bluuebunny/crossref_metadata_2025_split huggingface dataset:
P09.04 T2 hyperintense regions on MRI in gliomas: a comparison between routine clinical MRI and 7T MRI
Authors: Schmitz-Abecassis B , van Osch M J P , Dirven L , Taphoorn M J B , Koekkoek J A F , de Bresser J 
Published: September 2021

Abstract

BACKGROUND
Gliomas can be highly heterogeneous on brain MRI, especially at higher grades. These tumors often include a low-grade component and/or surrounding edema. Both these components appear as hyperintense regions on clinical T2-weighted MR images and cannot be accurately distinguished. Ultrahigh field 7T MR systems have the potential for a higher sensitivity due to its increase signal-to-noise ratio (SNR). This could allow for enhanced detailed visualization of gliomas. Therefore our goal was to assess the difference in extent of T2 hyperintense regions in glioma patients between clinical (1.5T/3T) and 7T MR images.

MATERIAL AND METHODS
We prospectively scanned 6 glioma patients (3 glioblastomas (GBM) WHO grade IV post-operative, 1 anaplastic diffuse glioma (ADG) WHO grade III, 1 biopsied oligodendroglioma (OD) WHO grade II and 1 suspected low-grade glioma (LGG); 4 Females, mean age: 56.8 years and 2 Males, mean age: 45.5 years) on a routine clinical MRI scanner (3T or 1.5T) and on a 7T MRI scanner (Philips Achieva). Resolution of the T2-weighted image at 7T, 3T and 1.5T: 0.75mm3, 3mm3 and 5mm3, respectively. T2-weighted scans were visually assessed by an independent researcher and experienced neuro-radiologist. The T2 hyperintense regions were measured in 3 directions and compared brain structures as reference points between the clinical and 7T scans (e.g. brain stem, gyri), also considering differences in slice thickness and spatial resolution.

RESULTS
T2 hyperintensity lesion measurements in the AP direction were as follows: GBM: 114.7mm (clinical field strength) vs 115.56mm (7T); ADG: 45mm vs 58.87mm and 24.7mm vs 25.55mm; OD: 45.1mm vs 48.5mm; GBM: 45.3mm vs 44.75mm; suspected LGG: 47.4mm vs 51.57mm; GBM: 105.8mm vs 114.5mm. We observed the largest difference between 3T and 7T T2 hyperintense region measurement to be 13.87mm (30%), belonging to a GBM WHO grade IV patient. For all patients the T2 hyperintense region was measured on average 8.3% larger at 7T MRI compared to the routine clinical MRI scan. Overall the T2 hyperintense regions at 7T appeared sharper and tumor boundaries were better defined. Likewise, the contrast between the tumor and healthy tissue was enhanced, most likely because of the increase in spatial resolution.

CONCLUSION
In gliomas the T2 hyperintense regions were more extensive at 7T MRI compared to the routine clinical MRI. These preliminary results might indicate that at clinical field strength the extent of the lesion is underestimated and that 7T MRI can potentially aid in detecting this more extensive disease process. Therefore, 7T MRI scan in gliomas might have a future role in treatment decisions regarding the extent of tumor resection and radiotherapy planning.
P10.01 Effect of mesenchymal cells on infiltration and phenotype of T cells in a 3D glioblastoma spheroid model
Authors: Svablova T , Ternerova N , Houdova Megova M , Busek P , Sedo A 
Published: September 2021

Abstract

BACKGROUND
Glioblastoma (GBM), the most malignant primary brain tumor with a median survival less than two years, is characterized by aggressive invasive growth, presence of hypoxic and necrotic regions, and T-cell dysfunction. Mesenchymal cells with characteristics of cancer associated fibroblasts are present in GBMs, but it remains to be established whether they contribute to T cell sequestration in the tumor stroma and functional inactivation similarly to extracranial tumors. Murine models do not reflect several aspects of human immune system and 2D cell culture systems often fail to recapitulate complex interactions in the tumor microenvironment. 3D spheroids prepared from patient-derived cell cultures offer higher degree of complexity and biological relevance. The aim of this study was to establish a 3D GBM spheroid model to determine the effect of patient derived mesenchymal cells on human T cell infiltration and phenotype.

MATERIAL AND METHODS
Glioma stem-like cell and mesenchymal cell cultures were derived from human GBMs. Naïve T lymphocytes were isolated from buffy coats of healthy donors by Ficoll paque gradient separation, followed by negative magnetic isolation techniques using Naïve Pan T Cell Isolation Kit (Miltenyi Biotec). 3D spheroids were prepared by embedding the cells in 20 µl of Geltrex (Thermo Fisher Scientific). T cells activated by magnetic beads with anti-CD2, anti-CD3 and anti-CD28 antibodies (Miltenyi Biotec) and IL-2 were subsequently added to the spheroids. After 5 days of co-culture, spheroids were dissociated, and viable cells were counted using automated cell counter (Biorad). Expression of a T-cell activation marker CD69 and immune checkpoint molecules LAG3, and PD-1 in CD3+ cells was analyzed by flow cytometry. Mesenchymal, stem cell and lymphocyte markers TE-7, Nestin and CD45 respectively, were analyzed by immunohistochemistry (IHC) on frozen spheroid sections.

RESULTS
We prepared spheroids comprising glioma stem-like cells with and without mesenchymal cells. Glioblastoma-derived cells were evenly dispersed throughout the spheroids as demonstrated by IHC. T cells infiltrated into both types of spheroids, but their number in spheroids containing mesenchymal cells was about 40% (p=0.002) lower compared to the ones without mesenchymal cells. In both types of spheroids, the presence of activated allogeneic T cells led to more than a 50% reduction of the glioblastoma-derived cells. Ongoing studies evaluate the effect of mesenchymal cells on the phenotype of spheroid infiltrating T cells.

CONCLUSION
We have successfully established a 3D spheroid model to study the role of mesenchymal cells in GBM microenvironment. Our results indicate that mesenchymal cells may influence the infiltration of T cells and modulate their phenotype.

SUPPORT
Project was financed by the Center for Tumor Ecology (CZ.02.1.01/0.0/0.0/16_019/0000785).
P12.05 Pulmonary embolism in neuroncological patients: Monoistitutional experience
Authors: Gaviani P , Simonetti G , Redaelli V , Botturi A , Corsini E , Silvani A 
Published: September 2021

Abstract

BACKGROUND
Venous thromboembolism (VTE) is a frequent and potentially fatal event in cancer patients. Patients with brain tumors in particular have one of the highest risk of developing VTE among cancer patients (25–39%), contributing significantly to mortality and morbidity. VTE is particularly high in the postoperative period, with almost half of the events occurring at that time, but it also persists in the first 12 months, with a risk ranging between 7–28%. Despite the high incidence of VTE in patients with brain tumors, to date there are no sufficient data to predict teh real risk or to lead to a standardized approach in the management of these patients. We conducted a retrospective analysis to assess the prevalence of pulmonary embolism complication in patients with brain tumors treated by our Institution in the last 3 years.

MATERIAL AND METHODS
Clinical data, treatment modalities, and patients outcome were analyzed and described. In particular, In particular, the dosages of D-dimer performed in the clinical suspicion of thromboembolic complication were reviewed, and the data of patients with pulmonary embolism confirmed by chest CT scan were recorded.

RESULTS
Overall 372 patients were treated at our Institute in the last 3 years for brain tumors. 14 patients (3.7%) 9 males and 5 females, with a median age of 62 years and a median KPS of 80, affected by glioblastoma (69%), cerebral lymphoma (23%) and low-grade gliomas (8%) had pulmonary embolism during the course of treatment. None of the 14 patients was on prophylactic anticoagulant treatment. One patient developed the embolic event during radio and chemotherapy concomitant treatment, 5 patients during chemotherapy only (2 with PCV scheme and 3 with fotemustine scheme), 2 patients with primary nervous system lymphoma during methotrexate infusion. Six patients were not receiving any chemotehrapy treatment at the onset of pulmonary embolism. At the time of pulmonary embolism diagnosis, more than half of the patients had clinical signs suggestive of deep venous thrombosis, confirmed by echocolor Doppler, 10/14 patients were treated with high-dose enoxaparin, the others with fondaparinux and calcium nadroparin.

CONCLUSION
Despite the high incidence of VTE in patients with brain tumors, there is currently no gold standard in the prevention and treatment of this complication. In fact, many questions are still open, for example the efficacy of low molecular weight heparins vs oral anticoagulants as a prophylactic treatment, the timing of onset and the real risk of bleeding. Future prospective studies should be designed to identify parameters for optimize stratification of thrombotic / haemorrhagic risk in this group of patients. This could allow patients at high risk to undergo more aggressive prophylactic therapy or closer clinical-instrumental surveillance, without incurring the opposite risk of bleeding.
P12.06 Unmet needs and wish for support of informal caregivers of primary brain tumour patients
Authors: Pointon L , Grant R , Peoples S , Erridge S , Sherwood P , Klein M , Boele F 
Published: September 2021

Abstract

BACKGROUND
Most primary brain tumour patients rely on informal caregivers (i.e. family members or friends) for practical and emotional support. While caregiving can be rewarding, it also commonly leads to significant burden. In developing support for caregivers, it is vital to distinguish between caregivers’ unmet needs, and their actual wish for support to resolve unmet needs. We aimed to 1) identify the presence and magnitude of unmet needs; 2) examine associations between unmet needs and desire for support; 3) evaluate perceived usefulness of caregiver needs screening in clinical practice.

MATERIAL AND METHODS
Family caregivers of patients with primary brain tumours were recruited and asked to complete an adapted version of the Caregiver Needs Screen (CNS). This covered the level of distress resulting from 33 common issues in neuro-oncology caregiving (scale 0–10), and wish for information or support for any issue (yes/no). In addition, participants were asked to rank (0–7) their experience of using the CNS based on items covering ‘ease of us’, ‘usefulness’ and ‘satisfaction’. Descriptive and correlational analyses were applied.

RESULTS
Caregivers (N=79) reported between 1–33 unmet needs (M=17.20, sd=7.98) but did not always wish for support for each need (range 0–28, M=4.71, sd=6.63). Most distressing items were patient’s fatigue (M=5.58), recognising signs of disease progression (M=5.23), changes in patients’ thinking or behaviour (M=5.04), patient distress or sadness (M=4.68), and changes in caregivers’ own emotional health (M=4.44). A weak correlation was found between the total number of unmet needs and the desire for support (r=0.296, p=0.014). Caregivers most often desired support with recognising disease progression (N=24), managing medications and side-effects (N=18), and least often with managing spiritual issues (N=0), communication with (grand)children (N=2) and communication with family members and friends (N=3). Caregivers evaluated the CNS tool positively (mean item scores ranging 4.19–6.21 out of 7).

CONCLUSION
Family caregivers of brain tumour patients experience distress resulting from many neuro-oncology specific needs, but this is not directly related to a wish for support or information. Caregiver needs screening could be useful to tailor support or information to suit caregivers’ preferences in clinical practice.
P12.08 Efficacy of trazodone slow release in insomnia associated with high-dose steroid therapy in neuro-oncological patients
Authors: Botturi A , Gaviani P , Redaelli V , Simonetti G , Lucchiari C , Silvani A 
Published: September 2021

Abstract

BACKGROUND
Insomnia linked to therapeutical intake of intravenous (IV) megadoses of steroid (Mgds, 8–16 mg) is a common side effect in neuro-oncology patients. Hypno-inducing drugs (IP) and Benzodiazepines (BDZ) can provoke drug interference and daytime sedation. Trazodone (Trz) is an atypical antidepressant with poor liver metabolism; it has moderate histamine-1 (H1) receptor antagonism and possesses some anxiolytic and hypnotic properties. We tested the use of the Trz retard (RP) formulation as a hypnotic drug in patients undergoing a therapeutic regimen with IV Mgds. To evaluate anxiety and side effects.

MATERIAL AND METHODS
10 patients (6 females and 4 males) admitted to the Neuro-oncology Department of the Neurological Institute “Carlo Besta” treated with Mgds IV. The average age was 55 years and the mean HAM-A score was 25. Instruments included the Hamilton Anxiety Scale (HAM-A), the Clinical Global Impression (CGI), and the Pittsburgh Sleep Quality Index (PSQI). Trz RP was administered at a dosage of 25-50-75 mg/day in the evening.

RESULTS
All 10 patients reported improved hypnotic profiles within the third day of Trz RP administration. Four patients improved on the first day. Reduction of the HAM-A score was found on the third day. No adverse events (epilepsy, daytime sedation, incontinence) were observed in 3 weeks.

CONCLUSIONS
Trz RP proved to have a swift beneficial effect on sleep and anxiety without side effects in the short term. Trz may be preferred to IP and BDZ in patients receiving IV Mgds, considering the lack of daytime sedation and the reduced pharmacological inference. Larger samples will enable future research to better describe the characteristics and the indication of Trz.
P13.12 Effect of tumor treating fields on tumor microtubes in glioma
Authors: Ratliff M , Schlieper-Scherf S , Hausmann D , Jung E , Maier E , Ratliff T M , Etminan N , Winkler F 
Published: September 2021

Abstract

BACKGROUND
Tumor microtubes (TMs) are ultralong membrane protrusions of tumor cells in astrocytic gliomas, including glioblastomas. TMs are used as routes for brain invasion and for cells to interconnect over long distances resulting in a functional network that allows multicellular communication. This network mediates resistance against the cytotoxicity of radiation and chemotherapy. One explanation for TM network protection is a better homeostasis of calcium ions that would otherwise increase to toxic intracellular levels in response to these therapies.
Our working hypothesis is that interfering with the integrity of the glioblastoma cell network is key to a potential breakthrough in glioma therapy. Many cellular structures are polarized and composed of charged elements and are thus potential subjects to electrical forces; this might also influence the complex intercellular calcium waves (ICWs) that are characteristic for glioma networks. We were therefore interested in the effect of TTF on glioma network maintenance.

MATERIAL AND METHODS
To examine the effect of TTF on glioma TMs we have established a 2D in vitro glioma model using glioblastoma stem cells (GBSCs) grown in high-glucose medium and a 3D model using glioma tumor organoids. Both models reliably reproduce functionality and complexity of morphological features we observe in our mouse model. We analyzed the disruption of tumor network complexity and disruption of functionality by measuring intercellular calcium waves. Tumor cell death and proliferation was investigated in the 2D in vitro glioma model using the inovitroTM-System.

RESULTS
A peculiar “cricked-TM” phenotype that rarely (0.2% ±0.14) occurred under standard or control conditions was observed in TTF-treated cells (16.22% ±5.12). Cell number was reduced by 75% in two lines of GBSCs after 5 days of TTF exposure; predominantly TM-rich GBSCs (&gt; 4 TMs) were affected. This reduction in tumor cell number corresponded with an increase in cell death (0.3% ±0.09 in untreated cells; 1.4% ±0.45 at day 5 of TTF exposure). The frequency of intercellular calcium transients, a measurement for calcium wave frequency in the glioma networks, was instantly reduced after TTF exposure to 58% ±20.42 of control levels in the primary GBSC 2D culture, and to 57.78% ±12.34 in tumor organoids derived from 3 glioblastoma patients.

CONCLUSION
This data suggests a potential effect of TTF application on tumor cell networks, at least in vitro. Interestingly, particularly those glioblastoma cells that have so far been proven to be resistant to radio- and chemotherapy appeared to be affected. We will confirm the observed effects of TTFs on tumor cell calcium signaling in our in vivo chronic cranial window mouse model. We anticipate that the results of our project will provide important insights into the underlying mechanism of TTF therapy.
P14.24 Estimating survival outcomes in elderly (70+ years) patients with primary glioblastoma
Authors: Zorman M J , Webb P , Nixon M , Sravanam S , Honeyman S , Nandhabalan M , Apostolopoulos V , Stacey R , Hobbs C , Plaha P 
Published: September 2021

Abstract

BACKGROUND
Elderly patients with glioblastoma are perceived to face a poor prognosis, with perceptions around older age and a relative lack of randomized data raising a concern about their undertreatment. The EANO guidelines recommend &gt;70-year-old patients with good performance status to undergo maximal safe resection followed by hypofractionated (40 Gy in 15 fractions, i.e. RT40/15) radiotherapy with or without concurrent and adjuvant Temozolomide (TMZ), depending on MGMT promoter methylation. This study evaluated the relative survival impact of biological, histological, surgical and oncological factors and aimed to devise a scoring system to estimate the survival of elderly glioblastoma patients, with an aim to more accurately guide treatment in this cohort.

METHODS
The records of 169 elderly (≥70 years) patients with a new diagnosis of IDH-wild type glioblastoma were retrospectively examined for gender, age, WHO performance status (PS), comorbidities, MGMT methylation, surgical intervention and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate survival of patients at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS).

RESULTS
The overall median survival (MS) of the cohort was 28.8 weeks. Subtotal resection (MS=27.7 weeks, 95%CI 24.1–31.6 weeks, HR=0.58) and gross-total resection (MS=77.8 weeks, 95%CI 67.0–88.6 weeks, HR=0.36) were associated with significant overall survival benefit compared to biopsy alone (MS=18.2 weeks, 95%CI 15.7–20.7 weeks, HR=5.23), p&lt;0.05. Hypofractionated radiation with Temozolomide (RT40/15+TMZ, MS=60.9 weeks, 95%CI 49.9–71.8 weeks, HR=0.13) was non-inferior to the Stupp protocol (RT60/30+TMZ, MS=50.6 weeks, 95%CI 32.4–66.7 weeks, HR=0.11), p=0.72. Negative prognosticators included age above 75 years, biopsy alone and no chemoradiotherapy. Subgroup analysis revealed that MGMT unmethylated 70–75 year old patients who received the Stupp protocol had significantly improved overall survival (MS=57.6 weeks, 95%CI 27.7–88.1 weeks) compared to standard of care RT40/15 alone (MS=29.7 weeks, 95%CI 7.1–51.6 weeks), p=0.002. EGSS and EGOS scores estimated survival with 65% and 73% accuracy, respectively.

CONCLUSION
When appropriate and safe, a subgroup of elderly glioblastoma patients may benefit from more aggressive surgical and oncological management. The proposed EGSS and EGOS scores takes into account important prognostic factors to help guide which patients should receive such treatment.
P14.25 Melanoma brain metastases in the era of novel therapies: a single-center, Dutch cohort study
Authors: Derks S H A E , Jongen J L M , Slagter C , Joosse A , Schouten J W , van den Bent M J , van der Veldt A A M 
Published: September 2021

Abstract

BACKGROUND
Until recently, patients with melanoma brain metastases (MBMs) had limited therapeutic options. With the arrival of immune checkpoint inhibitors (ICIs), targeted therapy (TT) and advances in stereotactic radiotherapy (SRT), treatment has improved. We evaluated treatments and patient outcome before and after the introduction of these novel therapies.

MATERIAL AND METHODS
In this retrospective, single-center study, patients presenting with MBMs at the Erasmus MC between November 2005 and January 2021 with sufficient follow-up were included. Overall survival (OS), measured from date of MBM diagnosis, was calculated using the Kaplan-Meier method. Patients were stratified according to MBM diagnosis before and after January 1, 2016, since novel therapies were mostly prescribed in our clinic after this date. Results were significant (p&lt;0.05), unless otherwise stated.

RESULTS
Overall, 413 patients were included. Median [IQR] age was 56.6 years [52–71] with a 60% male predominance. A BRAF mutation was present in 46.7% of patients. A single MBM was found in 29.3% and ≥4 MBMs were found in 49.0% of patients. Before January 1, 2016, 191 patients were treated, and 222 patients after that date. Chemotherapy was more frequently used before 2016, both prior to (3.9% pre-2016 vs. 0.9% post-2016) and after (7.0% vs. 0.0%) the diagnosis of MBMs. In contrast, treatment with TT was more frequent after 2016, both prior to (3.7% vs. 16.2%) and after (7.9% vs. 41.4%) the diagnosis of MBMs. Comparable changes were observed for treatment with ICIs (prior to MBM diagnosis: 0.5% vs. 25.2%; after MBM diagnosis: 18.3% vs 39.2%). The application of SRT did not differ significantly before and after 2016 (12.0% vs. 19.4%, p=0.89), while the application of whole brain radiotherapy (WBRT) decreased (52.4% vs. 13.5%). Surgical resection was not significantly different between those periods (15.7% vs. 16.7%, p=0.90). Before 2016, median OS [IQR] was shorter than after 2016 (4.6 [1.9–10.9] vs. 6.6 [1.8–24.5] months). The effect of novel therapies on OS was further analysed in patients diagnosed after 2016; treatment vs. no treatment was compared. ICI treatment prior to MBM diagnosis was associated with worse OS (median OS 4.0 vs. 7.5 months). ICI treatment after MBM diagnosis was associated with better OS (median OS 24.5 vs. 3.0 months). In patients with a BRAF mutation, TT before MBM diagnosis was associated with worse OS (median OS 1.8 vs. 9.4 months). TT after MBM diagnosis in those patients was not significantly associated with improved OS (median OS 7.6 vs. 5.2 months, p=0.96).

CONCLUSION
Recent therapeutic advances for MBM replaced WBRT and chemotherapy with SRT, TT and ICIs. In that period, prognosis of MBM patients increased significantly. OS in patients treated with ICIs or TT prior to MBM diagnosis is still poor, but OS is improved in patients treated with ICIs after the diagnosis of MBM.