bluuebunny/crossref_metadata_2025_split huggingface dataset:
QOL-12. NEURO-ONCOLOGY INCLUSION IN PSYCHOTHERAPEUTIC INTERVENTION TRIALS: LEARNING WHICH COGNITIVE ADAPTATIONS COULD SUPPORT PATIENT ENGAGEMENT?
Authors: Loughan Ashlee , Lanoye Autumn , Braun Sarah , Fox Amber , Zarrella Giuliana 
Published: November 2023

Abstract

BACKGROUND
Many patients with brain tumors experience double vulnerability—significant emotional distress coupled with cognitive decline—however, these cognitive changes often prohibit their inclusion in psychotherapeutic interventions that might otherwise improve their wellbeing. The primary goal of this analysis was to understand how best to accommodate the neurocognitive needs of patients with brain tumors so that they may effectively participate in future psychotherapeutic interventions. Our secondary goal was to assess potential differences in desired cognitive adaptations between patients with primary compared to metastatic brain tumors.

METHODS
In two recently completed Phase 2 proof-of-concept trials, patients with both primary and metastatic brain tumors (N = 27) participated in a 3-month psychotherapeutic intervention, Managing Cancer and Living Meaningfully (CALM). During exit interviews, participants reported whether evidence-informed accommodations would support their cognitive limitations and enhance engagement in future trials. Additionally, trial interventionists identified which accommodations were used in each session.

RESULTS
Participants recommended several accommodations: appointment reminders (100%), topic refreshers (94%), prior session summaries (88%), visual handouts (82%), time for consolidation (71%), transcription notepads (65%), and questionnaire completion assistance (24%). Interventionists documented using appointment reminders (66%), topic refreshers (53%), prior session summaries (60%), and time for consolidation (60%) in more than half of sessions. Visual handouts (2%), notepads (0%), and questionnaire assistance (17%) were rarely or never used.

CONCLUSIONS: RESULTS
were similar across the two brain tumor populations surveyed: primary and metastatic brain tumors. Accommodations that were recommended by patients and used by interventionists included: (1) appointment reminders to support session attendance, (2) topic refreshers and prior session summaries to support memory, and (3) additional time to assist with slower processing and support comprehension. Implementing supportive cognitive strategies is vital when promoting neuro-oncology inclusion in psychotherapeutic interventions and meeting the needs of this underserved population.
QOL-18. HIGHER VINCRISTINE DOSES CORRELATE WITH LONGER OVERALL SURVIVAL: A POST-HOC ANALYSIS OF PARTICIPANTS RECEIVING PCV ON RTOG 9402
Authors: Donovan Laura , Polly Mei-Yin , Cairncross J Gregory , Lassman Andrew , Iwamoto Fabio , Barani Igor , Souhami Luis , Pitot Henry C , Fisher Barbara , Werner-Wasik Maria , Bahary Jean-Paul , Whitton Anthony , Mishra Mark V , Huang Jiayi , Hartford Alan C , Fink Karen , Laperriere Normand , Won Minhee , Mehta Minesh 
Published: November 2023

Abstract
RTOG 9402 demonstrated procarbazine (P), lomustine (CCNU/C), and vincristine (V), collectively PCV, added to radiation therapy significantly improved survival for patients with newly diagnosed anaplastic oligodendroglial tumors. The improvement was most pronounced in 1p19q codeleted cases, and to a lesser extent, IDH-mutant cases, with no survival benefit in cases with neither biomarker. Analogous results were observed in other phase III trials. However, vincristine (V) can cause substantial toxicity and requires intravenous administration, both negatively affecting quality of life, with debatable contribution to PCV efficacy. As a randomized trial comparing PCV to PC is unlikely to be conducted, we explored correlations between survival and V-dosing in patients randomized to PCV in RTOG 9402. We performed post-hoc analyses of all evaluable participants (n = 143) randomized to PCV on RTOG 9402, supplemented by restricting the analyses to the chemosensitive molecular subsets (IDH-mutant and/or 1p/19q codeleted, n = 118). Total V dose by quartile (Q) was calculated. Survival from six months post-randomization was compared among V dose groups, adjusting for age, extent of resection (EOR), and Karnofsky Performances Status (KPS) in a Cox proportional hazards model. Higher V dose received correlated with longer survival in multivariate analyses (n = 134, median-Q3 vs. &lt; Q1, HR 0.40 (0.22, 0.73), p = 0.003; ≥Q3 vs. &lt; Q1, HR 0.39 (0.22, 0.72), p = 0.002). Excluding chemoresistant cases (IDH wild-type/not codeleted), survival was also significantly longer in evaluable participants receiving the highest doses of vincristine (≥Q3 vs. &lt; Q1 HR 0.42 (0.21,0.81), p = 0.01). In this post-hoc analysis, higher overall V-dose received correlated with longer survival in evaluable patients with anaplastic oligodendroglial tumors receiving PCV chemotherapy in RTOG 9402. Of note, as vincristine dosing was not assigned by randomization, confounding due to differences in patient characteristics among V dose groups cannot be ruled out. Caution should be exercised when considering discarding V from the PCV regimen.
QOL-24. FINANCIAL AID REQUESTS BY BRAIN TUMOR PATIENTS IN ONTARIO THROUGH GOFUNDME
Authors: Devaraja Kaviya , Avery Jonathan , Iyengar Yajur , Zhang Andy , Climans Seth 
Published: November 2023

Abstract
Brain tumors affect individuals globally including Ontario residents. Numerous Ontario brain tumor patients suffer the unequal burden of responsibility to pay for treatments like oral chemotherapy. In addition to chemotherapy, patients and their families have other costs associated with their diagnosis. However, less is known about other direct and indirect financial costs due to their diagnosis. GoFundMe, an online fundraising platform, provides worldwide brain tumor patients the opportunity to raise money for financial assistance with costs associated with their diagnosis The purpose of this study was to analyze publicly-available data from GoFundMe, an online fundraising platform, to explore the financial needs of brain tumor patients across Ontario, unaware and/or unable to get assistance elsewhere. A qualitative descriptive design drawing on thematic analysis was used to analyze GoFundMe requests to support individuals diagnosed with brain cancer in Ontario between 2014 and 2021. A coding framework was created to determine emerging themes using qualitative data analysis software NVivo 10. A final sample of 154 requests described financial strain from the loss of income experienced by the patient and their caregivers to afford cancer treatments. Requests highlighted 1) an overall lack of awareness of how and where access financial aid and affordable psychosocial support; 2) concerns over the long-term financial well-being of bereaving family members; 3) A call for more public awareness of the financial burden and emotional distress experienced by of those impacted by brain cancer. These GoFundMe requests highlight a connection between financial burden and emotional distress and an overall lack of awareness of where/how to seek financial and emotional support. These results will serve as the foundation to advocate for and raise awareness of the financial assistance needed by brain tumor patients and their families.
QOL-25. FOR THE LOVE OF WORK: NOVEL STUDY OF VOCATIONAL COGNITIVE REHABILITATION IN PRIMARY BRAIN TUMOR
Authors: Jamora Christina Weyer , Brie Melissa , Bracci Paige , Smith Ellen , Luks Tracy , Phan Stephanie , Braunstein Steven , Bush Nancy Ann Oberheim , Butowski Nicholas , Clarke Jennifer , Daras Mariza , de Groot John , Chang Susan , Taylor Jennie 
Published: November 2023

Abstract

BACKGROUND
Primary brain cancer survivors live longer, yet experience distress and cognitive impairments that negatively impact their quality of life (QOL), including at work. We present a novel study of vocational tele-cognitive rehabilitation in primary brain cancer survivors.

METHODS
Retrospective review, post-treatment, radiologically stable adult primary brain cancer patients who completed standardized neuropsychological, psychological, vocational, and QOL assessments. Wilcoxon rank sum and Fisher’s exact or Chi-square tests assessed between-group and within-group comparisons. Tests were two-sided and statistically significant for p &lt; 0.05.

RESULTS
79 patients with known baseline work status assessed for between-group comparisons (working versus not). Working (n = 38) and not working (n = 41) subgroups had similar ages, tumor grade/type, and history of radiotherapy. Working had worse executive functioning (p = .05). Not working (n = 41) had worse cognitive function (executive function, attention, verbal learning all p &lt; 0.05) and more engagement in survivorship services (p &lt; 0.04). Of the 79 work-status known patients, 38 underwent vocational tele-cognitive rehabilitation (median 11 sessions) treatment for within-group comparisons. 82% of the treatment group had improved work status compared to 34% in non-treatment. Baseline work status and age were not related to occupational improvements (all p &gt;0.20). Higher dose high radiotherapy dose inversely related to rehab improvements (p&lt; .05). Higher verbal memory (p = 0.05), processing speed (p = .06), executive functioning (p = 0.02), IDH mutation status (p = .06), and motivation for treatment (p = .04) was associated with improvement. Those with depressive symptoms who engaged in clinically indicated psychotherapeutic services significantly improved their work status (p = .01).

CONCLUSION
Occupational functioning improved after cognitive rehabilitation. Cognitive impairments, IDH mutation status, higher dose radiotherapy, and treatment motivation are important. Not working at baseline, despite more cognitive impairments, improved similar to their working counterparts. Those with depression benefitted from psychotherapeutic support. Vocational tele-cognitive rehabilitation shows promise for improving the work-based abilities of primary brain tumor patients and warrants further investigation.
RBIO-10. NEUROMODULATORY EFFECT AND DOSE RESPONSE OF FUNCTIONAL RADIOSURGERY ON CORTICAL NEURONS
Authors: Gholampourkashi Sara , Thivierge Jean-Phillipe , Nair Vimoj 
Published: November 2023

Abstract

PURPOSE
The effects of functional radiosurgery on neuronal circuits remain poorly understood. Neurons of the prefrontal cortex communicate via precisely-timed action potentials that control cognition. Here, we examined the dose response of ablative radiation dose on the patterns of communication of neural circuits in prefrontal acute slices. Materials and

METHODS
Escalating doses from 20 Gy to 100 Gy of ablative radiation were applied to rodent cortical neurons using the robotic Radiosurgery device (CyberKnife(R) G4). Neuronal communication within irradiated prefrontal slices were compared to control slices (sham radiation); and assessed by plating slices on a multielectrode array that captured high-resolution (18 kHz) extracellular activity across 4,096 channels simultaneously. Comparisons also with recordings of slices treated with a pro-epileptiform solution and finally, correlated with staining for cell death.

RESULTS
Compared to control slices (mean rate of 0.06 Hz), the post-radiosurgery slices yielded a 40-fold increase in discharge rates (mean rate of 2.87 Hz for 20 Gy, 2.44 Hz for 50 Gy, and 1.95 Hz for 100 Gy radiation). Pearson cross-correlations were computed across all pairs of channels, yielding a matrix of 4,096-by-4,096 interactions. Radiated slices exhibited decreased correlations relative to control slices. A total of 7,446 neuronal interactions were above a threshold correlation of 0.5 in control slices, compared to none following a 20 Gy dose, 50 interactions following a 50 Gy dose and 28 interactions following a 100 Gy dose. Slices treated with pro-epileptiform solution slices yielded large seizure-like events characterized by increased discharge rates and increased pairwise correlations.

CONCLUSION
Post-radiosurgery slices yielded a unique signature of neuronal activity with increased rates; but with a pronounced decrease in correlations; suggesting diminished communication across neurons to create a neuro-modulatory effect on target tissue; or result in cognitive toxicity on organ-at-risk respectively.
RTID-07. A RANDOMIZED WINDOW OF OPPORTUNITY TRIAL WITH DOSE ESCALATION TO EVALUATE FLUOXETINE AND TEMOZOLOMIDE IN GLIOMA
Authors: Singh Kirit , Railton Chelsea , Hotchkiss Kelly , Herndon James , Peters Katherine , Friedman Henry , Desjardins Annick , Ashley David , Johnson Margaret O , Patel Anoop , Friedman Allan , Lim Michael , Fecci Peter , Piccioni David , McGranahan Tresa , Nagpal Seema , Sulman Erik , Mischel Paul , Khasraw Mustafa 
Published: November 2023

Abstract
The blood brain barrier limits the efficacy of many drugs in brain tumors. Fluoxetine (Prozac) is FDA-approved and brain penetrant. Preclinical studies show synergy between fluoxetine and temozolomide (TMZ), resulting in lysosomal stress and enhanced DNA damage in human-derived glioma in vitro and in vivo. We present our randomized surgical window of opportunity trial (NCT05634707) in patients with recurrent IDH wild type glioma. The primary objective is to evaluate if fluoxetine induces tumoral lysosomal stress while exploratory objectives will determine if combination therapy enhances tumor DNA damage. We will randomize 30 patients, ≥ 24yo, with recurrent glioma and who are eligible for re-treatment with TMZ (MGMT methylated, progression &gt;6 months post TMZ). Following informed consent, patients will be randomized 1:2 to control or experimental arms. Control patients will receive 50 mg/m2 TMZ for 7 days pre-resection. The experimental arm will receive 20 mg/day fluoxetine for 5 days before escalating to 40 mg/day. If &lt; 3/10 participants receiving 40mg/day experience dose-limiting toxicity (DLT), subsequent experimental arm patients will escalate to 60 mg/day. All experimental arm participants will receive 50 mg/m2 TMZ for 7 days after starting fluoxetine, starting 21 days pre-resection. The regimen of 50 mg/m2 TMZ for 7 days is based on a similar pre-surgical trial combining TMZ with experimental therapy (NCT05188508). This reduced dose was chosen to limit potential synergistic toxicities like thrombocytopenia or neutropenia. Following resection, patients will continue TMZ, initially at reduced dose for the first post-op cycle, before reverting to standard doses of 150-200mg/m2 (up to 12 cycles or progression). All patients (control and experimental) will be offered fluoxetine post-operatively. The primary study outcome will be quantification of tumoral lysosomal stress via Lysosomal-associated membrane protein 1 (LAMP1) expression while DNA damage will be assessed via γH2A histone family member X (γH2AX) using immunohistochemistry.
SURG-12. MANAGEMENT OF ATLANTOAXIAL INSTABILITY IN THE SETTING OF CLIVAL CHORDOMA WITH EXTENSION TO THE CRANIOCERVICAL JUNCTION: A COMPREHENSIVE REVIEW OF CLINICAL MANAGEMENT
Authors: Brown Nolan , Musmar Basel , Nguyen Oanh , Kuo Cathleen , Gendreau Julian 
Published: November 2023

Abstract

INTRODUCTION
Clival chordomas that involve the craniovertebral junction (CVJ) are particularly challenging to remove due to risk for postoperative atlantoaxial instability. Preoperative instability can also be present due to mass effect from the clival lesion. Surgery involves a delicate balance of acknowledging existing preoperative instability, when present, and aiming for gross total resection (GTR) while determining the optimal time to fuse occiput to axial spine. This requires extensive knowledge of operative anatomy, neuro-oncology, and spinal biomechanics. Method Adhering to PRISMA guidelines, we examined all currently available neurosurgical literature pertaining to skull base chordomas with extension to the craniocervical junction.

RESULTS
Thirty studies featuring 435 patients (age range: 2-78 years) were identified, including 14 retrospective cohort studies, 6 case reports, and 3 case seriesdescribing surgical management with OCF. The remaining 7 studies (4 retrospective cohort studies and 3 case reports) reported surgical management without OCF. Our findings indicate that cervical instability due to the fracture or loss of the odontoid process in the pediatric population is an indication for OCF. With respect to timing, it appears that OCF can be conducted prior to or following tumor resection if there is clinical suspicion that a patient will eventually develop atlantoaxial instability (odontoid process removal is an indication for OCF).

CONCLUSION
OCF is indicated for patients when concern for craniocervical instability exists. Although it can be performed following surgical chordoma resection, as long as such instrumentation does not interfere with achieving surgical goals of GTR and/or maximal safe resection, results suggest that optimal outcomes may be obtained when OCF precedes tumor resection. In addition to the degree of instability present, brian stem compression, extent of resection, and amount of instrumentation to be performed are factors that should be discussed between a skull base surgeon-spine surgeon multidisciplinary team.
SURG-14. THE ARRAY OF TREATMENTS AVAILABLE FOR HYPOTHALAMIC HAMARTOMA IN THE SETTING OF INTRACTABLE SEIZURE: CURRENT STATE OF THE EVIDENCE FOR ENDOSCOPIC DISCONNECTION (AND RESECTION), LITT, AND RADIOTHERAPY
Authors: Brown Nolan , Singh Rohin , Koester Stefan , Nguyen Oanh , Musmar Basel , Gendreau Julian 
Published: November 2023

Abstract
Numerous minimally invasive approaches to hypothalamic hamartomas (HHs) have been developed though their efficacy in treating seizures has not been closely analyzed. A systematic review was performed using three databases per PRISMA in order to identify all studies comparing seizure outcomes for HHs treated via endoscopic disconnection (ED), resection (ER), ablation, and radiosurgery. Of the initial 235 studies, 67 studies which reported individual patient data were included for analysis encompassing a total of 229 patients (75/219 females). ED: A total of 82 (33 females, 40%) patients were treated via endoscopic disconnection. Mean follow-up was 18 months and 39 patients (48%) were Engel Class (EC) I, 23 patients (28%) were EC II, 15 patients (18%) were EC III, and 4 patients (4.9%) were EC IV. ER: A total of 31 (8 females, 26%) patients were treated via endoscopic resection. Mean follow-up was 18 months and 14 patients (45%) were Engel Class (EC) I, 8 patients (26%) were EC II, 0 patients (0%) were EC III, and 9 patients (29%) were EC IV. Ablation: A total of 83 (24 females, 32%) patients were treated via either LiTT or thermal ablation. Mean follow-up was 16 months and 57 patients (69%) were Engel Class (EC) I, 12 patients (14%) were EC II, 4 patients (4.8%) were EC III, and 10 patients (12%) were EC IV. Radiotherapy: A total of 33 (10, 32%) patients were treated via radiotherapy. Mean follow-up was 32 months and 18 patients (55%) were Engel Class (EC) I, 9 patients (27%) were EC II, 3 patients (9.1%) were EC III, and 3 patients (9.1%) were EC IV. Our findings suggest that patients treated with ablation had the highest percentage of seizure freedom, followed by radiotherapy, endoscopic disconnection, and endoscopic resection. Further studies are needed to determine the long-term efficacy and safety.
TMET-09. SEX DIFFERENCES IN SERINE-DERIVED GLYCINE BIOSYNTHESIS DRIVE RESPONSES TO COMBINED NUTRIENT DEPRIVATION AND PHARMACOLOGICAL INHIBITION IN GBM
Authors: Lu Jianyun , Marquez Camryn , Sponagel Jasmin , Chinnaiyan Prakash , Rubin Joshua B , Ippolito Joseph 
Published: November 2023

Abstract
Glioblastoma (GBM) is the most common and deadly primary brain malignancy. Male GBM patients occur at higher incidence and display more aggressive disease than females. Ambiguity of molecular mechanisms driving sexually dimorphic outcomes in GBM limits the implementation of clinically effective treatments. Therefore, our group seeks to determine and target the metabolic bases of sex-biased GBM proliferation and progression. We have identified glucose utilization as a unique determinant of male but not female GBM patient outcomes. Utilizing a mouse model for mesenchymal GBM (Nf1-/-DNp53), we demonstrated a male-specific decrease in proliferation in response to glucose-deprived media and glycolytic inhibition. Following labeling with [13C] glucose, males had significantly higher de novo serine biosynthesis, measured by enrichment of serine and glycine. This was confirmed with significant upregulation of several serine biosynthetic pathway enzymes in male cells. These mouse model data were validated by metabolomics and enzyme data from human GBM and lung cancer, including pan-cancer gene expression data, underscoring the broad translational importance of these findings. We then sought to determine if sex-biased responses to serine and glycine deprivation were similar to those observed following glucose deprivation. Utilizing serine and glycine-deprived media conditions, we identified a male-specific decrease in proliferation following pharmacological inhibition of the serine biosynthetic pathway. More precisely, in the absence of exogenous glycine, we discovered that pharmacological inhibition of de novo synthesis of glycine from serine drove male-specific decreases in proliferation. Additionally, we discovered that under serine and glycine-deprived conditions, inhibition of de novo synthesis of glycine from serine sensitized female transformed astrocytes to antifolates. These data highlight that de novo glycine synthesis drives sex differences in GBM cell proliferation. As well, our work suggests that dietary restriction of serine and glycine, in combination with pharmacological inhibition of de novo glycine biosynthesis, represents a novel GBM treatment paradigm.
TMET-16. ELUCIDATING MECHANISMS OF ENHANCED OXIDATIVE PHOSPHORYLATION IN MYC-AMPLIFIED MEDULLOBLASTOMA
Authors: Burwag Fares , Delaidelli Alberto , Yao Betty , Negri Gian Luca , Huang Yue Zhou , Huang Albert , Vislovukh Andrii , Langman Sonya , Hughes Christopher , Leprivier Gabriel , Sorensen Poul 
Published: November 2023

Abstract
Medulloblastoma (MBL) is the most commonly diagnosed pediatric brain tumour and the leading cause of childhood cancer deaths. MYC overexpression often accompanies poor prognosis in MBL patients, as MYC-driven transformation is known to promote mitochondrial oxidative phosphorylation (OXPHOS). However, it also induces a high metabolic demand that impairs cell survival under acute nutrient deprivation. We previously reported that eukaryotic Elongation Factor Kinase 2 (eEF2K), the master regulator of mRNA translation elongation, is overexpressed in MYC-driven MBL. Preliminary data suggests a relationship between eEF2K-mediated selective translation of mRNAs needed for efficient OXPHOS, and for the progression of MYC-driven MBL. Multiplexed enhanced Protein Dynamic Mass Spectrometry was carried out in eEF2K knockdown MYC-overexpressing D425 MB cells to identify mRNAs selectively translated upon eEF2K activation. 9 of 10 detected components of the OXPHOS pathway were selectively translated in eEF2K-active MBL cells. Genetic eEF2K knockout led to the disassembly of electron transport chain (ETC) complexes I-V and reduced complex activity, as observed via Blue Native PAGE and colorimetric assays. Furthermore, siRNA knockdown of Cytochrome c oxidase assembly factor 7 (COA7), a mitochondrial OXPHOS assembly factor differentially expressed in eEF2K active or inactive D425 cells, produces the same pattern of supercomplex (SC) loss as the inactivation of eEF2K in wild-type D425 cells. The assembly of ETC SC across D425 eEF2K active and inactive cells was further studied using blue native gel-based mass spectrometry to further characterize patterns in SC loss. In summary, control of translation elongation by eEF2K is critical for mitochondrial ETC complex assembly and efficient OXPHOS in MYC-overexpressing MBL, likely representing an adaptive response against acute metabolic stress. Future therapeutic studies will aim to combine eEF2K inhibition with caloric restriction mimetics.