tbuckley/cabot-search huggingface dataset:
P09.04.A BASELINE MR PERFUSION IMAGING OF BRAIN METASTASES PRIOR TO SRS (STARBEAM-X STUDY)
Authors: C B Dobeson, J Lewis, P Bhatnagar, M Birkbeck, S West
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Following treatment with SRS, radionecrosis and tumour progression often have similar appearances on conventional MR imaging, yet have different management approaches. The STARBEAM-X study (Study of assessment of radionecrosis in brain metastases using MR perfusion imaging) has been designed with the aim of assessing the clinical application of baseline MR perfusion imaging prior to SRS as part of the radiotherapy planning process, with the hypothesis that baseline perfusion imaging will aid post-treatment imaging interpretation by enhancing our understanding of how a metastasis’ perfusion characteristics change following treatment with SRS. In this report, we present the participants’ imaging data as proof of feasibility of baseline MR perfusion imaging. MATERIAL AND METHODS Participants underwent baseline MR perfusion (DSC) imaging on Siemens Magnetom Sola 1.5T scanner as part of their radiotherapy planning imaging. Relative cerebral blood volume (rCBV) perfusion maps were calculated in Syngo.Via software and interpretation performed by an expert neuroradiologist. RESULTS 39 patients underwent baseline MR perfusion - 25 (64.1%) were female, 14 (35.9%) were male. The composition of primary tumour sites were as follows: non-small cell lung cancer (NSCLC) - 14 (35.9%), breast - 10 (25.6%), renal - 5 (12.8%), melanoma - 6 (15.4%), ovary - 2 (5.1%), oesophagus - 1 (2.6%), colorectal - 1 (2.6%). Median age on the date of the MRI scan was 65.71 years (range 35.7 - 81.5 years, SD=11.57). 76 metastatic lesions were assessed in total. 14 (35.9%) patients were receiving systemic treatment at the time of MR perfusion scan. Of the 76 lesions treated, 51 (67.1%) were deemed assessable on perfusion imaging. Of the 51 assessable lesions - median volume was 0.821cm3 (mean 2.49cm3, range 0.19 - 12.75cm3, SD 3.09). Median rCBV ratio across all lesions was 3.24 (range 0.68 - 23.3, SD = 4.16). Median rCBV stratified to tumour site - NSCLC 2.845, breast 4.96, renal 5.88, ovary 4.95, melanoma 5.445 and colorectal 3.39. 24 lesions were not suitable for calculation of perfusion values - median volume was 0.069cm3 (mean 0.128cm3, range 0.011cm3 - 1.027cm3, SD 0.202). In 22 (91.7%) the documented reason for this was due to the peripheral nature of the lesion and overlap with normal brain vasculature. CONCLUSION At least two thirds of metastatic brain lesions are suitable for assessment with baseline perfusion MR imaging - factors that impact on suitability are size, peripheral location and proximity to vessels. Participant numbers in this initial study are too low to assess associations between lesional perfusion characteristics and primary tumour site. In individual participants with multiple brain metastases, there was wide variability in perfusion characteristics across the different lesions.
P20.15.B MOLECULAR CHARACTERIZATION OF ADULT NON-GLIOBLASTOMA CENTRAL NERVOUS SYSTEM (CNS) TUMORS TO IDENTIFY POTENTIAL TARGETTABLE ALTERATIONS
Authors: M Padovan, A Bosio, E Cella, M Maccari, G Cerretti, M Corrà, M Caccese, G Lombardi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND NGS panels in oncology offer personalized therapies based on genomic alterations, but data on their clinical use and efficacy for non-glioblastoma CNS tumors is limited. MATERIAL AND METHODS This study aimed to explore the molecular landscape of non-glioblastoma CNS tumors in patients (pts) who underwent FoundationOne®CDx testing between 11/2019 and 04/2023 at Veneto Institute of Oncology, Padua (Italy), while also assessing access to TT. Analysis was conducted on formalin-fixed paraffin-embedded tumor samples, comprising a cohort of 176 adult CNS tumor pts. Brain tumors were classified per WHO 2021. RESULTS Our cohort was constituted by: 19 Grade 2 IDH mut astrocytomas (A); 35 G3 IDH mut A; 34 G4 A; 29 oligodendrogliomas; 4 diffuse midline gliomas; 3 gangliogliomas; 3 pleomorphic xanthoA; 30 meningiomas; 4 medulloblastomas; 5 ependymomas; 2 neuroblastomas; 3 schwannomas; 4 pituitary adenomas; 1 hemangiopericytoma.The most frequent targettable molecular alterations (ESCAT ESMO Scale for Clinical Actionability of molecular Targets IIB-IIIB) were: PIK3CA/B mutations (14.2%), NF1 and NF2 mutations (10.2 and 13%, respectively), BRCA 1-2 mutations (8%), POLE mutation (7.4%), high tumor mutational burden (TMB) (&amp;gt;10 mut/megabase) (6.8%), PDGFRA alterations (6.2%), BRAF non-V600E alterations (5.1%), RET and ROS1 mutations (3.4% and 2.8% respectively), MDM2 amplification (2.3%), FGFR1-2-3 alterations and H3K28M (1.7%), MET amplification (1.7%), ALK rearrangements (1%). NTRK fusions and BRAF V600E mutations have not been detected. 3 of 4 medulloblastomas pts exhibited a PTCH1 mutation.4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. Immune checkpoint inhibitors have shown remarkable activity in a meningioma patient, who is undergoing treatment for 12 months and has achieved a complete response according to RANO criteria, while another has had stable disease with alectinib for 7 months. In other cases TT did not demonstrate activity in controlling disease. CONCLUSION The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
P25.04.B TEN YEARS EXPERIENCE OF THE “BRAIN TUMOR CENTER” OF ALMADA
Authors: C D Casimiro, M Silva, J Monteiro, C Viegas, M Cunha e Sá
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The growing scientific knowledge on brain tumors and the progressive complexity of therapeutic options requires a multidisciplinary approach in a specialized environment. Brain tumor centers (BTC) are crucial in various aspects of assistance given to patients. Since 2013 our BTC assists in the diagnosis, treatment and monitoring of neuro-oncological patients in a multidisciplinary setting involving neurosurgery, neuro-oncology, medical oncology, radiotherapy, neuroradiology, pathology, rehabilitation, neuropsychology, palliative care, nursing and social care. METHODS Review of the data-set and activities of our BTC since its foundation. RESULTS Our BTC maintained an initial yearly growth and admitted 2055 patients during this period (~206 yearly). Patients were referred via primary care, regional hospitals or by admission for urgent care. The average time between proposal and surgery was ~16 days, with ~23 days until pathology results. Primary tumors of the central nervous system (CNS), namely glial tumors, were most frequent (54% of patients in 2023), followed by metastatic disease (36%, notably from lung origin). During this period, 17% of the diagnosis were made by biopsy and 6% of tumors were resected during awake surgery. Follow-up was carried out in accordance with evidence based international clinical guidelines, within the framework of a multidisciplinary neuro-oncology discussion where cases are presented, and exams and treatments are reviewed. Around ~11 patients were discussed per meeting, with ~24 meetings yearly. Overall, chemotherapy was proposed to 30% of patients, radiotherapy to 26% and radiosurgery to 8,5%. DISCUSSION Our BTC was founded to solve shortcomings identified in the treatment of patients and to create an organizational structure to optimizes their care. The multidisciplinary meetings have a distinct importance allowing the individual analysis of each case. Data recording contributes to epidemiological registries and must embrace the continuous neuro-oncology updates. Our data reinforces the need to guarantee fluid coordination and continuity of care, avoiding duplication of services, delays and waste of resources. The role of a nurse-coordinator is essential for the monitoring, coordination and follow-up of patients. The importance of efficient administrative work also cannot be understated. Besides wanting to receive the best treatment, patients wish to be cared for with dignity and respect and have their opinion taken into account. A guidance manual is being updated with the main aspects surrounding clinical care. CONCLUSIONS The last 10 years of an organized BTC made possible to gather relevant clinical information and to improve on the multidisciplinary care given to our neuro-oncological patients.
P19.15.B TERT PROMOTOR MUTATIONS IN ATYPICAL MENINGIOMAS
Authors: R Meta, H Dai, W Sjursen, S Torp
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND In human meningiomas TERT promotor mutations have been shown to be associated with a potentially worse prognosis, thus favouring a CNS WHO grade 3. In this study we wanted to investigate whether this genetic event could distinguish between atypical meningiomas with variable clinical course. METHODS In our archives we found twenty human meningiomas among which 10 cases experienced recurrence and 10 cases did not. Formalin-fixed and paraffin-embedded (FFPE) material was analysed by means of Sanger sequencing to assess the occurrence of TERT promotor mutations. RESULTS No mutations were found in 17 cases. In 3 cases the DNA quality was too poor for sequencing. CONCLUSION We found no TERT promotor mutations in our series of atypical meningiomas, so the prognostic value of this genetic event in these tumours requires further studies. Since there were cases with poor DNA quality, such sequencing analyses on FFPE meningioma tissue may be problematic and may therefore represent a limitation in retrospective studies.
P20.22.B STEREOTACTIC RADIOSURGERY FOR VESTIBULAR SCHWANNOMA - TUMOUR CONTROL AND TOXICITY OUTCOMES FROM THE EAST OF ENGLAND
Authors: K Cullen, K Burton, S Jefferies, S Duke
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is a standard of care for small to intermediate size vestibular schwannoma (VS). Having implemented this technique in our centre in 2017, we examined our tumour control and toxicity rates to audit against published data. MATERIAL AND METHODS We performed a retrospective review of all patients treated with linear accelerator based SRS (12Gy/1# delivered to 80% isodose) for VS in our centre. Patients were excluded from analysis if they had NF2 or had yet to receive a follow-up. Toxicity outcomes focussed on balance, hearing, and facial/trigeminal nerve symptoms; data was collected on a template within clinic letters. For tumour control, clinical progression requiring surgery was the primary outcome, with an exploratory endpoint of tumour growth (mm). Maximum tumour diameter was collected from radiology reports prior to starting treatment and years 1,2,3 &amp; 5 post SRS. Radiotherapy dose metrics were obtained from radiotherapy plan data. Statistical tests used an unpaired T-test. RESULTS 140 adult patients with VS were treated with SRS between 2017 and 2023. The mean age was 64. Mean cochlea, brainstem Dmax and trigeminal Dmax doses were 7.7Gy, 9.09Gy and 8.1Gy respectively. Median follow-up was 46 months (range 6 weeks-76 months). One patient was referred for surgery 31 months after treatment due to continued tumour growth. In the 1st year, the median change in tumour size = 0 mm (range -10 to 4), in the 2nd year it was -1 mm (range -1 to 5), in 3rd year 0 mm (range -10 to 3), and in the 4th &amp; 5th years -1 mm (-4 to 0). The median rate of tumour size change was -0.67mm/year (range -6 to 3). 9.2% of patients experienced worsening facial/trigeminal nerve symptoms post-SRS with 90% improving within 2 years, 17% experienced decreased balance with 58% improving within 2 years and 25% experienced a subjective decrease in hearing with none improving within 2 years. 73% of patients with useful hearing retained it at most recent follow-up. There was no significant relationship between growth rate and age, tumour size, or tumour coverage. There was a relationship between higher cochlea dose and new balance problems (p=0.044). There was no significant relationship between symptom development and tumour growth, and many who had growth post-SRS had no new symptoms. CONCLUSION High rates of tumour control at early time points were seen as expected - only one patient (0.7%) needed surgery. While typically patients’ tumours shrunk or were stable, the inability to detect growth clinically, through symptom development, points towards the need for ongoing imaging follow-up. Although facial and trigeminal symptoms were uncommon and generally self-limiting, balance and hearing problems were more prevalent and persistent. This shows the need for following up these patients within a multi-disciplinary setting, reinforcing the case for our multi-disciplinary clinic.
P18.02.B ANALYSIS OF TUMOR RELAPSE PROBABILITY AND OVERALL SURVIVAL PREDICTION FOLLOWING CONCOMITANT RADIOTHERAPY WITH TEMOZOLOMIDE USING FET PET IN PATIENTS WITH GLIOBLASTOMA
Authors: I Stetter, J Werner, M Wollring, G Ceccon, P Lohmann, G Stoffels, F M Mottaghy, G R Fink, K Langen, N Galldiks
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Early after surgery and completion of concomitant radiotherapy with temozolomide, the evaluation of tumor relapse probability and overall survival prediction is of considerable interest for the management of patients with glioblastoma. MATERIAL AND METHODS Sixty-three adult glioblastoma patients (mean age 55.4 years, SD ± 14.6) who received dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET) after surgery or biopsy and completion of concomitant radiotherapy with temozolomide, were retrospectively included in the study. Static FET PET parameters such as maximum and mean tumor-to-brain ratios (TBRmax/TBRmean) and metabolic tumor volumes (MTV) and the dynamic FET PET parameter time-to-peak (TTP) were obtained. The prognostic value of FET PET parameters was evaluated concerning the progression-free and overall survival (PFS, OS). Using receiver-operating-characteristic (ROC) analyses, threshold values for FET PET parameters were acquired. Subsequently, univariate and multivariate survival estimates were performed to assess the prognostic value of these parameters to predict a significantly longer PFS (as a surrogate for tumor relapse probability) and OS. RESULTS ROC analysis revealed that the parameter TBRmax was the most powerful parameter to predict both a significantly longer PFS (17.8 vs. 9.0 months; P=0.003; threshold, 2.85) and OS (33.2 vs. 18.4 months; P=0.002; threshold, 2.75). MTV had a similar prognostic value for both PFS (15.9 vs. 7.2 months; P=0.002; threshold, 34.0 mL) and OS (28.2 vs. 14.4 months; P=0.003; threshold, 32.6 mL). At a lower level of significance, TTP was only prognostic for a significantly longer OS (27.7 vs. 17.5 months; P=0.037; threshold, 25 minutes). TBRmax and MTV remained significant in multivariate survival analysis, indicating independent predictors for both a significantly longer PFS and OS (all P≤0.04). CONCLUSION Our results suggest that FET PET parameters were highly prognostic in patients with newly diagnosed glioblastomas at an early stage of first-line therapy for predicting favourable PFS and OS.
P13.08.A INTRAOPERATIVE OR POSTOPERATIVE STEREOTACTIC RADIOTHERAPY FOR BRAIN METASTASES: TIME TO SYSTEMIC TREATMENT ONSET AND OTHER PATIENT-RELEVANT OUTCOMES
Authors: C Dejonckheere, J Layer, M Hamed, M Schneider, H Vatter, U Herrlinger, M Grimmer, F Kugel, S Garbe, F Giordano, G R Sarria
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. MATERIAL AND METHODS Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p &amp;lt; 0.001). CONCLUSION IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.
P20.18.A PRIMARY MENINGEAL MELANOCYTIC TUMORS (PMMT): A REVIEW FROM THE ULTRA RARE BRAIN TUMORS DOMAIN OF THE EURACAN
Authors: A Pellerino, R M Verdijk, L Bertero, L Nichelli, N H Andratschke, A Idbaih, R Goldbrunner
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION PMMT are ultra rare entities with distinct histological and molecular features as compared with other melanocytic or pigmented intracranial lesions. METHODS The EUropean Network for RAre CANcers (EURACAN) Task Force on Ultrarare Brain Tumors (domain 10) has perfomed a literature revision from January 1985 to December 2023 regarding the evidence of epidemiologic and clinical characteristics, histological and molecular features, radiological findings, and activity of local and systemic therapies. RESULTS Molecular analysis can detect specific mutations, including SF3B1, EIF1AX, BAP1, NRAS and BRAF, that are found in PMMT and not in other melanocytic lesions. Neuroimaging shows the leptomeningeal involvement with or without parenchymal lesions with meningeal base implant, delineate the extension with respect to adjacent structures, but cannot reveal the aggressiveness of the disease. Gross-total resection is the first choice in case of circumscribed meningeal melanocytoma and melanoma; conversely, meningeal biopsy may be reserved for patients with diffuse and multinodular leptomeningeal spread to achieve a definitive diagnosis. High-dose radiotherapy is rarely indicated in diffuse melanocytic tumors except as palliative treatment to alleviate symptoms. A definitive advantage of a specific systemic treatment over other could not be concluded, as most of the data available derive from case reports or small cohorts. CONCLUSIONS As PMMT are extremely rare, weak correlations between clinical characteristics, molecular profile, radiological findings at diagnosis and progression, and poor evidence on the best therapeutic approach are available thus far. There is the need to develop shared platforms and registries to capture more knowledge regarding these ultra rare entities
P06.10.A THE MIRNA 216B-5P ACTS AS A PROMISING TUMOR-SUPPRESSOR BY MANIPULATING CELL CYCLE PROGRESSION IN HIGH-GRADE GLIOMA CELLS
Authors: A Lang, S Bürger, L Mager, B Kiesel, S Madlener, G Ricken, A Lämmerer, S Spiegl-Kreinecker, M Hackl, M Pultar, J Reisecker, D Kirchhofer, M Mischkulnig, A S Berghoff, A Woehrer, K Rössler, T Roetzer-Pejrimovsky, W Berger, C N Jaunecker, J A Hainfellner, R Hoeftberger, G Widhalm, F Erhart, D Loetsch-Gojo
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Glioblastoma is the most common brain tumor in adults and with an approximate survival rate of 15 months, new treatment strategies are of utmost urgency. In our previous phase II clinical trial, applying immunotherapy with dendritic cells to glioblastoma patients, no differences in overall survival were observed. However, distinct miRNAs and in particular miR-216b, harbored a predictive power and were associated with therapy susceptibility. Thus, we hypothesize that amongst others, miR-216b is involved in glioblastoma aggressiveness and thereby impacting therapeutic success. MATERIAL AND METHODS First, we screened glioblastoma tissue samples (n=39) and several cell models for the expression of five different miRNAs. As miR-216b was generally low expressed compared to others, we investigated whether transfection with miR-216b “mimic” (upregulation) or “inhibitor” (blocking) had an impact on clonogenic survival, sphere-forming and migratory capacity in three patient-derived and two immortalized glioblastoma cell models. To gain deeper knowledge about miR-216b targets, miRNA sequencing was performed. Subsequently, predicted targets were confirmed by Western Blot, FACS analysis and drug sensitivity assays. RESULTS MiR-216b upregulation resulted in reduced cell proliferation and migration as well as in decreased stemness characteristics in the majority of the investigated high-grad glioma (HGG) models. RNA sequencing predicted target genes of miR-216b that are involved in cell division (e.g. CDK4). Accordingly, upon transfection with “miR-216b mimics”, protein levels of CDK4 and subsequently phosphorylation of RB were reduced, accompanied by an increase of cells in G0/G1 phase. When miR-216b was blocked, the sensitivity towards CDK4/6 inhibitors was distinctly increased, pointing towards a drug-targeting engagement. CONCLUSION Our data indicates that miR-216b acts as a tumor suppressor via the inhibition of CDK4 in glioblastoma cells. The prognostic and predictive value of this miRNA in glioblastoma is currently under investigation and harbors the potential to manipulate glioma cells into cell cycle arrest.