bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOUT-19. THE SHORT-TERM OVERALL SURVIVAL ASSOCIATED WITH SINGLE- VS. MULTI-AGENT CHEMOTHERAPEUTIC REGIMENS FOR 1p/19q-CODELETED WHO GRADE III ANAPLASTIC OLIGODENDROGLIOMAS: A NATIONAL EVALUATION
Authors: Touat Mehdi , Harary Maya , Kavouridis Vasileios , Smith Timothy , Iorgulescu Bryan 
Published: November 2019

Abstract

INTRODUCTION
Although diffuse gliomas of oligodendrocytic lineage demonstrate chemosensitivity, the survival outcomes associated with single- (i.e. temozolomide; TMZ) or multi-agent (i.e. PCV) chemotherapy regimens remain uncertain for anaplastic oligodendrogliomas (AO).

METHODS
Patients presenting between 2010–2016 with 1p/19q-codeleted WHO grade III AO were identified by ICD-O3 and site-specific factors from the National Cancer Database, which comprises >70% of cancers newly-diagnosed in the U.S. Predictors of receiving first-line single- vs. multi-agent chemotherapy were assessed by multivariable logistic regression. Overall survival (OS) was estimated by Kaplan-Meyer approaches and evaluated by multivariable Cox regression.

RESULTS
There were 952 patients with 1p/19q-codeleted WHO grade III AO and complete first-line chemotherapy data, with: 13.9% (n=132) no-, 75.0% (n=714) single-, and 11.1% (n=106) multi-agent chemotherapy. In logistic regression of chemotherapy-treated AOs, more recent diagnosis was associated with higher multi-agent (OR=1.48/year, 95%CI=1.25–1.74, p< 0.001) rates; otherwise there were no associations of single- vs. multi-agent chemotherapy with patient sex, age-at-diagnosis, race, insurance status (reference=privately insured), comorbidity index, tumor greatest dimension, tumor location (reference=frontal lobe) or crossing of midline, nor with radiotherapy or EOR (all p >0.05). Multi-agent usage rose from 3.6% in 2010 to 24.3% in 2016. Median follow-up was 34.9mos (IQR=18.8–54.8). The unadjusted 5yr-OS rate was 57.4% (95%CI=43.5–69.1) for no chemotherapy, 72.1% (95%CI=67.1–76.5) for single-agent, and 77.5% (95%CI=59.9–88.1) for multi-agent. Cox regression (adjusting for the above variables of radiotherapy and EOR, patient demographics, and tumor characteristics) demonstrated no significant OS difference between single- and multi-agent (HR=0.91, 95%CI=0.38–2.15, p=0.82) chemotherapy.

CONCLUSIONS
In a national database of AOs managed in the ‘real-world’ setting, there is increasing utilization of multi-agent (i.e. PCV) chemotherapy; but no significant difference in risk-adjusted short-term mortality (i.e. ~3-5yrs after diagnosis) between first-line multi- and single-agent (i.e. TMZ) chemotherapy. These findings provide preliminary data while we await the long-term PFS and OS results from the CODEL trial.
IMMU-25. MAGNETIC PARTICLE IMAGING FOR NON-INVASIVE TRACKING OF ADOPTIVE CELL TRANSFER IN CANCER IMMUNOTHERAPY
Authors: Rivera-Rodriguez Angelie , Hoang-Minh Lan , Marrero-Morales Leyda , Mitchell Duane , Rinaldi Carlos 
Published: November 2019

Abstract

BACKGROUND
Adoptive cell therapies (ACT) are strategies being explored to boost the immune response against cancer. ACT cancer immunotherapies are effective against metastatic melanoma, leukemia, and lymphoma, but face challenges in treating other solid tumors, such as in the brain. A critical step for the success of ACT in solid cancers is achieving trafficking and persistence of T-cells at tumor sites. Glioblastoma (GBM) is the most common and aggressive cancer of the central nervous system in adults, with a prognosis of 15-18-month average patient survival after diagnosis. Biomedical imaging is often used to track cell therapies. Magnetic Particle Imaging (MPI) is a novel biomedical imaging modality enabling non-invasive visualization of the distribution of biocompatible superparamagnetic iron oxide (SPIO) tracers.

OBJECTIVE
Label T-cells with SPIO to non-invasively track adoptive T cell transfer immunotherapy with MPI in the context of brain cancer.

METHODS
Murine pmel-DsRed T-cells were isolated from the spleen of a transgenic C57BL/6 mouse, and were exposed to different SPIO concentrations ex vivo. Cell viability, phenotype, and cytotoxic function were analyzed to determine if T-cells were affected by the SPIO labeling. Moreover, in vivo experiments were performed in a murine GBM model, and labeled T-cells were injected intravenously and tracked using MPI.

RESULTS
The SPIO-labeling of T-cells did not affected cell viability, phenotype, or cell cytotoxic function at all tested incubation conditions. The internalized SPIO can be quantified and spatially detected using MPI both in vitro and in vivo. In addition, MPI in vivo tracking shows T-cells accumulation in liver and lungs, as well in the spleen and brain, as showed ex vivo.

CONCLUSIONS
SPIO-labeling of T-cells did not affected its cytotoxic function and MPI allows for in vivo tracking of adoptively T-cell transfer. MPI will provide better understanding of ACT dynamics to accelerate development of novel treatments.
IMMU-27. IMMUNE CHECKPOINT BLOCKADE OF EX VIVO EXPANDED T CELLS FOR USE IN ADOPTIVE CELLULAR THERAPY (ACT) FOR GLIOBLASTOMA
Authors: Ogando-Rivas Elizabeth , Yang Changlin , Castillo Paul , Dechkovskaia Anjelika , Mitchell Duane 
Published: November 2019

Abstract

BACKGROUND
Despite aggressive treatments, GBM continues to have unacceptably high mortality rates. Immune-checkpoint blockade and ACT have shown excellent results in other solid tumors, especially in melanoma. Unfortunately, these results have not been extrapolated to GBM. We have developed a novel platform for ACT using tumor mRNA-pulsed dendritic cells(DCs) to in-vitro expand polyclonal populations of tumor-reactive T-cells. This platform has shown promising effects in preclinical brain tumor models (Flores et al OncoImmunology 2015, Wildes et al CCR 2018, Flores et al NatureComm 2018) and being evaluated in clinical trials at UF Health (NCT02465268,NCT03334305).

STUDY OBJECTIVE
Evaluate whether immune-checkpoint blockade during ex-vivo expansion of antigen-specific T-cells impact their use in ACT.

METHODS
CMVpp65 was used as model antigen for in-vitro activation of T-cells. Mature pp65 mRNA-pulsed DCs from CMV+ healthy donors were co-cultured with T-cells in IL2-containing medium for 15days. We tested four checkpoint inhibitor groups: PD1(n= 6), PDL1(n= 4), TIM3(n= 7) and PD1+TIM3(n= 6) that were compared with non-blockade group, respectively. Checkpoint blockade was performed every 3days. T-cell proliferation, immune-phenotyping, and IFN-g release were analyzed.

RESULTS
Cell proliferation was lower in all the blockade groups but significantly lower in the TIM3 (p= 0.03) and TIM3+PD1 (p= 0.01) blockade groups. TIM3 expression was significantly lower in the TIM3 (p= 0.006) and PD1+TIM3 blockade groups (p= 0.0001). There was a trend of reduced pp65 tetramer positive in the TIM3 and PD1+TIM3 blockade groups (PD1+TIM3 subgroup at 3mcg/mL, p= 0.02) and lower INFg release in the TIM3 and PD1+TIM3 blockade groups.

CONCLUSION
The exact role of checkpoints during expansion of T-cells for ACT is not well understood. In our study checkpoint blockade with PD-1 or TIM-3 alone or in combination did not enhance T-cell expansion or function, in fact, appeared to have an inhibitory effect on measured parameters. Our results suggest that TIM-3 may have an activating role in our system.
IMMU-32. RNA-NANOPARTICLE VACCINES MEDIATE T CELL TRAFFICKING NECESSARY FOR BBB PASSAGE AND ANTI-GLIOMA IMMUNE RESPONSE
Authors: Mendez-Gomez Hector , Wummer Brandon , Grippin Adam , Weidert Frances , Huang Jianping , Deleyrolle Loic , Mitchell Duane , Sayour Elias 
Published: November 2019

Abstract

BACKGROUND
The blood-brain barrier (BBB) remains a potent obstacle for development of new therapies against glioblastoma (GBM). While activated T cells can cross the BBB, immunotherapy has yet to be fully unlocked for malignant brain tumors due their heterogeneity and immunosuppressive microenvironments. To overcome these challenges, our group has developed a novel treatment platform, which leverages the use of a clinically translatable nanoparticles (NPs) combined with personalized tumor derived mRNA to peripherally activate T cells against a heterogenous source of tumor antigens and reprogram the intratumoral milieu into an immune activated state.

OBJECTIVE
We sought to assess if RNA-NPs could activate systemic/intratumoral dendritic cells (DCs) and mediate a peripheral T cell response that could penetrate the GBM microenvironment.

RESULTS
We uncovered that RNA-NPs elicit potent innate immunomodulating effects through release of interferon-α (IFN-α) from plasmacytoid DCs (pDCs). After only a single RNA-NP vaccine, the bulk of systemic and intratumoral DCs in mice display an activated phenotype; DCs, harvested from intracranial tumors, elicit expansion of antigen specific T cell immunity. Tumor-specific RNA-NPs elicited enhanced survival outcomes in immunocompetent animals bearing NF-1/p53 mutant gliomas with increased intratumoral memory CD8+T-cells. Unlike immune checkpoint blockade (anti-PD-L1 mAbs), we found that RNA-NPs increase LFA-1 on peripheral CD8 splenocytes, which is necessary for activated T cell passage across the BBB. RNA-NPs also increased CCR2 on peripheral CD8 cells, which was dependent on IFN-α/β, as the percentage of CCR2+CD8+ splenocytes and anti-tumor activity (mediated by RNA-NPs) was abrogated in animals receiving concomitant type I IFN receptor (IFNAR1) mAbs.

CONCLUSION
Since LFA-1 is important for T cell trafficking across the BBB and CCR2 may promote chemotaxis to the brain (as GBMs are known to secrete CCL2), RNA-NPs may offer a new treatment modality and immunologic mechanism for unlocking peripheral T cell immunity against malignant gliomas.
IMMU-51. PROFILING THE IMMUNE SYSTEM IN PRIMARY AND RECURRENT GLIOBLASTOMA
Authors: Maddison Kelsey , Graves Moira , Bowden Nikola , Vilain Ricardo , Fay Michael , Tooney Paul 
Published: November 2019

Abstract
Immunotherapy has been shown to have benefit in some solid tumours including melanoma where immune infiltration can be pronounced. Until recently the central nervous system was thought to be immune privileged. Whilst research has shown that immune cells are capable of infiltrating tumours from glioblastoma patients, to date immunotherapy trials have not consistently shown a benefit in these patients. The aim of this study was to profile the immune system in primary and recurrent tumours from glioblastoma patients. Formalin-fixed paraffin-embedded sections of primary and matched recurrent tumours from 13 patients with glioblastoma were processed for immunohistochemical labelling of a range of immune cell markers. Immune infiltration was scored on digitally scanned immunolabelled sections using a categorical system of 0 (absent), 1 (present), 2 (moderate) and 3 (marked). CD3+ cells were observed in three topographical locations within primary and recurrent glioblastoma tumours namely the tumour proper, perivascular spaces and associated with haemorrhages within the tumour. CD3+ cell infiltration into the tumour proper was present (Score = 1) in 7 of 13 primary and recurrent tumours. Only one case (case #9) had CD3+ infiltration scores > 1 for both primary (score = 3) and recurrent tumour (score = 2). CD3+ cells were observed in perivascular spaces in 10 of the 13 cases of primary and recurrent glioblastoma. Only case #9 had CD3+ cells in perivascular spaces that was scored >1 for both primary and recurrent tumours. In conclusion, whilst CD3+ infiltration was observed in the tumour proper and perivascular spaces within both primary and recurrent glioblastomas, the level of infiltration was quite low in this small cohort and as such requires further investigation in a larger cohort.
INNV-06. TREATMENT RESPONSE TO BEVACIZUMAB OVER TWO YEARS IN A PATIENT WITH GENETICALLY PROVEN SOMATIC NEUROFIBROMATOSIS TYPE 2 MOSAICISM
Authors: Basenach Elena , Förster Alisa , Raab Peter , Alzein Samer , Schmidt Gunnar , Krauss Joachim , Heidenreich Fedor , Hartmann Christian , Auber Bernd , Wiese Bettina , Weber Ruthild 
Published: November 2019

Abstract
Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by the development of schwannomas, especially bilateral vestibular schwannomas (VS), and meningiomas. Heterozygous pathogenic variants in the NF2 gene are known to cause NF2, whereby somatic mosaicism is present in ~25% of simplex patients. In schwannomatosis, a disorder phenotypically similar to NF2, heterozygous SMARCB1 or LZTR1 variants may be causative. Recently, bevacizumab has shown efficiency as therapy for VS in some NF2 patients. We report on a thirty-three-year-old patient with bilateral VS, fourteen additional schwannomas and one intracranial meningioma. Next generation sequencing using a cancer gene panel and Sanger sequencing of LZTR1 on blood and oral mucosa DNA revealed no pathogenic variants in NF2, SMARCB1 or LZTR1. Sanger sequencing on DNA from three schwannomas identified the known NF2 nonsense variant c.784C >T;p.(R262*) (NM_000268.3, GRCh37/hg19) in all tumors, leading to the diagnosis of somatic NF2 mosaicism. Because of hearing impairment and tumor progression the patient underwent an off-label therapy with 5mg/kg bevacizumab. To determine treatment response, we evaluated MRI scans from five pre-therapeutic and two therapeutic years as well as pure-tone audiometry. After 25 months of treatment, (i) the pure-tone average improved by 11.2 dB indicating a hearing benefit, (ii) four of seven non-vestibular schwannomas showed a volume reduction of ≥ 20%, (iii) the volume of three of seven schwannomas stabilized, and (iv) the growth rate of the meningioma decreased. In conclusion, in a patient with somatic NF2 mosaicism, an off-label therapy with bevacizumab was efficient with respect to hearing improvement and tumor shrinkage in over half of non-vestibular schwannomas over a period of two years.
INNV-13. A NOVEL TELEGRAM CHAT APPLICATION BASED BOT (FLORENCEBOT) FOR BRAIN TUMOUR AFFECTED PATIENTS
Authors: Puri Abhishek , Sandeman Kyle 
Published: November 2019

Abstract
The discoverability of reliable information online is difficult. As the network grows exponentially, unregulated content has the potential to cause harm. Telegram is a popular mainstream chat application. It allows automated software called bots that interact passively with an individual. Florence bot is unique in this space for the patient support; for those affected by brain tumours. It has been developed in PHP and hosted privately by the developer. Florence links to physician generated content (hosted externally on a blogging website) such as introduction, signs and symptoms of brain tumours and various treatment options along with their side effects. The content generates “web view” in Telegram itself, preserving written and multimedia formats. It ensures minimal overheads on the bot, making it responsive. It links to brain tumour channel (automated streamed information working as a public broadcast) and physician-administered support group. A physician designed bot is preferable to a third party mobile application to ensure the accurateness of information. No user-related information is available to bot developers as it does not have tracking and advertising elements; hence safeguards users privacy. It is more accessible and cheaper to deploy than a mobile application as it uses an instant messaging app as its container, which works across computing platforms. Florence bot is expected to bridge the gap for reliable information and real-time support independent of geographical limitations.
INNV-22. TO TREAT OR NOT TO TREAT – TREATMENT OUTCOMES OF VERY ELDERLY GLIOBLASTOMA PATIENTS
Authors: Baumgarten Peter , Prange Georg , Harter Patrick , Forster Marie-Therese , Wagner Marlies , Steinbach Joachim , Seifert Volker , Senft Christian 
Published: November 2019

Abstract

OBJECTIVE
The prognosis especially of older patients with glioblastoma is poor. Novel therapies are usually reserved for patients ≤65 years. As the population is growing older, the challenge remains as to how very elderly patients ≥75 years should be treated. Only limited outcome data exist for this patient subgroup.

METHODS
Between 2010 and 2018 we treated a total of 977 patients with glioblastoma at our institution. Of these, 144 patients were ≥75 years at diagnosis. The primary procedure was surgery or biopsy followed by adjuvant treatment, if possible. We retrospectively investigated progression-free and overall survival (OS) and looked at potential prognostic factors influencing survival, including Karnofsky performance score (KPS), surgical therapy, adjuvant therapy as well as MGMT promoter methylation status.

RESULTS
In our very elderly cohort, the median age was 79 years (range: 75–110). Biopsy only was performed in 108 patients, resection was performed in 36 patients. Median OS for the entire cohort was 5.9 months. Patients without adjuvant treatment fared worse than patients receiving either radiotherapy and/or chemotherapy (1.2 vs. 8.4 months, p< 0.001). Multivariate analysis showed that KPS at presentation (≥70 vs. ≤60), surgery vs. biopsy, and MGMT status (methylated vs. non-methylated) were significantly associated with OS (6.3 vs. 3.9 months, p=0.002; 12.6 vs. 4.9 months, p=0.003; and 10.5 vs. 5.0 months, p=0.009, respectively).

CONCLUSION
For patients with glioblastoma ≥75 years, the natural course of the disease is devastating, and there is a negative treatment bias in these patients. Very elderly patients, too, benefit from multimodal treatment including microsurgical tumor removal. Treatment options and outcomes should be thoughtfully discussed with patients before treatment decisions are made.
INNV-38. RATE OF EEG IN GLIOMA PATIENTS: SHOULD THIS BE PART OF STANDARD OF CARE FOR NEW BRAIN TUMOR PATIENTS?
Authors: Sherman Wendy 
Published: November 2019

Abstract
Current guidelines recommend antiepileptic drug (AED) therapy for glioma patients only in patients who have experienced a seizure. There is no current recommendation in regards to performing EEG monitoring in glioma patients. Thus, typically only clinical seizures have prompted AED therapy in glioma patients. Our purpose was to investigate the rate of EEG monitoring in glioma patients entered into our glioma registry, along with seizure and AED rates. Using our glioma registry to date, of 167 glioma patients, 119 patients had EEGs performed during their clinical course. Of those 119 patients, 104 glioma patients had either clinical or electrographic seizure activity and all 104 were on AEDs. This observation indicates that baseline eeg monitoring might be considered in all newly diagnosed glioma patients to reduce seizure incidence, potentially, starting AED prophylaxis if epileptiform activity is seen on EEG prior to clinical seizure activity to potentially reduce morbidity and healthcare costs related to clinical seizure activity. This warrants further prospective study.
INNV-40. TARGETED NEXT GENERATION SEQUENCING OF PEDIATRIC HIGH-GRADE GLIOMA AND ITS THERAPEUTIC IMPLICATIONS, MD ANDERSON EXPERIENCE
Authors: McCall David , Eterovic Agda , Moss Tyler , Baig Muhammed , Fuller Greg , Huse Jason , Sandberg David I , Rytting Michael , Gill Jonathan , Chandra Joya , Khatua Soumen , Shaw Kenna , Meric-Bernstam Funda , Zaky Wafik 
Published: November 2019

Abstract

INTRODUCTION
The new understanding of molecular pathways in cancer is paving the way towards personalized cancer medicine, especially in refractory disease. High-grade gliomas (HGG) are common pediatric brain tumors that tend to recur, with no available standard therapy upon recurrence. HGG are challenging tumors with illusive biology and poor outcome. We report here the molecular testing of 27 pediatric HGG patients.

MATERIALS AND METHODS
An analysis of pediatric patients with HGG treated at UT MD Anderson Cancer Center (MDACC) who underwent molecular genetic profiling using next generation sequencing with different genomic panels (AmpliSeq™Cancer Hotspot and Oncomine Panels – by Thermo Fisher Scientific).

RESULTS
27 patients with HGG (median age 14 years, range 3–18 years old) underwent genomic profiling. Primary diagnoses were glioblastoma multiforme (n=22), anaplastic astrocytoma (n = 2), gliosarcoma (n= 1), anaplastic pleomorphic xanthoastrocytoma (n= 1) and anaplastic oligoastrocytoma (n= 1). There are 46 genes common to the panels used. The most common mutation was in TP53 (73%). Other mutations included PIK3CA (19%), IDH1 (11.5%), 7.7% for ATM, EGFR and PTEN, and 3.8% for BRAF, FGFR1 and FGFR2. 24 out of 27 patients were tested at initial diagnosis and 3 upon relapse/progression. Patients at initial diagnosis received standard of care therapy of radiation and temozolomide. Only 5 patients received targeted therapy upon progression/recurrence. Some challenges of genomically-matched therapy included lack of clinical trials accepting pediatric patients, unavailability of a liquid form of a drug, and insurance disapproval for off-label use.

CONCLUSION
The next generation of therapy for childhood cancers will be based upon in-depth molecular phenotyping that may facilitate the development of rational risk-adapted and target-based therapies. This cohort, though limited by sample size, highlights the opportunity to perform molecular testing and identification of alterations in actionable genes.
MNGI-04. PATTERNS OF FAILURE AND FACTORS INFLUENCING LOCAL RECURRENCE OF MENINGIOMA TREATED WITH POSTOPERATIVE RADIATION THERAPY
Authors: Susko Matthew , Vasudevan Harish , Magill Stephen , Calixto-Hope Lucas , Villanueva-Meyer Javier , Nakamura Jean , Ann Oberheim-Bush Nancy , Theodosopoulos Philip , Solomon David , Braunstein Steve , Sneed Patricia , McDermott Michael , Raleigh David 
Published: November 2019

Abstract

BACKGROUND
Factors associated with meningioma recurrence after postoperative radiotherapy are poorly understood, and the optimal postoperative radiotherapy target delineation for meningioma is unknown. The objective of this study was to identify factors influencing meningioma recurrence after postoperative radiotherapy to inform patient selection and treatment design.

METHODS
Medical records were retrospectively reviewed for patients who underwent meningioma resection at a single institution between 1991 and 2015. Patients with sufficient tumor tissue for histologic classification and who received postoperative radiation therapy with external beam radiotherapy (EBRT), stereotactic radiosurgery (SRS) or brachytherapy, were included. Local freedom from recurrence (LFFR) was analyzed according to tumor and treatment characteristics using the Kaplan Meier method.

RESULTS
We identified 86 patients with 96 meningiomas who met inclusion criteria. Nineteen meningiomas (20%) were WHO grade I, 56 (58%) were grade II and 21 (22%) were grade III. Forty-one meningiomas (43%) were recurrent, and 55 (57%) were de novo. The postoperative radiotherapy modality was EBRT for 58 patients (60%), SRS for 20 (21%) patients and brachytherapy for 18 (19%) patients. With a median follow up of 4.3 years (IQR 2.1–8.8 years), there were 48 (50%) local failures that occurred a median of 17 months after immediate prior resection (IQR 9–33 months). WHO grade II/III and recurrent meningiomas had worse LFFR (p< 0.001). The 5-year LFFR was 53% after EBRT (95% CI 41–69%), 53% after SRS (95% CI 34–84%) and 15% after brachytherapy (95% CI 3–74%), although meningiomas that were treated with brachytherapy were significantly more likely to have received prior EBRT or SRS (86% versus 29%, p< 0.001).

CONCLUSIONS
These data provide a foundation for understanding patterns of meningioma recurrence after postoperative radiotherapy. Ongoing analyses aim to quantify the relationships between postoperative radiotherapy dose, target delineation and local control of meningioma.