bluuebunny/crossref_metadata_2025_split huggingface dataset:
P03.06.B Proton irradiation (PT) for benign meningiomas, Grade I clinical experience of the first 100 patients from REGI-MA-002015
Authors: Lütgendorf-Caucig C , Hug E , Pelak M , Flechl B , Mock U , Fossati P , Mumot M , Carlino A , Georg P , Georg P 
Published: September 2022

Abstract

Background
Meningiomas are the most common CNS tumors and the majority is regarded as benign. However, a subset of patients presents with complex tumors involving several anatomic compartments of the skull base - eluding any concepts of gross total resection. Proton therapy (PT) is applied as definitive treatment for primary or recurrent disease or postoperatively following subtotal resection. We report on the first 100 adult patients treated with PT at MedAustron.

Material and Methods
All patients were enrolled in a prospective registry trial (ClinicalTrials.gov Identifier: NCT03049072). Target volume definition was based on CT, MR and DOTA-PET/CT. PT treatment plans were generated by applying a Simultaneous Integrated Boost (SIB) concept with the Single Field-optimisation method and utilizing 2-4 beams per plan with a beam spacing of &gt;30°. Prescribed doses to PTV1 were 50.49Gy_RBE at 1.87Gy_RBE/fr and 54.0Gy_RBE at 2.0Gy_RBE/fr to PTV2 in overall 27 fractions. Follow up status was assessed by MRI at 6, 12 months and annually thereafter, side effects were assessed using CTCAE v4.0. and quality of life (QoL) using EORTC-CTC30 and BN20 questionnaires. The scores entered by the patients were added and normalized to 0-100 scale according to previously described protocols.

Results
Between 08/2017 and 04/2021, 100 patients were treated, 22% (n=22) male and 78% (n=78) female patients. Median age at therapy was 54a (25a-82a). In 57% (n=57) PT was the definitive treatment (no resection or surgery &gt;12 mo prior to PT). 43% (n=43) underwent postoperative PT with at least one surgery (range 1-3), and median time from last resection to start of PT of 6mo (3mo-11mo). 89% (n=89) meningiomas were located in the skull base with involvement of multiple anatomic compartments. The median GTV size was 24cc (1cc-226cc) and the median CTV 41cc (2cc-352cc), respectively. At median follow-up of 31.1 months (range 6.6-51.6), 2 local in-field failures were observed (both patients treated postoperatively) resulting in disease-specific survival of 100% and local control of 98% at 3 years, respectively. No &gt; Grade 2 acute toxicity was observed. During follow-up two Grade 3 toxicities occurred: One patient developed symptomatic radiation induced brain lesion (RIBL) which resolved within 12 month; one patient was hospitalized for new onset of epilepsy without corresponding radiographic findings. 9% (n=9) developed G1/G2 RIBL, which resolved spontaneously. The general QoL including the global health status and all functioning domains remained stable and did not decrease significantly following PT.

Conclusion
First clinical data demonstrate that PT based on a SIB concept is a safe and efficient treatment of anatomically complex, low grade meningiomas. Acute and late toxicity incidences in our series were low with excellent, prospectively assessed preservation of QoL.
P04.03.B Rapid DNA methylation-based classification of pediatric brain tumors from ultrasonic aspirate specimens
Authors: Simon M , Kuschel L P , von Hoff K , Hernáiz Driever P , Hain E G , Koch A , Capper D , Schulz M , Thomale U , Euskirchen P 
Published: September 2022

Abstract

Background
Cavitating ultrasonic aspirator (CUSA) devices are commonly used in neurosurgical procedures to carefully debulk tumor from adjacent healthy brain tissue. Here, we explore the feasibility of using ultrasonic minced tumor tissue to classify otherwise discarded sample material by DNA methylation according to the respective World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) using low pass nanopore whole genome sequencing.

Material and Methods
21 ultrasonic aspirated specimens from patients undergoing surgery in the department of pediatric neurosurgery at the Charité-Universitätsmedizin Berlin with either newly diagnosed cerebral lesions or pre-treated lesions were processed by nanopore sequencing to generate copy number profiles and ad-hoc random forest classification. Results were compared to microarray-based routine profiling. Tumor purity was assessed.

Results
In 19/21 (90.5 %) samples the minimum amount of 1,000 CpG sites were sequenced. In 20/21 (95.2 %) cases copy number variation profiles could be generated and matched microarray derived copy number profiles, allowing for identification of diagnostically or therapeutically relevant pathognomonic alterations. 12/17 (70.6 %) samples were concordantly classified to the corresponding microarray-based diagnosis by routine neuropathological workup. Applying recently defined thresholds for nanopore-based classification resulted in sensitivity of 64.7 % and specificity of 100 %.

Conclusion
CUSA referred sample material of pediatric brain tumors allows for methylation-based classification according to the respective WHO classification of CNS tumors with acceptable sensitivity and high specificity. Hereby, a promising opportunity for accurate classification of pediatric brain tumors by a time- and cost-efficient advanced molecular technique is offered using otherwise discarded tumor tissue.
P05.01.B Distribution of the staining agent sodium-fluorescein in cerebral neoplasia - a comparison between intraoperative confocal laser endomicroscopy and in vitro fluorescence microscopy
Authors: Brielmaier M C , Reifenrath J , Pensel N , Ganster F , Bierlein J , Wagner A , Gempt J , Schlegel J 
Published: September 2022

Abstract

Background
While conventional frozen sections and other ex vivo microscopy always come along with artefacts, in vivo confocal laser endomicroscopy (CLE) offers less invasive, less manipulated imaging of living tissues. Understanding the distribution of the staining agent sodium-fluorescein (NaFl) plays a key role in establishing in vivo CLE as a new opportunity for real-time transmitted, in vivo imaging.
By comparing the distribution of NaFl in in vivo and ex vivo CLE to conventional fluorescence microscopy of NaFl incubated tumor cell cultures we gain a better understanding of the staining mechanism.

Material and Methods
Sodium-fluorescein is the water-soluble sodium salt of fluorescein and is used as a fluorescent tracer in neurosurgery. The staining agent was applied intravenously at the beginning of the surgical procedure. In vivo CLE of the lesion was performed 30 to 50 minutes later and compared to ex vivo CLE imaging and conventional fluorescence microscopy. In addition, different tumor cell lines derived from malignant gliomas and carcinomas, respectively, were incubated with NaFl in vitro and the uptake of the fluorescent dye was monitored over time.

Results
From initial results, the intraoperative images showed specific fluorescein distribution depending on the architecture of the tumor entity. In most cases, glial tumors demonstrated higher accumulation of the staining agent in the extracellular tumor matrix, whereas the cells of carcinoma metastases appeared to take up NaFl intracellularly. These results were corroborated by NaFl uptake in cell culture experiments.
Compared to ex vivo CLE, in vivo imaging offered a faster assessment of the tissue, brighter images and higher staining levels. Due to movement artefacts and the narrow intraoperative imaging time frame, in vivo CLE images were sometimes impaired by lower image quality.

Conclusion
The specific distribution of the fluorescent agent NaFl allowed for a discrimination between the different neoplastic entities. Images from in vivo and ex vivo confocal laser endomicroscopy showed NaFl uptake in concordance with the results of NaFl incubated cell cultures.
Intraoperative, in vivo confocal laser endomicroscopy shows promising first results in the understanding of brain tumor histomorphology in situ. Being faster and less manipulated by artefacts than ex vivo investigations, it opens up wider opportunities for research and intraoperative diagnostics.
P06.06.B standardization of therapy and manufacturing using tumor-associated antigen-stimulated autologous dendritic cells co-cultured with cytokine-induced killer cells in cancer immunotherapy
Authors: Yen C M , Fu Y Y , Yang M Y 
Published: September 2022

Abstract

Background
The application of DC-CIK in the field of cancer immunotherapy has been shown to be an effective treatment. However, the cost of DC-CIK treatment is prohibitive for many patients, and the lack of standard manufacturing processes and treatment strategies are the main limitations.

Material and Methods
Our experiments used tumor lysate instead of tumor cell line as tumor-associated antigen source with DCs co-culture. We provide the most efficient method for obtaining autologous DC-CIK cells from peripheral blood. Flow cytometry was used to evaluate DCs activation, CBA assay was used to quantify cytokines secreted by CIK cells, and the antitumor activity of DC-CIK was evaluated in vitro by K562 cell line.

Results
We demonstrate that the manufacturing process of employing frozen Peripheral Blood Mononuclear Cells (PBMCs) can balance patient’s comfort and economic benefits. DC-CIK can effectively upgrade the immunological specificity of CIK cells to tumors in the presence of tumor-associated antigen. In vitro experiments showed that when the number of DC: CIK cells was co-cultured in 1:20 ratio on the 14th day, the amount of cytokine secreted by CIK cells was the largest, and the anti-tumor immune effect was the most potent. When the number of CIK: K562 cells was in 25:1 ratio, the cytotoxic activity of CIK on K562 cells was the highest.

Conclusion
We developed an efficient activated fashion of DC:CIK, established the optimal ratio of DC-CIK immunologic activity and the best cytotoxic model of CIK to K562 cells.
P07.01.A Topical Fluorescent Probe for Visualization of Glioblastoma
Authors: Kim D 
Published: September 2022

Abstract

Background
Glioblastoma (GBM) is the most aggressive form of cancer that originates within the central nervous system (CNS). GBM represents 15% of all primary brain tumors, but the cause is unclear, and there is no clear way to prevent it. At the moment, various sophisticated and specific surgical procedures are being used, but there are relatively few simple methods.

Material and Methods
In this work, we used a turn-on type fluorescent probe that can sense cysteine (Cys) amino acid in the GBM site, and developed topical treatment methods for image-guided surgery (IGS).

Results
The probe can distinguish the GBM cells and disease sites in clinical samples from individual patients. Besides, the probe has no short or long-term toxicity and immune response.

Conclusion
The present findings hold promise for the application of the probe to a relatively simple and straightforward following of GBM at clinical sites.
P07.02.B Neuro-oncological augmented reality planning (NOA-p)
Authors: Van Gestel F , Frantz T , Neuville Q , Klein S , Bruneau M , Jansen B , Scheerlinck T , Vandemeulebroucke J , Duerinck J 
Published: September 2022

Abstract

Background
When preparing for the resection of an intracranial lesion, neuronavigation with a tracked pointer is most often used to determine lesion borders and the optimal approach. This can sometimes prove challenging, especially for deep-seated lesions. Augmented Reality (AR), directly displaying the lesion on the patient’s skin, can simplify and improve this step.

Material and Methods
We developed a system for inside-out infrared tracking that does not require an external tracking camera or external computer and allows for heads-up displaying an AR scene on the Microsoft HoloLens II. Twenty patients planned for the resection of an intracerebral lesion were included in our study. After patient registration, the lesion outlines were marked on the patient’s skin by different participants, consecutively using the Brainlab neuronavigation system and the HoloLens. Each registration on both systems provided a registration transform that was compared for accuracy and consistency. The performance of the participants was measured in terms of duration and accuracy and compared to expert registration and delineation.

Results
Both registration and delineation were significantly faster with AR (p=0.02 and p&lt;0.001, respectively, and p&lt;0.001 for the total duration), taking 79.23±17.48 and 39.58±39.10 seconds while neuronavigation required 96.61±24.54 and 90.80±44.09 seconds. AR had a registration offset of 3.3mm and 3.4°, and was more consistent compared to neuronavigation. AR facilitated more accurate and detailed lesion delineation, while neuronavigation often overestimated lesion size.

Conclusion
Augmented reality provides a faster and more accurate alternative for resection planning. Lesion delineation is more intuitive while remaining high in accuracy. Future research should focus on further intraoperative implementations.
P07.04.B Heme biosynthesis factors and 5-ALA induced fluorescence: analysis of mRNA and protein expression in fluorescing and non-fluorescing gliomas
Authors: Mischkulnig M , Roetzer-Pejrimovsky T , Lötsch-Gojo D , Kastner N , Bruckner K , Prihoda R , Lang A , Martinez-Moreno M , Furtner J , Berghoff A , Woehrer A , Berger W , Widhalm G , Kiesel B 
Published: September 2022

Abstract

Background
The intraoperative visualization of adult-type diffuse gliomas with 5-aminolevulinic acid (5-ALA) induced fluorescence is widely used in the neurosurgical field. While visible 5-ALA induced fluorescence is found in the majority of high-grade gliomas, most low-grade gliomas lack visible fluorescence during surgery. Recently, the heme biosynthesis pathway was identified as crucial influencing factor for presence of visible fluorescence since it metabolizes 5-ALA to fluorescing Protoporphyrin IX (PpIX). However, the exact alterations within the heme biosynthesis pathway resulting in visible 5-ALA induced fluorescence in gliomas are still unclear. The aim of the present study was thus to compare the mRNA and protein expression of promising intramitochondrial heme biosynthesis enzymes/transporters in glioma tissue samples of different fluorescence behavior.

Material and Methods
A total of 19 strongly fluorescing and 21 non-fluorescing tissue samples from neurosurgical adult-type diffuse gliomas (WHO grades II-IV) were included in the current analysis. In these samples, we investigated the mRNA expression by quantitative real time PCR and protein expression using immunohistochemistry of the intramitochondrial heme biosynthesis enzymes Coproporphyrinogen Oxidase (CPOX), Protoporphyrinogen Oxidase (PPOX), Ferrochelatase (FECH) and the transporter ATP-binding Cassette Subfamily B Member 2 (ABCG2).

Results
Regarding mRNA expression analysis, we found a significantly decreased ABCG2 expression in fluorescing specimens compared to non-fluorescing samples (p=0.001), whereas no difference in CPOX, PPOX and FECH was present. With respect to protein expression, significantly higher levels of CPOX (p=0.005), PPOX (p&lt;0.01) and FECH (p=0.003) were detected in fluorescing samples. Similar to mRNA expression analysis, the protein expression of ABCG2 (p=0.001) was significantly lower in fluorescing samples.

Conclusion
Distinct alterations of the analyzed heme biosynthesis factors were found primarily on protein level. Our data indicate that heme biosynthesis pathway activity in general is enhanced in fluorescing gliomas with upregulation of PpIX generating enzymes and decreased ABCG2 mediated PpIX efflux outweighing the also increased further metabolization of PpIX to heme. Intramitochondrial heme biosynthesis factors thus constitute promising pharmacological targets to optimize intraoperative 5-ALA fluorescence visualization of usually non-fluorescing tumors such as low-grade gliomas.
P08.03.A Conversation tool for brain tumor patients - tailor-made support and guidance for the patient and their proxies
Authors: Dujardin K , de Peuter R , Dirven L , Gijtenbeek A , Manten-Horst E , Baas-Thijssen M 
Published: September 2022

Abstract

Background
An evaluation by the Dutch Neuro-Oncology Society (LWNO) showed that screening for psychosocial problems and the need for psychosocial care in glioma patients and their proxies is currently not optimal. Although tools to screen for psychosocial issues such as the Distress Thermometer exist, in daily practice they appear to be insufficient to discuss all disease-specific problems patients with brain tumors may encounter. We describe the development of a conversation tool to support the consultation between the patient with a brain tumor, their proxies and the health care professionals (HCPs).

Material and Methods
The development of the conversation tool for brain tumors was based on the tool used by the AYA Care Network in the Netherlands. Topics of importance for the entire care process were identified in a brainstorming session with 15 people (comprising HCPs, patients and proxies). Subsequently, the content of the conversation tool was determined by members of the LWNO and members of the LWNO-working group of nurses specialized in neuro-oncology (LWNO-v). Each topic in the conversation tool is supported by a visual, which was developed by a graphic design company in close collaboration with patients, proxies and HCPs.

Results
The conversation tool contains a total of 35 different topics covering six domains: physical health, daily life activities, psychological health, social relationships, loss of health and life, practical issues, all illustrated by a visual. The conversation tool can be given to the patient in booklet form before an appointment with the HCP, so they can prepare the conversation upfront. In addition, cards per domain will be available in the consultation room to be used during the appointment.
Conclusion:
By using the conversation tool, optimal individual guidance and support of patients with brain tumors is facilitated, as this patient population has unique issues that are often not covered by exiting tools. Using the conversation tool also promotes a nationally uniform way of working. Currently, an interactive tool for HCPs is being developed in which an overview of available interventions and best practices for the topics in the conversation tool are described, to ensure the needs of patients can be adequately addressed. The process of development of this tool can serve as an example for other cancer types.
P08.13.A CaPaBLE - Assessing the Patient Generated Index Methodology in High Grade Glioma Patients and Caregivers
Authors: Pakzad-Shahabi L , Tallant J , Le Calvez K , Wells M , Williams M 
Published: September 2022

Abstract

Background
CaPaBLE tests the feasibility and acceptability of assessing quality of life (QoL) using the patient-, or caregiver-generated index (PGI/CaGI) methodology in patients with HGG and their caregivers.

Material and Methods
CaPaBLE, (https://www.isrctn.com/ISRCTN45555598), followed patients and/ or their caregivers up to 6 months. Standard measures for patients were EORTC QLQ-C30/BN20, for caregivers the CarGOQOL questionnaire. The QoL topics raised through PGI/CaGI have been coded to the most relevant domain from their respective standard measure for an initial assessment of concordance.

Results
36 patients, 24 caregivers recruited to study; completing an average of 3 study assessment timepoints. PGI and CaGI generated 240 and 160 topics respectively. Patient concerns most frequently coded to EORTC domain of Role Functioning; Caregiver concerns mostly coded to CarGOQOL domain of Burden. Other topics frequently raised by patients such as the driving and sex life, and future planning by caregivers are not specifically raised in standard questionnaires.

Conclusion
Nearly all topics raised by patients and caregivers were mapped to the domains of their respective standard QoL measure. However, almost half of all topics raised by patients and caregivers mapped to a minority of the domains included in standard measures; whilst a notable number of topics are not specifically included in standard measures at all. This raises questions regarding the efficiency and relevance of such questionnaires to patient and caregivers’ daily lives.
P10.12.A CDK12/CDK13 inhibition disrupts a transcriptional program critical for glioblastoma survival
Authors: Lier S , Rein I , Lund S , Lång A , Lång E , Meyer N , Dutta A , Anand S , Nesse G , Johansen R , Klungland A , Rinholm J , Bøe S , Anand A , Pollard S , Lerdrup M , Pandey D 
Published: September 2022

Abstract

Background
Glioblastoma multiforme (GBM) is the most prevalent and aggressive malignant tumor of the central nervous system. With a median survival of only one year, GBM patients have a particularly poor prognosis, highlighting a clear need for novel therapeutic strategies to target this disease. Transcriptional cyclin-dependent kinases (CDK), which phosphorylate key residues of RNA polymerase II (RNAPII) C-terminal domain (CTD), play a major role in sustaining aberrant transcriptional programs that are key to development and maintenance of cancer cells.

Material and Methods
We used pharmacological inhibition and genetic ablation to study effects of CDK12/CDK13 depletion on the proliferatory and migratory capacity of GBM cells and mouse xenografts. SLAM-seq, CUT&RUN and cell cycle assays were used to study the mechanistic effects of CDK12/CDK13 depletion in GBM cells.

Results
CDK12/CDK13 depletion markedly reduced the proliferatory and migratory capacity of GBM cells, as well as in vivo growth. CDK12/CDK13 inhibition potentiated existing chemotherapeutic treatments. Mechanistically, inhibition of CDK12/CDK13 leads to a genome-wide abrogation of RNAPII CTD phosphorylation, which in turn disrupts transcription and cell cycle progression in GBM cells.

Conclusion
These results provide proof-of-concept for the potential of CDK12 and CDK13 as therapeutic targets for GBM.