bluuebunny/crossref_metadata_2025_split huggingface dataset:
P17.16.B INVESTIGATION OF REGORAFENIB TUMOR SENSITIVITY AND UNDERLYING TREATMENT INDUCED MOLECULAR MECHANISMS IN GLIOBLASTOMA RECURRENT TUMORS
Authors: Morelli M , Lessi F , Giacomarra M , Marranci A , Menicagli M , Santonocito O S , Aretini P , Pasqualetti F , Di Stefano A L , Franceschi S , Mazzanti C M 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma (GB) is the most aggressive brain malignant tumor with a highly unfavorable prognosis. Maximal surgery resection, temozolomide chemotherapy (TMZ), and radiotherapy (RT), currently remain the best treatment option. Recently the phase II REGOMA clinical trial, has shown that regorafenib (REGO), a multikinase inhibitor that targets angiogenic, stromal and oncogenic tyrosine kinase receptors, significantly improves survival in GB patients.The aim of this study was to investigate Regorafenib tumor sensitivity and underlying molecular mechanisms in GB recurrent tumors leveraging on an ex vivo drug response functional precision medicine approach, that we have developed recently consisting of an in vitro vital patient-derived GB 3D organoid model and NAD(P)H Fluorescence Lifetime Imaging (FLIM).

MATERIAL AND METHODS
In-vitro 3D GB organoids were derived from 17 patients’ resected recurrent GB tumors. For 5 of these we had the matched primary tumor, and for other 3 we collected also the tumor peripheral portion. Totally, we obtained 25 samples. After 3 days from culture, organoids were treated with TMZ and REGO and drug response, using NAD(P)H FLIM, was assessed in the following 72 hours to stratify tumors in Sensitive (S) and Non Sensitive (NS). Whole-exome was performed on 14 tissue samples, comprising 5 primary/recurrence tumor pairs and whole-transcriptome on 11 recurrent samples before and after treatment.

RESULTS
Stratification of tumor cases in S and NS groups was performed both for TMZ and REGO treatment. We found 32% (n=8) and 76% (n= 19) of TMZ and REGO S tumors, respectively. Interestingly there was never a TMZ S case that was NS to REGO. Heterogeneity was found in the TMZ and REGO responsiveness for the tumor core/peripheral pair portions and in the primary/recurrence tumors pairs. It is noteworthy that all primary tumors were responsive to REGO.The drug-responsive stratification performed using our approach was also well reflected at the molecular level, as shown from transcriptome and exome

RESULTS
, where differently expressed genes and mutated genes were found in S versus NS tumors.

CONCLUSION
GB recurrent tumors resulted more responsive to REGO when compared to TMZ treatment, as expected. Thanks to our functional precision medicine approach, we were able to study the molecular alterations occurring due to the treatment, discovering biomarkers of sensitivity or resistance.
P17.18.B RADIOTHERAPY IN GLIOBLASTOMA MULTIFORME COULD BE PLANNED WITH MARGINS LESS THAN 2 CM WITH LESS THAN 1 CM FROM THE SURGICAL BED
Authors: Oñoro Guzman. l H 
Published: September 2023

Abstract

BACKGROUND
The administration of radiotherapy (Rt) plus adjuvant temozolamide (TMZ) with IMR and VMAT techniques has become an increasingly valuable tool in the local control of glioblastoma multiforme with a survival current Rt techniques allow specific conformation with the use of better radiological images that allow us greater precision. For many years large Rt field sizes have been associated with significant adverse effects.Although we continue to give very wide margins that lead us to irradiate non-compromised organs at risk, which translates into a higher rate of radionecrosis and acute and chronic neurological toxicity.Therefore, we consider it valid to ask ourselves if we could reduce the standard margins applied in the planning of Rt.

MATERIAL AND METHODS
Analysis of 98 GBM patients treatedat the barros luco hospital between 2021 and 2023 with surgery followed by adjuvant therapy, radiotherapy plus concomitant chemotherapy at the Institute. Nacional de Cáncer de Santiago de Chile we reviewed the time of recurrence and the location in relation to the surgical margins vs. radiotherapy margins or other nearby areas.

RESULTS
After the analysis, we can see that 65% of the recurrences presented a dominant failure pattern, within the field and less than 1cm from the margin between the surgical bed and the radiotherapy margin, evaluated with perfusion brain resonance imaging and spectroscopy

CONCLUSION
n the local control of GBM, the application of adjuvant therapy is essential in a period of not less than 2 months after surgery, in this institutional analysis we can observe a considerable number of patients under 40 years of age with this pathology, for which reason to consider reducing the diameter of Rt margins can be considered an option, in order to limit deleterious effects in healthy organs in the times that there are advanced Rt techniques, the increasingly frequent application of brain radiosurgery (SRS) thatIt can be used as a rescue method in case of recurrences at the edge of the margin, using radiological images (MRI with perfusion and spectroscopy/C-methionine PET/CT. Figure we can see the CTV and PTV to be treated with modulated intensity technique, evidencing the large field size that receives radiation between 54 to 60 Gy.Radiation oncology must continue to develop and improve the delivery, targeting, and dose of radiation therapy in the GBM to improve its survival and treatment-associated toxicity.
P18.05.A THE GROWTH PATTERN OF MENINGIOMA CELLS IN CELL CULTURE UNDER DIFFERENT CONDITIONS
Authors: Linsler S , Moroldo A , Oertel J , Urbschat S 
Published: September 2023

Abstract

BACKGROUND
Cell cultures is an established method in tumor research. Thereby, the growth rate is important for the results. Depending on the experimental and clinical setting, the used tissue is exposed to different conditions. Interestingely, the different cell and tissue conditions are not well reported yet. Although, it is likely that the different conditions influence the growth pattern of cell cultures in primary cell lines. Here, the authors present their experimental analysis of cell culture of primary meningioma cells after different initial tissue conditions.

MATERIAL AND METHODS
From June to December 2022 ten primary human meningiomas were collected after surgery at the Neurosurgical Department of the Saarland University. Primary cell cultures (Passage 0 = P0) were set up on the day of surgery and one day postoperatively. These tissues were kept overnight in nutrient solution in the refrigerator. They were splitted in two P1 cultures (Passage 1). The termination of the cell culture occured when the flasks were fully grown. One P1 culture was used for Fluorescence in situ hybridization. The other one was frozen on liquid nitrogen. The latter is thawed after six months and cultivated again. Additionally, swab preparations were made for Fluorescence in situ hybridization. The frozen tissue of these meningiomas was also used for further cell cultures.

RESULTS
Eight of ten cases (80%) of the meningioma cell cultures (from the day of surgery and one day postoperatively) have grown. In one case only the cell culture from the day of surgery has grown and in another one there were only single cells, no growth out of this tissue. The cell cultures prepared from frozen tissues have not shown any culture growth. There were not any significant differences between the growth of the cell culture from the day of surgery and of the cell culture from one day after surgery. The results of the Fluorescence in situ hybridization have shown a loss of 1p in one meningioma, a loss of 22q in three meningiomas, a loss of 1p and 22q in three meningiomas and a normal chromosome set in three tumours. Further, there were not any differences between the evaluation of swab preparations and drop preparations. Until now, six out of six thawed cell cultures of the first three meningiomas can be cultured again after six months in liquid nitrogen.

CONCLUSION
It has been shown that the growth pattern of meningioma cell cultures is independent of the set up at the same day or one day after surgery if there are enough living cells in the tissue. On the other hand, meningioma cell culturing of frozen tissues is not possible in the same setting.
P18.10.B WHICH MENINGIOMAS BENEFIT MOST FROM METHYLATION PROFILING?
Authors: Ruiz F , D'Antona L , Dutt M , Mariathasan P , Merve A , Jaunmuktane Z , Sahm F , Brandner S 
Published: September 2023

Abstract

BACKGROUND
methylation profiling combined with copy number assay provide a better prognostication than WHO grade alone. Profiling all meningiomas is financially unsustainable in most centres, therefore pathologists and clinicians ask for guidance which meningiomas to analyse. Here, we analysed how the WHO grades resolve into methylation classes and risk strata, to provide guidance on which meningiomas to profile

MATERIAL AND METHODS
From 2018-2023 a subset of meningiomas diagnosed within our institution, and all referred meningiomas underwent methylation profiling with copy number assay. Using the classifier 12.6 we determined how the 3 CNS WHO grades (in short G1, G2, G3), resolve into the methylation classes (MC) benign, intermediate, or malignant, or the risk strata low, intermediate, and high [PMID 36377252, 34618539]

RESULTS
Of 1408 locally diagnosed meningiomas, 309 (22%) underwent profiling and 393 meningiomas were referred. Of these 702 meningiomas, 545 had a calibrated score of &gt;0.90. Of 253 G1 meningiomas 231 (91%) allocated to MC benign, and 22 (9%) into MC intermediate. Instead, of the 214 G2 meningiomas, 124 (58%) allocated to MC benign, 77 (36%) to MC intermediate and 13 (6%) into MC malignant. The 17 G3 meningiomas distributed approximately equally into the 3 MC’s. Similarly, when analysing the allocation to integrated risk scores, of the 214 G2 meningiomas, 71 (33 %) were low, 106 (50%) intermediate, and 37 (17 %) high risk. None of the 16 G3 meningiomas had a low risk score, whilst 5 had an intermediate, and 11 a high risk score. When stratifying G2 meningiomas by grading criterium (brain invasion, mitotic count, histological type) there was a similar risk score distribution across the 3 criteria.

CONCLUSION
G2 meningiomas show the most notable discrepancy between grade and methylation class or risk score, and thus should preferentially undergo methylation profiling. Instead, most G1 meningiomas have a low, and most G3 meningiomas a high risk score.
P19.03.B IMPLEMENTATION OF RESECT CATEGORIES FOR EXTENT OF RESECTION STRESS THE LONG-TERM CLINICAL BENEFIT OF SUPRAMAXIMAL CONTRAST ENHANCING RESECTION IN A RETROSPECTIVE COHORT OF NEWLY DIAGNOSED IDH WT GLIOBLASTOMA PATIENTS
Authors: Gambacciani C , Nizzola M G , Calvanese F , Villanacci F , Pieri F , Grimod G , Aquila F , Scudieri C , Cupini S , Stasi I , Zucchi V , Giusti A , Lastrucci L , Vannozzi F , Giuri A , Farina L , Pichiecchio A , Di Stefano A L , Santonocito O S 
Published: September 2023

Abstract

BACKGROUND
to assess the long-term benefit associated with supramarginal CE resection and to apply ReSECT criteria for extent of resection in patients with primary glioblastoma IDH wild-type.

MATERIAL AND METHODS
We performed a retrospective search in the institutional of Livorno Hospital for adult patients with primary GBM IDH wild-type. We assess residual tumor volumetry in the early post-operative magnetic resonance imaging by the 3dslicer software. We attributed EOR classes according to ReSECT criteria based on residual contrast and non-contrast enhancing tumor volumes. We performed multivariate analysis by Cox regression including main known prognostic factors and MGMT promoter status assessed by pyrosequencing. IDH wild-type status was defined on both IDH1 and IDH2 genes.

RESULTS
We identified 173 patients who underwent surgery for confirmed primary glioblastoma IDH wild-type in our institutions from 2016 and 2022. Male/female ratio was 1.6, median age at diagnosis 68 years old (yo) (range 30-83), median KPS before surgery was 80 (range 30-100) with no significant variation at the post-operative stage. Forty out of 173 (23%) patients received a supramarginal CE resection (class 1) in the whole cohort; prevalence of class 1 resection was the highest in the subgroup of patients aged ≤ 65 yo (27%) than the subgroup of &gt;65 ≤ 75 yo (22%) and the subgroup of &gt;75 yo (14%). The rate of class 1 resection was not different between patients with tumors located in the right and in left hemisphere (24% and 23% respectively). We analysed survival in patients treated with adjuvant RT-TMZ and found a significant longer OS in patients operated with resection class 1 (16.7 months) than other classes (p&lt;0.0001). Long term benefit resulted the strongest in the subgroup of patients aged ≤ 65 yo (median OS 23.8 months). Multivariate analysis confirmed EOR according to the ReSECT criteria as the strongest independent predictor factor of OS (HR 0.6, p=0.004).

CONCLUSION
We efficiently implemented ReSECT criteria for EOR in our retrospective cohort of patients with primary GBM IDH wild-type. Supramarginal CE resection defined as no residual CE and ≤ 5 cm of nCE on the post-operative imaging emerged as the strongest predictive factor of survival.
P19.07.A EXPRESSION STUDY OF SYNAPTIC PROTEINS BASSOON, DLG4, DLG1, MAGI2, SHANK1, AND HOMER1 IN GLIOMA
Authors: Timmer M , Lauer N , Kuhl S , Goldbrunner R 
Published: September 2023

Abstract

BACKGROUND
To thrive, glioma cells exploit pathways that are active in normal CNS cells, as well as in normal neurotransmitter signaling. In healthy excitatory synapses the postsynaptic submembrane space consists of multiprotein complexes called the postsynaptic density (PSD). The PSD is responsible for the structural organization, the functioning, and the regulation of neuronal signaling. The five MAGUK Proteins DLG4, DLG1, Magi2, Shank1, and Homer1 are part of the healthy PSD complex and play a crucial role not only in NMDA and AMPA receptor signaling. Investigating the role of these MAGUK proteins in glioma biology could bring further insight into which principal neurobiological features, including organization in communicating networks, are recapitulated by tumor cells of different stages in gliomas.

MATERIAL AND
Methods qPCR was used to determine expression levels of DLG4, DLG1, Magi2, Shank1, and Homer1 in 7 different glioma groups (GII, GIII, primary GBM before and after chemotherapy, secondary glioblastoma recurrence with and without chemotherapy). Western Blot was done for DLG4, DLG1, and Homer1. Immunohistochemical staining of frozen sections, paraffin sections and in vitro cells was performed. Results The expression levels of DLG4, DLG1, Magi2, Shank1, and Homer1 were reduced especially in high grade glioma compared to control tissue. A tendency of decreasing protein levels with increasing malignancy is visible for the majority of proteins. In cell culture all proteins were also present. siRNA experiments are ongoing. Conclusion The presence of these synaptic proteins in glioma tissue and moreover also primary cell culture could indicate a role in tumor biology and the connection of glioma cells with neuronal tissue.
P20.06.B SYSTEMIC CHEMOTHERAPY IN ADULT PATIENTS WITH DIFFUSE MIDLINE GLIOMA H3K27-ALTERED
Authors: Lombardi G , Simonelli M , Minniti G , Di Nunno V , Cerretti G , Di Muzio A , Asioli S , Antonelli M , Padovan M , Dipasquale A , Corrà M , De Biase D , Persico P , Caccese M , Tosoni A , Fernandes B , Franceschi E 
Published: September 2023

Abstract

BACKGROUND
Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and temozolomide even if only a few retrospective studies assessed the impact on survival of these approaches.

MATERIAL AND METHODS
We carried out a multicentric retrospective study of adult patients with DMG to assess the effective role of concurrent and adjuvant chemotherapy. All patients had a diagnosis of DMG - H3K27 altered. Results Overall we included 27 DMG H3K27 mutated patients with a median age of 40 years (range 20-66). Thalamus was the most frequent location (n =10, 37%). Overall, 16 patients (59.3%) underwent biopsy, 9 partial resections (33.3%), and 2 (7.4%) complete resections. The molecular assessment revealed TP53 as the most frequently altered gene (n = 4, 14.8%) followed by PIK3R (n = 2, 7.4%) and NF1 (n = 2, 7.4%). MGMT was methylated in 4 patients (14.8%). After surgery, 22 patients (81.5%) received postoperative radiation therapy (RT). Moreover, 12 patients received concurrent temozolomide (44.4%) and 11 (40.7%) adjuvant temozolomide. Patients receiving adjuvant temozolomide had a significantly longer overall survival (25.3 vs 10.5 months, HR 0.16, 95% CI 0.1 - 0.8, p= 0.02). Adjuvant temozolomide was confirmed to be associated with improved survival also when adjusted for age, surgery received, or tumor location. Conclusion In this multicentric retrospective study, the treatment with adjuvant temozolomide seems to prolong survival in DMG H3K27 altered patients. Further studies are needed to improve survival in these patients.
P20.08.B CLINICAL AND MOLECULAR ANALYSES OF A SERIES OF ADULT PILOCYTIC ASTROCYTOMA
Authors: Manzano-Benito I , Moreno Torres B , Cantero D , Hernández-Laín A , Romo Á , Rodríguez de Lope Á , Mollejo M , Meléndez B 
Published: September 2023

Abstract

BACKGROUND
Pilocytic astrocytoma (PA) is a rare, grade 1 subtype of glioma. It is most frequent during the first two decades of life, the incidence rate decreasing with age. PAs are usually located in the cerebellum, although they have also been described in other sites. They are circumscribed, solid-cystic, with low cellularity and generally slow-growing tumours with good prognosis in the paediatric age group. PA is associated with MAPK pathway dysregulation, most often showing BRAF gene alterations. PA is very rare in older adults and is associated in some cases with a worse prognosis. In this work we set out to analyse a series of adult PA from a clinical, morphological and molecular point of view.

MATERIAL AND METHODS
Clinical data were collected from a group of adult patients diagnosed with PA. Nucleic acid extraction was performed by automated extraction and the samples were analysed through a 30-gene targeted panel for gliomas by using Next-Generation Sequencing. Tandem duplication causing fusion of KIAA1549 and BRAF genes (K-B fusion) was analysed by RT-PCR.

RESULTS
Thirty-four patients were included, with a mean age of 34.4 years (range, 18-57 years). The male/female ratio was 26/8. Mean overall survival was 150.5 months, with more than 10 years of mean follow-up. At the time of the last review, 91% (30/33) of the patients remained alive, while the remaining 9% (3/33) died. Neuroanatomic locations (31 cases) were as follows: cerebrum/lobar 23% (7), cerebellum 39% (12), brainstem 10% (3), ventricle 6% (2), spinal cord 10% (3), optic nerve 13% (4). The K-B fusion was detected in 44% of cases (8/18). Of these, 87.5% (7/8) and 12.5% (1/8) showed fusions involving exons 16:9 and 15:9, respectively. K-B positive cases had a mean age of 40 years. Analyses by NGS revealed mutations in NF1 (15%), BRAF (11%), PDGFRA (11%), EGFR (7%) and PIK3CA (7%). Other variants observed in 4% of cases involved ATRX, CIC, IDH1, KEL, KRAS, MET, MSH6, PTPN11 and RB1. No alterations were detected in 3 of the cases, suggesting that other untested driver alterations could be present.

CONCLUSION
In this series, no significant differences with childhood PA in the frequency of molecular alterations were observed, in contrast to other gliomas where there are strong differences in the molecular alterations between adult and paediatric tumours. The most common genetic alterations in adult PA involved the MAPK pathway, as previously reported. In contrast to other adult PA studies, the frequency of K-B fusion was similar to that of paediatric PA. Molecular alterations related to an aggressive behaviour or to other glioma types were identified, such as mutations of ATRX, PDGFRA, NF1 or PI3KCA, which can suggest other tumour types. Our results suggest the need for multilayer histological and molecular diagnosis to appropriately manage adult PA.
P20.09.A FRACTIONATED STEREOTACTIC RADIOTHERAPY (FSRT) AS A TREATMENT FOR TRIGEMINAL SCHWANNOMAS
Authors: ARMIJOS L F , Maciá M , Lucas A , García N 
Published: September 2023

Abstract

BACKGROUND
Trigeminal schwannomas (TS) represent 1-8% of all intracranial schwannomas and 0.1-0.5% of all intracranial tumors Treatment strategies are mainly based on limited published data and case reports. The most common treatment is surgical resection. However, it can rarely be completed. Fractionated stereotactic radiotherapy (FSRT) has the potential to be a valuable and safe alternative to control growing or symptomatic TS. The aim of this review is to analyze clinical

RESULTS
, toxicity and tumor control rates obtained with this technique when treating this pathology in our short series of cases.

MATERIAL AND METHODS
Medical records of 18 patients treated from January 2007 to December 2018 were reviewed. 15 of them presented symptoms at the moment of diagnosis (83.3%) and the remaining 3 were radiological findings. Surgery was previously performed in 2 cases. Regarding radiotherapy scheme, all patients received 1.8-2Gy daily fractions to a median of 50,0 Gy. The median follow-up time was 62.7 months.

RESULTS
The outcome after radiotherapy was favourable in 16 of 18 patients (88.8%), clinical improvement was achieved in 52.94% while stability of symptoms was reached in 35.29%. Tumor growth was controlled in 82.35% of cases, even with tumor decrease observed in 5.88%. Acute toxicity was detected in 23.53% and it consisted in increased pain, sensitive alterations and diplopia. All well tolerated with adjusted corticoids and pain medication scheme. Clinical worsening and radiographic progression was shown in 2 out 17 patients and surgery was needed as salvage treatment in both cases (11.76%). However, one of them presented these outcomes in a period in which pseudoprogression could not be excluded (less than 2 years after treatment).

CONCLUSION
FSRT such as primary or adjuvant treatment accomplishes good clinical results and tumoral control, being an alternative for those patients with comorbidities not suitable for a surgical treatment or who preferred a non-invasive treatment. Regarding toxicity, FSRT is mainly a well tolerated treatment among patients. Prospective multicenter studies should be run in order to accomplish statistically significant results. Also, it is the second case series that reports the flare effect.