bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXTH-91. GALECTIN-3 INHIBITOR PAIRED WITH FOCAL LOW-INTENSITY NONINVASIVE TDCS CAN ACHIEVE MAXIMAL THERAPEUTIC BENEFIT IN CLINICALLY RELEVANT MENINGIOMA MOUSE MODELS
Authors: Das Arabinda , McDonald Daniel G , Yazdani Milad , Stephenson Connor , Mehrotra Shikhar , Welsh Cynthia A , Infinger Libby Kosnik , Vandergrift William A , Varma Abhay K , Patel Sunil J , Giglio Pierre , Zukas Alicia , Cachia David , Lindhorst Scott M 
Published: November 2022

Abstract
Atypical and anaplastic meningiomas (WHO Grade 2 and WHO Grade 3 respectively) represent a subgroup of meningiomas that tend to have higher rates of recurrence with associated’s higher morbidity and mortality than the more common WHO Grade 1 meningiomas. Our laboratory data demonstrated that galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed in these meningioma subtypes as compared to normal brain tissue. However, the root of the profoundly immunosuppressive tumor microenvironment in meningioma cells is not fully understood. To address this, we used a Gal-3 inhibitor TD 139 paired with low-intensity non-invasive transcranial direct current stimulation (tDCS) to suppress tumor growth and enhance the immune response in the preclinical model. Treatment of tDCS (50 mV/mm for 30 min) followed by 1 mM of TD139 induced cell death in anaplastic meningioma in vitro human triple co-culture model but has no effect on mouse cortical neurons. Furthermore, we demonstrated that inhibiting of Gal-3 expression significantly decreased the protein levels of urokinase-type plasminogen activator receptor as well as phosphorylation of Akt and upregulates Bax expression. Treatment with TD139 (1mg/kg per day for 14 days) with tDCS [350 μA (1 x 30 min/day) for 7 times (within 14 Days) showed a significantly (∼60%) decrease in MGS2 atypical meningioma tumor growth in orthotopic allograft model (at Day 41). The percent survival of tumor-bearing mice treated with TD139 and tDCS was significantly higher than an untreated tumor or single treatment. Following TD139 plus tDCS treatment, our results demonstrated significant meningioma cell death via a decrease in NDRG4 (Meningioma marker) and were associated with downregulation of Ki-67 in treated tumors. Based on our substantial preliminary data, we believe that this proposed translational work has the potential to be an effective combinational modality form of treatment for atypical and malignant meningiomas.
QLTI-07. IDENTIFYING RISK FACTORS FOR PROLONGED TRANSFUSION-DEPENDENT TEMOZOLOMIDE-INDUCED THROMBOCYTOPAENIA IN PATIENTS RECEIVING CONCURRENT CHEMO-RADIOTHERAPY FOR GLIOBLASTOMA (GBM)
Authors: Ismail Nashwah , Patel Karan , Parikh Tapan , Colaco Rovel , McBain Catherine 
Published: November 2022

Abstract

BACKGROUND
Temozolomide-induced thrombocytopaenia is a well-recognised clinical issue with significant inter-patient variation. However, knowledge of the extent of the problem and its potential risk factors remains limited. Our aim was to determine the incidence of patients requiring platelet transfusion and ascertain associated risk factors using real-world data.

METHODS
Data from patients with GBM receiving concurrent temozolomide-chemo-radiotherapy (CRT) from 01/01/18-31/12/2019 retrospectively reviewed. Patients receiving platelet transfusion identified (Local policy: transfusion for platelet count ≤ 30x109/L). Logistic regression and chi-squared tests used to compare variables in patients requiring platelet transfusion and those not.

RESULTS
111 patients with GBM received TMZ-CRT (60Gy/30#; 75mg/m2 temozolomide). 12/111 patients received platelet transfusion: 10 during concurrent-CRT and 2 during adjuvant-treatment. Numbers of transfusions: 1-2: 7 patients; 3-4: 2 patients; ≥ 5 transfusions: 3 patients. Median time from platelet count ≥ G3 to ≥ 100 in 11/12 patients: 38 days (range 6-72). 1 did not recover, patient died 84 days following start of TMZ-CRT with thrombocytopaenia. Comparison of the transfused vs the non-transfused cohort shows: transfused: 50% female; non-transfused: 36% female. Mean BSA: transfused: 1.73, SD0.21; non-transfused:1.96, SD0.22 (OR 0.01; 95% CI:0.0003 – 0.16). Mean age: transfused: 57, SD15.8; non-transfused: 58, SD10.7 . Mean baseline platelet count: transfused: 329, SD185; non-transfused: 319, SD117. Mean PTV: transfused: 400, SD115; non-transfused: 414, SD123. There were no statistically significant associations with demographics, age, blood parameters or planning target volume.

CONCLUSION
This study demonstrates a subset of patients who experience severe and prolonged thrombocytopaenia. Risk factors elucidated are female sex and lower BSA. Large-scale prospective trials evaluating a panel of predictors including concomitant medications, patient MGMT variants and temozolomide-metabolite concentrations would be valuable. Precise stratification of this vulnerable subgroup may permit consideration of temozolomide dose-capping in the future. Careful informed consent with all patients and caution with intensifying treatment under trials is vital presently.
QLTI-09. DEFINING GLOBAL BENCHMARK OUTCOMES FOR TRANSSPHENOIDAL SURGERY OF PITUITARY ADENOMAS: A MULTICENTER ANALYSIS OF 2862 CASES
Authors: Drexler Richard , Rotermund Roman , Smith Timothy , Kilgallon John , Honegger Jürgen , Nasi-Kordhishti Isabella , Gardner Paul , Gersey Zachary , Abdallah Hussein , Jane John , Marino Alexandria , Knappe Ulrich , Uksul Nesrin , Rzaev Jamil , Galushko Evgeniy , Gormolysova Ekaterina , Bervitskiy Anatoliy , Schroeder Henry , Eördögh Márton , Losa Marco , Mortini Pietro , Gerlach Rüdiger , Azab Mohammed , Budohoski Karol , Rennert Robert , Karsy Michael , Couldwell William , Antunes Apio , Flitsch Jörg , Ricklefs Franz 
Published: November 2022

Abstract
Benchmarks are important to measure and aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery are not available. Therefore, we aimed to establish robust, standardized outcome benchmarks for transsphenoidal surgery of pituitary adenomas. A total of 2862 transsphenoidal tumor resections from 12 high-volume centers in 4 continents were analyzed. Patients were risk stratified and the median values of each center’s outcomes were established. The outcome benchmark was defined as the 75th percentile of all median values for a particular outcome as defined by Staiger et al. Out of 2862 patients, 1201 (41.9%) defined the benchmark cohort. The proportion of benchmark cases contributing to the final cohort ranged across centers between 22.1% to 59.7%. Within the benchmark cases, 928 (73.3%) patients underwent microscopic (MTS) and 263 (21.9%) patients endoscopic endonasal resection (EES). The overall postoperative complication rate was 18.9% with an in-hospital mortality between 0.0-0.8%. Benchmark cutoffs were ≤ 3.3% for reoperation rate, ≤ 4.6% for cerebrospinal fluid leak requiring intervention, and ≤ 15.3% for transient diabetes insipidus. At 6 months follow-up, benchmark cutoffs were calculated as follows: readmission rate: ≤ 7.1%, new hypopituitarism ≤ 15.5%, new neurological deficit ≤ 1.2%, tumor remnant ≤ 25.5%. This analysis defines benchmark values for transsphenoidal resection of pituitary adenomas targeting morbidity, mortality, surgical and tumor-related outcomes. The benchmark cutoffs can be used to assess different centers, patients’ populations, and novel surgical techniques.
QLTI-18. LIQUID BIOPSY: CLINICALLY INTEGRATED RESEARCH IN THE MODERN PANDEMIC ERA
Authors: Nannapaneni Abhinav , Wigand Amanda , Tundo Kelly , Walbert Tobias , Snyder James 
Published: November 2022

Abstract
The COVID-19 pandemic forced a redesign of clinical research to adapt to an ever-changing situation while minimizing patient and provider risks and preserving scientific discovery. During the initial surge of COVID-19, elective healthcare services and non-critical research operations were halted. These changes inspired dispersed health care operations and streamlined clinical research. The first wave of COVID-19 hit Detroit, Michigan, in March 2020, consuming Henry Ford Health (HFH), in COVID-19 emergency care. HFH has a clinically integrated liquid biopsy (LB) program where enrolled patients provide an LB sample via venipuncture within 7 days of each MRI, typically in the clinic at the point-of-care. Prior to COVID-19, 183 neuro-oncology patients were actively providing LB samples in clinic with a mean of 29.9 specimens monthly. Institutional COVID-19 restrictions on non-critical interactions resulted in months were nearly all outpatient encounters utilized telemedicine and decentralized testing off-site from research operations. This halted LB procurement to 4.55 specimens monthly during early pandemic months. To reduce patient-provider exposure, LB specimens were then procured with the venipuncture for MRI which streamlined LB operations and improved the patient experience. After this change, LB specimen procurement returned to near pre-pandemic levels with a mean of 28.1 monthly specimens, despite a significant population utilizing video visits and imaging at satellite or non-HFH centers. The pandemic forced adaptations to patient encounters that have changed how healthcare is delivered, resulting in parallel changes in research that must be considered in the design of future studies.
QLTI-22. IMPROVING BRAIN CANCER PATIENT ACCESS TO CLINICAL TRIALS ACROSS SEVEN COMMUNITY HOSPITALS, THE PROVIDENCE SOUTHERN CALIFORNIA CLINICAL RESEARCH NETWORK
Authors: Carillo Jose , Wagle Naveed , Sharma Akanksha , Juarez Tiffany , Nguyen Minh , Truong Judy , Byun Timothy , Bott Thomas , Bozoyan Nanor , Park David , Kesari Santosh 
Published: November 2022

Abstract
Despite current FDA approved treatments for glioblastoma (GBM), prognosis remains poor. The rare patient population and limited access to clinical trials are factors in this poor prognosis. Clinical trials need to increase enrollment of patients with glioblastoma and other brain cancers to more rapidly develop more effective treatments. Clinical trials are featured on NCCN guidelines, and are considered “Standard of Care” by many experts. Multiple studies have shown that access to clinical trials is associated with improved survival in GBM, however, less than 25% of patients have access or are offered clinical trials. Access to clinical trials can be even more limited in community hospitals, while a large proportion of brain tumors are treated in smaller centers. Community hospitals care for a significant number of brain tumors annually. We have developed a Clinical Research Network for Neuro-Oncology within the Providence Network involving seven hospitals to date. In the past 3 years, we have grown the number of clinical trials available in outlying cities and counties spanning a distance of 60 miles. Between the seven hospitals in our network, we have 15 clinical trials currently open for brain cancer patients, of which, 3 trials were phase I studies. Over the past 2 years, we have enrolled 104 GBM patients in clinical trials. The ability to enhance access to clinical trials by Neuro-Oncologists treating patients in the community is feasible and promising.
QOL-02. FACTORS INFLUENCING COMPLIANCE IN TTF TREATMENT – THE COMPTUNE STUDY
Authors: Proescholdt Martin , Schmidmeier Melissa , Doenitz Christian , Schmidt Nils-Ole , Mühlberger Andreas 
Published: November 2022

Abstract

INTRODUCTION
Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (nGBM). A crucial parameter for TTFields efficacy is compliance to treatment. In this prospective study, we assessed 5 psychological domains known to influence treatment compliance using a standardized interview in nGBM patients. The results of this psychological assessment were correlated to TTF compliance.

METHODS
A cohort of 49 nGBM patients (female 22; male 27, median age 62 years) were recruited. Most patients received a gross total resection (51%), the postsurgical treatment consisted of concomitant radiochemotherapy plus TTF in most cases (81%), only 2 patients received chemotherapy only, and 7 patients were additionally enrolled in clinical drug trials. The psychological assessment system consisted of 5 domains: Social support, confidence in treatment efficacy, communication status about treatment, anxiety, and depression. The interview was repeated every 8 weeks over a period of 8 months or if patients stopped treatment or developed second tumor progression. Additional phone interviews were conducted every 4 weeks.

RESULTS
Median and mean compliance was 98% and 81.6%, respectively (range 5%-100%), drops of compliance below 75%, which were classified as a threshold value, occurred 2259 times. Over-dispersed Poisson and multivariate negative binomial regression analysis revealed depression to be significantly correlated with the number of drops below 75% and with the mean compliance in the first 4 months of treatment. In addition, at later time points, confidence in treatment efficacy significantly correlated with the number of drops below 75%. All other domains did not appear to be associated with TTF treatment compliance.

CONCLUSION
Overall, compliance to TTF was high, however, drops below 75% of compliance occurred frequently during the measurement periods. In the initial treatment phase, depression was associated with these events, whereas confidence in treatment efficacy was correlated at later time points.
QOL-12. “I’M JUST LIKE A BASKET FULL OF PROBLEMS”: QUALITATIVE STUDY OF COGNITIVE DYSFUNCTION AND QUALITY OF LIFE IN GLIOMA SURVIVORS
Authors: Van Dyk Kathleen , Wall Lucy , Ellingson Benjamin , An Nicholas , Lai Albert , Cloughesy Timothy , Brauer Eden R , Nghiemphu Phioanh L 
Published: November 2022

Abstract
For glioma survivors, cognitive impairment can be a central determinant of quality of life, but we need better understanding of their unique challenges and supportive care needs. In this qualitative study, we aimed to explore the post-treatment experiences of cognitive and functional challenges and their impact on quality of life from the perspectives of glioma survivors. Glioma survivors in an observational study were invited to participate in an in-depth qualitative interview. Using a semi-structured interview guide, interviews were audio-recorded and transcribed verbatim. Data were analyzed using a reflexive thematic analysis approach to develop key themes to inform clinical practice. Participants (n=9) ranged in age from 29 to 72 years, and were at least 4 years post-diagnosis. Under the overarching survivorship theme, three key themes were developed. The first theme, “Learning what my brain can and can’t handle,” centered on functional challenges related to cognitive impairments, including difficulties at work and managing home and family responsibilities. In response, participants described generating their own strategies to manage cognitive limitations in daily activities. The second theme, “Such an important crossroads”, reflected the significant emotional impact of persisting impairments (e.g., frustration, disappointment, reduced self-esteem, acceptance), increased anxiety around an uncertain future, and a shift in personal values towards an increased sense of gratitude, crystalizing of intentions, and focus on things of greatest importance. The final theme, “A solid foundation of people around me”, referred to the necessity of social support, in both emotional and instrumental terms. Many expressed a desire for and appreciation of coping tools and support for the support people in their lives. Nearly all participants expressed interest in cognitive rehabilitation – whether or not they were experiencing significant cognitive problems. These findings have implications for clinical practice and can inform the development of effective patient-centered supportive care interventions in this population.
QOL-20. PATTERNS AND PREDICTORS OF ANXIETY AND DEPRESSION SYMPTOM TRAJECTORIES IN PATIENTS DIAGNOSED WITH PRIMARY BRAIN TUMORS
Authors: Ernster Alayna , Body Anjelica , Deleyrolle Phuong , Clair Jennifer St , Sampson Deborah , Rahman Maryam , Tran David , Mitchell Duane , Ghiaseddin Ashley , Pereira Deidre 
Published: November 2022

Abstract

BACKGROUND
Patients diagnosed with primary brain tumors (pPBTs) exhibit high psychological distress. This study assessed how symptoms of anxiety and depression change over time in pPBTs and identified factors that may predict patients’ symptom trajectories.

METHODS
Ninety-nine adult pPBTs completed psychosocial assessments at routine neuro-oncology clinical appointments over 6 to 18 months, with a minimum 8-week interval between assessments. Symptoms of anxiety and depression were assessed with the PROMIS Anxiety and Depression Short-Forms. The prevalence and incidence of patients with clinically elevated anxiety and depression symptoms throughout follow-up were examined, along with the prevalence of patients that experienced clinically meaningful changes in symptoms between follow-ups. Linear mixed-effects models evaluated changes in symptoms over time at the group level and latent class growth analysis (LCGA) evaluated changes in symptoms over time at the individual level.

RESULTS
At baseline, 51.5% and 32.3% of patients exhibited clinically elevated levels of anxiety and depression, respectively. Of patients with any follow-up data (N = 74), 54.1% and 50% experienced clinically meaningful increases in anxiety and depression scores, respectively. The incidence of moderate to severe anxiety and depression was 15.6% and 8.3%, respectively. There was no significant change in symptoms over time at the group level, but better physical, functional, and brain-cancer well-being predicted significantly lower anxiety and depression symptoms (p&lt; .001). Results from LCGA showcased 5-unique subgroups of patients with distinct anxiety and depression symptom trajectories.

CONCLUSION
pPBTs commonly experience elevated anxiety and depression. Symptoms of anxiety and depression change in clinically meaningful manners throughout the disease, even in the absence of significant group-level time effects. Routine screening for elevated symptoms is needed to capture clinically meaningful changes in symptoms and identify factors affecting symptoms to intervene.
RBIO-01. ACTIVATING AN ION CHANNEL PROMOTES RADIATION-SENSITIZING IMMUNE-DRIVEN ANTI-TUMOR ACTIVITY
Authors: Toukam Donatien Kamdem , Bhattacharya Debanjan , Gawali Vaibhavkumar , Kallay Laura , Karve Aniruddha , Desai Pankaj , Cook James , Ahmed Taukir , Ionascu Trajan Dan , Tridandapani Susheela , Krummel Daniel Pomeranz , Sengupta Soma 
Published: November 2022

Abstract
Standard-of-care for melanoma brain metastases is moving to stereotactic radiosurgery (SRS) with immunotherapy. Although this combined approach shows improved patient survival, the responses are not durable. SRS can also cause adverse reactions such as radiation necrosis, which can result in significant morbidity and even mortality. Lowering SRS dose without negatively impacting its effectiveness would therefore be highly beneficial clinically. Our published data suggests that when treating syngeneic mouse model B16F10 melanoma tumors, the radiation dose can be reduced and its effectiveness can be improved, by activating intrinsic melanoma GABAA receptor (GABAAR) activity using a novel agent, AMLAL-101. This agent acts to enhance GABAAR mediated chloride transport in melanoma cells, which in turn triggers mitochondrial dysregulation associated with tumor regression in mice. While AMLAL-101 alone reduces tumor growth, combining it with radiation results in near complete regression of the irradiated tumor, as well as shrinking of tumor not in the radiation field due to an immune response, i.e., a potent abscopal effect. AMLAL-101 may also function to regulate immune cell infiltration into the tumor microenvironment. Analysis of AMLAL-101 treated tumors show increased infiltration into the tumor microenvironment of: (1) polyfunctional (TNFα/IFN-γ) CD8+ T cells; and (2) tumor-associated macrophages (TAMs) of the tumor inhibitory M1-phenotype, possibly due to IFN-γ stimulation. We posit that activating GABAAR with AMLAL-101 promotes both a ‘direct’ anti-tumor response and an ‘indirect’, immune-driven anti-tumor activity in metastatic melanoma tumors. AMLAL-101 may address an urgent unmet need for a non-toxic therapeutic that can potentiate radiation and mitigate its toxicity profile to positively impact clinical outcomes of patients with brain metastatic disease treated with radiotherapy.
RTID-05. TRIAL IN PROGRESS: DOSE-FINDING STUDY AND EVALUATION OF [177LU]LU-DOTA-TATE IN COMBINATION WITH STANDARD OF CARE IN NEWLY DIAGNOSED GLIOBLASTOMA AND AS A SINGLE AGENT IN RECURRENT GLIOBLASTOMA
Authors: Wen Patrick Y , Cloughesy Timothy , Demange Arnaud , Herrmann Ken , Weller Michael , Zor Evren 
Published: November 2022

Abstract
Patients with glioblastoma have a poor prognosis despite extensive efforts to develop new treatments. Standard of care for newly diagnosed patients is surgery followed by radiotherapy plus temozolomide. However, temozolomide only provides a clinical benefit to patients who have glioblastomas with a methylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promotor. Disease recurrence is inevitable and subsequent treatments have poor outcomes due to limited efficacy and a lack of established therapeutic regimens. [68Ga]Ga-DOTA-TATE is a radioligand imaging agent that selectively binds to somatostatin receptors (SSTRs) and is used with positron emission tomography (PET) for the molecular imaging of SSTR-positive neuroendocrine tumors. Glioblastoma tumoral PET scans have shown moderate uptake of [68Ga]Ga-DOTA-TATE. The radioligand therapy [177Lu]Lu-DOTA-TATE has the same SSTR-targeted ligand and demonstrated promising clinical activity in a pilot study in patients with Grade III/IV gliomas. This Phase 1b open-label dose-finding study (NCT05109728) will determine the recommended [177Lu]Lu-DOTA-TATE dose in three different groups of glioblastoma (newly diagnosed with methylated MGMT promoter [group 1], newly diagnosed with unmethylated MGMT promoter [group 2], and recurrent disease [group 3]). All participants will be scanned with [68Ga]Ga-DOTA-TATE imaging during screening and, for each group, approximately 15 participants will be enrolled in consecutive cohorts of 3–6 participants. All participants will receive up to 6 administrations of [177Lu]Lu-DOTA-TATE (initial dose 150 mCi with 3 provisional dose levels up to 250 mCi) using the Bayesian Optimal Interval design. Group 1 will receive [177Lu]Lu-DOTA-TATE every 4 weeks with concomitant radiotherapy and temozolomide, followed by temozolomide maintenance. Group 2 will receive [177Lu]Lu-DOTA-TATE every 4 weeks for 3 doses with radiotherapy then every 3 weeks as a single agent. Group 3 will receive [177Lu]Lu-DOTA-TATE only, every 3 weeks. The primary endpoint is incidence of dose limiting toxicity. Secondary endpoints include overall objective status (modified RANO criteria), progression free survival, overall survival and safety.