bluuebunny/crossref_metadata_2025_split huggingface dataset:
QOLP-08. UNDERSTANDING THE EXPERIENCE OF YOUNG ADULTS (YAS) DIAGNOSED WITH AN EPENDYMOMA FROM THE ADULT EPENDYMOMA OUTCOMES PROJECT AND RARE CNS OUTCOMES AND RISK STUDY
Authors: Acquaye Alvina , Wall Kathleen , Gilbert Mark , Armstrong Terri 
Published: November 2019

Abstract
Research in young adult (YA) patients is novel, particularly in central nervous system tumors like ependymomas. Stagnant survival outcomes in YAs are concerning compared to improvements within pediatric and older adults. Additionally, uncertainty of the impact of treatment on psychosocial and behavioral outcomes during an essential developmental stage warrants attention. The purpose of this report is to explore ependymoma YA outcomes data to inform care. Adult ependymoma (n=191) patients participating in a web-based outcomes study completed clinical data and validated questionnaires (EQ-5D, MDASI-BT). YAs 18–39 (n= 58) were compared to older adults (OAs) >40 (n=133). Participants were predominantly female (68%), with tumor location in brain (29%) or spine (71%). The majority of YAs (67%) reported seeing a physician within 6 months from symptom onset, whereas OAs were more likely to delay for 7 months or longer. Headaches (brain tumor 70%) and numbness (spine tumor73%) were common presenting symptoms for both age groups. 76% of YAs were working before diagnosis, however 27% stopped work, 18% reduced hours, 7% switched jobs and 2% lost their job after diagnosis. At time of participation, most participants were not on active treatment (61%), but both YA and OA frequently endorsed use of pain medication (37%). Tumor recurrence was more common in YAs (30%) compared to OAs (19%). Common moderate to severe symptoms in YAs included distress (27%) and fatigue/sadness (18%) with brain tumors compared to fatigue (56%) and distress/disturbed sleep/drowsiness (36%) with spine tumors. Over a third of YAs reported some impact on general health (usual activities, pain/discomfort, and anxiety/depression). Despite stable disease, YAs with ependymoma experienced mood and lifestyle challenges and reported significant symptoms and use of pain medication. Further exploration is needed on the impact of cancer-related effects on YAs to gain insight on appropriate management and care.
QOLP-09. IMPACT OF GLIOBLASTOMA (GBM) PATIENTS’ CLINICAL AND TREATMENT CHARACTERISTICS ON CAREGIVER BURDEN AND QUALITY OF LIFE (QOL)
Authors: Au Trang , Willis Connor , Peters Katherine , Colman Howard , Cohen Adam , Leia Nghiemphu P , Taylor Jennie , Reblin Maija , Ryan Ormond D , Willmarth Nicole , Menon Jyothi , Ma Junjie , Singh Prianka , Marshall Alexander , Watanabe Alexandre , Korytowsky Beata , Stenehjem David , Brixner Diana 
Published: November 2019

Abstract

BACKGROUND
GBM is an aggressive cancer with poor prognosis. We explored impact of disease on caregivers by characterizing caregiver burden and QOL associated with patient characteristics.

METHODS
Primary caregivers of living adult GBM patients with cognitive dysfunction completed a GBM-specific caregiver burden survey and the validated Caregiver Quality of Life Index–Cancer Scale (CQOLC). Patient data were abstracted from medical records (7/2018-4/2019). Patient characteristics were compared between highest and lowest tertile of CQOLC scores (range 0–140); higher scores suggest better QOL.

RESULTS
There were 140 patient-caregiver dyads enrolled in the study. Mean patient age was 57 years (range 24–63); majority white males (62.9%), unifocal lesion (90%) and normal activity level at diagnosis. Forty-percent had methylated MGMT promoter status. Caregivers were mostly white (61.4%), college-educated female spouses of similar age; 87.8% were caregiving for >6 months. Median CQOLC score was 82 (tertiles: < 76 and >92). More caregivers in the lowest vs highest CQOLC tertile reported ‘not employed due to caregiving’ (52.4% vs 12%, P< 0.01), ‘changes in patients’ personality’ (73.3% vs 42.6%, P< 0.01), ‘patient memory problems’ (93.5% vs 77.1%, P=0.02), and caring for patient with recurrence treated with ‘chemotherapy other than temozolomide’ ([TMZ], 27.7% vs 8.3%, P=0.01). There was > 10% difference in proportion of caregivers in the lowest vs highest CQOLC tertile for the following patient characteristics: largest lesion in right temporal lobe at baseline and partial resection at initial treatment. Conversely, there was > 10% difference in the highest vs lowest CQOLC tertile for Karnofsky score (> 80), largest lesion in right frontal lobe at baseline, surgical clean margins, TMZ for initial treatment, and surgery for recurrence.

CONCLUSION
Unemployment, patient personality/memory changes, and chemotherapy other than TMZ use had significant impact on caregiver burden/QoL. This may help identify caregivers to receive support and intervention.
QOLP-15. LONGITUDINAL PERCEPTION OF PROGNOSIS OF PATIENTS WITH HIGH GRADE GLIOMA COMPARED TO THEIR CAREGIVERS AND CLINICIANS
Authors: Sharma Akanksha , Wolfe Eric , Barrera Celina , Williamson Samantha , Farfour Hannah , Mrugala Maciej , Edwin Mark , Sloan Jeff , Porter Alyx 
Published: November 2019

Abstract

BACKGROUND
Treatment options and prognosis are limited for patients with high grade glioma (pwHGG), underscoring the importance of patient and caregiver understanding to prioritize goals of care and quality of life (QOL). Although addressed by multiple providers, patients and caregivers may experience discordance in understanding the prognosis. This may be related to patient/caregiver perception, cognitive decline as a result of the tumor and/or treatment, or failure by the clinician to clearly articulate this information under emotional circumstances. AIMS: To evaluate the longitudinal perception of prognosis of patients compared to their caregivers and their providers during the adjuvant treatment of newly diagnosed HGG.

METHODS
After IRB approval, 16 pwHGG, their caregivers and their providers reported an overall survival estimate at each monthly visit during adjuvant treatment, as part of a larger survey. Options included “weeks,” “weeks to several months,” “several months to years,” “indefinite number of years”, or “I do not wish to answer.”

RESULTS
Seven of the sixteen patient/caregiver clusters have completed the appropriate duration of the study with the remaining completing in November. The perception of the patient differs from the caregiver at almost each visit. Regardless of the counseling provided by provider, the perception of both tends to change at each visit and can vary from dismal to overtly optimistic. There does not appear to be discrepancy between the neuro-oncology and palliative care provider’s perception of prognosis.

CONCLUSION
Newly diagnosed pwHGG and caregivers vary in their perception of prognosis, deviating not only from each other but also differing at each visit throughout the course of their illness. The providers’ perception appeared to remain consistent but often varied from that of the patient and caregiver. Providers need to be aware that prognostic understanding appears to fluctuate throughout the course of illness and cannot be clarified via a single discussion.
QOLP-39. UNRAVELING THE TRUE COST OF CARE THROUGH ANALYSIS OF THE SOCIOECONOMIC IMPACT OF GLIOMA SURVIVORSHIP
Authors: Haider Sameah , Asmaro Karam , Kalkanis Steven , Lee Ian , Bazydlo Michael , Nerenz Sam , Salloum Ramzi , Snyder James , Walbert Tobias 
Published: November 2019

Abstract

BACKGROUND
There is a paucity of data describing the socioeconomic impact and long-term implications of glioma survivorship. Objective: To characterize the socioeconomic impact of glioma survivorship using the standardized Medical Expenditure Panel Survey – Household Component (MEPS-HC).

METHODS
89 of 107 eligible adult glioma survivors that were post-treatment with stable disease were enrolled. The MEPS-HC was utilized to assess the socioeconomic hardship referable to the patient’s tumor. Comparisons between groups were evaluated using a Fisher’s exact test.

RESULTS
89 patients responded to the survey (response rate = 85%, female =52%). Median follow-up from diagnosis was 6.0 years (4.3, 9.2). Pathology at diagnosis was high-grade (40%) and low-grade (60. The majority of glioma survivors were insured (91%), employed (79%), and reported annual household incomes slightly above national average. Nearly a quarter incurred debt because of their tumor (24%), 53% required extended unpaid time off, and 46% retired or were no longer working. While 85% had a Karnofsky Performance Score of > 90, the majority of respondents reported lost productivity and decreased ability to perform cognitive and physical tasks (69%). Financial burden and workforce morbidity were insensitive to tumor location, laterality, and annual household income. Patients with a gross-total resection (GTR) at initial surgery were less likely to report ongoing limitations in daily activities (45% v. 83%, p=0.004).

CONCLUSIONS
Despite the skewed population of high-functioning glioma survivors, financial burden and workforce morbidity was ubiquitous across all tumor subtypes, treatment paradigms, and income levels. Those with GTR were less likely to report ongoing limitations. There was a trend towards greater financial burden among those with frontal and temporal lesions.
RDNA-04. CIRCADIAN RHYTHMS AND RADIATION CHRONOTHERAPY IN GLIOBLASTOMA CELL LINES AND CENTRAL NERVOUS SYSTEM CELL CONTROLS
Authors: Shuboni-Mulligan Dorela , Dahut Madeline , Young Demarrius , Gilbert Mark , Armstrong Terri 
Published: November 2019

Abstract

BACKGROUND
Chronotherapy is the optimally timed administration of treatment based on the circadian clock. In non-CNS cancers, circadian rhythms (CR) drive the expression of mechanisms responsible for radiation sensitivity and associated toxicity. Our previous work has shown that cranial irradiation in GBM patients produces a high incidence of hypersomnolence and susceptibility is linked to circadian clock gene polymorphisms. This study determined if CR can be demonstrated using in vitro GBM and CNS cells and then if sensitivity to radiation is circadian time and tissue dependent.

METHODS
Rat GBM, fibroblasts, and suprachiasmatic nucleus (SCN) cells were used and compared to human U251 GBM cells. Cells were synchronized using the serum shook method; protein levels for PER2 expression over 24 hr in 4 hr intervals were quantified to confirm CR. Colony formation and 3D invasion assays after radiation (0-8Gy or 8Gy, respectively) 8 and 20 hrs after synchronization were evaluated.

RESULTS
All cell types demonstrated CR by PER2 expression (trough ~8hr post (CT8); peak ~20hrs post (CT20)). In rat, GBM (LD50 = 4Gy) and SCN cells (LD50 =5 Gy) showed lower sensitivity than fibroblasts (LD50= 2 Gy). Human U251 GBM cells had similar radiation sensitivity to rat GBM. Time-of-day effects were dependent on tissue type with both rat and human GBM cell lines more affected by radiation at CT20, with less invasion (CT20:-35488.5±2622.1 vs CT8:-23160.5±3273.4µm) and survival in the colony assay (F(1,71)=4.105,p< 0.05). Conversely, SCN cells which drive sleep-wake, showed the converse with greater effect at the 8hr compared with 20hr (F(1, 35)=19.93,p< 0.001).

CONCLUSIONS
These data suggest that timing of radiation could be optimized to improve detrimental effects on healthy tissue, while still providing effective intra-tumor doses. In future studies, we will interrogate the mechanisms driving time-of-day effects in cells and test radiation chronotherapy in our radiation-induced hypersomnolence mouse model.
RDNA-07. INCREASING EXTENT OF ABLATION – A SENOLYTIC APPROACH TO PROMOTE APOPTOSIS OF LATENT GLIOBLASTOMA FOLLOWING CHEMORADIATION
Authors: Rahman Masum , Olson Ian , Tang Zhi , Rajani Karishma , Carlstrom Lucas , Burns Terry 
Published: November 2019

Abstract

BACKGROUND
Despite best current therapies, median survival for glioblastoma remains little more than a year. There remains an urgent need for improved treatment strategies. Current therapies, including radiation and temozolomide, are known to induce senescence in tumor cells. Advances in aging research have identified drugs with “senolytic” properties to kill senescent cells. This work tests the hypothesis that induction of senescence pathways following radiation can provide a window of opportunity to eliminate residual glioblastoma cells using drugs that block senescent cell-associated pathways (SCAPs).

METHODS
Human glioblastoma cells were radiated with 10, 15, or 20 Gy and maintained in culture for 3 to 4 weeks to facilitate maturation of a senescent phenotype. Given existence of multiple SCAPs, we evaluated the IC50 for several senolytic candidates including Dasatinib, Quercetin, Fisetin, AMG-232, Onalespib, A1331852, and Navitoclax in radiated vs non-radiated cells.

RESULTS
Among these, the Bcl-XL inhibitors A1331852 and Navitoclax both selectively killed multiple lines of radiated, senescent tumor cells at lower concentrations as compared to unirradiated, non-senescent tumor cells. Across multiple GBM cell line, the average IC50 for senescent cells was 12.88 nM (95%CI= 9.068–18.58 nM), as compared to the IC50 of non-senescent cells of 103.2 nM (95%CI= 74.24–143.9 nM; p< 0.005). Such differential sensitivity to Bcl-XL inhibition after radiation was not observed in the non-GBM control cells evaluated to date.

CONCLUSION
Our findings suggest that blocking the anti-apoptotic pathway Bcl-XL in GBM cells rendered at least transiently senescent following radiation may provide an avenue to selectively ablate residual glioblastoma cells following radiation. Our data provide proof of principle that senolytic therapy may represent a previously untapped window of opportunity to increase extent of tumor ablation following completion of standard cytotoxic therapies.
RDNA-10. TTFIELDS TREATMENT PLANNING FOR TARGETING MULTIPLE LESIONS SPREAD THROUGHOUT THE BRAIN
Authors: Naveh Ariel , Yesharim Ofir , Bomzon Ze’ev 
Published: November 2019

Abstract
Tumor Treating Fields (TTFields) are approved for the treatment of Glioblastoma Multiforme (GBM) in supratentorium. When treating GBM in the suprtaentorial brain, TTFields are delivered using 2 pairs of transducer arrays positioned in close proximity to the tumor. This results in an increased TTFields dose in the affected tumor region, whilst reducing the dose in other regions, particularly the infratentorium. Brain metastases, occur in 10 to 30 percent of adults with cancer, and can occur throughout the brain, including in infratentorial regions. Therefore, when using TTFields to treat brain metastases, it is desirable to deliver TTFields at therapeutic intensities to the entire brain or to the infratentorium depending on the location of the lesions. We performed computational studies to identify array layouts for delivering TTFields at therapeutic intensities to the infratentorium and to the entire brain. The computer simulations utilized a realistic computerized head model of a 40+ years old human male prepared in-house. TTFields could be delivered effectively to the infratentorium using a layout in which a pair of arrays was placed on the lateral aspects of the neck below the ears, and the second pair on the upper head and lower neck yielded field intensities above 1 V/cm in the infratentorial brain. Other layouts in which one pair of arrays was placed on the right temple and left scapula, and the second pair placed on the left temple and right scapula yielded a uniform intensity distribution within the entire brain. This layout could be useful for treating multiple lesion spread in both the infratentorial and supratentorial regions. This study suggests that careful treatment planning could be used to optimize TTFields treatment targeting multiple lesions spread throughout the brain.
RDNA-11. LOW MITOCHONDRIAL DNA CONTENT INDUCES TREATMENT RESISTANCE AND CONFERS POOR PROGNOSIS IN GLIOBLASTOMA
Authors: Sravya Palavalasa , Nimbalkar Vidya , Kanuri Nandaki , Sugur Harsha , Rao Shilpa , Somanna Sampath , Kondaiah Paturu , Arimappamagan Arivazhagan , Santosh Vani 
Published: November 2019

Abstract

BACKGROUND
Investigation of mitochondrial DNA (mtDNA) content in glioblastoma has gathered speed in recent years. Our study focusses on the effect of mtDNA content depletion on treatment response in glioblastoma.

MATERIALS AND METHODS
The study consists of a survival cohort (n=130), a recurrent cohort (32 pairs) and 35 non neoplastic control brain tissues. Malignant glioma cell lines, U87 and LN229 were utilized for radiation biology experiments. Patient tumor tissue was molecularly characterized for IDH, ATRX and TERT promoter mutations, MGMT promoter methylation and EGFR amplification using established methods. Relative quantification of mtDNA content was performed using quantitative real time PCR. Ethidium bromide was used to deplete mtDNA in U87 and LN229 cells. Clonogenic assay and MTT assay were performed to assess sensitivity to radiation and chemotherapy.

RESULTS
mtDNA content was lower in glioblastoma than in controls. Lower range of mtDNA copy number was associated with poor overall survival (p=0.033) and with markers of tumor aggressiveness like wild type IDH (p=0.02), unmethylated MGMT promoter, amplified EFGR and mutated TERT promoter. Out of 32 recurrent GBM patients, only 19 had received radiation treatment (RT) between the two surgeries and in these patients, mtDNA content was significantly higher in the recurrent tumor when compared to the primary tumor(p=0.01). U87 and LN229 cells showed a higher mtDNA copy number post irradiation (p=0.002). mtDNA depleted U87 and LN229 cells showed higher survival fraction post radiation exposure when compared to parent lines. The IC50 of TMZ was also higher for mtDNA depleted U87 and LN229 cells.

CONCLUSION
Low mtDNA content is associated with poor survival and aggressive tumor markers in glioblastoma. Lowering the mtDNA content in GBM cells induces radiation resistance as well as resistance to chemotherapy. Irradiation leads to increase in mitochondrial DNA content in both patient samples as well as malignant glioma cell lines.
RDNA-13. DOSE RESPONSE CURVE FOR RADIATION-INDUCED HYPERSOMNOLENCE (RIH) IN A MOUSE MODEL OF CRANIAL RADIATION: BEHAVIORAL ANALYSIS OF SLEEP AND ACTIVITY
Authors: Young Demarrius , Dee Smart Dee , King Amanda , Gilbert Mark , Armstrong Terri , Shuboni-Mulligan Dorela 
Published: November 2019

Abstract

BACKGROUND
Radiation therapy is the standard of care for both primary and secondary brain tumors. The majority of patients experience radiation induced hypersomnia (RIH) to varying extents which may impact life quality and treatment tolerance. Previously, we demonstrated that risk is enhanced by presence of select clock gene polymorphisms. The purpose of this study is to establish a mouse model of RIH to test dose effects of cranial irradiation on behavioral sleep and activity prior to introducing tumor in transgenic mice.

METHODS
Twenty-four non-tumor bearing C57BL/6 mice received whole brain radiation at one of 4 doses (sham, 2Gy, 5Gy, and 15Gy) using a single fraction. Behavior, total activity (distance) and sleep quantity (seconds) were monitored using Phenotyper cages and Ethovision Software with data collected at baseline (10 days) and post-radiation (11 days); percentage of activity was calculated as post-radiation/baseline activity. Blood and tissue samples were collected.

RESULTS
Baseline activity was not significantly different between groups (F(3.23) = 0.649, p=0.593). Shams and 2Gy mice were not affected by the procedure and activity levels were unchanged, 99.76±1.3% and 103.3±3.5%, respectively. The higher doses, 5Gy and 15Gy, had suppression of general activity compared to baseline with 90.8±2.7% and 88.9±1.3%, respectively. Between the two groups, suppression of activity started after 2 days in 15Gy and 5 days in 5Gy mice. Across three days (8–10), 5Gy and 15Gy (19,872±577sec) had more sleep during their active phase (t=2.27, p=0.03) than sham or 2Gy (17,618±803sec).

CONCLUSION
Activity and sleep are affected by cranial irradiation in our RIH mouse model in dose dependent manner. This model closely resembles the effects seen in patients and provides a critical tool for interrogating the physiological drivers of RIH. In future studies, we will examine other behaviors and the association between circadian gene variants and RIH susceptibility as previously reported in patients.
RTHP-05. CONTRIBUTION OF ATM MUTATION TO THE IMPROVED RADIO-SENSITIVITY: RETROSPECTIVE ANALYSIS USING NEXT-GENERATION SEQUENCING DATA
Authors: In Yoon Hong , Kim Nalee , Hoon Kim Se , Hyung Moon Ju , Kang Seok-Gu , Suh Chang-Ok , Hee Chang Jong 
Published: November 2019

Abstract

PURPOSE/OBJECTIVES
To identify the association of somatic ATM mutation (mATM) with improved radiotherapy sensitivity, we retrospectively reviewed the next-generation sequencing (NGS) data from high grade glioma patients.

MATERIALS/METHODS
This analysis includes 48 consecutive individuals diagnosed with high grade glioma (diffuse astrocytoma IDH-wild type n=2, anaplastic astrocytoma n=18, and glioblastoma n=28) between June 2017 and October 2018. Patients who underwent subtotal (n=30, 62.5%), partial (n=17, 35.4%) removal or biopsy (n=1, 2.1%) were included in this analysis for interpreting radio-sensitivity of residual tumor. We investigated mATM by NGS of FFPE specimens with a TruSight Tumor 170 (TST-170) cancer panel.

RESULTS
Among 48 samples, mATM was detected in 17% of cases (n=8). There was no significant difference in patient or tumor characteristics. Among mATM patients, there were 5 patients with glioblastoma and 3 patients with anaplastic astrocytoma IDH-wildtype. Most mutation was missense mutation (n=7, 88%). Median variant allele frequency was 44.7% (Interquartile range, IQR, 10.5–59.9%). Median follow-up duration after radiotherapy was 11.4 (IQR, 8.0–15.8) months. Radiation-related change was observed in 34 patients (71%). Tumors with mATM were related to higher frequency of radiation-related change at 6 months than tumors without mATM, respectively (88% and 64%, p = 0.016). Cases with mATM exhibited significantly 1-year progression free survival (PFS, 100% vs. 54%, p = 0.036). On subgroup of IDH WT (n=39) known as poor prognostic molecular marker, patients with mATM showed significantly higher PFS than patients without mATM (p=0.016, 1yr PFS 100% vs 43%). On subgroup with sub-ventricular zone involvement (n=38) representative of aggressiveness, PFS of patients with mATM was significantly higher than others (p=0.026, 1yr PFS 100% vs 43.9%).

CONCLUSIONS
Our results demonstrated that mATM is involved in radio-sensitivity with immediate radiologic change after radiation therapy followed by favorable radiologic response and clinical outcome beyond the aggressive nature of high grade glioma.