bluuebunny/crossref_metadata_2025_split huggingface dataset:
P03.11 Finding a predictive marker for compliance to TTFields therapy - the comptune study
Authors: Proescholdt M A , Haj A , Doenitz C , Brawanski A , Mühlberger A , Schmidmeier M 
Published: September 2019

Abstract

BACKGROUND
Tumor Treating Fields (TTFields) imply the administration of alternating electric fields to induce mitotic arrest in Glioblastoma (GBM) cells. Based on the specific mode of action, which requires continuous exposure of the malignant cell pool to TTFields, compliance to TTFields treatment is a crucial parameter for treatment success. Correspondingly, a recent post hoc analysis of the EF-14 trial has demonstrated a strong correlation between TTFields compliance rate and treatment success. However, there is currently no data regarding predictive factors for individual compliance rate. We are therefore performing a prospective study designed to analyze specific parameters potentially influencing compliance to TTFields treatment employing a standardized psychological assessment battery in GBM patients who choose or not choose to undergo TTFields treatment in a longitudinal fashion. The results of the psychological profile will be correlated to the compliance rates of the individual patients.

MATERIAL AND METHODS
Forty adult patients treated for newly diagnosed GBM at the University Regensburg Medical Center will be recruited. The psychological assessment battery aims at assessing four categories relevant for treatment compliance: 1. Lack of communicative skills, 2. depressive and anxiety disorders, 3. interpersonal factors (e.g. social support), and 4. intrapersonal factors, (e.g. beliefs about benefit, self-efficacy). The study endpoints are: 1. willingness to undergo TTFields therapy and 2. compliance rate of the individual patient, provided by the technical support team. The first interview takes place after treatment consultation (T0), 2 weeks after diagnosis (T1), at the initiation of TTFields treatment (T2) and every 4 weeks during treatment either until second disease progression or after maximal 8 months observation time per patient. Additionally, demographic (gender, age, marital status), clinical (KPI, extent of resection) and biological factors (MGMT promoter status, IDH1 mutation) will be assessed.

RESULTS
The study has been approved by the local ethics committee and has recruited the first 23 patients within 8 months since initiation of the study. The most updated results will be presented at the meeting.

CONCLUSION
One of the most challenging aspects in the application of TTFields in clinical practice is the identification of influencing factors increasing patients’ compliance. This study is designed to provide a psychological profile predictive for high treatment compliance.
P04.03 Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? Case report and review of the literature
Authors: Kamel R , Van den Berge D 
Published: September 2019

Abstract

BACKGROUND
Subependymal giant cell astrocytoma (SEGA) is a low-grade glioma that occurs in patients with tuberous sclerosis complex (TSC). SEGA typically grows within the ventricles causing hydrocephalus and sudden death. Surgical resection is the traditionally preferred treatment and expert opinion advises strongly against the use of radiotherapy, insomuch that it is not even mentioned as a treatment option in reviews or guidelines. Nevertheless, surgical resection of big volume or bilaterally growing SEGA can be very challenging. Recently, success has been reported with the use of mTOR inhibitor, everolimus, in reducing tumor volume. However, regrowth was observed after drug cessation requiring long-term if not life-long drug administration and thus raising concerns regarding side effects and high treatment costs. Here, we report about a case with inoperable bilateral SEGA that was successfully treated with fractionated stereotactic radiotherapy alone (30x2Gy) with a follow up period of 8 years before being treated with everolimus for renal involvement of TSC. Currently, the patient has been followed up for 13 years.

MATERIAL AND METHODS
All of the patient’s pre and post treatment MRI’s were used for detailed volumetric assessment of the response of the SEGA on each side separately. Systematic review of the literature was conducted via PubMed and Up-to-date using the search terms: ‘treatment of SEGA’, ‘radiotherapy in SEGA’, ‘SRS in SEGA’, ‘treatment of tuberous sclerosis complex’, ‘radiotherapy treatment in low grade astrocytoma’, etc. The article references were queried for the terms ‘radiotherapy’, ‘induced tumors’ and ‘malignant tumors’. Secondary references were added to the database and reprocessed similarly. Reviews about radiation-induced tumors were also added to the database. Attention was given to reports containing data about irradiated SEGA and about high-grade brain tumors in TSC patients. The database was locked on 1-02-2018 containing 1298 article references and 780 full-text articles.

RESULTS
In our case, the successive volumetric assessments on MRI’s demonstrated 80% volume reduction after radiotherapy alone, further enhanced to 90% after everolimus administration. Literature review shows no valid evidence for contra-indicating fractionated stereotactic radiotherapy in SEGA and shows that surgery is still associated with high re-operation and post-operative complications rates.

CONCLUSION
A slow progressive response of SEGA on both sides to radiotherapy was observed similar to the response seen in other benign intracranial tumors. We believe that stereotactic radiotherapy alone or sequentially combined with everolimus deserves to be studied as an alternative to resection in difficult cases that do not require immediate volume reduction.
P04.05 The Effects and Mechanism Involved in Paclitaxel combined with Shikonin on U87 Glioma Cells
Authors: SHI J 
Published: September 2019

Abstract

BACKGROUND
Glioma is the most common intracranial primary tumor,chemotherapy seems to be the main treatment for brain glioma.Chemotherapy is currently widely used in clinical treatment of gliomas,however,drug-resistant always appears,so combination of chemotherapy has became an inevitable choice. Paclitaxel and shikonin are stable and efficient chemotherapy drugs which can promote apoptosis and ininhibite the growth of tumor.Recent research reports,paclitaxel and shikonin can respectively activate and inhibit the expression of p-ERK.The purpose of this study was to investigate whether we can inhibite the activation of p-ERK caused by paclitaxel to enhance the effect of paclitaxel,furthermore use the combination of the two drugs to reach a better effect of chemotherapy.

MATERIAL AND METHODS
1.Cell Culture2. Drugs Administration.3. Growth Inhibition Assays (CCK-8) .4.Scratch test to observe cell migration 5.Transwell assay for the determination of cell migration 6.Transwell assay for the determination of cell invasion 7. Annexin V-FITC and PI Assay for Flow Cytometry to Detect Apoptosis 8. PI Assay for Flow Cytometry to Detect Cell Cycle 9. Western Blot to Detect the Expression of P-ERK/ERK 10. Statistical Analysis.

RESULTS
1.The results tested by CCK-8 showed these two drugs have synergic effects with a CDI equals to 0.72 which means these two drugs are significant synergistic.2.Compared with paclitaxel group or shikonin group,the 1/2paclitaxel+1/2shikonin group had a significant inhibitory effect upon the migration of U87 cells.3.Compared with paclitaxel group and shikonin group,the 1/2paclitaxel+1/2shikonin group had a significant inhibitory effect upon the invation of U87 cells.4.Compared with paclitaxel group and shikonin group,the 1/2paclitaxel+1/2shikonin group had a significant promoting effect upon inducing apoptosis of U87 cells.5. The 1/2paclitaxel+1/2shikonin group significantly improved the apoptosis rate of U87 cells,the RNA content of the G1-phase was significantly increased in shikonin group, the RNA content of the G2- phase significantly increased in paclitaxel group and 1/2paclitaxel+1/2shikonin group.6.Compared with control group,the rate of p-ERK/ERK was increased in paclitaxel group(P<0.05),while the rate of p-ERK/ERK was significantly decreased in the shikonin group and 1/2paclitaxel+1/2shikonin group(P<0.05).

CONCLUSION
1. Compared with paclitaxel group and shikonin group,the combination group with half dosage can make synergic effects and significantly inhibit the proliferation,migration and invation ability of U87 cells,besides promote apoptosis of U87 cells and block U87 cell cycle.2. Paclitaxel combined with shikonin could decrease the expression of p-ERK/ERK,which may be involved in the synergic effects of these two drugs.
P04.06 The incidence and impact of post-operative stroke in surgery for LGG
Authors: berger A , Tzarfati G , Costa M , Serafimova M , Korn A , Alfasi T , Kashinian A , Ram Z , Grossman R 
Published: September 2019

Abstract

BACKGROUND: INTRODUCTION
Postoperative neurological deficits may outweigh the benefit conferred by maximal resection of gliomas. Ischemic complications are a common cause of such deficits. In this study, we evaluated the incidence of ischemic events in patients undergoing surgery for low-grade gliomas (LGG) and the long-term neurological and cognitive implications of those events.

METHODS
Between 2013–2017, 168 patients underwent surgical resection or biopsy for LGG at our center. A full dataset, including pre- and postoperative magnetic resonance imaging (MRI) and long-term clinical evaluation findings, was available in 82 patients that underwent resection, and they comprised our study cohort. We retrospectively analyzed pre- and postoperative demographic, clinical, radiological, anesthetic, and intraoperative neurophysiology data to characterize associated ischemic complications. Overall and progression-free survival, as well as functional and neurocognitive outcomes were evaluated as well.

RESULTS
The immediate postoperative MRI showed evidence of an acute ischemic stroke adjacent to the tumor resection cavity in 19 patients (23%), 13 of whom developed new neurological deficits as a result of the ischemic event. Infarcts were more common in patients undergoing surgery for a recurrent tumor, especially those involving the Sylvian fissure (p<0.05). Surgery for insular gliomas had the strongest association with postoperative infarcts (multivariate analysis: odds ratio =12.4, 95% confidence interval 2.21–69.8). There was no difference in survival between patients with or without a postoperative infarct. The median Karnofsky Performance Status was lower for the infarct group compared to the non-infarct group at 3 months after surgery (p=0.016), with a gradual significant improvement for the former over one year of follow-up (p=0.04). Immediately after surgery, 27% of the patients without infarcts and 58% of those with infarcts experienced a new motor deficit (p=0.037), decreasing to 16% (p=0.028) and 37% (p=0.001), respectively, at one year. Neurocognitive analysis findings before and 3 months after surgery were unchanged, but there was a significant decrease in naming in patients who experienced an infarct (NeuroTrax computerized battery score of 100±9 and 83±19, p=0.04 respectively). Confusion during awake craniotomy was a strong predictor of the occurrence of an ischemic stroke.

CONCLUSIONS
Intraoperative strokes are more prevalent among patients who undergo recurrent surgeries, especially procedures in the insula. Although they do not affect survival, these strokes negatively affect the patients’ activity and performance status, especially during the first 3 postoperative months, with gradual functional improvement over one year.
P04.15 Impact of histone lysine methyltransferases SETDB1, SETD2, SUV39H1, MLL2, EZH2and their corresponding histone marks in pediatric astrocytomas
Authors: Klonou A , Korkolopoulou P , Gargalionis A N , Themistocleous M , Sgouros S , Papavassiliou A G , Piperi C 
Published: September 2019

Abstract

BACKGROUND
Pediatric brain tumors are characterized by altered epigenetic profiles and deregulated chromatin remodelling that affects gene expression. Histone lysine methylation has emerged as important chromatin function regulator, with potential role in glioma formation. Τhis study investigates the expression of histone lysine methyltransferases (SETDB1, SUV39H1, EZH2, MLL2, SETD2) and their corresponding methylation marks (H3K9me3, H3K27me3, H3K4me2/3, H3K36me3) in pediatric astrocytomas.

MATERIAL AND METHODS
Thirty-four (34) archival pediatric astrocytomas [27 low grade (I/II) and 7 high grade (III/IV) tumors; 21 males, 13 females; 1–15 years old] and 5 postmortem normal brain samples were studied. Methyltransferases expression and histone marks were detected by immunohistochemistry as H-score (intensity multiplied with cell percentage, 0–300) and validated by western blot.

RESULTS
Elevated nuclear SETD2 and SETDB1 staining was observed in all astrocytomas (median H-score:165 and 110, respectively). SETDB1 and SETD2 expression levels were positively associated (p=0.004), being higher in high grade compared to lower grade tumors (p=0.001, p=0.027, respectively). Furthermore, SETDB1 staining was significantly increased in male children (p=0.051) and negatively associated with patients age (p=0.028). A moderate nuclear and cytoplasmic staining was obtained for MLL2 at low grade (median H-score:84) compared to high grade tumors (median H-score:144). In accordance, lower SUV39H1 nuclear and cytoplasmic expression was detected in low grade tissues (median H score:85) compared to high grade (median H-score:160). EZH2 presented no significant nuclear expression. Increased nuclear staining of H3K9me3 and H4K20me3 repressive marks was observed in astrocytomas (median H-score:297 and 270, respectively), being positively associated (p=0.02). Elevated nuclear staining of H3K4me3 active mark (median H-score:210) was detected in astrocytomas, being significantly higher in high grade tumors (p=0.025) and in male children (p=0.036).

CONCLUSION
SETDB1, SETD2, SUV39H1 and MLL2 may play a significant role in modulating gene expression in pediatric astrocytomas. Increased presence of H3K9me3, H4K20me3 and H3K4me3 histone marks signifies their possible participation in gliomagenesis.
Larger cohort studies need to elucidate the functional significance and underlying molecular mechanisms of these chromatin-modifying enzymes and respective histone changes in pediatric astrocytomas.
P06.02 Tumor Treating Fields therapy application in 3-year-old grade 4 glioma patient is feasible and safe
Authors: Kietz S , Stein M 
Published: September 2019

Abstract

BACKGROUND
High-grade gliomas (HGG) are aggressive brain tumors affecting both children and adults. In adult patients a new treatment modality was recently established for patients with newly diagnosed (nd) and recurrent glioblastoma (GBM). Low intensity intermediate frequency alternating electric fields, known as Tumor Treating Fields (TTFields), demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in adult ndGBM patients. For pediatric HGG patients only few treatment options are available. Here, we report on a pediatric patient who is receiving TTFields therapy in combination with temozolomide.

MATERIAL AND METHODS
A three-year-old male presented with a grade IV glioma with H3K27M expression located pontine on the right occipital. A stereotactic biopsy was performed; further analysis revealed no IDH1 mutation, no TERT promoter mutation and no MGMT promoter methylation. The patient recieved radiochemotherapy with temozolomide. TTFields therapy was initiated after completion of radiochemotherapy in combination with temozolomide. Due to the location of the tumor, the infratentorial transducer array layout was used for TTFields application.

RESULTS
At the beginning of TTFields therapy the patient and his family needed time to get used to the new therapy, due to this the adherence to TTFields therapy was on a low level in the first month. The TTFields usage rate improved every month from about 40 % in the first two months to about 80 % after 5 and 6 months. After the initial time for adaption to the therapy, the average usage rate in months 4 to 8 was 75.87 %, which is above the independent prognostic threshold of 75 %. The patient is on TTFields therapy for more than 8 months and no therapy-related adverse events were observed during this time. To-date the patient is still on TTFields therapy and clinically stable. MRI analysis revealed stable disease with a slightly reduced area of contrast-enhancement.

CONCLUSION
In this case, the TTFields usage rate was low in the beginning, the patient and his relatives demonstrated a successful adaption to the therapy over time. This case demonstrates that TTFields therapy can be continued at high adherence, although the usage rate might be low in the beginning. Moreover, in this presented patient TTFields therapy is feasible and safe in a pediatric patient at 3 years of age at initiation of therapy. In conclusion, TTFields therapy can be offered to pediatric patients with HGG. Safety and efficacy in pediatric patients should be further investigated in clinical trials.
P08.02 Israeli experience with Patient Reported Outcomes (PROs) in the field of neuro oncology - Quality of Life Assessment Metrics (QAM)
Authors: Wagner T , Jan E , Bley S , Cohen R , Furman O , Talianski A , Zach L 
Published: September 2019

Abstract

BACKGROUND
With the development of personalized medicine, it is necessary to take into consideration PROs, including quality of life (QOL) to adjust the treatment and follow up. Trends of QOL outcomes are of special interest for neuro oncologic patients in the setting of chemo-radiotherapy due to the high incidence of pseudo progression (worse MRI with no tumor progression). There are several QAM in the field of neuro oncology. We used the quality of life questionnaire (QLQ-30) for brain cancer with the QLQ-BN20 supplement, and Functional assessment of chronic illness therapy (FACIT) with the FACT-Br supplement (version 4). We looked at the level of agreement between the two assessment tools for QAM for Israeli patients with different brain tumors.

MATERIAL AND METHODS
Forty patients were recruited between September 2017 to May 2018 at Sheba Medical Center after local IRB approval. Patients fulfilled the two types of questionnaires at 4 time points: before radiotherapy, with radiotherapy completion, at three months follow up and before another intervention. The difference between the two metrics was measured by t-test and performed by Bland-Altman plot. The association between QAM and MRI after radiotherapy and doctor assessment was measured by Linear regression.

RESULTS
Forty patients completed 162 questionnaires overall (QLQ-30 and FACIT): 8 patients completed questionnaires at all 4 time points, 7 patients completed questionnaires - 3 times, 6 patients- twice, and 19 patients- once. Three patients didn’t answer FACIT questionnaires and 3 other patients didn’t answer QLQ questionnaires. Patients population included 40% (16/40) with astrocytoma [25% (4/16), 31.2% (5/16), 43.8% (7/16) of them with WHO Grade 2,3,4 respectively], 25% (10/40) with meningioma [60% (6/10), 20% (2/10), and 20% (2/10) of them with WHO Grade 1,2 and 3 respectively], 20% (8/40) with brain metastasis, and other tumors (6/40) consisted 15% of the patient population. We found a significant difference between QAM means of agreement of the two metrics used (p<0.001). There was a significant correlation between QAM and MRI after radiotherapy (p=0.013; R2=0.369 and p=0.025; R2=0.292 for QLQ and FACIT questionnaire, respectively). There was no significant correlation between physician examination and QAM metrics (p=0.880; R2=0.002 and p=0.724; R2=0.009 for QLQ and FACIT questionnaires respectively).

CONCLUSION
Patients’ evaluation success depends on the appropriate assessment metrics. QLQ questionnaires were a more appropriate tool in our patient population confirmed by MRI assessment compared to physicians’ evaluation. Our study shows a significant difference between two well validated tools. Further research is needed to establish the source of this difference and adjust QAM for neuro oncologic patients accordingly.
P09.01 case series: meningioma in young adult male
Authors: Diansari Y , Karindang N , Anggraeni D 
Published: September 2019

Abstract

BACKGROUND
Intracranial meningiomas are most common among patients in their fifth to seventh decade of life, typically found in older women. Meningiomas are rare in children and young adults; they represent 1–3% of all intracranial tumors in individuals up to age 20 years and 13.5% of intracranial tumors in the 20–34 age group. Meningioma in young adult male is a rare finding. Management of meningioma is similar between young or older patient. The prognosis is depent on the histology finding and type of resection. This case series was made to report an uncommon case including clinical characteristic and management of meningioma in young adult male.

MATERIAL AND METHODS
We reported 2 cases of meningioma in young adult male. The first patient was hospitalized on 2016 and diagnosed with atypical meningioma (WHO grade II). The second patient was hospitalized on 2018 and diagnosed with trantitional meningioma (WHO grade I).

RESULTS
First case: 23 y.o male was hospitalized because of severe headache. His physical exam showed weakness of his left side of the body. There was diplopia that significant for bilateral six nerves palsy. Funduscopy examination revealed papil edema in both eyes correlated with his complained of blurry visions. There was no cranial irradiation from his past medical history. Second case, a male 22 y.o was because of decreased of visual acquity progressively since two month before. There was history of throbbing headache in his left head with mild to moderate intensity. On his neurological examination, there was mild weakness in his right body side. Visual acquity on his right and left eyes were 1/300 and 1/60. Bilateral papil edema was found in funduscopy examination. In his past medical history, there was no history of cranial iradiation. Both cases showed similar initial symptoms consist of headache and others neurological deficit. Radiological examination was performed with result leading to meningioma in convexity area in both cases. Craniotomy tumor removal with gross total resection as simpson grade 2 was achieved in both patients. In the second case pre-operative embolization was performed in order to achieve optimal resection. Histopathology examination confirmed as atypical (WHO grade II) in the first case and trantitional Meningioma (WHO grade I) in second case. Follow up imaging post operation showed no residual mass lesion in both patients. There were no further management in these patients. Both of patients showed improvement in their neurologic function and able to activity without restriction in daily living. Serial imaging examination is planned to observe reccurence of the tumor.

CONCLUSION
Clinical presentation and management of meningioma in these patients are similar as meningioma commonly. Both of patients showed clinical improvement after craniotomy tumor removal succesfully.