bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDTM-35. MODELLING MEDULLOBLASTOMA WITH MOUSE MODELS AND HUMAN CEREBELLAR ORGANOIDS
Authors: Tiberi Luca 
Published: November 2019

Abstract
Malignant medulloblastoma (MB) is the most common brain tumor affecting children and it remains responsible for a high percentage of morbidity and mortality among cancer patients. During the past few years, studies on human MB and mouse models have uncovered the existence of four major MB groups, with specific pathological and molecular features: WNT, SHH, Group 3 and Group 4. Of the four groups, patients with Group 3 MB have the worst outcome with nearly 50% of the tumors metastatic at the time of diagnosis. Therefore, developing “humanized “ mouse model of Group3 Medulloblastoma would be of paramount importance for the identification and testing of new drugs for pediatric patients, tailored on the genetic condition of the patient itself. We performed an in-vivo screen to identify new cancer-inducing genes starting from the published genome-wide analyses of MB patients. This screen led to the identification of novel driver gene combinations required for tumorigenesis. To study Medulloblastoma in human cells, we generated human cerebellar organoids. Organoids are cellular structures that resemble whole organs and can be generated from pluripotent stem cells or isolated organ progenitors. We were able to induce cerebellar progenitors to self-form neuro-epithelial structures that mimic early human cerebellar plate, composed by cerebellar progenitors, cerebellar neurons (interneurons, Purkinje cells, and granule neurons) and glial cells. Notably, we have generated human putative iPSC-derived cancer organoids with gene combinations mimicking human Group3 MB. Indeed, organoids that mimic cancer can be used as an alternative system for drug testing that better recapitulate effects in human patients as compared to other in-vitro and in-vivo systems.
PDTM-37. GALECTIN-3 PROMOTES CXCR2 EXPRESSION IN MEDULLOBLASTOMA
Authors: Das Arabinda , Eskandari Ramin , Alshareef Mohammed , Kosnik Infinger Libby , Patel Sunil , Cachia David 
Published: November 2019

Abstract
Brain tumors are the leading cause of childhood cancer mortality, with medulloblastoma (MB) representing the most frequent malignant tumor. The identification of cancer stem cell (CSC) populations in MB has play a vital role in drug resistance, and cancer relapse. Galectin-3 (Gal-3) a multifunctional β-galactoside-binding protein is known to participate in tumor progression and drug resistance. However, the exact role of Gal-3 in medulloblastoma tumor pathophysiology is yet unknown. In this study, we observed higher levels of stem/progenitor cell markers, such as Oct4, Sox2, CD133 and Nanog in MB slices. Among the Gal family, Gal-3 in particular was highly expressed in MB tumor slices. To further investigate Gal-3’s role in the pathophysiology of MB, we used either small interfering RNA (siRNA) to knock down Gal-3 expression or Gal-3 inhibitor, TD139 to suppress Gal-3 expression in ex vivo slice culture model. Upon suppressing Gal-3 in parental MB slices, drug resistance (MDR1and MPR1) and stem cell related gene expression were all significantly decreased. Furthermore, CXCL6, CXCL7 and CXCR2 were down-regulated in Gal-3-knockdown or Gal-3 inhibitor treated MB tumor slices, while CXCR2 overexpression in Gal-3-knockdown or Gal-3 inhibitor treated MB slices restored their viability. These results indicate that highly expressed Gal-3 may up-regulate CXCR2 to augment MB invasiveness and progression. Gal-3 may be a prognostic and innovative target for the treatment of MB.
PDTM-41. INHIBITION OF DNA DOUBLE STRAND BREAK REPAIR PATHWAYS AS A PROMISING THERAPEUTIC TARGET IN DIFFUSE INTRINSIC PONTINE GLIOMAS (DIPGs)
Authors: Pal Sharmistha , Bian Jie , Price Brendan , Chowdhury Dipanjan , Haas-Kogan Daphne 
Published: November 2019

Abstract

New approaches to the treatment of diffuse intrinsic pontine gliomas (DIPGs) are desperately needed. DNA damage response is essential for cells to maintain genome integrity as DNA is damaged by both endogenous and exogenous stressors. Many cancer cells exhibit hyper-dependency on specific DNA repair pathways due to either defects in DNA repair mechanisms and/or high levels of endogenous stress leading to accumulation of DNA damage lesions. Identification of DIPG-specific DNA repair deficiencies and resultant dependencies may establish novel therapeutic strategies for DIPGs.

METHODS
To identify pathways critical for DIPG cell survival, genome wide CRISPR-Cas9 screen was performed on patient derived DIPG cell lines followed by gene set enrichment analyses. To monitor the effects of pathway inhibition on survival, apoptosis, DNA damage and repair, assays were performed to measure cell proliferation, cleaved-caspase3, gamma-H2AX and reporter based-DNA repair efficiency.

RESULTS
Our unbiased CRISPR approach to uncover vulnerabilities in DIPGs identified DNA double strand break (DSBs) repair pathways as essential for DIPG cell proliferation and survival. Further studies revealed high basal DSBs in DIPG cells compared to neural stem cells and primary astrocytes that suggest dependence of DIPG cell survival on specific DSB repair pathways. We confirmed the intrinsic reliance of DIPG cells on the specific DSB repair pathway of mutagenic end-joining, and defined a key role for DNA repair in suppressing endogenous DNA damage-induced apoptotic cell death.

CONCLUSION
DIPG cells have high endogenous DNA damage levels and escape catastrophic genomic instability and cell death by engaging DNA repair pathways, in particular the mutagenic end-joining DNA repair pathway. Inhibition of this specific DNA repair pathway represents a promising new avenue for the treatment of DIPGs.
PDTM-42. CROSS-PLATFORM PROFILING OF ctDNA USING ddPCR: STANDARDIZATION OF THE LIQUID BIOPSY FOR PEDIATRIC DIFFUSE MIDLINE GLIOMA
Authors: Li Daphne , Bonner Erin , Stallard Stefanie , Panditharatna Eshini , Huang Tina , Lulla Rishi , Koschmann Carl , Nazarian Javad , Saratsis Amanda 
Published: November 2019

Abstract

INTRODUCTION
Pediatric diffuse midline glioma (DMG) with histone H3 mutations (80%), are highly morbid tumors with poor response to therapy. We previously detected H3 mutations in circulating tumor DNA (ctDNA) from CSF derived from children with DMG and high grade glioma. Here, we describe a high-throughput, sensitive and specific approach for H3 mutation detection and quantification in plasma and CSF specimens, validated across multiple centers.

METHODS
DNA extracted from tissue-validated H3.3K27M specimens (4 tumor, 5 CSF, 4 plasma) and pediatric glioma cell lines (1 wild-type, 1 H3.3K27M) were used to standardize ddPCR workflows. ctDNA extracted from 500uL of CSF or plasma was pre-amplified using sequence-specific primers, then analyzed on RainDance and BioRad ddPCR systems using two sets of custom primers and fluorescent LNA probes (Assays A and B). H3 mutation allelic frequency (MAF) was determined across specimens, and validated through parallel analysis of additional matched H3.3K27M tumor tissue, CSF and plasma specimens (n=3).

RESULTS
ctDNA processing and detection was standardized across three institutions and two platforms with sensitive, specific and reproducible H3 mutation detection. H3K27M mutations were detected in as little as 0.3-2pg input DNA on both platforms, with comparable MAFs across instruments and assays. RainDance yielded greater overall positive droplet number detection (increased sensitivity). Differences in optimal sample input volume between platforms were circumvented by vacuum concentration or dilution to maintain equal input DNA. Assay A yielded superior specificity so was used for subsequent matched specimen analysis. Mutation detection in plasma, as in previous studies, remained challenging due to low [ctDNA], while CSF analysis yielded reliable results across assays and platforms.

CONCLUSIONS
We demonstrate the utility of liquid biopsy for identifying H3K27M mutations in plasma and CSF via ddPCR with low starting [DNA], representing a rapid, minimally invasive method for diagnosis and therapeutic monitoring of DMG.
QOLP-16. DISTRESSED (D TYPE) PERSONALITY, PREOPERATIVE PSYCHOLOGICAL DISTRESS, COGNITIVE FUNCTIONING, QUALITY OF LIFE, AND TREATMENT OUTCOMES OF GLIOMA PATIENTS: PROSPECTIVE STUDY
Authors: Pranckeviciene Aiste , Saudargiene Ausra , Deltuva Vytenis , Tamasauskas Arimantas , Bunevicius Adomas 
Published: November 2019

Abstract

BACKGROUND
This study aimed to evaluate impact of distressed (D type) personality on preoperative psychological distress, cognitive functioning and quality of life (QoL) as well as short-term and long-term treatment outcomes of glioma patients.

METHOD
One-hundred and seventy patients (93 men, mean age=51.1±14.5 years) participated in the study. Fifty-four (31.8%) patients were diagnosed with low grade (WHO grade I-II), and 116 (68.2%) with high grade (WHO grade III-IV) tumors. Psychological assessment was performed 2–3 days before surgery using a set of self-report questionnaires (NCCN Distress thermometer, EORTC-QLQ-C30, EORTCQLQ-BN20, HADS, DS-14) and a short battery of neuropsychological tests. Functional status at the discharge was assessed using the GOS. Follow-up period was 40 months.

RESULTS
Thirty-nine (22.9%) of patients met criteria for D type personality. D-type patients relative to non D-type patients reported significantly worse QoL, higher number tumor related symptoms, greater depression and anxiety symptoms, and demonstrated slowing of psychomotor speed in neuropsychological tests. However, no personality related differences were observed in level of functioning at time of discharge as well as long-term patients’ survival. Path analysis using SEM revealed non-direct impact of D-type personality traits on patients QoL (Chi-square value=16.73, df=13, p=0.212). The model indicated statistically significant indirect effects of D-type Negative Affectivity on QoL (IPC -0.285, 95% CI [-0.386; -0.178], p=0.003) and tumor related symptoms (IPC 0.196, 95% CI [0.117; 0.296], p=0.002) mediated via depression and anxiety. Social Inhibition was also indirectly associated with QoL (IPC -0.047, 95% CI [-0.120; -0.002], p=0.035) and symptoms (IPC 0.033, 95% CI [0.002; 0.097], p=0.032) through depression and anxiety.

CONCLUSION
D-type personality contributes to impairment of QoL and higher number of reported symptoms in glioma patients via increased susceptibility for depression and anxiety.
QOLP-18. A TIME-BASED MODEL OF EARLY PALLIATIVE CARE INTERVENTION IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA, A SINGLE INSTITUTION FEASIBILITY STUDY
Authors: Johnson Margaret , Ramirez Luis , Herndon James , Massey Woody , Lipp Eric , Affronti Mary , Kim Jung-Young , Friedman Henry , Desjardins Annick , Randazzo Dina , Ashley David , Casarett David , Peters Katherine 
Published: November 2019

Abstract

OBJECTIVE
There is no validated model for delivering palliative care (PC) in the glioblastoma (GBM) population. The primary objectives were to assess the feasibility and determine the acceptability of a time-based model of integrated specialty PC to patients and providers. Secondary objectives were to estimate the impact on healthcare utilization and quality of life (QoL) compared to historical controls.

METHODS
We consented and referred patients to PC at their initial Neuro-Oncology consultation between 4/2018 and 5/2019. We conducted QoL assessments (NCCN Distress Tool; Functional Assessment of Cancer Therapy-Brain (FACT-BR); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); Epworth Sleepiness Scale (ESS)) at (1) baseline (2) immediately after chemoradiation, and (3) 6 months following chemoradiation. Ongoing PC follow-up was at the discretion of the PC provider. We administered the Edmonton Symptom Assessment System (ESAS) before and after PC visits. We measured patient and referring provider satisfaction using FAMCARE-16 and a PC departmental survey, respectively.

RESULTS
We did not meet our goal enrollment of 50 patients. 32 were offered participation, 12 consented and 8 attended at least one PC visit. The mean number of PC visits was 1.6. Mean age was 62 (42–79). 75% had a KPS ≥80. Of those that did not complete the study, 2 died and 5 either withdrew consent or declined further visits. At baseline, 91.7 % had a NCCN distress score ≥4. Patients were overall satisfied with the intervention.

CONCLUSION
Introduction of specialty PC at the time of GBM diagnosis is challenging. Participants reported their experience as overall positive. Results from referring providers are pending. Due to low-enrollment we did not pursue further statistical comparisons regarding healthcare utilization compared to historical controls.
QOLP-23. IDENTIFICATION OF CHARACTERISTICS THAT DETERMINE BEHAVIORAL AND PERSONALITY CHANGES IN GLIOMA PATIENTS
Authors: Zwinkels Hanneke , Dirven Linda , Bulbeck Helen , Grant Robin , Oberg Ingela , Koekkoek Johan , Habets Esther , Oliver Kathy , Pace Andrea , Rooney Alley , Taphoorn Martin 
Published: November 2019

Abstract

BACKGROUND
Glioma patients may experience behavioral and personality changes (BPC), which have a negative impact on the lives of both brain tumor patients and their relatives. The extent of BPC is currently unknown, and it is unclear if available assessment tools cover all aspects of BPC that are relevant for glioma patients. This study aimed to determine which characteristics of BPC are relevant for glioma patients.

METHODS
Possible characteristics of BPC were identified in the literature and based on expert opinion. Next, these 49 items were presented to patients and caregivers/former caregivers in an online survey launched via the International Brain Tumour Alliance. Participants were requested to indicate the relevance for each characteristic on a 4-point Likert scale ranging from ‘not at all’ to ‘very much’. In addition, they had to indicate which three characteristics had most impact on their daily life, and if characteristics were missing.

RESULTS
Completed surveys were obtained from 141 respondents, of which 36% were patients, 50% caregivers and 14% unknown. Most patients had grade II or IV glioma (29% vs 38%). Of 49 characteristics, 35 were reported as relevant in at least 25% (range all characteristics: 7–44%). Patients (n=50) and caregivers (n=70) rated different characteristics as most important. Common characteristics were lack of motivation, change in being socially active, not able to finish things and change in level of irritation. There were no characteristics reported to be missing by ≥5 respondents.

CONCLUSION
The majority of characteristics were rated as relevant in >25% of respondents, and patients and caregivers differed in which were most relevant. A clear definition based on these results is therefore difficult to establish. A next step would be to perform a cluster analysis of patients and caregivers separately, and discuss the results with experts, to reach consensus on an appropriate definition.
QOLP-26. PATIENT REPORTED SOCIAL FUNCTION AND SURVIVAL IN GLIOMA PATIENTS
Authors: Hardy Sara , Pandya Chintan , Mohile Nimish , Janelsins Michelle , Milano Michael 
Published: November 2019

Abstract

PURPOSE
Research among patients with cancer suggests that health related quality of life (HRQOL) may be more predictive of survival than performance status. Social function is a HRQOL outcome influenced by both physical and mental health. To our knowledge, no work has analyzed the potential association between survival and social function in patients with brain tumors.

METHODS
In the SEER Medicare Health Outcomes Survey, 158 patients were identified with 1) diagnosis of glioma between 1976 and 2013 2) no other cancer diagnosis 3) at least one post-diagnosis HRQOL survey. We examined the relationship between social function and mortality using a multivariable Cox proportional hazard model. We also examined factors correlated with social function score using linear regression.

RESULTS
At last follow up, 48% of the patients had died, 53% were female, 59% had trouble with ≥1 ADL, 53% were married, 27% had glioblastoma, 74% were white, and 32% had no reported comorbidities. Median time from cancer diagnosis to survey was 79 months and median age at survey was 60 years. For patients alive at last follow-up, there was a difference of >5 points for the social function subscale (38.2 vs 30.6) compared to those who died during the median 163 month follow up interval. On multivariable Cox proportion hazard model adjusting for covariates, higher social function scores were significantly associated with improved survival (5 point increase in score, HR 0.86, p = 0.0029). Worse social function was associated with patient-reported neurologic deficits in vision and speech and report of depression, but not marital status, sex, race, or patient-reported income.

DISCUSSION
Patient-reported social function score on post-diagnosis surveys, even after accounting for important clinical factors, was significantly associated with survival. The impact of patient reported social function in those with glioma should be further examined in confirmatory longitudinal studies.
QOLP-28. THE USE OF VIRTUAL REALITY FOR SYMPTOM MANAGEMENT: APPLICATION IN NEURO-ONCOLOGY
Authors: Leggiero Nicole , Armstrong Terri , Vera Elizabeth , Gilbert Mark , King Amanda 
Published: November 2019

Abstract
Patients with primary central nervous system (CNS) tumors are highly symptomatic due to the functional sequelae of their disease and an unfavorable prognosis. Virtual reality (VR) immersive technology has demonstrated benefit in improving patients’ symptom burden, such as distress, pain, anxiety, and fatigue. However, this has not been explored in a CNS tumor population. This project explored the potential use of VR for symptom management in CNS tumor patients. A descriptive analysis of MDASI-BT/MDASI-SP/PROMIS-Anxiety patient-reported outcomes (PROs) for 535 CNS tumor patients was performed to identify the common moderate-severe (> 4 on a 0–10 scale) symptoms. Additionally, a systematic review of literature was performed addressing the question “For adult patients with solid tumors, what effect does VR have on their self-reported symptoms, such as distress, anxiety and pain?” The systematic literature review resulted in 17 studies using VR in other solid tumor populations, which demonstrated improvement in pain, anxiety, and distress. However, study designs often lacked rigor and none incorporated any biomarkers to correlate with PROs. CNS tumor symptom review of our patient cohort revealed that the majority of the patients were Caucasian (83%) males (58%) with a median age of 50 years (range, 18–83). At the time of diagnosis, 35% had a gross total resection. Glioblastoma was the most common diagnosis (32%) and 50% had a high-grade glioma. The most prevalent moderate-severe symptoms in this sample was fatigue (34%), with (14%) anxiety, (18%) pain, and (19%) distress. Given the high symptom rate in our patients, the promising but limited data that VR technology could improve distress and other symptoms provides strong support for this intervention in the CNS tumor population. Further research is needed to assess feasibility and efficacy of VR, as well as incorporation of correlative biomarkers, to better determine potential improvement in patient symptom burden.
QOLP-29. MINDFULNESS MEDITATION PRACTICE IN MALIGNANT GLIOMA PATIENTS THROUGHOUT CONCOMITANT RADIATION AND TEMOZOLOMIDE: A FEASIBILITY STUDY
Authors: Randazzo Dina , Jackman Jenny , Herndon James , Affronti Mary , Lipp Eric , Cort Nicole , Desjardins Annick , Johnson Margaret , Landi Daniel , Ashley David , Friedman Henry , Glass Oliver , Porter Laura , Peters Katherine 
Published: November 2019

Abstract
With a bleak prognosis for malignant glioma, maintaining quality of life (QoL) and decreasing distress of the patient are important in the clinical care of the patient. Mindfulness meditation is a mind-body therapy that has been recently investigated in the oncology field as a non-pharmacological strategy to ameliorate cancer symptoms and to improve QoL. This practice has not been studied in the primary brain tumor population. We initiated a pilot study among newly diagnosed brain tumor patients with the hypothesis that mindfulness meditation practice may benefit the patient by decreasing stress and anxiety and provide a means to cope with their new diagnosis. The specific aim of this pilot study is to determine the feasibility of a mindfulness meditation program to this population during standard of care chemoradiation and to determine whether it merits additional research in a subsequent trial. The intervention consists of six weekly one hour telephone-based mindfulness sessions followed by one in- person mindfulness session consisting of: mindfulness and healing, understanding stress, abiding in kindness, working with difficult emotions, finding peace, going forward and living fully. Subjects are provided with downloadable guided meditations. We plan to enroll fifteen newly diagnosed WHO grade III or IV malignant glioma subjects prior to their 6 week chemoradiation course. We will determine the percentage of subjects approached vs enrolled, number of sessions that each subject attends, completion of study questionnaires and satisfaction of the subjects. QoL surveys include: Functional Assessment of Cancer Therapy- Brain, Functional Assessment of Cancer Therapy- Cognitive Function, Pittsburgh Sleep Quality Index, Functional Assessment of Chronic Illness Therapy-Fatigue and the Five Facet Mindfulness Questionnaire – short form. 13 subjects have been approached and 8 signed consent over a two-month period. We will provide final study results at time of presentation.
QOLP-32. PATTERNS OF CARE AT END OF LIFE IN PATIENTS WITH GLIOMA
Authors: Barbaro Marissa , Blinderman Craig , Iwamoto Fabio , Kreisl Teri , Welch Mary , Odia Yazmin , Donovan Laura , Evans Katharine , Lassman Andrew 
Published: November 2019

Abstract

OBJECTIVE
To understand patterns of care at end of life in glioma patients.

BACKGROUND
Patients with gliomas often inquire about end-of-life issues. Understanding common clinical outcomes of tumor progression and end-of-life circumstances may reduce anxiety among patients and caregivers and inform care planning.

METHODS
Following IRB approval, we retrospectively analyzed circumstances surrounding death among patients with intracranial gliomas at Columbia University Irving Medical Center from 1/2014-2/2019, including immediate cause and location of death and implementation of palliative measures. Information unavailable from the medical record was supplemented by caregivers.

RESULTS
Data were available for 152 patients (95 men, 57 women; median age at death 61.5 years). Failure to thrive with transition to supportive care (n=117, 77%) was the most common immediate cause of death. Others included infection (19, 13%; with pulmonary (12, 8%), urinary tract (5, 3%), CNS (4, 3%), and GI (2, 1%) sources); seizures (8, 5%); intracerebral hemorrhage (5, 3%); cerebral edema (4, 3%); pulmonary embolism (4, 3%); autonomic failure (2, 1%); hemorrhagic shock (2, 1%); respiratory failure of unknown cause (2, 1%); pulmonary edema (1, 1%); and cardiac arrhythmia (1, 1%). Ten patients had multiple causes of death. Seventy-three patients (48%) died at home with hospice. Other locations were inpatient hospice (40, 26%); acute care hospital (34, 22%) including 27 (18%) with and 7 (5%) without comfort measures; skilled nursing facility (4, 3%) including 3 (2%) with and 1 (1%) without comfort measures; or religious facility (1, 1%) with comfort measures. Acute cardiac and/or pulmonary resuscitation was performed in 20 patients (13%); 8 (5%) died with no comfort measures.

CONCLUSIONS
Failure to thrive with transition to supportive care was the most common (77%) immediate cause of death followed by infection (13%). Hospice and/or palliative measures were implemented in 95% of patients, though resuscitative efforts were performed in 13%.