bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-41. IMMUNOLOGICAL TARGETING OF SLOW-CYCLING CELLS TO PREVENT RECURRENCE IN GBM
Authors: Chakraborty Avirup , Conforti Cole , Sobanjo Olusegun , Hodge Ethan , Engelbart Mia , Castillo Paul , Flores Catherine , Huang Jianping , Mitchell Duane , Deleyrolle Loic 
Published: November 2023

Abstract
Glioblastoma (GBM) is the most common primary malignancy of the central nervous system (CNS) and is typically fatal due to recurrence despite aggressive treatment. Targeting residual cells after surgical tumor removal is challenging due to the infiltrative nature of GBM. It is crucial to develop effective adjuvant therapies that can combat the drivers of disease recurrence. Traditional anticancer treatments tend to eliminate rapidly dividing cells while sparing dormant or infrequently dividing populations. Numerous studies have identified slow-cycling cells (SCCs) in various cancers, including high-grade glioma, which are resistant to therapies. Our laboratory has discovered SCCs in high-grade glioma, which are highly infiltrative and treatment-resistant cells responsible for driving recurrence. It is imperative to develop an effective strategy to specifically eliminate this cell population in order to reduce recurrence and improve survival rates. Importantly, these cells have a defined cellular niche that contains potentially immunogenic neoantigens, making them suitable targets for immune-based therapies. Our primary objective is to utilize SCC antigens in the form of RNA or peptides to stimulate the immune system and enable it to identify and target treatment-resistant clones. By focusing on these crucial drivers of recurrence, our aim is to achieve strong and effective tumor control. Our research findings indicate that our approach effectively primes T cells to identify and target treatment-resistant cells in glioma. Our results demonstrated that T cells specific to slow-cycling cells (SCC-T cells) showed greater activation when exposed to treatment-resistant tumor cells, as evidenced by increased differentiation of CD8 cells and enhanced development of effector and memory cells. Furthermore, SCC-T cells exhibited the highest level of anti-tumor activity, resulting in a significant reduction in tumor cell proliferation and an increase in apoptosis. Taken together, these results highlight the effectiveness and superiority of our SCC-based immunotherapy platform in targeting treatment-resistant glioblastoma cells.
IMMU-45. REVERSIBLE PARKINSONISM AFTER BCMA-DIRECTED CAR T CELL ADMINISTRATION
Authors: Gewirtz Alexandra , Mailankody Sham , Usmani Saad , Santomasso Bianca 
Published: November 2023

Abstract
B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR)T cell therapy has revolutionized the treatment of patients with relapsed or refractory multiple myeloma (MM), resulting in FDA-approval of two products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). In addition to immune effector cell associated neurotoxicity syndrome (ICANS), a novel hypokinetic movement disorder resembling parkinsonism has been reported with BCMA-targeting CAR. Cases reported to date have been irreversible or fatal, and guidance on how to manage this complication is limited. Here we describe a patient with MM who developed features of parkinsonism on day 24 post ide-cel infusion which were apparently reversible with supportive care and dexamethasone. A 77 year-old man with MM received standard lymphodepletion followed by ide-cel. He developed grade 1 cytokine release syndrome (CRS) for which he received tociluzumab, followed by transient expressive aphasia (grade 2 ICANS) on day 23. Brain MRI showed no structural abnormality. On day 24 he developed new tremor and gait impairment. Neurologic examination revealed cogwheeling in bilateral wrists, hypomimia, soft speech, and slowed gait. Lumbar puncture and electroencephalogram were unremarkable. FDG-PET brain did not show basal ganglia hypometabolism or abnormal avidity. Lymphocyte percentage was elevated and correlated with a high level of circulating CAR+ T cells. He was started on dexamethasone 10 mg q day, receiving a total of 17 days of steroids with improvement in symptoms. At day 60, ambulation was improved and cogwheeling and hypomimia resolved. By day 90, all neurological symptoms had resolved. Improvement remained sustained as of last follow up day 120. To our knowledge, this is the first case report of steroid responsive parkinsonism after BCMA-CAR therapy. Our report supports close neurological monitoring of patients beyond 30 days after BCMA-CAR and suggests that intervening early in the setting of hypokinetic movement disorders may lead to sustained reversal of symptoms.
IMMU-52. LOW-INTENSITY PULSED ULTRASOUND CONDUCTS ANTIGEN-INDEPENDENT T CELL HOMING INTO THE BRAIN PARENCHYMA WITH THE INTACT BLOOD-BRAIN BARRIER
Authors: Gallus Marco , Saijo Atsuro , Haegelin Jeffrey , Chuntova Pavlina , Yamamichi Akane , Lakshmanachetty Senthilnath , Okada Hideho 
Published: November 2023

Abstract
The blood-brain barrier (BBB) protects the brain parenchyma from excessive inflammation but also leads to poor immune cell homing, hampering the success of immunotherapies, such as ones for low-grade glioma, where the BBB is intact. Low-intensity pulsed ultrasound (LIPU) combined with the application of microbubbles allows the non-invasive, transient opening of the BBB and recent studies have observed immune cell infiltration into malignant gliomas following LIPU. While these data warrant mechanistic investigations on the effects of LIPU in preclinical settings, most mouse models of malignant glioma already display BBB disruption. Therefore, to study whether LIPU affects antigen-specific immune cell trafficking through the BBB, we created a novel immunocompetent mouse model of non-tumor bearing mice that display an intact BBB and express a minigene cassette encoding for four immunogenic peptides in glia cells under the glial fibrillary acidic protein (GFAP) promotor. These peptides are either presented by major histocompatibility complex (MHC) class I: human melanoma antigen glycoprotein (gp) 100 and lymphocytic choriomeningitis virus (LCMV)gp31) or class II: LCMV gp66 and tyrosinase-related protein 1. Minigene expression in astrocytes induced antigen-specific T cell proliferation and Interferon-γ release in vitro. Intravenous adoptive T cell transfer of naïve or respectively CD3/CD28-coactivated antigen-specific CD 8 T cells targeting gp100 peptide followed by immediate LIPU treatment induced T cell homing into the CNS parenchyma, and astrocyte-T cell interaction was confirmed by ex-vivo two-photon imaging. Furthermore, some animals that underwent immediate LIPU treatment after transfer of preactivated antigen-specific T cells developed neurological deficits such as ataxia, while no deficits were observed in those animals that underwent LIPU but did not receive T cells or received activated T cells but did not undergo LIFU treatment. In conclusion, LIPU might be a novel effective tool to support antigen-independent immune cell homing with the intact BBB.
IMMU-55. THERAPEUTIC WINDOW ENABLING ERADICATION OF RESIDUAL GLIOMA STEM CELLS BY INTRACRANIAL NK CELL AND EXTRACELLULAR VESICLE-MEDIATED THERAPY FOLLOWING TEMOZOLOMIDE-INDUCED TUMOUR DEPOPULATION
Authors: Meehan Brian , Adnani Lata , Zhu Xianbing , Tawil Nadim , Garnier Delphine , Nakano Ichiro , Huang Sidong , Rak Janusz 
Published: November 2023

Abstract
Glioblastoma (GBM) is an incurable brain cancer, where dismal outcomes result from disease recurrence driven by tumour-initiating glioma stem cells (GSCs). GSCs survive and expand in the brain after surgery, radiation and temozolomide (TMZ) amidst weak immune and natural killer (NK) cell surveillance. NK cell-mediated killing of GBM cells occurs at effector to target rations precluding effective eradication as enforced by clinical trials with autologous NK cells in an adjuvant setting. Here we explore in a human GSC xenograft model whether tumor depopulation using high dose Temozolomide (TMZ) could create a window of curative opportunity for endogenous or exogenous NK cells. We observed that while subcutaneous (sc) xenografts of patient derived GSCs are infiltrated by endogenous functional (NCR1+) NK cells in SCID mice, the corresponding intracranial (ic) tumours remained NK cell depleted. In NK-deficient NSG mice, neither site contained functional NK cells. Notably, while TMZ caused near complete regression of GSC xenografts in both strains of mice and both locations (sc and ic), this was followed by recurrence of drug resistant lesions in all cases except NK-infiltrated sc SCID xenografts. This effect was obliterated by anti-sialo GM1 treatment. To explore whether direct delivery of NK cells into depopulated intracranial tumours would change the lethal course of the disease, mice were injected with GSCs ic, and upon tumour formation were treated with a sequence of TMZ (systemically), and two days later with irradiated NK92MI. Remarkably, this combined therapy completely obliterated recurrent disease. To assess whether NK92MI cells could be replaced by their derived extracellular vesicles (NK-EVs), the latter were injected i.c. post TMZ in GSC xenograft bearing mice. A single injection of NK-EVs resulted in tumour eradication in some but not all mice. Thus, chemotherapy-dependent tumour depopulation may create a unique window of opportunity for curative NK-mediated immunotherapy in GBM.
INNV-04. RAPID CLINICAL AND RADIOLOGICAL RESPONSE TO BEVACIZUMAB IN A PATIENT WITH SCHWANNOMATOSIS
Authors: Yankelevich Maxim , Kaiser Kaydee , Zakalik Karol , Krishnan Anant , Fullmer Joseph 
Published: November 2023

Abstract
Limited evidence exists for optimal management of schwannomatosis, the least common neurofibromatosis syndrome characterized by multiple schwannomas and intractable pain in the absence of vestibular schwannomas and germline NF2 mutation. We present a case of a 32-year-old man with a family history of schwannomas who had been dealing with multiple paraspinal schwannomas throughout entire spine, neurological deficits and chronic severe pain since high school. He had multiple laminectomies with resection of schwannomas. By the time neurooncologist saw the patient he had been on daily narcotics for more than 10 years, was not ambulatory due to paraparesis and was dependent on chronic Foley catheter for urination. He was found to have SMARCB1 c.93G &gt;A germline mutation that has not been reported before. Total spine MRI demonstrated further progression of multiple spinal schwannomas with cord compression. The patient started on bevacizumab 10 mg/kg IV every 4 weeks (the first dose 5 mg/kg) but had to have an 8-week interval between his second and third cycle because of slowly healing pressure ulcers over bilateral upper buttocks. The patient started to show improvement in leg movements and strength after 2 cycles, his urinary catheter was discontinued, and he started urinating on his own after 3 cycles of bevacizumab. MRI obtained after 3 cycles demonstrated decreasing size and enhancement of multiple schwannomas. The patient continued bevacizumab every 4 – 6 weeks and continued with clinical improvement of strength and mobility. He started to stand with support for several minutes after 6 cycles of bevacizumab and reported better control of pain. He started outpatient physical therapy sessions. The plan is to continue bevacizumab therapy long term. This case demonstrated efficacy of bevacizumab as an alternative treatment option to improve quality of life and avoid surgeries in patients with this rare debilitating condition.
INNV-11. USE OF IVOSIDENIB IN THE TREATMENT OF LOW GRADE GLIOMAS
Authors: Ribeiro Anatevka , Ney Douglas 
Published: November 2023

Abstract
IDH 1 and IDH 2 are crucial metabolic enzymes which covert isocitrate to alpha-ketoglutarate. During this process, NADP is reduced to NADPH. Mutant IDH produces an oncometabolite, D-2 hydroxyglutarate (2-HG). Elevated 2-HG levels interfere with epigenetic regulation and cellular metabolism leading to oncogenesis and have been postulated to play a role in multiple malignancies. Mutations in IDH1 and IDH2 have been found in AML, cholangiocarcinoma, myeloproliferative, myelodysplastic syndromes, and low-grade gliomas. IDH inhibitors, although not FDA approved for treatment of glioma, have shown promise as a treatment for low-grade gliomas with IDH mutation in clinical trials. Ivosidenib is an orally available inhibitor of IDH1. We examined patients with oligodendroglioma treated off-label with ivosidenib. RANO criteria for low grade glioma was used to determine radiographic response following ivosidenib initiation. Patient ages 28 , 37 , and 37 females with oligodendroglioma, IDH1 mutated, 1p/19q co-deleted, WHO grade 2 were treated with ivosidenib. Treatment was initiated between August 2022 and March 2023. Two patients had two prior recurrences each while the third patient was treated in the neoadjuvant setting following subtotal resection. Two had stable disease as best response at follow-up of 7 and 17 months while the third is awaiting interval follow up. Duration of ivosidenib therapy was 9, 19, and 3 months respectively and is ongoing in all patients. Only grade 1 leukopenia was observed in one patient which resolved without intervention. No seizures since surgery were observed in two patients, while yearly focal seizures occurred in the third patient. Median progression free survival was not able to be determined, however preliminary data reveals stable disease as best response in all three patients without side effects or increased seizure frequency. IDH inhibitors continue to be an area of interest and ongoing research in the treatment of low-grade glioma.
INNV-12. DEMOGRAPHICS, PRESCRIBING PATTERNS, AND SATISFACTION OF HEALTHCARE PROVIDERS WHO PRESCRIBE TUMOR TREATING FIELDS (TTFIELDS) THERAPY TO PATIENTS WITH GLIOBLASTOMA
Authors: Shockley Shermona , Gwyn P Gage , Palmesino Elena , Batzianouli Eleni , Johnson Heather 
Published: November 2023

Abstract

BACKGROUND
TTFields are electric fields that disrupt cellular processes critical for cancer cell survival. TTFields therapy was approved for recurrent and newly diagnosed glioblastoma (GBM) in 2011 and 2015, respectively, and here we report on the demographics, prescribing patterns, and satisfaction of TTFields therapy from healthcare providers (HCPs) throughout the US.

METHODS
In 2022, HCPs completed surveys regarding their satisfaction in prescribing TTFields therapy to patients with GBM, based on their experiences with the device system (NovoTTF-200A; Novocure® GmbH).

RESULTS
Overall, 32 HCPs completed the survey; all respondents had prescribed TTFields therapy in the prior 6 months. Respondents were physicians (66%), nurse practitioners/advanced practice registered nurses (22%), and physician’s assistants (12%); specialties included radiation oncology (50%), neuro-oncology (41%), medical oncology (7%), and neurosurgery (3%). A balance in practice settings was represented: academic/university (34%), cancer specialist center (28%), private practice (22%), and community (16%). Overall, 44% of HCPs reported having ≥37 months experience prescribing TTFields therapy. Most respondents (69%) had prescribed TTFields therapy to 1–5 patients, with 75% reporting no change in volume of treated patients over the past 6 months. Satisfaction was high for patient support services (66% very satisfied; 16% satisfied) and prescription support processes (66% very satisfied; 31% satisfied). There were high overall satisfaction levels with the use of virtual educational resources, certification training, and educational materials for providers and for patients (≥88% very satisfied/satisfied rating each).

RESULTS
were similar for academic and non-academic respondents.

CONCLUSION
These survey data provide insights regarding the demographics and prescribing patterns of HCPs providing TTFields therapy to patients with GBM. These data indicate a high degree of satisfaction with the prescription process and support. Increasing awareness of support programs and resources remains important in overcoming barriers to TTFields therapy initiation to optimize patient experience.
INNV-13. PREDICTION OF MGMT METHYLATION FOR GLIOBLASTOMAS USING AI MODELS. A COST-EFFECTIVE FRAMEWORK FOR LOW AND MIDDLE-INCOME COUNTRIES
Authors: Restini Felipe , Yoshimoto Fernanda Hayashida , de Brito Leticia Hernandes , Vaz Nascimento José Eduardo , Mancini Anselmo , Mendes de Sousa Cecilia Feliz Penido , Starling Maria Thereza Mansur , Hanna Samir Abdallah , Marta Gustavo Nader , Neves Junior Wellington Furtado Pimenta 
Published: November 2023

Abstract

BACKGROUND
MGMT methylation (MGMTmet) is prognostic and predictive for patients with glioblastoma (GBM). However, financial constraints limit access to molecular tests, especially in low and middle-income countries. Artificial intelligence (AI) tools have emerged as a potentially cost-effective solution for identifying MGMTmet. Therefore, we are investigating if an AI model could select those at higher risk to present positive results for molecular confirmation, thus making a better resource allocation.

METHODS
We have selected GBM patients from the public image bank, The Cancer Imaging Archive, and we included all patients with a molecular evaluation of MGMTmet. We defined our volume of interest based on the ESTRO-ACROP 2016 guideline for GBM radiotherapy contouring and then extracted the radiomic features. The collected features underwent structured analysis, and a prediction model for MGMTmet was developed. We used a Random Forest algorithm to identify the most relevant features. Subsequently, the dataset was divided into training and validation sets.

RESULTS
We examined 100 patients with histologically classified high-grade gliomas and wild-type IDH, Sixty-one were unmethylated, and 39 were methylated. In this cohort, over 39,000 features were extracted. To avoid noise and overfitting, the 13 most predictive features were selected. They belong to the following feature classes: demographic, first order, Gray Level Size Zone Matrix, and Gray Level Co-occurrence Matrix. The preliminary model achieved an accuracy of 80% for predicting MGMTmet.

CONCLUSION
our preliminary results show a promising role for AI models in screening patients for molecular testing. This initiative demonstrates the utilization of research to bridge the public health gap. By sharing experiences and fostering collaboration, physicians can work towards mitigating healthcare inequalities in low-middle-income countries. In our future perspectives, we plan to enhance the algorithm's efficacy by incorporating qualitative human-generated features and expanding our sample size.
INNV-15. OPTIMIZING THE ROLE OF THE ADVANCED PRACTICE PROVIDER IN THE MANAGEMENT OF A SINGLE PATIENT INVESTIGATIONAL NEW DRUG (IND)
Authors: Jacobs Susanne D , Johnson Margaret O , Miller Elizabeth S , Patel Mallika , Affronti Mary L 
Published: November 2023

Abstract

BACKGROUND
Single patient Investigational New Drug (IND) applications are a way through which experimental therapies may be accessed by patients with cancer especially if a clinical trial is not available. However, initiating and managing a single patient IND is complex. We will outline our approach used at an academic teaching center to leverage the skills and scope of practice of advanced practice providers (APPs) to facilitate successful initiation and monitoring of individual patients who may be receiving an investigational drug under a single patient IND.

METHODS
We describe a single case of a 52-year-old male with a left thalamic glioblastoma treated with standard of care and monitored off therapy from May 2021 until November 2022. Extended genomic profiling of his tumor at time of biopsy revealed a FGFR3-TACC3 fusion and MGMT promoter methylation, and the decision was made to pursue a single patient IND for anlotinib for use in combination with temozolomide.

RESULTS
Following permission from the US Food and Drug Administration (FDA) to proceed and IRB chair concurrence, the MD and APP conferred with the investigational and clinical pharmacists regarding procurement and dispensing of the drug, in addition to surveillance and associated toxicities. The APP obtained consent, collected data on monitoring parameters and adverse events, checked for drug interactions with the patient’s routine medications, ordered and reviewed all treatment related MRIs, labs, and EKGs, and coordinated with ophthalmology for baseline and monthly eye exams. Performance of initial and follow-up exams, ongoing toxicity review and management, and care coordination with the local oncology team were completed by the APP.

CONCLUSION
As first point of contact for the patient and family, the APP plays a key role in glioma research within the multidisciplinary team by providing ongoing symptom management, education, and monitoring for patients receiving investigational drugs.
INNV-21. EXTENDED SURVIVAL OF RECURRENT ANAPLASTIC OLIGODENDROGLIOMA PATIENT WITH GOOD FUNCTIONAL STATUS ON LONG TERM PEMBROLIZUMAB AND BEVACIZUMAB THERAPY - A CASE REPORT
Authors: Moldenhauer Matthew , Myung Joon , Fu Beverly Dan , Kong Xiao-Tang 
Published: November 2023

Abstract

INTRODUCTION
Anaplastic oligodendroglioma (AO) is a rare high-grade glioma. Standard of care include resection, radiotherapy followed by chemotherapy. However, effective treatment for recurrent AO is limited. Here we report pembrolizumab (Pembro) + bevacizumab (Bev) therapy for recurrent AO.

CASE
A 55-year-old male had a brain mass discovered on MRI in 2012 and received no treatment until resection in 2014. He underwent second tumor resection in late 2016 and pathology demonstrated an AO, WHO grade 3. He received radiation followed by PCV regimen in 2017. Ten months later in March 2018, he had tumor progression on PCV. Temozolomide was started. Two months later, Bev (10 mg/kg) was initiated in May 2018 due to further progression. After 12 months of Bev therapy, in mid-2019, Pembro was added due to new and enlarged lesions on MRI. After 18 months of q-3-week Bev (10mg/kg) + Pembro, Bev was on hold in December 2020 due to multiple TIAs. Single agent Pembro was continued for 6 months until April 2021 when his brain MRI showed increased enhancement. Then q-3-week Bev was resumed at a reduced dose (7.5mg/kg). These dual agents continued for 14 months until June 2022 when Bev dose was further reduced to 5mg/kg due to side effect. Bev was on hold again in December 2022 due to high Urine Protein/Creatinine ratio. Single agent Pembro was continued until May 2023 when lower dose Bev (2.5mg/kg) was resumed after MRI showed one subcentimeter new lesion. The small lesion is stable again on q-3-week 2.5 mg/kg Bev+Pembro. The patient has been clinically functional on Bev+Pembro treatment.

DISCUSSION
Four years of adjuvant pembrolizumab and tailored dose of bevacizumab have resulted in long term repeated stabilization of recurrent AO. The dose and duration of bevacizumab use need to be tailored to minimize adverse effects and to maintain positive effects.