bluuebunny/crossref_metadata_2025_split huggingface dataset:
OS07.5A Diagnostic Instrument for Mild Aphasia (DIMA): sensitive and valuable addition to standard language assessment in glioma patients
Authors: Mooijman S , Vincent A , De Witte E , Visch-Brink E , Satoer D 
Published: September 2021

Abstract

BACKGROUND
Low-grade glioma (LGG) patients typically suffer from mild aphasia that often cannot be detected with standard aphasia tests. The Diagnostic Instrument for Mild Aphasia (DIMA) is the first standardized test-battery to assess mild language disorders. We investigate pre- and postoperative linguistic abilities of LGG and high-grade glioma (HGG) patients with the DIMA.

METHODS
The DIMA consists of subtests that tap phonology (word, compound, non-word, sentence repetition), semantics (odd-picture-out), and syntax (sentence completion). Additionally, we administered the Boston Naming Test, Category- and Letter Fluency, and the Token Test. Patients were assessed before awake surgery (T1, N=98), three-months (T2, N=69), and one-year (T3, N=30) postoperatively. DIMA performance was compared to healthy controls (N=214). Group differences were examined with parametric (t-test) and nonparametric (Mann-Whitney-U, Wilcoxon) tests.

RESULTS
DIMA: Preoperatively, patients deviated on sentence repetition and sentence completion (p&lt;0.05). HGG patients performed worse than LGG on word, non-word, and sentence repetition (p&lt;0.05). There was no effect of hemispheric tumor localization. At T2, compound repetition and odd-picture-out also became impaired (p&lt;0.05) and there was a decline compared to T1 on all repetition tasks (p&lt;0.05). At T3, only sentence completion remained impaired (p&lt;0.01) with a deterioration compared to T1 (p&lt;0.01).
Standard tests: At T1, patients were impaired on BNT, Category- and Letter Fluency (p&lt;0.01). HGG patients performed worse than LGG patients on BNT and TT (p&lt;0.01). Patients with left-hemispheric tumors performed worse on BNT and Letter Fluency compared to right-hemispheric tumors (p&lt;0.05). At T2, TT also became impaired (p&lt;0.05) and patients declined compared to T1 on Verbal Fluency tests (p&lt;0.01). At T3, only BNT and Category Fluency remained impaired (p&lt;0.05), with no significant declines compared to T1.

CONCLUSION
The DIMA is the first test-battery to detect peri-operative impairments at different linguistic levels (phonology, semantics, syntax) in patients with left- or right-hemispheric gliomas. It even appeared more sensitive to detect surgical effects than standard tests: all phonological DIMA subtests captured short-term decline (T1-T2), in line with earlier evidence for the value of (non-)word repetition. DIMA sentence completion detected long-term decline (T1-T3), reflecting earlier spontaneous speech analyses. As expected, Verbal Fluency was also sensitive to short-term postoperative decline. Left-hemispheric tumor localization only affected standard test performance. HGG patients had more severe impairments than LGG on DIMA repetition and standard tests (BNT and TT). We advise adding the DIMA to standard language evaluation of glioma patients, as it allows for more detailed counseling about language outcome.
OS09.3.A Caregiver burden of glioma patients: the impact of informal care
Authors: van den Borg R , Weerdesteijn-Prinsen A , Nijboer C M , Postma T J , Kouwenhoven M C M , Schuur M 
Published: September 2021

Abstract

BACKGROUND
Each year 1.300 new patients are diagnosed with a glioma in the Netherlands. Patients experience a substantial physical and cognitive decline during the course of the disease. The impact of neurological deterioration on social and family life is substantial. Caregivers give high demanding care to their partners for long periods of time, while they combine this care with many other tasks, as: care for children, administrative household tasks and securing the families financial situation through work. As a consequence caregivers experience a high burden.In this study, we evaluated the degree of caregiver burden, its impact on daily life and the preferred support needed. With better insight in caregivers needs, support for the caregivers can be optimized.

MATERIAL AND METHODS
The study was conducted at the Brain Tumor Center Amsterdam, the Netherlands, between March and June 2019. We prospectively collected information using two Dutch questionnaires: the “Experienced Burden of Care” (EDIZ) and the “Features of Caregiver Care” questionnaire. The questionnaires were handed out to 93 caregivers of glioma patients at the outpatient clinic. The data were analysed using descriptive statistics.

RESULTS
In the studied population, 36,6% of caregivers experienced a high burden (score 7–9 on EDIZ questionnaire). The features of caregiver care questionnaire showed that 11,2% was overloaded (score &gt;31), and 57,3% nearly overloaded (score 22–30). Caregivers indicated that the continuous care for the patient and lack of time for their own needs were a major cause for the high burden they experienced. One third of the caregivers reported a substantial change in physical, mental and behavioural functioning of the patient during the study. Caregivers experienced a lack of support and information; they felt a need for more psychological support (34,9%) and advice how to deal with the cognitive and behavioural decline of the patient (33,3%). The need for information of caregivers varied, ranging from information on the course of the disease (28,6%) to information on the social support act (23,8%). The question when to receive additional information was answered by most caregivers to a ‘self-chosen point in time’ instead of set time points by the medical team.

CONCLUSION
The burden of caregivers of glioma patients is high; nearly 70% of caregivers are even (nearly) overloaded. Caregivers need information and support on different aspects of the disease. As these aspects vary between different caregivers and possibly during the disease course, support to caregivers should be structurally assessed. A better understanding of the caregivers needs in combination with active support could prevent dropout of caregivers and improve the quality of life of both caregivers and patients.
OS10.3.A Predicting delirium after craniotomy in neuro-oncology
Authors: Kappen P R , Kappen H J , Dirven C , Klimek M , Osse R , Vincent A 
Published: September 2021

Abstract

BACKGROUND
Post-operative delirium (POD) is a frequent and severe complication after neurosurgical operations. Good prediction of POD after craniotomy in neuro-oncologic patients is important to install prophylactic measures, increase recognition and apply early treatment. Hence, we compared logistic regression with machine learning to build an accurate predictive model in a large dataset.

MATERIAL AND METHODS
POD was defined in case of a Delirium Observation Scale (DOS) ≥ 3 or start of antipsychotic treatment for delirium within 10 days after surgery. Adult patients undergoing a craniotomy for a neuro-oncologic disease in the Erasmus Medical Centre in Rotterdam were retrospectively included. The cohort was split into a training (75%), after three-fold cross validation, and test set (25%). Logistic regression and Lasso Elastic-Net Regularized Generalized Linear Models (GLMNet) were trained based on 19 pre- and intra-operative features and risk factors were identified based on the superior model.

RESULTS
We included 1025 neuro-oncologic craniotomies between June 2017 and September 2020. Overall incidence of POD was 18.6% (95%CI 17.4–19.8). Compared to logistic regression, Lasso GLMNet performed superior (AUC 0.73 vs. 0.76) based on the optimal tuning parameters (α=1, λ=0.014). Several non-modifiable risk factors such as age (OR1.01), prior delirium (OR1.04), memory problems (OR1.12), surgery duration (OR1.01) and modifiable risk factors, such as low potassium (OR0.97) levels and opioid administration (OR1.03), were identified.

CONCLUSION
POD is a frequent complication after craniotomy in neuro-oncologic patients. Lasso GLMNet was useful in predicting POD in this cohort. Validation in a prospective cohort of this model should be applied to further evaluate its value in diminishing POD.
OS12.4.A MHC class II-restricted transgenic T cell receptor therapy targeting mutant capicua transcriptional repressor in experimental gliomas
Authors: Kilian M , Friedrich M , Sanghvi K , Green E , Pusch S , von Deimling A , Wick W , Sahm F , Platten M , Bunse L 
Published: September 2021

Abstract

BACKGROUND
Glioma subtypes are classified according to their characteristic mutations and show a high degree of resistance to standard therapeutic interventions such as radiotherapy and alkylating chemotherapy. Some of these characteristic mutations have shown to generate immunogenic neoepitopes that can be targeted with immunotherapy. 70% of oligodendrogliomas carry capicua transcriptional repressor (CIC) inactivating mutations.

RESULTS
In a screen for potential immunogenic glioma neoepitopes we identified recurrent CIC hotspot mutations at position 215 (CICR215W/Q) expressed in a subset of oligodendrogliomas as an immunogenic major histocompatibility complex (MHC) class II-restricted neoepitopes. Peptide-based vaccination of MHC-humanized mice resulted in the generation of robust mutation-specific T cell responses against CICR215W/Q, restricted to MHC class II. Droplet-based single cell T cell receptor (TCR) sequencing from CICR215W-specific T cell lines enabled retrieval of MHC class II-restricted CICR215W-reactive TCRs. By retroviral transduction of T cells, we established a flow cytometry-based testing platform of retrieved TCRs and were able to show the top reactive TCR against CICR215W to be shared between individual mice. Using a newly developed glioma model in MHC-humanized mice induced by CRISPR-based delivery of tumor suppressor targeting guide RNAs, we show that adoptive intraventricular transfer of CICR215W-specific TCR-transgenic T cells exert anti-tumor responses against CICR215W-expressing syngeneic gliomas.

CONCLUSION
The integration of immunocompetent MHC-humanized orthotopic glioma models in the discovery of shared immunogenic glioma neoepitopes facilitates the identification and preclinical testing of HLA-restricted neoepitope-specific TCRs for locoregional TCR-transgenic T cell adoptive therapy.
P03.05 The use of subcortical intraoperative electrical stimulation mapping for assessment of executive functions: A summary of the evidence so far
Authors: Landers M J F , Sitskoorn M M , Rutten G J M , Mandonnet E , De Baene W 
Published: September 2021

Abstract

BACKGROUND
Over the past years, the functional subcortical architecture of the brain has been increasingly acknowledged in neurosurgical planning. A method to study anatomo-functional correlations is direct electrical stimulation (DES). DES is widely used by neurosurgeons and considered as a reliable tool to minimize the occurrence of permanent postoperative motor, language and visual deficits. In recent years, DES has also been used for mapping of other cognitive functions, such as executive functions.

MATERIAL AND METHODS
We systematically summarized the evidence so far from DES studies on subcortical pathways that are involved in the following three executive functions: (1) inhibitory control, (2) working memory and (3) cognitive flexibility.

RESULTS
We only found twelve articles that reported on intraoperative electrical stimulation of white matter pathways to map executive functions and explicitly clarified which subcortical tract was stimulated. The results indicate that the second branch of the right superior longitudinal fasciculus (SLF-II) is involved in inhibitory control, the first branch of the right superior longitudinal fasciculus (SLF-I) and the third branch of the left superior longitudinal fasciculus (SLF-III) are involved in working memory and the cingulum is involved in cognitive flexibility.

CONCLUSION
We were unable to draw any specific conclusions, nor unequivocally established the pathways involved in executive functions due to heterogenous study characteristics, methods and tasks, and the limited number of studies that assessed these relationships. Clearly, neurosurgical groups are exploring novel methods to assess cognition during awake neurosurgery, but are far from consensus on indications and protocols, which complicated the comparison and summarization of findings. We will discuss possible approaches for future research to obtain converging and more definite evidence for the involvement of subcortical pathways in specific executive functions.
P04.23 Multinodular and vacuolating neuronal tumor - advanced MRI features
Authors: Ivan R , Mitrică M , Sîrbu O M , Sîrbu C A 
Published: September 2021

Abstract

BACKGROUND
A rare pathology, multinodular and vacuolating neuronal tumors (MVNT) have been first described in 2013 and included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System as having a distinctive radiological and cytoarchitectural appearance.
This study aims to evaluate the imaging features of MVNT, it’s differential diagnosis, and possible involvement in adult-onset epilepsy.

MATERIAL AND METHODS
We present the case of a 29-year-old male, smoker, and drug abuser, who developed a seizure after 25 hours’ sleep deprivation, alcohol, energy drinks, cigarettes, and cocaine consumption. Cerebral CT, MRI, electroencephalogram, MR spectroscopy, and tractography was performed.

RESULTS
The MRI performed revealed a right, cortico-subcortical pseudo-nodular temporal lesion, non-enhancing, with a slight thickening of the adjacent cortex and right hippocampal involvement. The neurological examination was normal, but the electroencephalogram showed a right temporal irritative pattern. MR- Spectroscopy described a slight increase of choline (Cho), reduction of N-acetylaspartate (NAA), and also increased myo-inositol peak, ruling out a high-grade tumoral substrate. A tractography was also performed, excluding the other alternative diagnosis of focal cortical dysplasia, thus leaving MVNT to be the most probable explanation for the lesion.

CONCLUSION
Advanced MRI features were useful to increase the diagnosis accuracy. The future management consisted of image surveillance, anticonvulsant treatment, and lifestyle improvement. Adult-onset seizures are among the most frequent discovery possibilities for MVNT. In our case, it is to be seen whether the lifestyle changes and medication will prevent future seizures.
P06.02 Efficacy of Arc based Radiation in children & young adults with Medulloblastoma
Authors: Mathew S M , U A S , V C V , Lokesh V 
Published: September 2021

Abstract

BACKGROUND
To compare doses to Organs At Risk and assess low dose radiation bath by Cranio Spinal Irradiation in children and young adults with Medulloblastoma between different Techniques.

MATERIAL AND METHODS
30 Patients [Median Age: 8(5–23), M: F= 2:1] with Medulloblastoma, planned for Craniospinal Irradiation by Arc based Radiotherapy (VMAT- Elekta) also had an alternative Radiotherapy Plan (IMRT/ 3DCRT) to compare radiation doses to critical OARs (Cochlea, Thyroid, Heart) and low dose radiation bath to Vertebral Body and Supratentorial normal brain). Mean doses of Organs in parallel, Maximum doses of organs in series and Integral Dose was compared. Pre radiation Vertebral Body CT Density (HU) and the absorbed dose to it at various levels was estimated for each patient on the TPS. With the PTV coverage being 95% to the volume, dosimetrically superior plan was chosen for therapy.

RESULTS
The cohort had a risk stratum in the ratio 4:1 (Standard: High). IHC based molecular subtyping showed WNT, SHH and Non WNT/ Non SHH sub type (3:1:2). For ease of Analysis, the sample was divided among age groups into &lt;8 years, 8–12 years and &gt;12 years. Among the various Age groups, children &lt; 8 years received the lowest dose of 21 Gy to Thyroid via Arc Therapy [(27Gy±4Gy) vs (31Gy± 3Gy)]. Children at 8–12 years received the lowest mean dose of 35 Gy with Arc plan to B/L Cochlea. [(36Gy± 4Gy) vs 41Gy± 4 Gy)]. Significant reduction of Mean dose to the heart was noted in &gt;12 years with Arc [(8 Gy± 1Gy) vs(10 Gy± 2 Gy)]. The Mean CT density by HU of Vertebral Body (Thoraco-Lumbar) estimated were 145 HU, 195 HU and 315 HU in three age groups. Mean Doses to the Vertebrae was significantly lower with VMAT in kids &lt; 8 years. ([3211 cGy ± 80 cGy] vs [3397 cGy ± 70cGy]). Supratentorial brain (basi frontal) received an additional [373.9 cGy ± 0.2Gy] vs[425 cGy ±0.3 Gy]) during PF Boost.

CONCLUSION
Arc Therapy in Medulloblastoma reduces in field normal tissue radiation dose (Thyroid, Cochlea and heart) at respective ages of &lt;8 years, 8–12 years and &gt; 12 years as well as the low dose radiation bath to structures (Vertebral body and Supratentorial brain) beyond the target volume which may reduce long term complications in children and young adults.
P11.06 Health-related quality of life and emotional wellbeing connected to glioblastoma; a longitudinal follow-up of patients and relatives
Authors: Ståhl P , Henoch I , Smits A , Rydenhag B , Ozanne A 
Published: September 2021

Abstract

BACKGROUND
Glioblastoma is the most common malignant brain tumor in adults and also the most aggressive one. At present, there is only palliative treatment available. The aim of this study is to investigate the HRQoL and emotional well-being of patients with glioblastoma by surveying them and their relatives from a time point before surgery until 2 years later.

MATERIAL AND METHODS
Patients and their relatives answered the validated questionnaires SF-36 and HADS at several time points: preoperatively, at 3 weeks postoperatively, at 12 weeks postoperatively, at 6 months postoperatively, at 1 year postoperatively, at 1.5 years postoperatively, and at 2 years postoperatively. At baseline, the paired patients and their relatives came to consist of 63 patients and 63 relatives. Descriptive statistics and the Wilcoxon signed-rank test were used.

RESULTS
Relatives scored more symptoms of anxiety than patients on all occasions except at 1.5 years postoperatively, with the largest significance preoperatively with p&lt;0.001 and at 3 weeks postoperatively with p&lt;0.001. 50% or more of the relatives reported the presence of symptoms of anxiety on all measured occasions. Furthermore, relatives scored worse for the SF-36 mental component summary (MCS) on all occasions except at 1.5 years postoperatively. Patients scored the SF-36 physical component summary (PCS) worse than the relatives on all measured occasions e.g., preoperatively p&lt;0.001, at 3 weeks postoperatively p&lt;0.001, at 12 weeks postoperatively p&lt;0.001 and at 6 months postoperatively p&lt;0.001. A comparison was also made between patients’ PCS and MCS with an age and gender matched population, patients scored MCS significantly worse than the general population preoperatively p&lt;0.001 with effect size r=0.5, at 3 weeks postoperatively p&lt;0.001with effect size r=0.5 and at 1.5 years postoperatively p=0.013 with effect size r=0.6.

CONCLUSION
The comparison between the HRQoL and emotional well-being of patients with glioblastoma and their relatives from presurgery to one and a half years postsurgery shows that patients on most occasions scored worse physical HRQoL and that relatives mostly scored worse mental HRQoL and emotional well-being. When comparing the patients in the present study with an age and gender matched reference population, it was found that the patients with glioblastoma scored worse HRQoL than the reference population.
P13.17 CD95 gene silencing affects growth and invasiveness of glioma-initiating cells in a CD95L-independent manner
Authors: Quijano-Rubio C , Weller M 
Published: September 2021

Abstract

BACKGROUND
CD95 (Fas/APO-1) holds a dual role of potential relevance in tumor development. CD95-CD95 ligand (CD95L) signaling regulates apoptotic cell death in CD95-expressing cells, but non-apoptotic, tumor-promoting CD95-CD95L signaling has been likewise described. Therapeutic stimulation of apoptotic CD95 signaling is associated with major clinical side effects. However, inhibition of tumor-promoting CD95 signaling may represent a promising treatment strategy for human cancers where potential tumor-promoting CD95 functions include invasiveness and cancer cell stemness, including glioblastoma.

MATERIAL AND METHODS
In this study, CD95 and CD95L expression was characterized in human glioma-initiating cells (GIC) in vitro and in vivo. CD95 and CD95L gene knockout (KO) GIC were generated by means of CRISPR-Cas9 and the effects of gene silencing were evaluated by assessing growth, clonogenicity, invasiveness and tumorigenicity in nude mice.

RESULTS
CD95 expression and sensitivity to exogenous CD95L-induced apoptosis were confirmed in selected GIC in vitro. CD95L expression was not detected. Upon CD95 KO, all GIC acquired resistance to CD95L-induced apoptosis. Furthermore, despite the confirmed absence of CD95L expression in vitro, CD95 KO S-24 GIC revealed decreased cell growth, inferior sphere forming capacity and decreased invasiveness. These data suggested a CD95L-independent tumor-promoting role of CD95 in S-24 GIC. In vivo, however, CD95 KO did not prolong the survival of glioma-bearing mice. Analyses of further GIC models are ongoing.

CONCLUSION
These data demonstrate that, unlike CD95, CD95L is not expressed in cultured human GIC and that CD95-CD95L interactions are not required for tumor-promoting CD95 signaling. Although CD95 KO is detrimental for S-24 GIC in vitro, CD95 KO alone does not affect survival in S-24 human GIC xenograft-bearing mice.