bluuebunny/crossref_metadata_2025_split huggingface dataset:
P15.03.A The value of 7 Tesla MR spectroscopic imaging for improved preoperative determination of the tumor grade and IDH status in gliomas: preliminary data
Authors: Hangel G , Sharma S , Cadrien C , Furtner J , Furtner J , Roetzer-Pejrimovsky T , Preusser M , Bogner W , Rössler K , Trattnig S , Widhalm G 
Published: September 2022

Abstract

Introduction
A new generation of MR spectroscopic imaging (MRSI) methods using 7T scanners have demonstrated the capability to resolve more neuro- and oncometabolites at higher resolutions than clinical routine MRSI. In a cohort of glioma patients, we explored the automated preoperative and noninvasive classification of IDH-mutation status and tumor grade based on 7T MRSI.

Methods
This retrospective study included 36 patients (15 female) with histologically confirmed diffusely infiltrating glioma WHO grade 2-4 (9 grade 2, 9 grade 3 and 18 grade 4) and known IDH status (21 IDH1-mut, 15 IDH-wt) with an available 7T MRSI scan of sufficient data quality. The 3D MRSI scan had a 3.4 mm isotropic resolution and 15 minutes acquisition time. 12 spectral components were classified voxel-wise, including choline, glutamine and glycine. Within a tumor segmentation based on routine 3T imaging, we used a random forest algorithm for the voxel-wise classification of IDH mutation and grade (into low or high grade). Training used the leave-one-out cross validation method (i.e., for every patient data set, the other 35 datasets were used as training set) and feature selection out of the available combinations for metabolite ratios (e.g., glutamine to choline). The resulting voxel classifications were aggregated into a mean probability per patient that was the base for receiver-operator characteristic (ROC) curves both for grade and IDH status.

Results
The classification algorithm obtained an area under the curve (AUC) for IDH determination of 0.85 (e.g., 75% sensitivity and 95% specificity). For grade determination, the AUC was 0.88 (e.g., 87% sensitivity and 89% specificity). In comparison, the AUC per voxel would have resulted in an AUC of 0.66 for both. Further, classification by individual metabolite ratios resulted in lower AUCs in all cases.

Conclusions
According to our preliminary data, preoperative 7T MRSI is capable to determine the correct glioma grade and IDH status with high sensitivity and specificity by leveraging the extended metabolic panel width and voxel amount. By increasing this cohort in future, we intend to confirm our initial results and we also plan to extend classification to more molecular-pathological features (e.g., TERT). Thus, even a voxel-wise classification of tumor microenvironments could be attempted. Further improvements in 7T MRSI methodology such as absolute instead of relative quantification would also aid these attempts.
In summary, 7T MRSI has shown its potential for improved preoperative characterization of gliomas.
P17.05.A Re-irradiation with bevacizumab for large volume chemo-refractory glioblastoma after prior high-dose chemoradiotherapy
Authors: Horsley P , Tong E , Wheeler H , Venkatesha V , Chan J , Kastelan M , Back M 
Published: September 2022

Abstract

Background
There are limited options for salvage treatment of glioblastoma. The role of re-irradiation (reRT) for large-volume chemo-refractory relapse is not established due to concerns regarding potential toxicity, which may be overcome with use of bevacizumab.

Material and Methods
Patients who received initial post-operative chemoradiotherapy with 60Gy (EORTC-NCIC protocol) for glioblastoma across two centres from 2007-2021 were entered into a prospective database. Patients with progressive chemo-refractory disease, including some progressing on bevacizumab, were considered for reRT. Pseudoprogression and late RT necrosis was actively excluded using sequential MRI and PET. Clinico-pathologic characteristics of the reRT cohort and patients who had progressed but did not undergo reRT were compared. Kaplan-Meier survival analysis was used to assess overall (OS) and progression-free survival (PFS) from diagnosis in the overall and reRT cohorts as well as OS post-reRT. Factors associated with improved survival post-reRT were assessed.

Results
Of 447 patients treated for glioblastoma, 372 had progressed of which 71 received reRT. Median follow up for surviving patients was 26 and 37 months from diagnosis for the reRT and overall cohorts respectively. Median PFS and OS from initial diagnosis were 11.6 (95% CI: 9.4-14.2) and 23.6 (95% CI: 21.0-33.1) months respectively for re-RT patients, compared to 11.8 (95% CI: 11.0-12.5) and 18.0 (95% CI 17.0-19.1) months for the overall cohort. The reRT subgroup were more likely to be younger (median 53 vs. 59 years, p&lt;0.001), have ECOG performance status at diagnosis 0-1 (86% vs. 69%, p=0.002) and have MGMT promoter methylation (54% vs. 40% p=0.083). There was no difference in extent of initial resection (p=0.59). The most common reRT schedule was 15 fractions to a total dose of either 40 Gy (32 patients) or 35 Gy (28 patients). Sixty (85%) had progression on bevacizumab prior to reRT; bevacizumab was continued during reRT in these cases. A further 10 (14%) received salvage bevacizumab after reRT. Median reRT PTV volume was 135cc (IQR 69-207cc). Median OS following reRT was 7.1 months (95% CI: 6.3-7.9). Six (8%) patients were admitted to hospital within 30 days of reRT, only one due to reRT toxicity. Median OS post-reRT was 7.7, 6.4 and 6.0 months for patients aged &lt;50, 50-70 and &gt;70 years respectively (p=0.021) and 8.1 vs. 6.3 months for patients with ECOG performance status of 0-1 and 2-3 respectively (p=0.039). Distant versus local progression (p=0.87), anatomical location of disease (p=0.65), MGMT methylation status (p=0.77) and PTV volume (p=0.91) did not predict post-reRT survival.

Conclusion
Large volume reRT for patients with recurrent glioblastoma is feasible, well-tolerated, associated with favourable overall survival and produces meaningful post-radiotherapy survival times.
P17.11.A Experience of ketogenic diet with support of liquid formula 3:1 and high-grade gliomas: Case series
Authors: Zapata Laguado M I , Luna-Meza A , Gonzalez Hurtado D , Aya Ramos L 
Published: September 2022

Abstract

Background
High-grade gliomas, including glioblastoma, are the most common primary malignant brain tumors in adults. Despite the efforts to develop new therapies, treatment options remain limited and the prognosis is poor. Ketogenic diet, is an emerging complementary therapy for high-grade gliomas. It is hypothesized that through the change of the energy source from glucose to ketones and the inability of glioma cells to metabolize ketone bodies with the same ease due to inefficient oxidative phosphorylation, tumor growth is slowed. The feasibility of a ketogenic diet is a matter of concern. Its influence on the quality of life of patients with advanced cancers showing that even though it may cause constipation and reflux, quality of life is generally not affected

Material and Methods
We reported a case series of patients with high-grade gliomas using ketogenic diet with liquid formula 3:1 ratio (KDS) as a complementary treatment. We describe baseline characteristics, and EORTC-QLQ30 score and symptom evaluation

Results
We describe the case of 3 patients (2 women and 1 man) with diagnoses of grade 4 glioblastoma (2) and grade 3 oligodendroglioma (1), mean age 46.7 years (38- 56 years), ECOG 1 (2) and ECOG2 (1), gross tumor resection (1 glioblastoma patient), subtotal resection (1 glioblastoma patient), and biopsy (1 oligodendroglioma patient). All patients received radiotherapy, 66.7% (n=2) stupp protocol, and 33.3% (n=1) received hypofractionated therapy and adjuvant treatment with temozolomide. All patients received first line with temozolomide, and 33.3% received a total of four lines of chemotherapy. All the patients were fed orally and managed with KDS at the last progression. Median follow up time was 4 months. KDS didn’t impact corporal weight and a positive impact was noted in seizure episodes (&gt; 3 per day before vs &lt; 3 per day after DKS) and quality of life (EORTC-QLQ30 61,3 [60 - 66,8] at the begining vs 70,9 [69,8 - 71,2] at the last visit). Regarding tolerance, one patient presented diarrhea and/or constipation grade 1 the first 5 days of treatment. Compliance was measured by days with a median adherence of 90%. Current disease status is stable disease (RANO criteria) in the three patients.

Conclusion
KDS could be an interesting therapy complementary to standard treatment in patients with high grade gliomas, especially in those patients who debut with seizures, improving quality of life and number of convulsive crises. More studies in adult patients are required to confirm this hypothesis
P17.18.B Augmentative craniotomy in recurrent glioblastoma. Preliminary clinical and radiological outcomes
Authors: Arcidiacono U A , Berra L , Serraino A , Cedrone G , Venditti E , Armocida D , Quinzi A , Brunetto F , D'Angelo L , Di Norcia V , Frati A , Familiari P , Santoro A 
Published: September 2022

Abstract

Background
The compression of peritumoral healthy tissue in brain tumor patients is considered a major cause of life-threatening neurologic symptoms. This condition is associated with an increase in intracranial pressure. The literature reports that GBM has a mass effect in 72% of autoptic brains of patients who died of brain tumor, with herniation in 50% of all cases.

Material and methods
We present a preliminary clinical series on 5 cases. The patients are chosen based on criteria of recurrent glioblastoma without the possibility of a gross total resection with a recurrence after STUPP protocol. The surgeries include cytoreduction and augmentative craniotomy. The aim is to increase the intracranial volume and reduce the intracranial pressure in evolving glioblastoma. Clinical and radiological follow-up considers different objective scales and contrast enhancement MRI performed every 3 months. We evaluate KPS, survival rate, complication rate, quality of life using QOL-BN20 and neuropsychological assessment.

Results
The 12 months of follow-up shows a mean survival rate of 9 months after the surgery. This procedure has no negative impact on the survival rate, complication rate, and quality of life reduction. The neuropsychological evaluation does not show an impact on self-perception of aesthetic appearance. The surgery does not show surgical wound complications. The mean operative time was 225 minutes and was comparable with standard recurrence glioblastoma procedure.

Conclusion
This work has the main limitation of being preliminary results on small population. However, these results show encouraging outcomes and could be an innovative and salvage therapy for recurrent and incurable glioblastoma. Further follow-up and study must be performed.
P18.03.B Long term effects of therapeutic embolization of radiographically suspected meningiomas regarding tumour- and necrosis volume as well as patients' symptoms
Authors: Pedersen M , Eibl T , Nania A , Voit-Höhne H , Schrey M , Steiner H , Holtmannspötter M 
Published: September 2022

Abstract

Background
Preoperative embolization of radiographically suspected intracranial meningiomas is performed to reduce intraoperative blood loss and to facilitate resection. However, there is paucity of evidence examining the effect of embolization as a sole intervention on the tumor volume and the patient's neurocognitive symptoms. The objective of this study was to investigates the influence of therapeutic embolization on tumor- and necrosis volume and neurocognitive symptoms in absence of surgical intervention.

Material and Methods
Between January 2019 and June 2021, 4 patients (median age 82, 1 female) with 5 radiographically suspected intracranial meningiomas, underwent endovascular embolization with liquid embolizate and coils, without subsequent surgery. Indication for embolization was history of previous multiple surgery contraindicating further surgical intervention or patients will. Neurological status (on admission, discharge from hospital and 5 months after embolization), medical history, medication, MRI (location, tumor- and necrosis volume, development of edema, complications), DSA (extent of embolization, arterial supply) and procedural complications were recorded. In 3 patients with 4 tumors, an MRI scan was performed. The calculation of tumor- and necrosis volume was done manually with a semiautomatic segmentation tool. One patient with one tumor received CT scans due to a cardiac pacemaker and was therefore excluded from volumetric analysis.

Results
The average tumor volume was 44,83 ± 13,82 cm3 on admission, 45,33 ± 16,3 cm3 5 days after embolization (+1%) and 39,93 ± 29,39 cm3 (-11%) after 5 months. The average necrosis diameter was 41,76 ± 9,33 mm after 5 days and 6,05 ± 6,43 mm after 5 months. The perifocal oedema decreased in 2/3 Patients. Tumor blood supply was via 2,4 ± 1,34 vessels, 1,2 ± 0,45 vessels were embolised. On admission, 3 patients showed neurocognitive symptoms. At discharge and in the follow-up, in 2 patients the symptoms had improved, one patient experienced a complete symptom regression. In one patient the embolization was complicated by dissection of the middle meningeal artery. The same patients perifocal oedema increased in the further clinical course with accompanying deterioration of the pre-existing hemiparesis from moderate to severe. Supported with dexamethasone medication, the oedema and symptoms declined to a mild residual paresis. None of the patients developed a long-term neurocognitive deficit related to embolization.

Conclusion
Therapeutic endovascular embolization of radiographically suspected intracranial meningiomas reduced the tumor volume and led to long-term improvement of pre-existing neurocognitive symptoms. In the future, these effects should be verified in larger studies.
P18.06.B ETS-Transcription Factor inhibitors are effective inTERT promoter mutated meningioma cells in vitro
Authors: Neumayer K , Kastler L , Laaber M , Roschger C , Lenz S , Lötsch-Gojo D , Berger W , Gruber A , Spiegl-Kreinecker S 
Published: September 2022

Abstract

Background
TERT promoter mutations in meningiomas were recently found to be strongly prognostic and associated with malignant progression and risk of recurrence. As result, the mutation in the TERT promoter generates a binding site for E twenty-six (ETS) transcription factors. Consequently, ETS-transcription factor inhibition might represent a novel strategy to impede meningioma growth. In a prior study we could demonstrate effectiveness of the ETS-transcription factor inhibitor YK-4-279 in TERT promoter mutant meningiomas. Recently, TK216 the clinical derivative of YK-4-279 was developed. Therefore, we aimed to clarify whether TK216 might have an increased effect as compared to YK-4-279 in TERT promoter mutated meningioma cells in vitro.

Methods
A meningioma-derived cell line (BTL695) generated from a TERT promoter mutated (C228T) anaplastic meningioma served as cell model for the experiments. BTL695 was characterized by high telomerase activity and TERT mRNA expression as analysed by the TRAP assay and RT-PCR, respectively. Genomic aberrations were verified using Ion Torrent Oncomine Comprehensive Assay v3-based next-generation sequencing (NGS). The sensitivity of BTL695 to YK-4-279 and TK216 was determined using an MTT-based viability assay (EZ4U). To elucidate the effectiveness of TK216 on cell cycle and apoptosis, cells were stained with PI and annexin V, respectively, and measured by flow cytometry. The effect of TK216 on the protein expression of the cleaved poly(ADP-ribose) polymerase-1 (PARP-1), indicative for apoptosis, was investigated by western blot. Additionally, a TK216-resistant cell model (BTL695res) was generated and analysed by NGS.

Results
BTL695 was significantly more sensitive to TK216 as compared to YK-4-279 (p&lt;0.0001) characterized by the distinctly lower IC50 value of TK216 exposed cells (0.7 µM TK216; 1.6 µM YK-4-279). Flow cytometry analysis revealed a TK216 induced G2M cell cycle arrest and increased apoptosis rate, which was additionally verified by the expression of cleaved PARP-1 expression using western blot. Genomic aberrations were found in 18 genes including NF2, CDKN2A/B, ARID1A and PTEN. Interestingly, although the majority of genomic alterations was persistent in the TK216 resistant cell model, a p53 mutation was newly acquired as compared to the parental cell line.

Conclusion
In summary, our results indicate that ETS transcription factor inhibition by TK216 exerts antitumour activity in our TERT promoter mutant meningioma cell model. Additionally, the sensitivity against TK216 is superior to YK-4-279 and therefore TK216 may represent a promising new therapeutic option for patients with aggressive, TERT promoter mutated meningioma.
P18.07.A Hippo signaling pathway is strongly involved in meningioma tumorigenesis
Authors: Mougel G , Mondielli G , Appay R , Querdray A , Roche C , Jijon A , Konstantinova I , Soude A , Graillon T , Barlier A 
Published: September 2022

Abstract

Background
Recurrent and aggressive meningiomas remain an unmet medical need in neuro-oncology. In mammals, Hippo signaling pathway is responsible for the growth of organs by regulating cell proliferation and apoptosis. The tumor suppressor NF2 protein belongs to the core of the Hippo pathway and a defect of its gene is present in 50% of meningiomas. Absence of NF2 keeps Hippo pathway inactive allowing the translocation of YAP/TAZ to the nucleus and the formation of a complex with TEADs. This complex then promotes the transcription of anti-apoptotic and proliferative genes such as CTGF, CYR61 and AXL. Here we present experimental results on human meningioma fragments and primary cell cultures supporting that Hippo pathway plays a critical role in meningioma tumorigenesis.

Material and Methods
The role of the Hippo pathway was studied on 57 meningiomas, well characterized at clinical, histological and molecular level. The genomic profile, target transcripts of the complex YAP/TAZ-TEADs, cell viability, and cell proliferation were analyzed after siRNA transfection targeting YAP, TAZ, YAP+TAZ and TEADs.

Results
Fifty-seven meningiomas were randomly selected including 27 WHO grade II and III tumors. Thirty (53%) presented a defect on the NF2 gene (NF2def) including 19(65%) grade II/III. NF2def meningiomas presented a significant increase of expression levels of Hippo pathway target transcripts CTGF, CYR61 and AXL in comparison with NF2 wild-type tumors (p&lt;0.0001, p=0.0072 and p=0.0191, respectively). This increase was not correlated with the grade, the sex or with the cerebral localization of the meningiomas. On the other side, IHC analysis suggested this increase was correlated with the nuclear localization of YAP. Disturbing the YAP/TAZ-TEADs complex using siRNA on 10 meningiomas (5 NF2 wild-type and 5 NF2 def) induced a significant decrease on cell proliferation but not on cell viability. This decrease was more important when TAZ was turned off in comparison to turning off of YAP.

Conclusion
Our experimental results strongly support the importance of the Hippo pathway in meningioma tumorigenesis, supporting its relevance as a new target in meningioma therapy. A.Barlier reports receiving research grants from Inventiva Pharma. No potential conflicts of interest were disclosed by the other authors.
P18.08.B Fully automatic meningioma segmentation using T1-weighted contrast-enhanced MR images only
Authors: Boelders S M , De Baene W , Rutten G J M , Gehring K , Ong L L 
Published: September 2022

Abstract

Background
Manual segmentation of brain tumors requires expertise, is time-consuming, and is subject to inter-rater variability. Fully automatic brain tumor segmentation is possible for glioma and meningioma when volumetric T1, T1 contrast-enhanced (T1c), T2, and Fluid-attenuated inversion recovery (FLAIR) MRIs are available. In clinical care of meningiomas, however, often only volumetric T1c scans are available. In this work, we trained a deep learning network to segment meningiomas using only T1c scans for use in clinical research.

Material and Methods
NnU-Net, a deep learning model that is optimized for medical image segmentation, was trained to segment meningiomas from T1c images. This was performed on a large clinically collected meningioma dataset (n=374) of T1c scans with semi-automatically generated enhancing tumor masks and additional data from the BraTS2020 glioma dataset. Model performance was compared against inter-rater reliability, between different models, between anatomical tumor locations, and against models using multiple MRI modalities.

Results
The best performing model obtained a Dice score of 0.90. This performance was 0.03 points lower when compared to inter-rater reliability (Dice=0.93) and almost equal to models using multiple MRI modalities. Model performance split over anatomical tumor locations was between 0.90 and 0.97 (Dice).

Conclusion
Fully automatic meningioma segmentation using only T1c images is possible with an accuracy that is similar to inter-rater reliability and models using multiple imaging modalities.
P18.10.B Natural history of meningiomas - a serial volumetric analysis of 240 tumors
Authors: Thomann P , Häni L , Vulcu S , Schütz A , Frosch M , Jesse C M , El-Koussy M , Söll N , Hakim A , Raabe A , Schucht P 
Published: September 2022

Abstract

Background
The management of asymptomatic intracranial meningiomas is controversial. Through the assessment of growth predictors, we aimed to create the basis for practicable clinical pathways for the management of these tumors.

Material and Methods
We volumetrically analyzed meningiomas radiologically diagnosed at our institution between 2003 and 2015. For this purpose, we used exclusively thin-layered MR images (i.e. ≤ 2mm slice thickness). The primary endpoint was tumor growth defined as a 14.35% increase in tumor volume. We identified predictive clinical and radiological characteristics and used the significant variables from a multivariable regression model to construct a decision tree based on the exhaustive Chi-squared Automatic Interaction Detection (exhaustive CHAID) algorithm.

Results
Of 240 meningiomas, 159 (66.3%) demonstrated growth during a mean observation period of 46.9 months. On multivariable logistic regression analysis, older age (OR=0.979 (0.958-1.000), p=0.048) and presence of calcification (OR=0.442 (0.224-0.872), p=0.019) had a negative predictive value for tumor growth, while T2-signal iso-/hyperintensity (OR=4.415 (2.056-9.479), p&lt;0.001) had a positive predictive value. A decision tree model yielded three growth risk groups based on T2-signal intensity and presence of calcifications with a proportion of growing tumors of 34.1% in the low risk group, 60.0% in the intermediate risk group and 80.2% in the high risk group. Median tumor volume doubling time (Td) was 185.7 months in the low risk, 100.1 months in the intermediate risk and 51.7 months in the high risk group (p&lt;0.001). While 0% of meningiomas in the low and intermediate risk group had a Td of ≤12 months, 8.9% in the high risk group did so (p=0.021).

Conclusion
Most meningiomas demonstrated growth during follow-up. The presence or absence of calcifications and the signal intensity on T2-weighted imaging allow a practical and simple stratification of meningiomas into low, intermediate and high risk tumors. Small tumors in the low or intermediate risk categories can be monitored with longer follow-up intervals, whereas in the high risk category proactive management decisions can be justified.