bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXTH-83. BIRC3 AS A PREDICTOR OF OUTCOME AND A NEW THERAPEUTIC TARGET IN TMZ RESISTANT GLIOBLASTOMA TUMORS
Authors: Morelli Mariangela , Franceschi Sara , Lessi Francesca , Aretini Paolo , Pastore Aldo , Corradi Elena , Marranci Andrea , Gambacciani Carlo , Pieri Francesco , Grimod Gianluca , Montemurro Nicola , Giacomarra Manuel , Menicagli Michele , Ferri Gianmarco , Pasqualetti Francesco , Sanson Marc , Picca Alberto , Stefano Anna Luisa Di , Santonocito Orazio Santo , Mazzanti Chiara Maria 
Published: November 2023

Abstract
Glioblastoma (GBM) is an incurable malignant brain tumor, with a highly unfavorable prognosis. Apart from MGMT promoter methylation and TMZ response, molecular biomarkers associated with therapeutic response or survival prognosis are still lacking in GBM. Previously, using NAD(P)H-fluorescence lifetime imaging, a new drug screening precision medicine ex-vivo approach, we perturbed patients-derived vital GBM tumor explants (GB-EXPs) by TMZ treatment and obtained a stratification in TMZ responder (Res) and non-responder (Non-Resp) tumors, identifying several genes differentially expressed between the two groups. To validate the approach we enlarged our glioblastoma case study. Transcriptome analysis was performed to characterize TMZ Res and Non-Resp cases. In-silico and functional cellular investigations were carried on to explore the biomarker's efficiency. The majority of the genes found dysregulated in the previous study, showed the same directional regulation of expression and we confirmed, in TMZ-resistant samples the statistically significant upregulation of BIRC3, a strong inhibitor of apoptosis. The TCGA dataset provided an opportunity to fully assess the BIRC3 mRNA expression complementarity with the MGMT status as a predictor of outcome. BIRC3 was validated as a prognostic factor of survival also in large French and Italian glioblastoma cohorts. Most importantly, AZD5582 drug, which is a specific antagonist of BIRC3, combined with TMZ treatment, is able to reverse the TMZ resistance, in glioblastoma cell lines, by restoring apoptosis, and in GB-EXPs that were resistant to TMZ treatment. BIRC3 represents a potential biomarker of prognosis and a predictor of TMZ treatment response in GBM and complements MGMT status as an outcome predictor. The level of BIRC3 expression could stratify patients who will benefit from AZD5582 or its combination with TMZ. Our study provides a potentially new treatment approach and valuable leads to determine whether functional precision medicine combined with BIRC3 expression assessment become a standard tool in glioblastoma clinical oncology.
QLTI-01. HIGH-GRADE ASTROCYTOMA WITH PILOID FEATURES RESPONSE TO TREATMENT WITH CARBOPLATIN AND VINCRISTINE
Authors: Cielo Brandon 
Published: November 2023

Abstract
High-grade astrocytoma with piloid features (HGAP) is a brain tumor that requires distinct DNA methylation profiling for diagnosis. The current literature on HGAP response to treatment is limited. This case details the response to treatment of a young female patient initially with a pilocytic astrocytoma that at progression transformed into HGAP, both diagnoses confirmed with methylation testing. At 12 years old, the patient initially presented with unremitting headaches and syncopal episodes. Imaging revealed a non-enhancing non-cystic lesion in the roof of the fourth ventricle measuring 5 mm in the greatest dimension. She was followed by serial surveillance until undergoing surgical resection four years later. Histologically the tumor was grade I pilocytic astrocytoma containing a KIAA1549-BRAF fusion; the diagnosis was subsequently confirmed with methylation array testing. The patient transitioned to serial surveillance until she was lost to follow-up. At 27 years old, she presented with progressive headaches, gait instability, and agraphia. MRI revealed a posterior fossa cerebellar mass and surgical resection was performed. Histologically this was an anaplastic pilocytic astrocytoma with KIAA1549-BRAF fusion; however, DNA methylation profiling confirmed the diagnosis of HGAP. The patient was treated with postoperative radiation and demonstrated asymptomatic tumor progression in the left cerebellar hemisphere fourteen months later. She received carboplatin and vincristine with radiographic response and stability for four months until discontinuation due to tumor progression with infiltrative disease within the posterior fossa and brainstem. Her treatment was transitioned to selumetinib with mixed radiographic response but continued clinical deterioration after three months. Selumetinib was terminated and best supportive care was initiated. The patient died 216 months from initial presentation with pilocytic astrocytoma and 28 months from transformation into HGAP. To our knowledge, this is the first report of HGAP with treatment response to carboplatin and vincristine. Further research into the best treatments for HGAP is needed.
QLTI-06. EVALUATING TWO DECADES OF GLIOBLASTOMA CARE IN THE UNITED STATES VETERANS HEALTH ADMINISTRATION
Authors: Johnson Margaret O , Tseng Chin-Lin , Rowe Kerry , Passero Vida A , Kelley Michael J , Ahmed Sara T , Mooney Michael A 
Published: November 2023

Abstract

BACKGROUND
The Veterans Health Administration (VHA) provides healthcare for U.S. military Veterans, including specialized care for glioblastoma (GBM). This study aimed to understand patterns of care and outcomes for Veterans with GBM.

METHODS
We derived a retrospective cohort of U.S. Veterans with histological diagnosis of GBM in 2000-2021 from the VHA cancer registry system (CRS), with follow-up times through May 31, 2022. Data sources were patient-level electronic health records, CRS, and other data from the VHA corporate data warehouse. Using descriptive statistics, we describe demographics, treatments, clinical outcomes, referral patterns, and overall survival (OS).

RESULTS
We identified 3,802 Veterans with GBM (median per year = 176, range 76-225). Among the 465 veterans diagnosed in 2018-2021, 192 (41%) had unknown IDH mutational status. The median age at diagnosis was 66 years (range 20-101), most were male (97%), non-Hispanic (78%) and white (70%). 32% were considered rural and 2% highly rural. 71% received radiation and 61% (n = 2,301) received systemic therapy with the most common being temozolomide (96%), bevacizumab (16%), and lomustine (6%). First use of Novo-TTF was February 2020 with a total of 25 total users to-date. Between 2018-2021, 57% (range 54-63%) of veterans received cancer-related community referrals (i.e. medical oncology, radiation oncology, or neurosurgery). The yearly rate of palliative care referrals remained ≥40% since 2008 and was highest in 2021 (64%). Median OS was 6.9 months (95% CI:6.6-7.3).

CONCLUSIONS
Using the largest cohort of Veterans with GBM, we identified gaps in molecular testing data and note a large fraction that received community care referrals. Patterns of cancer-directed therapy appear consistent with best practices, although the unadjusted median OS for Veterans was shorter than reported in other populations. In response to these findings, VHA is developing strategies to improve access, quality and research for Veterans with GBM.
QLTI-12. ADULT NEURO-ONCOLOGY TRIAL LANDSCAPE IN THE UNITED STATES OVER FIVE DECADES
Authors: Smith Emily , Naik Anant , Goel Mahima , Wen Patrick , Lim Michael , Chang Susan , Germano Isabelle 
Published: November 2023

Abstract

PURPOSE
The unmet therapeutic needs in neuro-oncology remain significant due to the biological and clinical challenges. Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances. This study aims at analyzing the landscape of neuro-oncology trials to identify completion and failures and guide strategies for the path forward.

METHODS
US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019) to include funding source, trial type, scope, phase, and subjects’ demographics. Trial failures comprised “terminated,” “withdrawn,” and/or “suspended” trials. Univariate and multivariate analysis were used to detect differences across factors and over time.

RESULTS
Our search yielded 4522 trials, 1257 eligible for this study. In 25 US States, neuro-oncology trials availability is &lt; 0.85/100,000 population. Over time, completed trials have decreased with a significant increased percentage of trial failures from 22% to 36% (p &lt; 0.001). Overtime, NIH funding decreased from 47% to 24% (p &lt; 0.001). Inclusion of subjects ≥ 65-year-old and women increased in the last decade (p &lt; 0.001) while inclusion of Hispanic subjects has decreased (p &lt; 0.001). The top two reasons for failure included accrual and operational difficulties. Industry-funded trials had a trend toward higher failure rate than NIH-funded. A larger proportion of women (p &lt; 0.001), non-Hispanic subjects (p = 0.001), and older adult (p &lt; 0.001) patients were enrolled in completed trials than in failed trials.

CONCLUSION
Our study is the first report on the neuro-oncology clinical trial landscape in the US over time. The data support the concept that strategies to further the availability of clinical neuro-oncology trials within the US are necessary. As these are developed, attention is needed to identifying and modifying factors contributing to clinical trial failures.
QOL-08. LONGITUDINAL EFFECTS OF A PSYCHOLOGICAL INTERVENTION FOR CAREGIVERS OF PATIENTS WITH PRIMARY MALIGNANT BRAIN TUMORS: SECONDARY ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL
Authors: Strander Sumita , Podgurski Alyx , Datta Shibani , Pintro Kedie , Horick Nora , Greer Joseph , Traeger Lara , El-Jawahri Areej , Sannes Timothy , Temel Jennifer , Jacobs Jamie , Forst Deborah 
Published: November 2023

Abstract

BACKGROUND
Caregivers of patients with primary malignant brain tumors (PMBT) experience high rates of anxiety. In our randomized controlled trial assessing the effects of a caregiver-directed, telehealth-based psychological intervention (“NeuroCARE”), NeuroCARE participants had significantly lower anxiety symptoms (primary outcome) and depression symptoms, and better self-efficacy and coping immediately post-intervention compared to usual care (UC). We subsequently examined the longitudinal effects of NeuroCARE on caregiver-reported outcomes across all study timepoints.

METHODS
We enrolled and randomized 120 caregivers of patients with PMBT to NeuroCARE (N = 60) versus usual supportive care (N = 60). Eligible participants had significant baseline anxiety symptoms (Generalized Anxiety Disorder-7 score ≥ 5). We collected caregiver-reported anxiety symptoms (Hospital Anxiety and Depression Scale (HADS)–Anxiety Subscale), depression symptoms (HADS–Depression Subscale), self-efficacy (Lewis Cancer Self-Efficacy scale), coping (Measure of Current Status), quality of life (QOL; CareGiver Oncology Quality of Life survey), caregiver burden (Caregiver Reaction Assessment) and post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for DSM-5) at baseline, 11 weeks (immediately post-intervention) and 16 weeks (one-month post-intervention). We used mixed effects linear regression models to assess longitudinal intervention effects on study outcomes.

RESULTS
Enrolled caregivers had a mean age of 53 years; the majority were female (99/120; 82.5%) and were the patient’s spouse/partner (84/120; 70%). NeuroCARE participants experienced greater improvement than UC in depression symptoms (change/week [slope]: -0.09 vs. -0.01, p = 0.041), self-efficacy (slope: 0.64 vs. -0.17, p = 0.006) and coping (slope: 0.31 vs. -0.01, p &lt; 0.001). We observed non-statistically significant differences between NeuroCARE and UC for change in anxiety symptoms (slope: -0.13 vs. -0.05, p = 0.059) and QOL (slope: 0.26 vs. 0.04, p = 0.050). Study arms did not differ in longitudinal trajectories for caregiver burden or PTSD symptoms.

CONCLUSIONS
NeuroCARE participants experienced greater improvements over time in depression symptoms, self-efficacy, and coping than UC participants, highlighting the sustained benefits of this caregiver-directed supportive intervention.
QOL-23. BASELINE TOTAL BRAIN VOLUME PREDICTS FOR POORER QOL AND REDUCED OVERALL SURVIVAL AFTER CRANIAL RADIOTHERAPY IN OLDER PATIENTS WITH GLIOBLASTOMA (GBM): RESULTS FROM THE PROSPECTIVE BRITER STUDY
Authors: Lorimer Cressida , Chalmers Anthony , Mills Samantha , Thompson Gerard , Glendenning Jennifer , Coombes Isobelle , Brock Juliet 
Published: November 2023

Abstract
GBM incidence peaks in the 7th and 8th decades of life with prognosis worsening with age. Short-course partial brain radiotherapy, +/- chemotherapy, extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy related side effects. BRITER, a prospective multicentre observational trial, recruited patients with newly diagnosed GBM aged ≥ 65 planned for cranial radiotherapy. Baseline MRI scans were analysed for 5 putative markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in QoL. 126 patients were enrolled; mean age 72 years (range 65-83); 67% men, 33% women. 4% had a radiological diagnosis, 19% biopsy and 77% had debulking surgery. 21% received palliative radiotherapy alone (25% 30Gy/6#, 75% 40Gy/15#), 79% received radiotherapy with concurrent TMZ (47% 40Gy/15#, 53% 60Gy/30#). Median OS was 11.3 months. After accounting for age, sex, treatment and baseline MoCA score, there was a significant relationship between baseline CSF:TIV ratio and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV ratio, there was a corresponding decrease in EORTC QLC C30 QoL score by a factor of 1.27 (coefficient -1.27, 95% CI -3.24 to -0.19 p = 0.02). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV ratio was related to risk of non-attendance (OR 1.35, 95% CI 1.01-1.80, p = 0.04). Cox regression models were fitted for time to death in 88 participants who had analysable baseline MRI sequences. Baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19-1.66, p &lt; 0.001). This unique prospective study indicates that baseline imaging parameters can predict the impact of cranial radiotherapy on QoL and OS.
QOL-29. ILLNESS UNDERSTANDING AND RELIGIOUSNESS IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Fortunato John , Walsh Leah , Polacek Laura , Panageas Katherine , Reiner Anne , Walbert Tobias , Thomas Alissa , Buthorn Justin , Sigler Allison , Prigerson Holly , Applebaum Allison , Diamond Eli 
Published: November 2023

Abstract

BACKGROUND
Glioblastoma (GBM) is an aggressive neurologic malignancy with invariably poor prognosis. However, there is evidence that patients with GBM often have unrealistic perceptions of their prognosis. Strong religious beliefs have been shown to be associated with limited illness understanding (IU) in patients with advanced cancer, but IU and religiousness have not been investigated in patients with GBM.

METHODS
Patients enrolled in a prospective multi-center study of recurrent GBM (Coping with Glioblastoma; NCT02375841) completed surveys after a clinical encounter with their oncologist revealing GBM progression. Psychometrically validated measures assessed parameters of IU and religiousness. IU was compared between participants with at least a moderate or high degree of religiousness (vs. not) using Fishers-exact test.

RESULTS
Twenty-four adult patients (median age 57) completed surveys. Fifteen (63%) identified their illness as terminal. Six patients (25%) correctly identified their life expectancy (months), eight patients predicted life expectancy of years (33%) and ten (42%) did not know or answer. Eleven (46%) reported being moderately or very religious, while nine (38%) were slightly or not at all religious. There was significantly less frequent awareness of terminal illness amongst patients identifying as religious, spiritual, or as feeling God’s presence (all p &lt; 0.05). There was significantly less frequent IU amongst patients identifying as spiritual or believing in miracles (both p &lt; 0.05).

CONCLUSION
IU is infrequent in recurrent GBM and is significantly less frequent in patients endorsing religiousness and spirituality. Strategies to improve IU, broadly and in alignment with religious and spiritual beliefs, are warranted.
RBIO-11. BASAL BCL-2-INTERACTING MEDIATOR OF CELL DEATH (BIM) RESPONSIVENESS CORRELATES WITH RADIOSENSITIVITY IN MENINGIOMA
Authors: Harary Maya , Fernandez Elizabeth , Casaos Joshua , Vitte Jeremie , Nathanson David , Na Brian , Prins Robert , Giovannini Marco , Everson Richard 
Published: November 2023

Abstract

INTRODUCTION
Radiotherapy remains the primary adjunctive treatment for recurrent or progressive meningioma. Nevertheless, varied clinical response to radiotherapy in meningioma remains a challenge, particularly in higher grade tumors. Currently there is a paucity of predictors of radio-sensitivity. Bim peptide is an intrinsic mediator of apoptosis, and Bim-responsiveness has been postulated as a metric of general sensitivity to apoptotic stress. Herein we investigated its utility as a metric of radio-sensitivity in meningioma.

METHODS
In an in vitro model of meningioma, a number of immortalized human and murine meningioma cell lines and patient-derived primary cultures (WHO grades 1 + 2), were exposed to ionizing radiation at range of doses (0, 2, 4, 8, 16Gy); cells were counted (Celigo, Nexelcom) to assess for growth. Separately, cultures were irradiated at 4Gy and apoptosis was analyzed 24H later using Annexin/PI staining by flow cytometry (Attune NxT). Lastly, untreated cultures were exposed to Bim peptide as a range of doses (0.01uM-10uM); induction of apoptosis was assessed via cytochrome C staining by flow cytometry.

RESULTS
We were able to recapitulate a wide range of radio-sensitivities both by growth metrics and radiation-induced apoptosis. Immortalized lines showed more radiation-induced growth inhibition relative to primary cultures (p = 0.03). Activation of apoptosis in response to Bim exposure demonstrated a similarly wide range of basal apoptotic sensitivities, akin to that seen for radio-sensitivity. In fact, there was a significant correlation (Pearson, p &lt; 0.01) between Bim-responsiveness and levels of radiation-induced apoptosis.

CONCLUSIONS
We identify basal state Bim-responsiveness as a potential predictor of radio-sensitivity in meningioma. Further work in this vein may shed light on mechanisms of radio-resistance in meningioma, particularly with respect to the interaction of Bim with the anti-apoptotic members of the Bcl-2 family.
RTID-06. THE PIVOTAL METIS (EF-25) STUDY OF TUMOR TREATING FIELDS (TTFIELDS) THERAPY FOR BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER (NSCLC) FOLLOWING RADIOSURGERY
Authors: Mehta Minesh , Brown Paul , Harat Maciej , Roberge David , Ahluwalia Manmeet 
Published: November 2023

Abstract
INTRODUCTION: TTFields are electric fields that disrupt processes necessary for cancer cell survival and can stimulate an antitumor immune response in preclinical NSCLC models. TTFields therapy is a noninvasive and locoregional treatment approved for glioblastoma, which has recently demonstrated a survival benefit when applied to the thorax with standard of care (SOC) systemic therapy in patients with metastatic NSCLC that progressed on/after platinum. Here we describe the pivotal METIS study (EF-25, NCT02831959) evaluating the efficacy and safety of TTFields therapy applied to brain metastases from NSCLC. TRIAL DESIGN: Patients (270) with 1–10 brain metastases from NSCLC will receive stereotactic radiosurgery (SRS), followed by 1:1 randomization to TTFields (NovoTTF-200M [150 kHz] applied to the head ≥ 18 h/day) with best SOC, or best SOC alone. Key inclusion criteria are life expectancy ≥ 3 months, a new diagnosis of 1 inoperable or 2–10 supra and/or infratentorial brain metastases from NSCLC, that are amenable to SRS. Patients who had prior whole brain radiotherapy, or have single operable, leptomeningeal, or recurrent brain metastases, certain genetic mutations, or severe comorbidities or contraindications, are not eligible. The primary endpoint is time to first intracranial progression. Secondary endpoints include time to neurocognitive failure, overall survival, radiological response rate, time to second intracranial progression, time to first/second intracranial progression by modified RECIST v1.1, rate of intracranial progression, time to distant progression, rate of cognitive decline, quality of life, neurocognitive failure-free survival, and safety. The study is powered at 80% (2-sided alpha of 0.05) to detect a hazard ratio of 0.57. In July 2021, an independent Data Monitoring Committee reviewed the study data and recommended continuation. The study includes 128 sites in Europe, Israel, mainland China, North America, and Hong Kong. The final patient was enrolled in March 2023.
SURG-02. SURGICAL OUTCOME OF SUPRATENTORIAL MENINGIOMA PATIENTS AGED ≥80 YEARS – RETROSPECTIVE INTERNATIONAL MULTICENTER STUDY
Authors: Schwartz Christoph , Rautalin Ilari , Grauvogel Jürgen , Bissolo Marco , Masalha Waseem , Steiert Christine , Schnell Oliver , Beck Juergen , Ebel Florian , Bervini David , Raabe Andreas , Eibl Thomas , Steiner Hans-Herbert , Shlobin Nathan A , Nandoliya Khizar R , Youngblood Mark W , Chandler James P , Magill Stephen , Romagna Alexander , Lehmberg Jens , Fuetsch Manuel , Spears Julian , Rezai Arwin , Ladisich Barbara , Demetz Matthias , Griessenauer Christoph J , Niemelä Mika , Korja Miikka 
Published: November 2023

Abstract

BACKGROUND
Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas, Objective: To evaluate outcome of supratentorial meningioma patients aged ≥80 years. This multicenter study aims to report neurofunctional status after resection, to identify factors associated with outcome, and to validate a previously proposed decision support tool.

METHODS
Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (&lt; 10 cm3), medium (10-50 cm3), and large ( &gt;50 cm3).

RESULTS
The study population consisted of 262 patients. Median age at surgery was 83.0 years. Median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. Median tumor and PTBE volumes were 30.2 cm3 and 27.3 cm3; large PTBE volume correlated with poor preoperative KPS status (P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year-increase of age associated with 44% (23–70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5cm (odds ratio 1.87 (1.12–3.13)) and large tumor volume (odds ratio 2.35 (1.01–5.50)) associated with an increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery.

CONCLUSION
Patients with poor preoperative status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.