bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMU-51. SINGLE-CELL ANALYSIS OF TUMOR-ASSOCIATED MICROGLIA AND MACROPHAGES FROM HUMAN GLIOBLASTOMA
Authors: Anand Atul , Andersen Rikke Sick , Burton Mark , Harwood Dylan Scott Lykke , Poulsen Frantz Rom , Halle Bo , Pedersen Christian Bonde , Kruse Torben , Thomassen Mads , Kristensen Bjarne 
Published: November 2021

Abstract
Patients with glioblastoma, the most frequent and malignant primary brain tumor type, have a poor prognosis with a median survival of 14 months. A major therapeutic problem is chemoresistance. In surgically removed glioblastoma tissue, tumor-associated microglia and macrophages (TAMs) constitute up to 30 % of the total cells. TAMs are capable of secreting cytokines, chemokines and growth factors, thereby influencing the tumor microenvironment. However, the existence of different TAM subtypes and their role in glioblastoma is not fully comprehended and rarely considered therapeutically. This could explain why many glioblastoma clinical trials fail despite of promising preclinical results. This project aims to interrogate the existence and characteristics of different TAM subtypes in human glioblastoma biopsies in order to identify novel subpopulations and therapeutic targets. To study the heterogeneity in TAMs, CD11b+ cells were isolated from glioblastoma patient′s tissue, and single-cell RNA sequencing was performed using the 10X Genomics Chromium platform for single-cell generation and an Illumina NovaSeq6000 system for sequencing. We have sequenced TAMs from three glioblastomas and CD11b+ cells from brain tissue adjacent to two brain metastases samples. In the filtered data set of almost 71,000 CD11b+ cells, we were able to identify recently described TAM populations, such as an interferon-induced, a phagocytic, a hypoxic and a proliferating subset. Interestingly, we also discovered potential novel TAM subsets, such as a pro-angiogenic subset. We have detected a TAM population which is more complex than the established M1 and M2 phenotypes, constituting novel TAM subsets. We are currently investigating these findings to validate specific markers associated with these subpopulations, and for the identification of novel clinically relevant targets.
INNV-10. TUMOR TREATING FIELDS (TTF) AS MAINTENANCE THERAPY FOR AN OLIGODENDROGLIOMA CASE AND LONG-TERM FOLLOW-UP
Authors: Ko Uvin , Du Steven , Moldenhauer Matthew , Kong Xiao-Tang 
Published: November 2021

Abstract

INTRODUCTION
Recurrence of low- and high-grade gliomas is observed often after radiation and chemotherapy. Despite continued research on glioma management, there is limited knowledge regarding maintenance treatment after standard care. Tumor Treating Fields as maintenance therapy after radiation and chemotherapy may potentially help prevent recurrence.

CASE REPORT
In 2011, a 35-year-old male reported headaches to a local ED. A non-enhancing mass was detected on his brain MRI. Observation was advised by his local surgeon. The patient presented with seizures in early 2014, and his brain MRI found the mass developed new enhancement. In late 2014, the patient had multiple seizures, and significant progression of the tumor was discovered. The patient underwent craniotomy and biopsy in the middle cerebral artery distribution area in early 2015. Pathology reported grade II oligodendroglioma; however, the patient only underwent a biopsy, which might have missed the high-grade glioma region. His brain MRI showed a significant enhancing lesion with rapid growth, which was clinically more consistent with grade III oligodendroglioma. Radiation therapy was conducted followed by 6 cycles of PCV chemotherapy throughout 11 months. Post-radiation-chemotherapy brain MRI was stable with a moderate size residual tumor at the right insula region. Following patient wishes, NovoTTF-100A, or Optune, was administered 6 weeks after completion of chemotherapy as maintenance therapy for 2 years to prevent tumor progression. Now, after 3 years being off Optune, the patient is stable without new neurological symptoms or tumor progression. DISCUSSION: Our case highlights the potential effect of Tumor Treating Fields as maintenance therapy after initial radiation and chemotherapy for low- and high-grade oligodendrogliomas. The patient had rapid tumor progression prior to diagnosis and only underwent a biopsy without resection, yet uncommonly, has survived since initial image diagnosis 10 years ago and tissue diagnosis 6 years ago and is fully functional currently.
INNV-13. UNDERSTANDING FACTORS THAT INFLUENCE THE DECISION OF ACCEPTING TUMOR TREATING FIELDS (TTF) THERAPY
Authors: Kumthekar Priya , Lyleroehr Madison , Lacson Leilani , Stupp Roger , Lukas Rimas , Lezon Ray , Mora Kellie , Schmidt Karyn , Dixit Karan , Kaiser Karen 
Published: November 2021

Abstract

BACKGROUND
Tumor Treating Fields (TTF) Therapy is an FDA-approved therapy in the first line and recurrent setting for glioblastoma. Despite Phase 3 evidence showing improved survival, it is not uniformly utilized despite its availability. This qualitative prospective study interviewed glioblastoma patients to better understand key driving factors for decision making.

METHODS
Adult glioblastoma patients who were offered TTF and who signed IRB approved consent were included. Patients participated in a one-time recorded interview with the researchers from the Northwestern University Department of Medical Social Sciences and were asked about factors shaping their decision to use or not use TTF.

RESULTS
40 patients were enrolled with a mean age of 53 years, 92.5% were white and 60% were male. Of the 33 (82.5%) participants who accepted TTF, 23 (69.7%) reported their physician recommending TTF, 8 (24.2%) reported physician neutrality toward TTF, and 2 (6.1%) said their physician advised against TTF. Among the 7 (17.5%) participants who did not choose TTF, 4 (57.1%) reported physician neutrality, 2 (28.6%) reported that their physician advised against TTF, and 1 (14.3%) reported that their physician recommended TTF. Participants who decided against TTF stated that head shaving, appearing sick, and inconvenience of wearing/carrying the device most influenced their decision. For those choosing to use TTF, the most influential factors were extending life and following their doctor's opinion; other factors included level of familial support and the clinical evidence supporting TTF.

DISCUSSION
This clinical study was a collaboration with the Medical Social Sciences team to better understand the key factors that drive patient decision making with TTF. Findings suggest that physician support and positive Phase 3 results are among the key decision-making factors. Properly understanding the path to patients’ decision making is crucial in optimizing use of TTF and other therapeutic decisions for glioblastoma patients.
INNV-15. PROTEIN TYPING AND MRNA ANALYSIS OF CIRCULATING EXOSOMES FOR GLIOBLASTOMA THERAPY USING PLASMONIC-ENHANCED INTEGRATED MAGNETO-ELECTROCHEMICAL SENSOR
Authors: Lin Hsing-Ying , Huang Chen-Han , Hsu Peng-Wei , Lu Yu-Jen , Chou Peter C Y , Chen Hugo C H , Liu Vicky Y H 
Published: November 2021

Abstract
Monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem. Glioblastomas shed large quantities of exosomes into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Recently, we develop a highly sensitive and rapid analytical technique for profiling circulating exosomes directly from serum plasma of patients with glioblastoma. Exosomes are labeled with target-specific metal nanoparticles and detected by a miniaturized integrated magneto-electrochemical sensing system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate GBM exosomes from nontumor host cell–derived exosomes. We also show that circulating GBM exosomes can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.
INNV-16. CNS-TAP TOOL RECOMMENDATIONS OF TARGETED ANTI-CANCER AGENTS COMPARED TO THOSE SELECTED BY A MULTIDISCIPLINARY TUMOR BOARD IN A MOLECULARLY-DRIVEN DIPG CLINICAL TRIAL (PNOC003)
Authors: Roberts Holly , Ravi Karthik , Schepers Allison , Marini Bernard , Kline Cassie , Mueller Sabine , Koschmann Carl , Franson Andrea 
Published: November 2021

Abstract
Genetic sequencing of diffuse intrinsic pontine gliomas (DIPG) has revealed genomic heterogeneity, sparking an interest in individualized and targeted treatment options for this particularly devastating disease. A feasibility study, PNOC003: Molecular Profiling for Individualized Treatment Plan for DIPG (NCT02274987), was completed within the Pacific Pediatric Neuro-Oncology Consortium. In this study, a multidisciplinary tumor board reviewed detailed molecular and genomic profiling of each participant’s tumor and made molecularly-targeted treatment recommendations. Separately, our team developed the Central Nervous System Targeted Agent Prediction (CNS-TAP) tool, which combines pre-clinical, clinical, and CNS penetration data with patient-specific genomic information to derive numeric scores for targeted anticancer agents, aimed to objectively evaluate these therapies for use in patients with CNS tumors. We hypothesized that highly-scored agents within CNS-TAP would overlap with the agents recommended by the tumor board in PNOC003. For each study participant, we used the genomic profiling report to identify actionable alterations and incorporated these data into CNS-TAP to identify the highest-scoring agents. We compared high-scoring agents within CNS-TAP with recommendations from the tumor board for each of the enrolled 28 participants. Overall, 93% of patients (26/28) had at least one agent recommended by both the tumor board and CNS-TAP. Additionally, 38% of all agents (36/95) recommended by the tumor board were also selected by CNS-TAP. We identified factors that likely contributed to the differences in therapy recommendations between these two methods: CNS-TAP requires additional clinician input to account for drug-drug interactions, includes only classically-defined anticancer agents, and cannot easily be updated in real-time as new data emerge. However, CNS-TAP provides an objective evaluation of targeted therapies, whereas tumor boards are inherently subjective. A prospective study incorporating both CNS-TAP and a molecular tumor board for targeted therapy selection in high-grade glioma is currently ongoing to further compare and objectively evaluate these methods.
INNV-17. RESPONSE TO AVAPRITINIB IN A PEDIATRIC SPINAL CORD H3K27M-MUTANT GLIOMA PATIENT
Authors: Mayr Lisa , Madlener Sibylle , Verena Rosenmayr , Schmook Maria , Stepien Natalia , Baumgartner Alicia-Christina , Dorfer Christian , Haberler Christine , Müllauer Leonhard , Dieckmann Karin , Peyrl Andreas , Kim Sean , Hsieh Antony , Dimitrijevic Sasa , Gojo Johannes 
Published: November 2021

Abstract
H3K27M-mutated diffuse midline glioma (H3K27M-DMG) may arise in the pons, thalamus and spinal cord generally having a dismal prognosis. Notably, H3K27M-DMG are driven by oligodendrocyte precursor-like cells which are partly sustained by PDGFRA signaling. Co-mutations including TP53, ACVR1, PDGFRA, KIT and PI3K pathway alterations are present in a subset of cases, and molecular profiling may allow detection of additional targetable alterations. However, small-molecule inhibitors often have limited efficacy associated with low blood-brain-barrier (BBB) penetration. Here, we report on a patient with spinal, leptomeningeal disseminated H3K27M-DMG treated with avapritinib, an orally administered, BBB-penetrant and highly selective KIT and PDGFR inhibitor, provided through a compassionate-use program. Initial therapy consisted of subtotal resection, focal radiotherapy and temozolomide (TMZ) resulting in disease stabilization. Ten months after diagnosis, leptomeningeal metastases were detected, biopsied and treated with local irradiation and TMZ. The patient subsequently received systemic and intrathecal chemotherapy augmented with dasatinib. Molecular analyses of the biopsy revealed the H3F3A and TP53 mutations present in the primary tumor, as well as de novo PDGFRA and KIT amplifications with gene copy numbers of 25 and 21, respectively. Upon further disease progression, therapy with avapritinib was initiated. Assessment of treatment response according to RANO criteria after four months revealed stable disease of the target lesion in the cerebellum and partial response of all non-target lesions. Avapritinib was generally well tolerated with lower limb edema (Grade 2), small intratumoral bleeding (Grade 1) and unrelated hydrocephalus (Grade 3) as reported adverse events. As precaution, treatment was interrupted and re-initiated after one week as the bleeding was stable. A ventriculoperitoneal shunt was implanted resolving the hydrocephalus. Pharmacokinetic analyses revealed up to 65% avapritinib plasma exposure and clinically relevant levels in cerebrospinal fluid. In summary, we report on first effective therapy of treatment-resistant H3K27M-DMG with avapritinib as clinical proof of concept.
INNV-23. CASE REPORT OF CISPLATIN + ETOPOSIDE FOR THE TREATMENT OF METASTATIC MALIGNANT MENINGIOMA
Authors: Nguyen Minhdan , Truong Judy , Sharma Akanksha , Kesari Santosh , Carrillo Jose , Chow Jared , Landa Eve , Griffiths Chester , Kelly Daniel , Wagle Naveed 
Published: November 2021

Abstract

INTRODUCTION
Meningioma have an annual incidence of 5 per 100,000 and is the most frequent primary tumor of the central nervous system. Risk factors include radiotherapy and hormone intake. Most meningioma are grade I benign tumors, but up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological criteria. Extra-CNS metastasis is exceedingly rare but carry a poor prognosis. Surgical resection and radiation therapy are the only approved therapies for the treatment of high grade or recurrent meningioma. Chemotherapy options have been limited and none have shown significant response rates.

METHODS
We report a case of a 33 year old male with an anaplastic meningioma (WHO Grade III) with metastasis to the lungs and rapid progression despite repeat resection. The subject was previously treated with resection and radiation therapy to a skull base/sinonasal lesion. Progression occurred at anterior cranial fossa, which required repeat resection. Within a month, the meningioma showed substantial progression with invasion into the orbit and nasopharynx as well as metastasis to the lung. The subject experienced significant clinical decline which included bilateral vision loss. The subject was treated with Cisplatin and Etoposide for 4 cycles.

RESULTS
The patient had immediate clinical improvement after the first cycle. Repeat MRI imaging of the brain showed partial response with approximately 40% tumor reduction, and CT of the chest showed complete response. The subject’s performance status also improved significantly with treatment including recovery of eyesight bilaterally.

CONCLUSION
This case showed that the use of Cisplatin + Etoposide for metastatic malignant meningioma can have significant objective and clinical response. The use of this regimen warrants further investigation. A clinical trial is currently being developed.
INNV-25. RITUXIMAB MONOTHERAPY FOR TREATMENT OF RARE LOW GRADE PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; A CASE REPORT AND LITERATURE REVIEW
Authors: Tobin Grace , Neil Elizabeth 
Published: November 2021

Abstract
Primary central nervous system lymphoma (PCNSL) is a specific variant of non-Hodgkin's lymphoma confined to the brain, leptomeninges, spinal cord, and/or eyes. The majority of PCNSL is diffuse large B-cell lymphoma (DLBCL), however, a small percentage are categorized as low-grade lymphomas (LGL). Compared to high-grade and aggressive DLBCL, LGL are indolent; allowing for targeted and less neurotoxic first-line treatments. There is currently no consensus for LGL treatment. A patient at our institution was diagnosed with LGL without extra-CNS involvement 11/2018 and then, successfully treated with rituximab monotherapy. This 65 year-old, immunocompetent woman presented with one month of right leg weakness and numbness. Brain MRI demonstrated a subtly enhancing infiltrative left thalamic lesion extending into the left frontal lobe with surrounding edema. Flow cytometry on spinal fluid showed rare monotypic B-cells. Brain biopsy results showed an atypical predominantly perivascular lymphoid infiltrate. These atypical small lymphoid cells had mature-appearing nuclear chromatin, absent nucleoli, and uniformly expressed CD79a and CD20 with variable PAX-5 expression, lacked CD56 and CD117 expression, and had plasmacytic differentiation; thus consistent with marginal zone lymphoma, a type of indolent B-cell lymphoma. There was no evidence of extra-CNS involvement on PET scan, bone marrow biopsy, or ocular exam. She had normal cognitive functioning on neuropsychological testing. Interestingly, SPEP showed a monoclonal IgM immunoglobulin of kappa-light chain-type that became a monoclonal protein in the gamma fraction. Additionally, CT abdomen initially showed splenomegaly that resolved on repeat imaging a year later. Radiation therapy was deferred due to high risk. Weekly rituximab 500mg/m2 was initiated for 4 doses, then monthly for 4 doses. Therapy was well tolerated and she noted clinical improvement plus there was positive response on brain imaging. Repeat ophthalmology exam and CT body without any evidence of cancer. She is now 29 months progression-free since completing rituximab.
INNV-31. NEURO-ONCOLOGY OUTPATIENT SATISFACTION IS MAINTAINED IN THE ERA OF COVID-19 TELEMEDICINE
Authors: Petitt Zoey , Herndon James , Gottfried Oren , Cone Christina , Landi Daniel , Khasraw Mustafa , Friedman Henry , Ashley David M , Desjardins Annick , Peters Katherine , Johnson Margaret 
Published: November 2021

Abstract

INTRODUCTION
The use of telemedicine increased during the COVID-19 pandemic. However, the impact on patient satisfaction in the Neuro-oncology population is unknown. This quality improvement project compares outpatient satisfaction before and during the COVID-19 pandemic as well as in-person versus telemedicine platforms during the pandemic.

METHODS
We performed an IRB-exempt retrospective analysis of aggregate de-identified outpatient satisfaction scores among Neuro-oncology patients seen at The Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke University. The Clinician & Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) is a survey developed and distributed by Press Ganey Associates, and is the most widely used outpatient satisfaction survey in the United States. We compared pre-COVID-19 CG-CAHPS scores from patients who received in-person care at the PRBTC between April 2019 and March 2020 to COVID-19 pandemic CG-CAHPS scores (i.e. those who received either telemedicine or in-person care at the PRTBTC) from April 2020 to March 2021.

RESULTS
Approximately 1448 surveys were completed for both in-person and telemedicine visits. During the pandemic, 48.6% of surveys represented telemedicine, with monthly variations from 84.6% (April 2020) to 21.4% (March 2021). Patient satisfaction scores pre-COVID-19 were similar to those during the pandemic: overall provider rating from 0-10 (9.28 v 9.36), knowledge of medical history (96.9% v 95.4%), listens carefully (96.6% v 96.9%), shows respect (97.2% v 98.1%), and time spent (93.2% v 95.5%). During the COVID-19 pandemic, in-person and telemedicine demonstrate similar levels of satisfaction: overall provider rating from 0-10 (9.29 v 9.48), knowledge of medical history (94.9% v 96.1%), listens carefully (95.4% v 99.0%), shows respect (97.5% v 99.0%), and time spent (94.7% v 96.7%).

CONCLUSION
Outpatient satisfaction prior to and during the COVID-19 pandemic was similar. Patients reported similar satisfaction between in-person and telemedicine platforms. We support the ongoing use of telemedicine for outpatient Neuro-oncology.
INNV-35. A MULTI-DISCIPLINARY REVIEW OF NEWLY DIAGNOSED HIGH GRADE GLIOMA REFERRALS TO THERAPIES, AND IMPLEMENTATION OF A SCREENING TOOL TO IMPROVE ACCESS TO THERAPIES AT THE ROYAL MARSDEN HOSPITAL (RMH)
Authors: Jethwa Joanne , Jagger Charmaine , Williams Leanne , Jenkins Lizzy , Ashforth Kate 
Published: November 2021

Abstract
Brain tumours make up 3% of all cancers. The disease and treatment have significant impact on function and quality of life (QoL). Early outpatient rehabilitation can improve function. National Institute of Clinical Excellence recommends patients have access to rehabilitation across the pathway, but unmet need is prevalent in this population. We recognised late referrals in our Trust and poor patient awareness of Therapies, resulting in reduced access to rehabilitation. METHOD: A retrospective notes review of new neuro-oncology patients (n=56) referred to RMH from July - December 2018 was undertaken to identify therapy needs and timeliness of referrals. A therapy screening tool was devised and piloted from July – December 2019. Additionally, an MDT questionnaire was circulated to gain feedback regarding this service. RESULTS: Retrospective review revealed that of those patients with identified therapy needs, 16% of physiotherapy (PT), 10% of Occupational Therapy (OT) and 9% of Speech and Language Therapy (SLT) were referred late. Additionally, referrals were not received for 40% of patients with OT needs, 32% for PT and 30% for SLT. Following implementation of the screening tool, referrals occurred earlier in the pathway, and rates increased by 60% in SLT, 59% in PT, and 25% in OT. An MDT questionnaire revealed 100% consensus that screening was beneficial to patients and the MDT with improved access to therapies. CONCLUSION: Brain tumour patients require prompt therapy intervention to improve and maintain function and QoL. We identified high levels of unmet need which was eliminated by a screening tool and subsequently increased referral rates. Patients and the MDT had improved awareness of the role of Therapies, as well as earlier access. The neuro-oncology MDT benefitted from the effects of therapy intervention improving patient tolerance to oncological treatment. Therapists were able to identify and manage impairments earlier, improving QoL.