bluuebunny/crossref_metadata_2025_split huggingface dataset:
P16.02.B Leptomeningeal dissemination in gliomas in National Research Institute of Oncology in Gliwice experience
Authors: Nowicka E , Grzbiela H , Widera K , Zarudzki L , Grządziel A , Tarnawski R 
Published: September 2022

Abstract

Background
The leptomeningeal dissemination (LMD) in the course of gliomas is rare. According to literature it can affect 4.7% of all patients with gliomas. LMD can be diagnosed at the initial presentation or at the time of recurrence. The standard therapy has not yet been determined. We aimed to present the clinical features and prognosis in retrospective analysis of patients with LMD in gliomas in National Institute of Oncology in Gliwice, Poland experience.

Material and Methods
Twenty patients with leptomeningeal dissemination in course of treatment of brain gliomas were identified. There were 16 men and 4 women. Median age of pts was 35,5 y (range 18-51). All tumours were supratentorial at diagnosis. There were 6 Diffuse Astocytomas, 3 oligodendrioglimas and 11 glioblatomas. In two patients LMD was found at initial diagnosis of GBM. The majority of patients (15 pts) presented clinical symptoms and in 5 asymptomatic pts LMD was diagnosed in MRI. The diagnosis was confirmed in craniospinal MRI. One patient was operated due to rapid clinical progression of spinal compression symptoms. All but one patient were offered palliative therapy. Radiotherapy was prescribed to 16 patients: in 7 pts for whole brain to C2, in 3 pts for craniospinal axis, in 7 for spinal canal and in 2 pts local therapy was performed. Mean dose of RT was 28,7 Gy/g (range 18-45 Gy/g). In 8 patients radiotherapy was combined with chemotherapy and chemotherapy as sole treatment was prescribed to 2 pts (Lomustin, EP).

Results
Mean time from initial diagnosis to LMD diagnosis was 46 mo (range 0,4-199 mo) for all patients and for non-GBM and GBM patients were 81,4 mo (16-199 mo) and 14,0 mo (0,4-27 mo) respectively. In 7 patients LMD was diagnosed concurrently with local relapse. In remaining mean time from local relapse to LMD was 4,6 mo (1,2-20,0 mo). Mean OS dated from time of LMD diagnosis for whole group was 5,9 mo (0,4-27 ), for non-GBM and GBM patients were 9,2 mo (3,6-27 mo) and 2,94 (0,4-12,7 mo) respectively. The palliative effect as improvement in clinical symptoms was achieved in 15 pts.

Conclusion
LMD in gliomas is rare but should be kept in mind while clinical symptoms in glioma patients occur. The prognosis of LMD is poor. Radiotherapy have palliative intent and it can affect the clinical symptoms and survival.
P17.01.A Reradiation by Glioblastoma recurrence with VMAT technique
Authors: Theodorou M , Polycarpou I 
Published: September 2022

Abstract

Background
Patients who have been treated with reirradiation for recurrent glioma reported survival benefits.
This study aims to investigate whether re-irradiation of recurrent glioma with 45Gy dose can increase the overall survival of patients.

Material and Methods
A retrospective analysis of 35 patients re-irradiated for high-grade glioma recurrence between 2012 and 2020 was performed. All included patients met the following criteria: a) histopathological confirmation of primary brain cancer at initial diagnosis; b) a history of initial primary radiation; c) histological and/or imaging modality confirmation of recurrence. Outcome metrics included overall survival, prognostic factors for survival, and treatment-related toxicity.

Results
After the end of re-irradiation the median overall survival was 11 months (95% confidence interval, 7-14 months). From the patients evaluated in the current study after the end of re-irradiation the progression free survival was 6 months (3.8 - 8 months) while after the end of first radiation was 13 months (8 - 17.9 months). Our findings suggest that re-irradiation might prolong survival rates.

Conclusion
Recurrent Glioblastoma WHO IV is associated with a median overall survival of less than a year and the majority of patients have profound tumor-related symptoms .The results of this study suggest that re-irradiation may prolong the overall survival.
P17.03.B Modelling migration of glioblastoma patient-derived cells using human iPSC-derived neural spheroid and high content analysis
Authors: Tsang V S , Lieberam I , Danovi D 
Published: September 2022

Abstract

Background
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour in adults. Despite current advances, the existing standard of treatment is ineffective, and the survival prognosis remains just over a year from diagnosis. Migrating tumour cells have been implicated in the therapeutic resistance of GBM. They spread by interacting with structures such as white matter tracts and inevitably cause recurrence of the tumour. Valuable cell models able to capture the invasiveness of GBM are critically needed to develop innovative therapies targeting migrating GBM cells.

Material and Methods
We established an in vitro model mimicking the GBM microenvironment by co-culturing patient-derived GBM cells and human induced pluripotent stem cell-derived cortical neural spheroids with radiating axons. Using high content imaging, we developed a robust workflow to quantify the GBM cells infiltration of the neural spheroid in endpoint assays. Images were acquired on the Operetta CLS high content device (Perkin Elmer) and analysed using the built-in Harmony Imaging and Analysis Software. We also performed live imaging assays using the Livecyte quantitative phase imager (Phasefocus), in which we studied the directionality, displacement and speed of the GBM cells engaged on axons.

Results
Our data indicate that GBM cells change morphology when cultured on axons and that they migrated towards the neural spheroid once engaged on axons. We showed that cell lines from different patients vary in migratory properties as well as in levels of infiltration capability. Finally, we used this model to test several antagonists to pathways involved in migration of GBM cells.

Conclusion
The main deliverable of this project is the setup of a novel model able to mimic the GBM migration on axons and able to screen for compounds affecting cell migration. This could potentially offer innovative precision-medicine therapies.
P17.07.A Metronomic temozolomide therapy in heavily pretreated patients with recurrent glioblastoma: a large mono-institutional retrospective study
Authors: Bosio A , Padovan M , Caccese M , Cerretti G , Zagonel V , Lombardi G 
Published: September 2022

Abstract

Background
Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite advances in surgical and first-line treatment, all pts relapse. The aim of this study is to evaluate the benefit of metronomic Temozolomide (mTMZ) for recurrent GBM.

Material and Methods
All pts treated at Veneto Institute of Oncology from September 2013 to March 2021 were retrospectively reviewed. Major inclusion criteria were: first-line therapy with Stupp protocol, relapse after first or subsequent line of therapy, treatment with mTMZ schedule (50mg/m2 continuously), hystologically confirmed diagnosis of GBM. RANO criteria and CTCAE v 5.0 were used for response and toxicity assessment.

Results
120pts were enrolled. Median follow-up was 15.6ms. Median age was 59ys (range 18-81), ECOG-PS was 0-2 in 107pts (89%) and 3 in 11 (9%). MGMT was methylated and IDH mutated in 66 of 105 (62%) and in 9 of 106 (8%) evaluable pts, respectively. Median number of prior lines of treatment was 2 (range 1-7) and 41% of pts received the therapy beyond the third line. Median time between the last standard maintenance TMZ (sTMZ) cycle and the mTMZ administration was 6ms (range 1-50) and 40% of pts started mTMZ after 3ms from sTMZ. All pts were evaluable for response: 3 (2%) and 48 (40%) showed PR and SD. mOS from the start of mTMZ was 5.4ms (95% CI 4.3-6.4), mPFS was 2.6ms (95% CI 2.3-2.8). At univariate analysis, MGMTmet and MGMTunmet pts had a mOS of 5.6 and 4.4ms (p=0.03); mOS for patients with ECOG-PS &gt; or ≤2 was 2.3 and 6.0ms (p&lt;0.001); number of prior lines of therapies, time between sTMZ and mTMZ and age were not significant. At multivariate analysis, MGMT methylated status (HR=2.3, 95% CI, p=0.004) and ECOG-PS (HR=0.5, 95% CI, p=0.017) remained statistically significant for PFS, while ECOG-PS (HR=0.4, 95% CI, p=0.001) was the only factor significantly associated with OS. The most common grade 3-4 hematologic toxicities were lymphopenia (10%) and thrombocytopenia (3%). Grade 3-4 nonhematologic toxicities were uncommon.

Conclusion
Rechallenge with mTMZ can be a well tolerated treatment option for recurrent GBM, even in heavily pretreated pts. Pts with MGMTmet and good ECOG-PS might report the major benefit.
P17.08.B Single institutional retrospective review of re-irradiation in High Grade Gliomas in a tertiary UK centre
Authors: Manik V , Brazil L , Swampillai A , Chia K , Al-Salihi O 
Published: September 2022

Abstract

Background
Recurrent high grade gliomas (HGG) pose a treatment challenge as no definite guidelines exist. Re-excision could be appropriate in some cases while systemic therapy options are only a handful. We thus need to resort to the option of re-irradiation at some point but there could be a wide variety of techniques, volumes & doses to choose from due to lack of robust evidence. The UK wide BRIOCHe study for Glioblastoma Multiforme (GBM) will help in providing some standardisation. With this retrospective study, we aim to review our institutional practice with re-irradiation & our patient outcomes.

Material and Methods
Electronic health records over a period of 3 years from 1 Jun 2019 to 30 May 2021 were searched for patients with HGG that underwent a course of re-irradiation. Various patient factors, tumour & treatment factors at baseline and at recurrence and survival data were collected.

Results
Total of 8 patients received re-irradiation with all except one having a performance status of 1 at the time of treatment. Seven patients had GBM, one had transformation from baseline G2 glioma and the eighth patient had anaplastic oligodendroglioma (ODG). MGMT was methylated in 62.5% patients while IDH mutation was present only in the transformed glioma. Majority patients had radiotherapy dose of 60Gy/30 fractions with concurrent temozolomide (TMZ) at baseline to a median CTV volume of 186cc. A median of 6 cycles of TMZ were given in the adjuvant setting. Median time to recurrence from completion of adjuvant treatment was 6.7 months (range: 0.9 - 171.6 months). Most recurrences were in the same or an adjacent lobe whereas 1 patient had a multi-focal recurrence. Half the patients at recurrence underwent a re-resection. All patients had salvage chemotherapy at the time of recurrence with a median of 2 regimens and a median of 6 cycles prior to re-irradiation. All patients received a re-irradiation dose of 35Gy in 10 fractions to a median CTV volume of 149cc. The median interval from previous radiotherapy was 18.9 months (range: 11.6 - 190.5 months). The median time to progression from re-RT was 5.4 months (CI: 3.4 - 7.4) and median survival from re-RT was 7 months (CI: 6.2 - 7.8). The median overall survival since diagnosis was 35.1 months (CI: 22.2 - 48.1), one patient was lost to follow up.

Conclusion
Re-irradiation is a safe & feasible treatment option in carefully selected cases of high grade glioma.
P17.10.B Identification of mechanisms involved in the recurrence of glioblastoma by transcriptomic, proteomic and spatial profiling analysis
Authors: Ritz M , Shekarian T , Martins T , Hogan S , Schmassmann P , Burger B , Hutter G 
Published: September 2022

Abstract

Background
Glioblastoma (GBM) is the most aggressive and common brain tumor. Despite multimodal therapy which consists of complete tumor removal, chemo- and radiation therapy in most patients, the tumor recurs, and the overall survival of only 14 months remains very poor. To identify tumor-induced immune evasion and treatment resistance mechanisms induced during GBM recurrence, we aimed at characterizing the immunological/molecular changes in patient-matched treatment-naïve and recurrent GBM samples.

Material and Methods
Proteins and total RNA were extracted from 16 patient-matched treatment-naïve (primary) and recurrent GBM fresh frozen tumor samples. The expression of genes involved in brain immune responses were compared using Nanostring panels encompassing Cancer and Neuroinflammation genes. Proteomic was conducted using 6 patient-matched primary and recurrent tumor samples. Immunostaining was performed on a tissue microarray containing matched primary and recurrent tumor samples to identify tumor cells and microglia in order to assess spatial transcriptome of these specific cell types in situ using GeoMX technology. Moreover, correlation analysis of differentially genes and proteins with time to relapse was performed.

Results
Genes significantly differentially expressed between primary and recurrent tumors revealed genes overexpressed in recurrent tumors belonging to “FCGR-mediated Phagocytosis” and “synapse pruning” pathways. Proteomic confirmed the synaptic signalling considering overexpressed proteins. Correlation studies with the time to relapse indicated that higher expression of FCG receptors, complement molecules and synaptic components correlate with shorter time to relapse, sharing similarities with neurodegenerative/cognitive disorders such as schizophrenia and Alzheimer disease. The source for these molecules is under evaluation with the spatial transcriptomic analysis.

Conclusion
Upregulation of specific proteins such as FCG receptors, complement and synaptic components may result in more favourable conditions for tumor regrowth and may therefore be identified as negative predictors patient outcome. Interfering with these molecules may represent novel therapeutic options after initial GBM surgery.
P17.13.A Verteporfin inhibits autophagy in glioblastoma cell lines
Authors: Casati G , Giunti L , Iorio A , Marturano A , Sardi I 
Published: September 2022

Abstract

Background
Glioblastoma (GBM) is the most common primary brain tumor with a poor prognosis, characterized by a high cellular heterogeneity and invasiveness. Multi-drug resistance (MDR), the blood brain barrier (BEE) and DNA repair systems let the survival of tumor cells, making the treatment with chemo and radiotherapy not effective. Autophagy is a physiological mechanism that allows the recycling of damaged proteins and organelles, in order to protect the correct cell turnover. However, in GBM this process promotes survival and proliferation in stressful conditions such as after a chemo and / or radiotherapy treatment. The Hippo pathway is an extremely important molecular signaling because it is involved in various tumorigenesis processes, for instance the epithelium-mesenchymal transition (EMT), in the increase of stemness, mechanotransduction and chemoresistance.

Material and Methods
The modulation of autophagy was evaluated in GBM cell lines (U87MG, T98G and A172) exploiting a fluorescent detection that allowed the quantification of the autophagosomal activity present into the cell lines. The rate of autophagy was assessed after the cell lines pharmacological treatment with Hippo pathway inhibitors, Verteporfin 2uM (VP) for 24h, Latrunculin 0,5uM (LAT) for 3h and Cytochalasin 1uM (CIT) for 3h, with Doxorubicin 0,5uM (DOX) for 24h and with the drugs combination (DOX-VP, DOX-LAT and DOX-CIT). Moreover, the expression of the autophagy marker LC3II / I was evaluated in all three GBM cell lines by Western Blotting (WB) experiments. To perform this technique, the cells were treated with DOX and Hippo pathway inhibitors respecting the pharmacological treatment previously used. Then, the proteins were extracted, quantified and finally the WB was performed.

Results
The results obtained showed that the three GBM cell lines without any drugs were marked by high levels of autophagy, similar to the cells treated with Rapamycin, an autophagy inducer. Moreover, the autophagy rate was definitely reduced after treatment with VP and DOX-VP in all three cell lines, including the chemoresistant T98G. Conversely, the other two Hippo pathway inhibitors (LAT-CIT) and DOX did not significantly change the rate of autophagy. The expression of LC3II / I was particularly low after treatment with VP and DOX-VP in all three cell lines while the other two inhibitors did not significantly change its expression.

Conclusion
In conclusion, these data demonstrated that the three GBM cell lines (U87MG, T98G and A172) are characterized by high levels of autophagy and the inhibition of the Hippo pathway with VP and especially the combination DOX-VP reduced the activation of this protumoral molecular mechanism in GBM cell lines.
P17.15.A Neoadjuvant immunotherapy in the treatment of recurrent glioblastoma: an overview of last decade
Authors: Nogueira B V , Cyntia Fonseca Lima Rodrigues A , Almeida I M 
Published: September 2022

Abstract

Background
Recurrent glioblastoma (ArGB) is one of the most common primary malignant brain tumors in adults, with a poor prognosis, with low patient survival even after treatment. Because of this, several studies were carried out evaluating different therapies for the treatment of ArGB, more recently studies have emerged regarding the use of neoadjuvant immunotherapy and its possible advantages in the treatment of such patients. Therefore, the present study aims to analyze the efficacy of neoadjuvant immunotherapy and its effect on the survival of patients with recurrent glioblastoma.

Material and Methods
A search was performed in PubMed, Embase and Cochrane databases using the keywords: “Immunotherapy, “neoadjuvant” and "recurrent glioblastoma". Articles from the last 10 years were selected and those that did not meet the inclusion criteria were excluded from the research, totaling 7 selected articles.

Results
Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy after surgery, had significantly prolonged survival compared to patients who were randomized to receive adjuvant post-surgical PD-1 blockade alone. Neoadjuvant PD-1 blockade was associated with up-regulation of T cells and interferon-γ-related gene expression, but with down-regulation of cell cycle-related gene expression within the tumor, which was not observed in patients receiving adjuvant therapy. isolated.

Conclusion
Neoadjuvant immunotherapy, through a PD-1 inhibitor, in patients with ArGB, results in positive biological effects, in addition to the clinical benefit of, on average, increasing overall survival considerably due in large part to the improvement of the immune response , with no noticeable adverse effects, thus being advantageous, although these results are early and the current studies are not very comprehensive. Larger studies are needed for greater reliability and statistical relevance.
P18.01.A The applicability of established clinical and histopathological risk factors for tumor recurrence during long-term perioperative care in meningioma patients
Authors: Lüthge S , Steinbicker A , Schipmann S , Streckert E M S , Hess K , Grauer O , Paulus W , Stummer W , Brokinkel B , Spille D C 
Published: September 2022

Abstract

Background
Risk factors for the prediction of late-onset tumor recurrence in meningioma patients are sparse but needed to estimate duration and control intervals during long-term follow-up in meningioma patients. In this study, we therefore analyzed the value of established risk factors for postoperative meningioma recurrence for the prediction of long-term prognosis in a large, single-center series.

Material and methods
Correlations of established clinical (age, sex, tumor location, extent of resection), radiological (postoperative tumor volume) and histopathological variables (WHO grade, brain invasion) with tumor relapse were analyzed separately after 3, 5, and 10 years following microsurgery for primary diagnosed intracranial meningioma between 1991 and 2021 in uni- and multivariate analyses. The prognostic value was compared to findings in the entire cohort.

Results
Within a median follow-up of 29 months (range: 0-307 months), recurrence was observed in 141 patients (12%) after a median PFS of 36 months. PFS among the entire cohort (n=1218) at 3, 5, 10 and 15 years postoperatively were 90%, 84%, 74% and 70%, respectively. Among all patients included, skull base location (HR: 1.51, 95%CI 1.05-2.16; p=.026), Simpson ≥IV resections (HR: 2.41, 95%CI 1.52-3.84; p&lt;.001), high-grade histology (HR: 3.70, 95%CI 2.50-5.47; p&lt;.001) and male gender (HR: 1.46, 95%CI 1.01-2.11; p=.042) were independent risk factors for recurrence. Skull base location (HR: 1.92, 95%CI 1.17-3.17; p=.010 and HR: 2.02, 95%CI 1.04-3.95; p=.038) and high-grade histology (HR: 1.87, 95%CI 1.04-3.38; p=.038 and HR: 2.29, 95%CI 1.07-4.01; p=.034) but not subtotal resection (HR: 1.53, 95%CI .68-3.45; p=.303 and HR: 1.75, 95%CI .52-5.96; p=.369) remained independently correlated with recurrence after an event-free PFS of at least three (n=485) and five years (n=346), respectively. Similarly, postoperative tumor volume was related with recurrence in the entire cohort (p&lt;.001) but not beyond a follow-up of ≥ three years (p&gt;.05). In 147 patients with a follow-up of ≥ ten years, ten recurrences occurred, and no correlation was found with any of the analyzed variables.

Conclusion
Skull base tumor location and high-grade histology but not the extent of resection should be considered when planning follow-up duration and intervals following ≥5 years after meningioma surgery. Tumor relapses following more than ten years after surgery are very rare, and corresponding predictors are lacking.