tbuckley/cabot-search huggingface dataset:
P18.16.A DTI FIBER-TRACKING PARAMETERS ADJACENT TO GLIOMAS: THE ROLE OF TRACT IRREGULARITY VALUE IN OPERATIVE PLANNING, RESECTION, AND OUTCOME
Authors: D Armocida, A Pesce, M Salvati, F Cofano, A Frati, D Garbossa, A Santoro
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The goal of glioma surgery is maximal tumor resection associated with minimal post-operative morbidity. Diffusion tensor imaging-tractography/fiber tracking (DTI-FT) is a valuable white-matter (WM) visualization tool for diagnosis and surgical planning. Still, it assumes a descriptive role since the main DTI metrics and parameters showed several limitations in clinical use. New applications and quantitative measurements were recently applied to describe WM architecture adjacent to the tumor area (BAT), which can be adopted as predictive values and a guide for safe tumor resection. MATERIAL AND METHODS This is an observational prospective study on an extensive series of glioma patients who performed magnetic resonance imaging (MRI) with pre-operative DTI-FT analyzed on the BAT by two different software. We examined DTI parameters of Fractional anisotropy (FA mean, min-max), Mean diffusivity (MD), and the shape-metric “tracti irregularity” (TI) grade, comparing it with the surgical series’ clinical, radiological, and outcome data. RESULTS The population consisted of 118 patients, with a mean age of 60.6 years. 82 patients suffering from high-grade gliomas (69.5%), and 36 from low-grade gliomas (30.5%). A significant inverse relationship exists between the FA mean value and grading (p=0.001). The relationship appears directly proportional regarding MD values (p=0.003) and TI values (p=0.005). FA mean and MD values are susceptible to significant variations with tumor and edema volume (p=0.05). TI showed an independent relationship with grading regardless of tumor radiological features and dimensions, with a direct relationship with grading, ki67% (p=0,05), PFS (p&amp;lt;0.001), and EOR (p&amp;lt;0.01). CONCLUSION FA, MD, and TI are useful predictive measures of the clinical behavior of glioma, and TI could be helpful for tumor grading identification and surgical planning.
P14.04.A A PROSPECTIVE STUDY OF TUMOR-TREATING FIELDS COMBINED WITH SYSTEMIC THERAPY IN RECURRENT GLIOBLASTOMA
Authors: C Guo, Q Yang, Z He, H Duan, J Lu, C Ke, H Xie, Z Chen, R Liu, X Zhang, Y Mou
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Tumor-treating Fields (TTFields) monotherapy was approved for recurrent glioblastoma. However, TTFields combined with systemic therapy has not been well studied in China. This study aims to explore the efficacy and safety of such combination therapy for recurrent GBM. MATERIAL AND METHODS This study is a prospective, single-arm, open-label clinical trial (NCT04689087) planning to enroll 40 recurrent supratentorial GBM patients and use TTFields combined with physician chose systemic therapy. Kaplan-Meier survival curve was used to estimate PFS, OS and survival rate. The primary endpoint was 6-months OS rate (OS6). Secondary endpoints were PFS, PFS6 and safety. OS and PFS were computed from the day of initiating TTFields. RESULTS Fourty recurrent supratentorial GBM patients was enrolled from July 2020 to May 2023. The average age was 51 and median KPS score was 80. Sixty-eight percent (27/40) of them underwent total resection surgery and 5% (2/40) only experienced biopsy as their newly diagnosed GBM surgery. Eighty-eight percent (35/40) of patients started TTFields when they were first diagnosed as recurrence, while 12.5% (5/40) patients started TTFields at their second-time recurrence or latter. Median time from diagnosis of recurrence to initiating TTFields was 27 days. Median duration time of TTFields was 8.7 months and average compliance of TTFields was 87% (20.9 hours/day). As for molecular biomarkers, 50% (20/40) patients were MGMT protein positive and 32.5% (13/40) were TERT mutant. Chemotherapy was included in the systemic therapy in 80% (32/40) patients, antiangiogenic therapy in 60% (24/40) patients, BRAF inhibitor therapy in one patient and immune checkpoint inhibitor therapy in one patient. At data cut-off date of March 20, 2024, the median follow-up period was 20.8 months. The primary endpoint OS6 was 87.2%, the median OS was 20.2 months (95%CI 11.9-NR). Median PFS was 8.5months (95%CI 6.2-NR). PFS6 was 67.5% while the historical reference of physician’s best choice of active chemotherapy from EF-11 study showed a PFS6 of 15%. Scalp adverse events were the most common AE. Seventy-eight (31/40) of patients experienced grade 1 or 2 scalp adverse events which can be relieved by topical corticosteroids. CONCLUSION TTFields combined with systemic therapy showed favorable efficacy and safety in Chinese recurrent GBM patients.
P22.02.B ACCOMMODATING LIFE DISRUPTION: AN INTERPRETIVE EXPLORATION OF LIVING WITH LOW-GRADE GLIOMA
Authors: D M Legge, D Langbecker, P Yates
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Significant treatment and resource allocation are directed towards improving the support and services for people with high-grade glioma, recognising this diagnosis brings significant care burden and high supportive care needs. People diagnosed with the less common low-grade glioma (LGG) often live for an extended period of time following diagnosis, needing to find ways to manage family, work, health, and relationships. In this study, we explored social processes these people undertake to accommodate a diagnosis of LGG. MATERIAL AND METHODS Symbolic interactionism was used as a lens for this work, incorporating Charmaz’s grounded theory methods to identify the social processes undertaken in accommodating LGG. Semi-structured interviews were conducted with adults diagnosed with LGG, purposively selected for their rich contribution to the data. Interviews were audio-recorded and transcribed verbatim. Data analysis occurred concurrently with interviews to enable co-construction of social processes, ensuring the emerging concepts remained grounded in the data. Concepts were confirmed through coding and constant comparison. Data analysis was managed using NVivo v11.4 software. RESULTS Interviews were conducted with 13 people with grades 2 and 3 glioma between June and December 2016, lasting a median of 67 (range: 52-82) minutes. Participants were from Australia, rural and urban areas, aged between 21 - 65 years with a median of 4.5 years since diagnosis. A core concept of ‘Accommodating Life Disruption’ emerged with three supporting social processes describing how people dealt with a diagnosis of LGG: 1) Dealing with contradictions; identifying the ambiguous clinical context and the language and narrative used in LGG; 2) Defining time; where LGG marks a point in time, with people taking stock of their resources and values; and 3) Re-negotiating identity; describing how people with LGG take control, make connections and go about creating a good life. CONCLUSION This interpretive study highlights the nuanced social processes people undertake to accommodate the diagnosis of LGG and identifies clear targets for improving supportive care resources and survivorship practices for people with LGG. The findings also offer an opportunity to consider and improve how health professionals interact and communicate the diagnosis for people with LGG and their families.
P20.02.B ANAPLASTIC ASTROCYTOMA AS A SECOND PRIMARY BRAIN MALIGNANCY IN PATIENT WITH NON-HODGKIN LYMPHOMA
Authors: R Ardhini
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Malignant lymphoma survivor can develop second primary malignancies, but have been rarely reported to occur in central nervous system. Risk factor increasing second primary tumor is not well determined, possibly due to lymphoma subtype, patients demographic, previous chemotherapy or radiation therapy. We report a very rare case of anaplastic astrocytoma in patient with remission of non-Hodgkin’s lymphoma (NHL). CASE PRESENTATION 43-year-old man presented with progressive weakness on the left extremity for the past two months followed by progressive headache and left pacial palsy. Patient had a history of diffuse large B-cell lymphoma (DLBCL) in the lower leg in the previous 5 years and had received systemic chemotherapy. He was on regular follow-up without any evidence of relapsing disease. Brain MRI showed heterogenous intraaxial lesion in the right periventricular white matter of frontal lobe with large peritumoral edema suggestive secondary central nervous system lymphoma. There were no evidence of reccurence disease in the lower leg or other active disease, and no blast cells were found in CSF examination. Craniotomy was performed and histopathological examination revealed Anaplastic astrocytoma, NOS, WHO grade III (based on the WHO 2016 classification). Then the patient received concomittant chemoradiation and adjuvant Temozolomide. CONCLUSION Second primary brain malignancy is extremely rare in patient with treated diffuse large B-cell lymphoma. Surgical management and pathological examination must be performed to obtain a definite diagnosis, and to rule out secondary central nervous system lymphoma.
P17.18.B RECURRENT PINEOBLASTOMA WITH LEPTOMENINGEAL METASTASES
Authors: J D White, D Baykal, M J Webb, B Neth, A Mahajan, R Kowalchuk, J Schwartz, U Sener
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Pineoblastoma is an aggressive, rare tumor of the pineal gland. Due to rarity of pineoblastoma, no large-scale prospective clinical trial data is available to guide clinical practice. Patients often receive treatment based on approaches to other high-grade embryonal central nervous system (CNS) tumors such as medulloblastoma. Multimodality treatment typically consists of maximal surgical resection followed by radiation therapy and chemotherapy. Despite treatment, recurrence is common and five-year survival rate is 60-70%. Pineoblastoma can disseminate through the leptomeninges, which is associated with poor survival. No therapy is known to confer a survival benefit in the setting of leptomeningeal disease (LMD) related to pineoblastoma. MATERIAL AND METHODS We report radiographic response and longer than expected survival for a patient with LMD related to pineoblastoma treated with single-agent temozolomide chemotherapy. RESULTS A 22-year-old male with a history of pineoblastoma presented with periodic headaches and leptomeningeal enhancement on surveillance imaging. 5 years prior to presentation (age 17), he was initially diagnosed with pineoblastoma after gross total resection followed by treatment with proton craniospinal radiation and adjuvant carboplatin/vincristine chemotherapy. Surveillance craniospinal MRIs identified diffuse leptomeningeal enhancement involving the posterior fossa and diffusely throughout the spine and lumbosacral nerve roots. While cerebrospinal fluid (CSF) cytology was negative for tumor cells on three separate occasions, CSF cell-free DNA (cfDNA) analysis isolated tumor DNA. He was started on temozolomide chemotherapy with near complete resolution of leptomeningeal enhancement on MRI after 2 cycles and complete resolution after 6 cycles. Treatment was well-tolerated with grade 1 fatigue as the only toxicity. Patient remains alive 20 months after initial diagnosis of LMD with resolution of headaches and durable radiographic response. CONCLUSION This case highlights utility of CSF cfDNA as a companion tool for diagnosis of LMD. Durable clinical and radiographic response achieved suggests temozolomide can be considered as a salvage treatment option for recurrent pineoblastoma with LMD.
Gut microbiota determines the fate of dietary fiber-targeted interventions in host health
Authors: Wenjing Wang, Zhexin Fan, Qingqing Yan, Tong Pan, Jing Luo, Yijiang Wei, Baokun Li, Zhifeng Fang, Wenwei Lu
Journal: Gut Microbes (2024)

Epidemiological investigation confirmed that the intake of dietary fiber (DF) is closely related to human health, and the most important factor affecting the physiological function of DF, besides its physicochemical properties, is the gut microbiota. This paper mainly summarizes the interaction between DF and gut microbiota, including the influence of DF on the colonization of gut microbiota based on its different physicochemical properties, and the physiological role of gut microbiota in destroying the complex molecular structure of DF by encoding carbohydrate-active enzymes, thus producing small molecular products that affect the metabolism of the host. Taking cardiovascular disease (Atherosclerosis and hypertension), liver disease, and immune diseases as examples, it is confirmed that some DF, such as fructo-oligosaccharide, galactooligosaccharide, xylo-oligosaccharide, and inulin, have prebiotic-like physiological effects. These effects are dependent on the metabolites produced by the gut microbiota. Therefore, this paper further explores how DF affects the gut microbiota's production of substances such as short-chain fatty acids, bile acids, and tryptophan metabolites, and provides a preliminary explanation of the mechanisms associated with their impact on host health. Finally, based on the structural properties of DF and the large heterogeneity in the composition of the population gut microbiota, it may be a future trend to utilize DF and the gut microbiota to correlate host health for precision nutrition by combining the information from population disease databases.
P04.01.B DECIPHERING GLIOBLASTOMA METABOLIC SIGNATURE: MOLECULAR PROFILING AND NADH-FLIM IMAGING
Authors: M Morelli, O Santonocito, F Lessi, G Ferri, M Menicagli, P Aretini, G Grimod, C Gambacciani, F Pieri, L Schweizer, M Ronellenfitsch, M Sanson, A Picca, L Garofano, A Iavarone, C Mazzanti, A Di Stefano
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Recent breakthroughs in single-cell analysis reveal distinct metabolic cellular states, leading to a novel classification of glioblastoma (GBM). An RNA Sequencing methodology optimized for FFPE tumor tissue of GBM allows for the detection of GBMs which are dependent on oxidative phosphorylation (OXPHOS). OXPHOS GBM show vulnerabilities to anti-mitochondrial agents, both in vitro and in vivo, and are currently the target population of clinical trials in newly diagnosed GBM patients (Optimum NCT04945148). To date, RNA Sequencing is the sole standardized method for the retrospective and prospective identification of OXPHOS GBM. OBJECTIVE To evaluate the efficacy of Fluorescence Lifetime Imaging (FLIM) microscopy of NADH, an intracellular enzymatic cofactor, in discerning the metabolic profile of FFPE GBM tumor tissue, with a focus on identifying OXPHOS GBM subtypes. METHODS We analyzed 3’ mRNA NGS FFPE tumor tissue from a retrospective series of IDHwt glioblastomas, newly diagnosed from 2021 to 2023. The OXPHOS logODDS ratio, GPM logODDS ratio, and the simplicity score were considered as quantitative criteria to select prototype cases. We selected OXPHOS mitochondrial and glycolytic/plurimetabolic cases for the NADH-FLIM microscopy study on FFPE slides. NADH-FLIM images were analyzed quantitatively. For each cases 10-16 subareas were analysed. Areas of necrosis were excluded from the quantitative analysis. RESULTS RNA Sequencing of 28 consecutive newly diagnosed IDHwt GBM patients from the Livorno Hospital found 9 OXPHOS, 6 glycolytic/plurimetabolic (GPM), 1 neuronal (NEU), 9 not classifiable, and 3 proliferative (PPR) cases. In the OXPHOS subgroup, 5 patients showed the highest score of association with the OXPHOS signature and were the subject of the NADH-FLIM study compared to the top 5 GPM cases. NADH bound/free distribution curves significantly differed between the OXPHOS’ and GPM’ subgroups, with higher values for GPM cases [GPM: median 0.21, range 0.0-0.93; OXPHOS: median 0.02, range 0.0-0.99; p&amp;lt;0.0001]. We noticed different skewness (0.53 vs 1.21) and kurtosis (-1.25 vs -0.15) parameters in NADH bound/free curves between GPMs and OXPHOSs, respectively. CONCLUSIONS OXPHOS and GPM glioblastoma clusters significantly differed in NADH bound/free distribution curves. Supplementary cases are currently under study to confirm preliminary results and to assess the power of NADH-FLIM to predict the metabolic status of GBM samples.
P03.03.A GAMMAKNIFE RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: B V Nogueira, L Palavani, H Chen, M Vilardo, L Mitre, J Landeiro
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Vestibular Schwannomas (VS), benign CNS tumors originating from Schwann cells on the eighth cranial nerve, typically present with symptoms such as trigeminal and facial neuropathy, tinnitus, vertigo, dizziness, and progressive hearing loss. Due to their anatomical location, proximity to important structures, and size, treating VS poses a significant challenge. Treatment strategies must carefully consider the impact on the patient’s quality of life and neurological function, ranging from surgical resection to observational management with magnetic resonance imaging to radiosurgery. This systematic review and meta-analysis specifically aims to assess the safety and efficacy of Gamma Knife radiosurgery in treating VS. MATERIAL AND METHODS This systematic review and meta-analysis was conducted in accordance with the Cochrane Collaboration Handbook and PRISMA guidelines. A comprehensive literature search was performed across multiple databases, including Medline, Embase, Web of Science, and the Cochrane Library. Eligible studies included those reporting data from primary GK treatment or GK with prior surgery. The primary endpoints analyzed were new or worsened symptoms, tumor control, and complication rates. Statistical analyses were conducted using R Studio, utilizing a random effects model, with results presented as proportions accompanied by 95% confidence intervals. RESULTS The analysis included data from 43 studies comprising 6,634 patients with an approximate median age of 56.0 years. Primary GK reatment showed a tumor regression rate of 56%(95% CI: 0.46 to 0.65, I² = 86%), tumor stability rate of 37% (95% CI: 0.26 to 0.48, I² = 92%), and tumor progression rate of 6% (95% CI: 0.04 to 0.08, I² = 76%); new or worsened facil neuropathy rate of 3% (95% CI: 0.01 to 0.05, I² = 86%), post-GK serviceable hearing rate of 48% (95% CI: 0.38 to 0.58, I² = 97%), major complication rate of 3%(95% CI: 0.01 to 0.05, I² = 84%), minor complication rate of 11% (95% CI: 0.04 to 0.18, I² = 95%), and VS-related mortality of 0% (95% CI:0.00 to 0.00, I² = 0%). In comparison, GK with prior surgery had a tumor regression rate of 61% (95% CI: 0.53 to 0.68, I² = 0%), tumor stability rate of 20% (95% CI: 0.08 to 0.31, I² = 58%), tumor progression rate of 17% (95% CI: 0.7 to 0.27, I² = 53%); new or worsened facil neuropathy rate of 23%(95% CI: 0.04 to 0.43, I² = 90%). CONCLUSION Our findings indicate that Gamma Knife radiosurgery (GK) is a feasible and safe treatment option for Vestibular Schwannomas (VS). It demonstrates effective tumor control, low complication rates, and considerable symptom management.
P09.12.B INFLUENCE OF PATIENT CHARACTERISTICS AND ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY ON FET UPTAKE IN THE REFERENCE REGION IN PATIENTS WITH GLIOMAS
Authors: G S Ceccon, M Wollring, I Stetter, J Werner, P Lohmann, G R Fink, K Langen, N Galldiks
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND In PET imaging, the uptake of radiolabeled amino acids in the reference region is frequently used to calculate tumor-to-brain ratios in patients with gliomas. Nevertheless, besides patient characteristics, our understanding of the alkylating chemotherapy’s influence on the uptake of radiolabeled amino acid in the reference region in patients with CNS WHO grade 3 or 4 gliomas is incomplete. MATERIAL AND METHODS We evaluated the effects of sex, age, and adjuvant chemotherapy with temozolomide on the uptake of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) in the reference region in newly diagnosed glioma patients who had undergone surgery and radiotherapy with concomitant temozolomide chemotherapy. FET PET was performed at baseline and after the second cycle of adjuvant temozolomide chemotherapy. Besides, we calculated standardized uptake values (SUV) of FET in the reference region located in the contralateral, unaffected hemisphere. Unpaired Student’s t-tests were used to test differences between independent groups (e.g., females and males). The paired Student’s t-test was used to compare background SUV at baseline and follow-up. The Pearson’s correlation coefficient determined correlations between clinical parameters and SUV in the background region. RESULTS Sixty-three patients with gliomas (females, n=32) were retrospectively evaluated (CNS WHO grade 4 glioblastoma, n=55; CNS WHO grade 4 H3K27-mutant diffuse midline glioma, n=2; CNS WHO grade 4 astrocytoma, n=4; CNS WHO grade 3 astrocytoma, n=1; CNS WHO grade 3 oligodendroglioma, n=1). SUV in the reference region did not significantly differ between female and male patients at baseline (P=0.259) and follow-up (P=0.384). Patients’ age at initial diagnosis was positively correlated with background SUV at baseline (r=0.384; P=0.002). After two cycles of adjuvant temozolomide chemotherapy, the SUV in the reference region at follow-up was not significantly different from baseline (P=0.485). CONCLUSION Our data suggest that the reference SUV was unaffected by adjuvant temozolomide chemotherapy. In contrast, age has a modest influence on the physiological FET uptake. Further studies to evaluate the impact of patient characteristics and treatment are warranted.