bluuebunny/crossref_metadata_2025_split huggingface dataset:
P03.08.B Proton Therapy and recurrent Lower Grade Glioma: clinical and radiological aspects, intraoperative findings and histo-pathological features
Authors: Conti Nibali M , Rossi M , Sciortino T , Gay L , Lopci E , Fernandes B , Rudà R , Bello L 
Published: September 2022

Abstract

Background
Radiation therapy (RT) plays a central role in management of central nervous system disease, in particular in the multimodality management of low(er) and high-grade CNS gliomas. New strategy that involved Proton Therapy (PT) have been experienced in the last years. No data are available about re-surgery of lesion irradiated with protons.

Material and Methods
We reviewed our single Unit experience of re-surgery of Lower-Grade Glioma patients that received, in their neuro-oncological history, a treatment with PT. We collect clinical data, intra-operative findings, histopathological features and oncological and clinical outcome after surgery.

Results
We collected three cases of young with an IDH1-mutated tumor that underwent to Proton Therapy (PT). In two cases PT was performed due to progression of disease, in one case as adjuvant therapy after first surgical treatment. In all cases we performed surgery within three years after PT. All patients complained drug resistant epilepsy after PT with symptom relief after surgery and one patient complained a spine fracture due to corticosteroids intake to control radionecrosis’s symptoms after PT. In the pre-operative work-up all patient performed a 11-C-Methionin PET scan that revealed an increase of tracer uptake in the suspected area of tumor progression. In one case advanced MRI protocol with PWI was performed to further distinguish and sample area of pseudoprogression and tumor progression. In two patients area of gliosis and necrosis was find at the histological examination.

Conclusion
Our experience, although limited to three case, provided a clinical and radiological example of the small cohort of patients that performed surgery after a Prothon Radiotherapy. Clinical presentation was heterogenous except a poor seizure control. Despite time elapsed since PT, areas of radionecrosis were found in the histopathological samples of 2/3 of patients. Moreover, we need to collect more data to draw a complete picture in this complex field.
P05.02.A 18F-FACBC PET/MRI in diagnostic assessment of gliomas
Authors: Pedersen L K 
Published: September 2022

Abstract

Background and Theory
MRI and histopathological tissue sampling are routinely done as part of the diagnostic work-up of patients with glioma. MRI provides anatomical images with high resolution and excellent soft-tissue contrast. But this modality has limitations in identifying tumor grade, true tumor extension and differentiate viable tumor tissue from treatment induced changes. PET can provide quantitative information of cellular activity and metabolism, and may therefore have additional value compared to MRI alone.

Objective
The aim of this study was to find the sensitivity of [18F]FACBC PET in gliomas, and evaluate if PET imaging with this tracer can improve differentiation between low-and high-grade gliomas.

Methods
Patients with suspicion of primary (n=19) or recurrent gliomas (n=8) were recruited to this study from St. Olavs hospital, Trondheim University Hospital, Trondheim, and from the University Hospital of North Norway, Tromsø. PET acquisitions (30-45 min post injection) using the amino acid radiotracer [18F]FACBC (3 MBq/kg) were performed simultaneously to MRI acquisitions (T1 with and without contrast, FLAIR, and UTE for attenuation correction. The sensitivity of [18F]FACBC PET in glioma detection was assessed using histopathology as reference. Tumor-to-background ratios (TBRs) were compared to tumor subtype and grade to assess the diagnostic value of this tracer for glioma diagnostics.

Results
Histopathology revealed 2 WHO grade 1 gliomas (pilocytic astrocytoma n=1, pilocytic astrocytoma/ganglioglioma n=1), 7 WHO grade 2 gliomas(astrocytoma n=4, oligodendroglioma n=3), 7 WHO grade 3 gliomas(astrocytoma n=5, oligodendroglioma n=2) and 12 WHO grade 4 tumors(astrocytoma n=1, glioblastoma n=11). [18F]FACBC PET provided a sensitivity of 74.1% in the detection of gliomas. PET uptake was observed in all grade 4 tumors, 5/7 grade 3 tumors, 2/7 grade 2 tumors, and all grade 1 tumors. TBRpeak was high with a median value of 9.4 (range: 2.1-34.9) in PET positive tumors. Only tumors with a TBRpeak &gt; 2.0 were detected with [18F]FACBC PET. TBRpeak was highest for grade 1 gliomas with a median value of 20.6, and increased significantly from grade 2 to grade 4 tumors with median values of 1.7 (grade 2), 6.2 (grade 3) and 12.4 (grade 4) (Kruskal-Wallis, p=0.001).

Conclusion
[18F]FACBC PET demonstrated high uptake in the majority of gliomas, and there was a clear tendency to higher uptake in the higher grade tumors. [18F]FACBC PET may be useful in the differentiation between glioms grades and subtypes. A future study using the same patient data will be performed to evaluate the assessment of [18F]FACBC PET in neurosurgical treatment planning. Image-localized biopsies from different regions of each tumor will be correlated to fused PET/MRI images to evaluate if [18F]FACBC PET can be used to guide surgical resection and to improve accuracy in histopathological tissue sampling.
P06.07.A Natural killer cells lyse glioblastoma stem cells and increase their sensitivity to chemotherapy
Authors: Breznik B , Ko M , Chen P , Senjor E , Majc B , Novak M , Habič A , Jewett A 
Published: September 2022

Abstract

Background
Glioblastoma is the most common and lethal brain tumor in the adult population and immunotherapy is playing an increasingly central role in the treatment of many cancers. Nevertheless, the search for effective immunotherapeutic approaches for glioblastoma patients continues. In this study, we aimed to explore the therapeutic potential of allogeneic highly activated super-charged natural killer (NK) cells in glioblastoma.

Material and Methods
Chromium release- and calcein release-based cytotoxicity assays, ELISA, ELISPOT, and multiplex cytokine assays were used to determine NK cell cytotoxicity against glioblastoma stem cells (GSCs) and secretion of cytokines. Cell surface marker expression using flow cytometry and cell growth in vitro and in vivo were measured to determine GSC phenotype. NK cell killing and penetration in 3D were measured using confocal microscopy of GSC tumorospheres.

Results
Super-charged NK cells efficiently lysed patient-derived GSCs in 2D and 3D models potentially reversing the immunosuppression observed in patients. NK-cells secreted IFN-γ, upregulated GSC surface expression of CD54 and MHC class I and increased sensitivity of GSCs to chemotherapeutic drugs. Co-localization of NK cells with GBM cells in perivascular niches in glioblastoma tissues and their direct contact with GSCs in tumorospheres suggests their ability to infiltrate glioblastoma tumors and target GSCs.

Conclusion
Allogeneic super-charged NK cells appear to be a potential therapeutic approach for glioblastoma by selectively killing therapy-resistant cancer stem cell population, increasing their immune-related surface markers and enhancing their sensitivity to chemotherapy. Due to GSC heterogeneity and plasticity personalized immunotherapeutic strategies should be developed to effectively target glioblastomas.
P09.04.B The importance of treatment tolerability for people with glioma: registry review and qualitative findings from the COBra Study
Authors: Baddeley E , Retzer A , Sivell S , Seddon K , Bulbeck H , Nelson A , Adams R , Grant R , Watts C , Aiyegbusi O , Rivera S , Kearns P , Dirven L , Calvert M , Byrne A 
Published: September 2022

Abstract

Background
Gliomas are the commonest form of primary brain tumour, accounting for 80% of malignant brain tumours. Gliomas represent a heterogeneous group of cancers with variable outcomes, traditionally graded from I to IV (least to most aggressive). The poor prognosis of some glioma patients and high symptom burden has led to a growing emphasis on their quality of survival. Maintaining cognitive function, physical function and other health-related quality of life aspects throughout the disease trajectory are key considerations, particularly for patients with aggressive forms of glioma. It is therefore important that glioma intervention studies collect data aligned with patient priorities that enables assessment of the net clinical benefit of treatments and facilitates informed decision-making. In particular, and of increasing recognition, is the importance of monitoring the incidence of adverse events during and after the course of an intervention, and understanding their impact upon patients, and patients’ own assessment of, tolerability.

Material and Methods
A trial registry review, a systematic review of the qualitative literature and semi-structured interviews with patients and caregivers were undertaken. Outcomes were extracted from these sources to formulate a longlist during the development of a core outcome set for glioma interventional trials (the COBra study).

Results
The registry review (n=91), systematic review (n=21) and semi-structured interviews (n=19) identified many important outcomes and concepts, one of which was tolerability. Tolerability, adverse events, toxicity or safety was reported to be collected as an outcome in 46 trials. Outcomes related to tolerability were identified from 7 articles included in the systematic review. Themes related to tolerability emerged from the qualitative interviews. These included tolerability of side effects of treatment; trade-offs of side effects versus potential benefits in deciding on, and willingness to, undertake further treatment; and self-directed strategies for coping.

Conclusion
There is a growing acknowledgement of the importance of treatment tolerability in the wider field of cancer research. In glioma research specifically, its significance is yet to be reflected in outcomes collected in trials. Our qualitative findings indicate tolerability is of high significance to patients and those close to them. Participants reported how their preconceptions and experience of tolerability influenced treatment decisions and treatment uptake. However, outcomes related to tolerability were collected in just over half of trials in our sample. Tolerability and items relating to the patients’ experience of adverse events should be collected and reported in trial findings to reflect patients’ priorities and enable informed treatment decisions.
P09.05.A Caregiver café in a neuro-oncological context
Authors: Mathiasen M , Bang Rasmussen C , Piil K 
Published: September 2022

Abstract

Background
Caregivers to patients with primary brain tumors often play a vital role in the direct care and support of the patient. Great responsibility is placed on their shoulders to manage practicalities during the cancer trajectory. Caregivers are asked to carry out procedures, report patient-related evaluations, coordinate care and treatment and deliver proper information to the healthcare providers. Hence, they tend to neglect their own physical and emotional needs as they priorities other tasks including financial issues, household and work while coping with family adjustment. Caregivers of patients with brain tumors experience a high level of burden and distress. It is shown in literature that caregiver interventions can reduce caregiver burden, distress and anxiety, and improve coping, relationships and physical functioning
Aim: The aim of this study is to offer caregivers to join a caregiver café at the neuro-oncological department to 1) relax, meet and support each other, (2) be provided with information and answers to their questions, and (3) be recommended appropriate caregiver services.

Material and Methods
This is a user-based sequential three phase project. Applying a co-creation process with informal caregivers we first investigate their preferences, needs and considerations in relation to establishing a caregiver café. A user survey consisting of demographic characteristics and five study-specific and open-ended questions are conducted. Secondly, a project protocol with the design, content and practical planning will be outlined and presented for the patient/relative-user panel at the oncological department. After the final adjustment, a feasibility testing will take place in phase three.

Results
This three-phase project rest on a sequential project development, and findings from one phase will led to the detailed adjustment in the next. Due to its nature of following a participatory design we consider the results to be highly relevant to the users of health-care services. Results from phase I and II is ready to be presented in autumn 2022 including the preliminary results of the feasibility study (recruitment, adherence, safety etc).

Conclusion
Nurses working within neuro-oncology are e.g responsible for providing support, information and education for family caregivers. This project may inspire other nurses to carry out similar initiatives in clinical practice. Thereby we seek to strengthen the evidence on how, what and when the caregivers’ needs and concerns are best addressed with innovative solutions.

Acknowledgement
We like to thank the nurses at the neuro-oncology department, Rigshospitalet for their valuable input and for their participating with the user survey.
P10.14.A Caught in a trap: Silk fibroin, hyaluronic acid, and heparin sponges to capture residual glioblastoma cells
Authors: Ferreira N H , Molina-Pena R , Najberg M , Roy C , Roncali L , Avril S , Mansor M H , Boury F , Alvarez-Lorenzo C , Garcion E 
Published: September 2022

Abstract

Background
Recurrent glioblastoma (GBM) is today inevitable, even using an aggressive treatment protocol (surgery, radiotherapy, and chemotherapy). It mostly occurs within 2 cm of the resection cavity due to the invasion ability of GBM cells. The aim of this work is to test and qualify a local integrative approach using a nano-based chemokine-cancer cell trap concept to lure the residual GBM cells by releasing chemoattractive molecules and, ultimately, confine and kill them in a biomimetic nanostructured polymeric scaffold.

Material and Methods
The stromal cell-derived factor 1α (SDF-1α) was used here as a chemoattractant due to its synergy with the CXCR4 receptor, and the correlation of this axis to the migration of infiltrating GBM cells. Freeze-dried sponges (20 to 140μm/pore size) composed of silk fibroin (SF), hyaluronic acid (HA), and heparin (hep) charged with SDF-1α was evaluated as a GBM cell trap. First, the cytocompatibility and biodegradability of the sponges were evaluated both in vitro and vivo. Secondly, molecular and functional responses of GBM cells to SDF-1α treatment were evaluated using U87MG-CXCR4+ cells, that constitutively and stably expressed both the CXCR4 receptor and RFP, as reporters. To assess the cell migration in response to the SDF-1α gradient in vitro, transwell, under-agarose, and agarose drop assays were used. U87MG-CXCR4+ spheroids were cultivated in the sponges to verify the hosting capacity of the scaffolds. Finally, syngeneic and xenogeneic models were developed to evaluate the bioperformance of the sponges in vivo.

Results
SF-HA-hep sponges presented low cytotoxicity and complete biodegradation after 4 months of implantation. Histological analysis revealed only local reaction, as an immune response in the short-term study, but no signs of acute inflammation or fibrotic process were found at the resection cavity-brain margin in the long-term study, demonstrating fine tolerability in vivo. Relevant molecules involved in chemotaxis (Akt, Erk, and Paxillin) were activated upon treatment with SDF-1α. U87MG-CXCR4+ cells were directionally attracted to the SDF-1α-loaded sponges, and also a larger neurosphere infiltration area was observed in these sponges compared to controls. Preliminary observations have shown cell clusters detached from the main tumor mass towards the cavity with the implanted SDF-1α-loaded sponge. This may be indicative of chemoattraction, as DAPI correlated with Ki67 staining in the migration front. Further analyses including CXCR4, CD44, paxillin, and galectin-1 immunolabeling will be performed to confirm this hypothesis.

Conclusion
Overall, the results showed that the sponges are biocompatible and the SDF-1α suitable to use as a chemoattractant for GBM cells. This strategy can be used to overcome the treatment resistance in GB, and potentially be transferred to the clinic in the future.
P10.19.B An immunotoxin targeting CD317 for the treatment of glioblastoma
Authors: Gramatzki D , Weiss T , Hänsch L , Silginer M , Rushing E J , Roth P , Gramatzki M , Peipp M , Weller M 
Published: September 2022

Abstract

Background
CD317 is an interferon-inducible cell surface receptor expressed in several solid cancer types. HM1.24-ETA’ is a small immunotoxin with a CD317 single-chain variable fragment (svFv) antibody fused to a truncated version of Pseudomonas aeruginosa exotoxin A (ETA’) that is explored as a novel therapeutic approach in CD317-expressing tumors.

Material and Methods
CD317 mRNA expression in human gliomas and its association with survival was analyzed using the database of the Cancer Genome Atlas (TCGA). CD317 protein levels in human gliomas were assessed by immunohistochemistry. CD317 mRNA expression was assessed by RT-PCR and CD317 protein levels by flow cytometry in 13 human glioma cell lines in vitro. Efficacy of HM1.24-ETA’ was analyzed in acute cytotoxicity assays in vitro. Finally, HM1.24-ETA’ was evaluated in the intracranial human LN-229 glioma xenograft nude mouse model after intravenous injection.

Results
Interrogation of the TCGA database showed that increased CD317 mRNA expression correlated with grade of malignancy among isocitrate dehydrogenase (IDH) wildtype and IDH-mutant gliomas. Enhanced CD317 mRNA expression was associated with inferior survival in glioblastoma and astrocytoma, IDH-mutant, WHO grade 4. Immunohistochemistry confirmed CD317 overexpression in human glioblastoma compared to lower grade astrocytomas. CD317 was expressed heterogeneously on mRNA and protein levels in glioma cell lines in vitro. HM1.24-ETA’ induced acute cytotoxicity in CD317-positive glioma cells in vitro. CD317 expression and susceptibility to HM1.24-ETA’-induced cell death were enhanced by interferon-β. HM1.24-ETA’ prolonged survival in the LN-229 xenograft nude mouse model.

Conclusion
These data define CD317 as a novel target for treatment of human gliomas with immunoconjugates.
P11.14.A Systematic review of phase III trials in newly diagnosed glioblastoma 2005-2021
Authors: Oster C , Lazaridis L , Feldheim J , Schmidt T , Kleinschnitz C , Kebir S , Glas M 
Published: September 2022

Abstract

Background
Despite a plethora of studies since the EORTC/NCIC trial in 2005, glioblastoma (GBM) prognosis remains poor. We here identify and compare glioblastoma phase III trials in terms of efficacy and baseline characteristics in an attempt to summarize the experience of the past 16 years.

Methods
A systematic literature search using PubMed and ClinicalTrials.gov was conducted to provide an overview of clinically relevant GBM phase III trials (years 2005-2021) of adult patients younger than 70 years of age. Search results were screened according to predefined inclusion criteria and either excluded or included in further analysis on study design, baseline characteristics, and survival results.

Results
Eleven trials from the literature and clinical trial database fulfilled the search criteria. Among these trials, a total of three GBM phase III trials reported overall survival (OS) benefit, including the EORTC/NCIC study (NCT00006353), EF-14 (NCT00916409) and CeTeG/NOA09 (NCT01149109). All three studies demonstrate similar hazard ratios, which translate into risk reduction of about 40%. Furthermore, low toxicity profile and mostly preserved quality of life were attributed to the treatments tested. Looking at the study designs, eight out of eleven trials were open label randomized trials, including all of the positive ones, and only three negative trials employed treatment blinding and a placebo control. Canonical baseline characteristics (extent of resection, age, gender, MGMT promoter methylation status) did not significantly differ between positive and negative trials. IDH mutation status was analyzed in only two trials, each showing a small percentage of IDH-mutant tumors only.

Conclusion
This analysis on GBM phase III trials conducted between 2005 and 2021 revealed that the majority of trials did not show a significant improvement in overall survival. CeTeG/NOA-09 and EF-14 are the only two studies with positive overall survival outcome since the EORTC/NCIC trial in 2005.
P11.36.A Could a transcriptome profile predict local control for glioblastoma?
Authors: Antelo G , Valduvieco I , Comas S , Serrano S , Molero J , Balañá C , Villà S , Moreno S , Mollà M , Gomà C 
Published: September 2022

Abstract

Background
Glioblastoma (GB) is the most frequent and aggressive primary brain tumor in adults. The standard of care is surgery followed by radiotherapy in combination with temozolomide. GB molecular subtypes (Classical [CL], Mesenchimal [MES] and Proneural [PN]) have been correlated with prognosis. In the preclinical setting, CL and MES glioma stem-like initiating cells have also been shown to be more radioresistant than PN subtype. If confirmed in patients, the molecular subtype could predict the specific benefit of adjuvant treatment. The aim of this work is therefore to investigate whether GB molecular profiles are associated with treatment resistance in vivo.

Material and Methods
We analyzed the spatiotemporal pattern of recurrence (progression-free survival [PFS] and local control) in 37 GB patients treated with adjuvant radiotherapy (30 x 2 Gy, following EORTC contouring guidelines) plus temozolomide in the context of a multi-centric study. Relapse was defined following the RANO criteria (gadolinium enhanced area on MRI T1 sequence) and classified into 3 groups: in-field relapse (Dmean &gt; 57 Gy), out-of-field relapse (Dmean &lt; 48 Gy) and not-defined relapse (no follow-up MR data or marginal relapse). We used three different classification algorithms (SVM, K-Nearest Neighbor and single sample gene set enrichment analysis) for the transcriptomic classification of tumor samples, and we only assigned a molecular profile when all three classifications agreed, otherwise we called it Mixed profile. Patients with a not-defined spatial pattern of recurrence were included in the PFS analysis, but excluded from the local control analysis.

Results
The transcriptomic classification resulted in 14 CL, 1 MES, 9 PN and 13 Mixed. Median PFS after radiotherapy was 6 months, with a mean follow-up of 11 months. No differences in PFS were found between CL, PN and Mixed groups (the single MES case was excluded). Local control was analyzed in 24 patients (10 CL, 4 PN, 10 Mixed). Non- statistically significant differences were found between PN/Mixed and CL subtypes, with a median in-field relapse-free survival of 6.9 months (PN), 6.3 months (Mixed) and 4.7 months (CL).

Conclusion
Although there is no difference in PFS among GB molecular subtypes, these results suggest that the Classical subtypes seem to relapse faster inside the radiotherapy field. This would suggest a higher radioresistance compared to Proneural and Mixed subtypes, in agreement with preclinical data. Due to the low number of patients these differences are statistically non-significant, but they provide the rationale for further investigation in a larger patient cohort. Grant: Marató -TV3