaling and Na+/K+-ATPase β2 (AMOG) was also evaluated. Human (NG97) GB cells were treated with twelve subfractions (SFs - obtained by HPLC from PnV). Migration and invasion were evaluated by scratch wound heling and transwell assays, respectively. Cell morphology and actin cytoskeleton were shown by GFAP and phalloidin labeling. The assay with fibronectin coated well plate was made to evaluate cell adhesion. Western blotting demonstrated ROCK and AMOG levels and a ROCK inhibitor was used to verify the involvement of this pathway. Two (SF1 and SF11) of twelve SFs decreased migration and invasion compared to untreated control cells. Both SFs also altered actin cytoskeleton, changed cell morphology and reduced adhesion. SF1 and SF11 increased ROCK expression and the inhibition of this protein abolished the effects of both subfractions on migration, morphology and adhesion (but not on invasion). SF11 also increased Na+/K+-ATPase β2. All components of the venom were evaluated and two SFs were able to impair human glioblastoma cells. The RhoA effector, ROCK, was shown to be involved in the mechanisms of both PnV components. It is possible that AMOG mediates the effect of SF11 on the invasion. Further investigations to isolate and biochemically characterize the molecules are underway. Support: FAPESP #2015/04194-0; CNPq #431465/2016–9.
IMMU-11. DUAL TARGETING OF IL-6 AND CD40 OVERCOMES GLIOBLASTOMA RESISTANCE TO IMMUNE CHECKPOINT BLOCKADE
Authors: Yang Fan , Brem Steven , Fan Yi 
Published: December 2020

Abstract
Glioblastoma (GBM) is refractory to current T cell-based immunotherapies such as checkpoint blockade. GBM is characterized by extensive infiltration of immunosuppressive macrophages (Mφs) that contribute to the treatment resistance. Here we develop a dual-targeting strategy to synergistically activate tumor-associated Mφs, which overcomes GBM resistance to therapeutic blockade of the PD1 and CTLA4 checkpoints. Consistent with a previously established role of IL-6 in alternative Mφ polarization, we show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T cell infiltration and enhances animal survival in a genetically engineered mouse GBM model. However, IL-6 inhibition does not synergize PD-1 and CTLA-4 blockade in GBM. Interestingly, we reveal that anti-IL-6 therapy reduces CD40 expression in GBM-associated Mφs. Our transcriptome analysis identifies a Stat3/HIF-1a-mediated axis, through which IL-6 regulates CD40 expression in Mφs. Finally, we show that combination of IL-6 blockade with CD40 stimulation robustly reverses Mφ-mediated tumor immunosuppression, enhances T cell infiltration, and sensitizes GBM to PD-1 and CTLA-4 blockade treatment, cumulating in inhibited tumor growth and extended animal survival. These findings illustrate a cellular mechanism that regulates Mφ-mediated tumor immunity, and suggest that dual-targeting IL-6 and CD40 may offer exciting opportunities for improving immunotherapy against GBM.
IMMU-35. TRANSCRIPTIONALLY DEFINED IMMUNE CONTEXTURE IN HUMAN GLIOMAS AT SINGLE-CELL RESOLUTION
Authors: Gupta Pravesh , Dang Minghao , Bojja Krishna , M Tuan Tran , Shehwana Huma , Kamiya-Matsuoka Carlos , Li Jianzhuo , Kassab Cynthia , Ott Martina , Gumin Joy , Maheshwari Atul , de Groot John , Lang Frederick , Balasubramaniyan Veerakumar , Navin Nicholas , Heimberger Amy , Wang Linghua , Bhat Krishna 
Published: December 2020

Abstract
The brain tumor immune microenvironment (TIME) continuously evolves during glioma progression and a comprehensive understanding of the glioma-centric immune cell repertoire beyond a priori cell types and/or states is uncharted. Consequently, we performed single-cell RNA-sequencing on ~123,000 tumor-derived immune cells from 17-pathologically stratified, IDH (isocitrate dehydrogenase)-differential primary, recurrent human gliomas, and non-glioma brains. Our analysis delineated predominant 34-myeloid cell clusters (~75%) over 28-lymphoid cell clusters (~25%) reflecting enormous heterogeneity within and across gliomas. The glioma immune diversity spanned functionally imprinted phagocytic, antigen-presenting, hypoxia, angiogenesis and, tumoricidal myeloid to classical cytotoxic lymphoid subpopulations. Specifically, IDH-mutant gliomas were enriched for brain-resident microglial subpopulations in contrast to enhanced bone barrow-derived infiltrates in IDH-wild type, especially in a recurrent setting. Microglia attrition in IDH-wild type -primary and -recurrent gliomas were concomitant with invading monocyte-derived cells with semblance to dendritic cell and macrophage/microglia like transcriptomic features. Additionally, microglial functional diversification was noted with disease severity and mostly converged to inflammatory states in IDH-wild type recurrent gliomas. Beyond dendritic cells, multiple antigen-presenting cellular states expanded with glioma severity especially in IDH-wild type primary and recurrent- gliomas. Furthermore, we noted differential microglia and dendritic cell inherent antigen presentation axis viz, osteopontin, and classical HLAs in IDH subtypes and, glioma-wide non-PD1 checkpoints associations in T cells like Galectin9 and Tim-3. As a general utility, our immune cell deconvolution approach with single-cell-matched bulk RNA sequencing data faithfully resolved 58-cell states which provides glioma specific immune reference for digital cytometry application to genomics datasets. Resultantly, we identified prognosticator immune cell-signatures from TCGA cohorts as one of many potential immune responsiveness applications of the curated signatures for basic and translational immune-genomics efforts. Thus, we not only provide an unprecedented insight of glioma TIME but also present an immune data resource that can be exploited to guide pragmatic glioma immunotherapy designs.
INNV-15. COMPARISON OF READIBAND™ ACTIGRAPH AND ASSOCIATED SLEEP/WAKE CLASSIFICATION ALGORITHMS WITH PATIENT-REPORTED SLEEP QUALITY AND FATIGUE IN GLIOBLASTOMA
Authors: Tipps Megan , Tierney Meghan , Monson Caitlin , Jackson Kelsey , Banerji Nilanjana , Ellenberger Amy , Trusheim John 
Published: December 2020

Abstract

INTRODUCTION
Fatigue and sleep disturbances are among the most common side-effects reported by patients with glioblastoma and contribute significantly to the quality-of-life for this population. Non-invasive monitoring of long-term sleep patterns and fatigue levels in this population would allow for comparison between iatrogenic sleep disturbances, disease progression, treatment tolerance, and self-reported levels of fatigue. Here, we describe initial results from the implementation of the Readiband™ Sleep Tracker (Fatigue Science), a wearable actigraph device, for monitoring sleep patterns and fatigue in patients with newly diagnosed glioblastoma.

PATIENTS AND METHODS
Patients were prospectively enrolled and asked to wear the Readiband™ Sleep Tracker for a maximum of twelve months or until disease progression. Patients were also asked to report fatigue levels and sleep quality via the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Pittsburg Sleep Quality Index (PSQI) questionnaires. Demographic, pathologic, and clinical information was abstracted from electronic medical records.

RESULTS
When data across all participants was combined, FACIT-F and PSQI scores were negatively correlated (r= -0.78, p&lt; 0.001). Significant correlations were also seen between the Readiband™ measures for alertness, sleep quality, and sleep efficiency (p&lt; 0.05 for all). However, we did not observe any correlations between the Redaiband™ measures and subjective survey responses. Interestingly, when patients were sub-divided based on tumor recurrence, we did see significant correlations between both survey scores and sleep quality and sleep efficiency measures (p&lt; 0.05 for all) in patients that recurred during the study period.

CONCLUSION
The Readiband™ Sleep Tracker is a convenient and viable approach for monitoring sleep and fatigue in glioblastoma patients. Our preliminary findings suggest that actigraph measures may be a better indicator of subjective sleep quality and fatigue levels in specific sub-sets of this population. Ongoing research is exploring other clinical factors that might impact the accuracy of Readiband™ measures.
INNV-22. PROSPECTIVE ANALYSIS OF UTILIZATION OF TELEMEDICINE IN NEURO-ONCOLOGY
Authors: Kalra Aman 
Published: December 2020

Abstract

OBJECTIVE
to offer neuro-oncology care to patients in rural/suburban settings that may not otherwise have access to urban amenities, specialists, and clinical trials. To test the feasibility of telemedicine in Neuro-Oncology by measuring cost savings, travel time savings, and burden of care. To screen patients for clinical trials.

BACKGROUND
Neuro-Oncology services are primarily available only at tertiary care hospitals. This increases the burden of care for patients who live in suburban and rural areas, as they have to travel long distances for their care. Hence, some families and patients do not seek care as travel time increases the stress on patients and their caretakers who are already dealing with the devastating diagnosis of a brain tumor. Similarly, these patient groups do not have access to clinical trials.

METHODS
To help ease above hardships on patients, we built a telemedicine Neuro-Oncology program that is studying the quality of care compared with daily routine visits in the cancer center. We are enrolling 30 patients in each cohort of the study, cohort A, telemedicine visits and cohort B, regular clinic visits for a total of 60 patients after obtaining written consent. We are providing them survey identifying quality measures of care (24 questions). The survey is provided to the patients and their caregivers at the end of their visit.

RESULTS
Survey answers are inputted into Survey Monkey. After the completion of 60 total patient visits, surveys will be evaluated and the results will be analyzed.

CONCLUSION
We are looking for the long-term feasibility of utilizing telemedicine care in rural/suburban settings for Neuro-Oncology patients. We anticipate that there will be cost savings, travel time savings and reduction in burden of care without compromising patient satisfaction or quality of care provided. We are also studying the feasibility of screening patients for clinical trials.
INNV-25. PATIENT CENTERED MULTI-DISCIPLINARY NEURO-ONCOLOGIC CARE AS DIRECTED BY NEW PATIENT STAKEHOLDERS
Authors: Hunt Rachel , Robin Adam , Scarpace Lisa , Gay Nestelynn , Lee Ian , Walbert Tobias , Snyder James 
Published: December 2020

Abstract
Multidisciplinary oncology care requires a team of experts which should include patient stakeholders. The Henry Ford Health System (HFHS) Hermelin Brain Tumor Center (BTC) patient and family advisory council (PFAC) recommended a focus group of patient stakeholders newly diagnosed with glioblastoma(GBM) to better understand this experience. Our PFAC, comprised primarily of long-term survivors and patient advocates, felt the perspective of newly diagnosed patients may not be adequately represented. We reviewed the BTC tumor board records, identified patients within six months from GBM diagnosis, and invited these patients and their advocates to participate in an in-person session held November 2019. The BTC Patient Resource Coordinator who is also a brain tumor survivor led the session. Predefined questions prompted discussion of their neuro-oncologic care experience. Patient perspectives and recommendations were disseminated to the BTC PFAC and health system leaders. Nine patients and ten caregivers participated. Key feedback included the need for improved communication in the peri-operative period (symptom presentation until pathology results consultation). Participants requested more information prior to surgery on what to expect after surgery and with a brain tumor diagnosis. The PFAC-developed BTC experience handbook was declared useful, but patients did not receive this book until 2-weeks after surgery. As a result, we ensured that patients received a copy of the handbook at the time of diagnosis. Additionally, the development of a brain tumor surgery “prehab” course is underway. Use of a focus group to obtain input from patients recently diagnosed with GBM provided valuable insight into their experience that can be used to align care pathways with patient needs. Feedback was used to improve the delivery of neuro-oncologic care and enhance patient communication. In the constantly evolving landscape of GBM diagnosis and treatment, it is important to remain attuned to our patients’ perspectives on the care we deliver.
INNV-28. TEMOZOLOMIDE IN RENAL DYSFUNCTION
Authors: Garzio Kayla , McElroy Kelly , Grossman Stuart , Holdhoff Matthias , Ozer Byram , Yankulina Olga 
Published: December 2020

Abstract

BACKGROUND
Temozolomide (TMZ) is a cytotoxic DNA alkylating agent. It is the only chemotherapy known to improve survival in patients with high grade astrocytomas. The active alkylating species, methylhydrazine, is not recovered in the urine and thus renal function is not expected to affect clearance of this agent. It has never been formally evaluated in adults with eGFR &lt; 36 mL/min/1.73 m2, and it is often recommended to administer with caution, dose reduce, or withhold therapy. However, lacking other effective therapies, we have elected to administer TMZ at full dose to these patients. This IRB approved retrospective study was conducted to evaluate the safety of this practice.

METHODS
The primary endpoint was to characterize the incidence and severity of thrombocytopenia in patients with renal impairment defined as eGFR &lt; 60 mL/min/1.73 m2 who received TMZ for the treatment of their high grade gliomas (HGG) or primary CNS lymphoma (PCNSL). Secondary endpoints included incidence and severity of neutropenia, lymphocytopenia, hepatotoxicity, and number of cycles administered. Medical records were reviewed for adult patients with HGG or PCNSL treated with TMZ from October 1, 2016-September 30, 2019.

RESULTS
Thirty-four patients met criteria for inclusion. Of the 7 patients with eGFR &lt; 36 mL/min/1.73m2, 33/34 cycles (97%) were completed successfully without grade 3–4 thrombocytopenia. No patients experienced grade 3–4 neutropenia, and grade 3–4 lymphocytopenia occurred in 5 cycles (15%). One patient required discontinuation of TMZ 7 days prior to completion of radiation due to thrombocytopenia.

CONCLUSION
The side effect profile from TMZ administered to patients with eGFR &lt; 36 mL/min/1.73 m2 appears to be similar to that of patients with normal renal function. This is not an unanticipated finding given what is known about the metabolism of the drug.
NCOG-17. PREDICTORS OF SURVIVAL IN ELDERLY PATIENTS UNDERGOING SURGERY FOR GBM
Authors: Voisin Mathew , Zadeh Gelareh 
Published: December 2020

Abstract

BACKGROUND
Despite the median age of diagnosis of GBM being 64 years old, there is only a paucity of studies on elderly patients with GBM. Furthermore, the majority of these studies examine treatment paradigms, and there is limited research on clinical and hospital factors on overall survival. The purpose of this study is to determine predictors of survival in elderly patients undergoing surgery for GBM.

METHODS
We searched our hospital brain tumour biobank database for all consecutive patients over a 14-year period from 2005 to 2018. All patients 65 years of age or older at time of surgery with a pathological diagnosis of de novo primary GBM were included. Kaplan-Meier survival curve and Cox proportional hazards model were constructed for overall survival vs age, sex, KPS, medical co-morbidities, extent of resection by surgeon, length of stay, postop complications, and discharge destination.

RESULTS
A total of 150 patients were included. The median age at time of surgery was 74 years old (range: 65-94). Median overall survival was 9.4 months (95% CI: 7.8-12.2). Variables associated with worse survival included longer length of stay (HR: 1.15, 95% CI: 1.02-1.30, p = 0.02), discharge destination other than home (HR: 1.91, 95% CI: 1.01-3.6, p = 0.04), and any postop complication (HR: 3.7, 95% CI: 1.87-7.3, p = &lt; 0.001). The presence of any or multiple medical comorbidities was not associated with worse survival (p = 0.93 and 0.19, respectively).

CONCLUSIONS
The presence of medical comorbidities is not associated with worse survival in elderly patients undergoing surgery for GBM. In order to maximize survival in these patients, avoidance of postoperative complications is paramount, along with a short hospital stay and attempt to discharge these patients to their home.
NCOG-37. NATURAL LANGUAGE ASSESSMENT CORRELATES WITH HEALTH-RELATED QUALITY OF LIFE IN ADULT GLIOMA PATIENTS
Authors: Ammanuel Simon , Almeida Nyle , Kurteff Garret , Kakaizada Sofia , Molinaro Annette , Berger Mitchel , Chang Edward , Hervey-Jumper Shawn 
Published: December 2020

Abstract

PURPOSE
Impairments of speech are common in glioma patients and negatively impact health-related quality of life. The benchmark for clinical assessments is task-based measures that miss essential components of quality of life status. In this study, we test the hypothesis that variations in natural language (NL) correlate with health-related quality of life status.

MATERIALS AND METHODS
Natural language use was assessed using audio samples from 18 patients with newly diagnosed low- and high-grade gliomas collected unobtrusively. NL measures were correlated with the Quality of Life in Neurological Disorders (Neuro-QoL) outcomes at baseline. Spearman’s rank-order correlation was used to determine relationships between Neuro-QoL scores and NL measures.

RESULTS
Speech rate negatively correlated with functional domains of the Neuro-QoL (satisfaction with social roles: rho=-0.62, p=0.007; participate in social roles: rho=-0.74, p&lt; 0.001;) while positively correlated with impairment domains(fatigue: rho=0.58, p=0.009).

CONCLUSIONS
Assessments of baseline natural language may be a useful tool in the context of treatment planning and monitoring outcomes.