bluuebunny/crossref_metadata_2025_split huggingface dataset:
SURG-27. DIRECTIONALLY NON-ROTATING ELECTRIC FIELD THERAPY (DNEFT) DELIVERED THROUGH IMPLANTED ELECTRODES: A NOVEL SURGICAL PLATFORM FOR GLIOBLASTOMA IMMUNOTHERAPY
Authors: Ma Jun , Singh Shilpi , Li Ming , Seelig David , Molnar Gregory , Wong Eric , Dhawan Sanjay , Kim Stefan , Helland Logan , Chen David , Tapinos Nikos , Lawler Sean , Singh Gatikrushna , Chen Clark 
Published: November 2024

Abstract

BACKGROUND
While directionally rotating Tumor Treating Fields (TTF) therapy has garnered considerable clinical interest in recent years, there has been comparatively less focus on directionally non-rotating electric field therapy (dnEFT).

OBJECTIVE
Here, we explore dnEFT generated through implanted electrodes as a glioblastoma therapeutic platform, with the goal of facilitating clinical translation.

METHODS
Using custom-designed electrode arrays to study the effect of dnEFT using in vitro and in vivo glioblastoma models.

RESULTS
In vitro, dnEFT generated using a clinical grade spinal cord stimulator showed anti-neoplastic activity against independent glioblastoma cell lines. In support of the results obtained using the clinical grade electrode, dnEFT delivered through a customized, two-electrode array induced glioblastoma apoptosis. To characterize this effect in vivo, a custom-designed four-electrode array was fabricated such that tumor cells can be implanted into murine cerebrum through a center channel equidistant from the electrodes. After implantation with this array and luciferase expressing murine GL261 glioblastoma cells, mice were randomized to dnEFT or placebo. Relative to placebo treated mice, dnEFT reduced tumor growth (measured by bioluminescence) and prolonged survival (median survival gain of 6.5 days). Analysis of brain sections following dnEFT showed a notable increase in the accumulation of peri-tumoral macrophage/microglia with increased expression of M1 genes (IFNγ, TNFα, IL-6) and decreased expression of M2 genes (CD206, Arg, IL-10) relative to placebo tumors.

CONCLUSIONS
Our results suggest therapeutic potential in glioblastoma for dnEFT delivered through implanted electrodes as a novel immunotherapy platform, supporting the concept of a proof-of-principle clinical trial using commercially available deep brain stimulator electrodes.
SURG-29. EXTENDED RESECTION IMPROVES PATIENT SURVIVAL OUTCOMES AFTER GROSS-TOTAL RESECTION OF GLIOBLASTOMA
Authors: Tanaka Kazuhiro , Nagashima Hiroaki , Yamanishi Shunsuke , Muragaki Yoshihiro , Sasayama Takashi 
Published: November 2024

Abstract
In recent years, the effectiveness of extended resection (ER) beyond the contrast-enhanced (CE) lesion has been reported as a surgical strategy for glioblastoma. This study was to determine whether ER of FLAIR-hyperintense area beyond the CE tumor affected the overall survival (OS) and progression-free survival (PFS) of patients with glioblastoma after gross-total resection (GTR). From October 2019 to March 2022, a total of 62 patients who underwent resection of glioblastoma (GBM) at Kobe University Hospital were retrospectively examined. Volumetric measurements of the CE area and surrounding FLAIR-hyperintense area were performed, and clinical variables related with OS and PFS were analyzed. In total, 33 patients with GBM who underwent GTR of the CE tumor met the inclusion criteria. The mean volume of CE tumor and FLAIR hyperintensity area before resection was 36.5 cm3 and 77.2 cm3 respectively. The mean excision rate of FLAIR-hyperintense area was 18.2%. Removal rates of 20% or more in the FLAIR-hyperintense region significantly increased OS and PFS (p=0.040 and 0.026, respectively). In multivariate analysis, age ≥ 65 years (HR 2.73; 95% CI 1.09–7.22; p=0.032) were associated with shorter OS, but ER ≥ 20% (HR 0.41; 95% CI 0.17–0.99; p=0.049) and MGMT promotor methylation (HR 0.36; 95% CI 0.15–0.85; p=0.020) were associated with longer OS. ER of FLAIR-hyperintense lesions of 20% or more in glioblastoma contributed to prolonging patient survival. It is necessary to validate the effect of ER in prospective clinical trials.
SURG-30. SURVIVAL AND OUTCOMES ANALYSIS OF PATIENTS TREATED WITH LASER INTERSTITIAL THERMAL THERAPY FOR LARGE-VOLUME GLIOBLASTOMA
Authors: Berke Chandler , Knott Maxon , Shah Khushi , Khalafallah Adham , Rivera Cameron , gurses muhammet , Shah Ashish , Komotar Ricardo , Iva Michael 
Published: November 2024

Abstract

INTRODUCTION
Laser interstitial thermal therapy (LITT) has shown increased patient survival and outcomes in glioblastoma multiforme (GBM). However, its safety and survival in large-volume GBM tumors has been poorly elucidated.

OBJECTIVE
To evaluate the use of LITT in large-volume GBMs.

METHODS
A retrospective cohort of adult patients with grade IV IDH-wt GBM measuring ≥ 10 cm3 who were treated with LITT was compared to a control group with volumes &lt;10 cm3. A Kaplan-Meier analysis, followed by a Cox-proportional hazards model with overall survival (OS) as the timeline and death as the event, were performed with volume group, mFI-11 score, 30-day readmission, age at surgery (AOS), recurrent vs. primary lesions, and EOA as covariates.

RESULTS
The cohort consisted of 46 large-volume patients (mean: 22.0 cm3, STD: 10.8) with a mean age of 63 years and 57% male predominance, compared to 41 controls (mean: 4.4 cm3, STD: 2.8). Lesions were primary in 78% and 60%, and recurrent in 22% and 40%, of the large and small-volume groups, respectively. Kaplan-Meier analysis showed no significant survival difference between the large (OS=245 days) and small-volume (OS=358 days) groups (p=0.261). No covariate showed significant risk of hazard in the large compared to small-volume cohorts (p&gt;0.05). Across the entire cohort, mFI-11 score, recurrent lesions, and EOA showed no significance as individual predictors of death (p&gt;0.25). AOS (p&lt;0.005) and 30-day readmission (p&lt;0.005) showed significantly increased hazard for the entire cohort. Importantly, volume group did not significantly increase hazard (1.16 [0.68, 1.98], p=0.60).

CONCLUSION
This is the first study evaluating the safety and efficacy of LITT in large-volume GBMs, specifically, with a larger cohort than any existing analysis sub-grouped by volume. We show LITT can be safe and efficacious, without significantly increased mortality compared to in small-volume GBMs.
SURG-33. INTRAOPERATIVE ULTRASSOUND X SODIUM FLUORESCEIN FOR GLIOMA SURGERY: WHICH IS BETTER?
Authors: Campos Paiva Aline Lariessy , Araujo João Luiz Vitorino , Lovato Renan Maximillian , Santos Gabriel José dos , de de Mendonça André Luca Barongeno , de Andrade Hallison Rodrigues , de Oliveira Jean Gonçalves , Veiga José Carlos Esteves 
Published: November 2024

Abstract

BACKGROUND
Improve quality of life with a maximum surgical resection is the main goal of neurosurgeons. A better delimitation of intrinsic brain tumors are required for achieving a maximum tumor removal. There are several technologies that may help. Considering two of them that have an easier access and are cheaper, we compared a high definition ultrasound (BK 3000) and sodium fluorescein (SF) during glioma surgeries.

METHODS
Adult patients with main radiological hypothesis of low or high grade glioma were included in a PhD study previously approved by ethics committee. 3-5mg/kg of SF was administered by intravenous infusion during anesthetic induction. An specific craniotomy transducer was used in all cases. All procedures were guided by the same neurosurgeon.

RESULTS
High definition ultrasound allows an excellent tumor delimitation in high and low grade tumors. However the gray scale and distinction of brain structures and residual lesion was difficult for surgeons who are not habituated to ultrasound use. SF did not help low grade glioma removal, and in these cases ultrasound were superior. Increased fluorescence is easily detected when compared to ultrasound information’s. For small residual tumor, SF helps more than US. For both technologies, when the surgical site had blood, the evaluation about grade of resection is not accurate because in ultrasound appears a posterior shadow and considering SF it seems that there are not further tumor because blood does not have increased fluorescence.

CONCLUSIONS
US showed superiority for low grade gliomas resection. Considering high grade, both technologies helps in different moments during the surgery and are complimentary. We used an specific probe for neurosurgery that has high quality and allowed detailed evaluations. These technologies helps surgeons take quick decision and optimized brain tumor removal. The neurosurgeon should be more familiar to US images because provide a real time evaluation with low cost. KEY WORDS: ultrasound; fluorescein; gliomas; brain tumors
SURG-40. PEDIATRIC LOWER GRADE GLIOMA SURGERY IN THE ERA OF GENOMIC MEDICINE
Authors: Gomi Akira 
Published: November 2024

Abstract

INTRODUCTION
In the 2021 WHO Brain Tumor Classification, pediatric-type gliomas are distinctly categorized from their adult counterparts. The continual evolution of cancer genomics has significantly broadened the spectrum of available treatment options. Here we would like to consider surgery for pediatric low-grade gliomas.

METHODS
We retrospectively analyzed 41 cases of low-grade gliomas or glioneuronal tumors in pediatric patients who underwent surgery at our institute from 2002 to 2023. We discussed surgical strategies based on molecular classification.

RESULTS
Among the cases, there were 34 gliomas and 7 glioneuronal tumors. According to the new WHO classification, they corresponded to 1) Adult-type diffuse gliomas, 2) Pediatric-type diffuse low-grade gliomas, 3) Circumscribed astrocytic tumors, or 4) Glioneuronal and neuronal tumors. Cases without molecular diagnosis were also considered in light of the new WHO classification. Among molecularly diagnosed astrocytomas involving the cerebral hemisphere, brain stem, spinal cord, there were no cases of 1), and 2) 3) were the main cases. It is important in surgical selection to note that these cases generally have a more favorable prognosis compared to the adult type and have usefulness in diagnosing MAPK pathway abnormalities leading to the selection of molecularly targeted drugs. 3) includes pilocytic astrocytoma, subependymal giant cell astrocytoma, and pleomorphic xanthoastrocytoma. Among these, in the treatment of pilocytic astrocytoma of the visual tract and hypothalamus, biopsy is essential for molecular diagnosis and therapeutic agent selection. 4) is mainly an epilepsy-related tumor. While their removal contributes to genetic diagnosis and epileptic seizure control, total removal may not always be deemed necessary.

CONCLUSION
Based on the new WHO classification, a reevaluation of treatment strategies for pediatric brain tumors is necessary.
SURG-42. THE T1/T2 RATIO IS ASSOCIATED WITH RESECTABILITY IN PATIENTS WITH IDH-MUTANT ASTROCYTOMAS CNS WHO GRADES 2 AND 3
Authors: Weller Jonathan , de Dios Eddie , Katzendobler Sophie , Corell Alba , Dénes Anna , Schmutzer-Sondergeld Michael , Javanmardi Niloufar , Thon Niklas , Tonn Joerg-Christian , Jakola Asgeir Store 
Published: November 2024

Abstract

PURPOSE
IDH-mutant astrocytomas CNS WHO grade 2 and 3 show heterogenous appearance on magnetic resonance imaging (MRI). In the pre-molecular era, the discrepancy between T1 hypointense and T2 hyperintense tumor volume in absolute values has been proposed as a marker for diffuse tumor growth. We set out to investigate if a ratio of T1 to T2 tumor volume (T1/T2 ratio) is associated with resectability and overall survival in patients with IDH-mutant astrocytomas.

METHODS
Patient data from two centers (Center A: Sahlgrenska University Hospital, Gothenburg, Sweden; Center B: LMU University Hospital, Munich, Germany) were collected retrospectively. Inclusion criteria were as follows: pre- and postoperative MRI scans available for volumetric analysis (I), diagnosis of an IDH-mutant astrocytoma between 2003-2021 (II), and tumor resection at initial diagnosis (III). Tumor volumes were manually segmented. The T1/T2 ratio was calculated and correlated with extent of resection, residual T2 tumor volume, and overall survival.

RESULTS
The study comprised 134 patients with 65 patients included from Center A and 69 patients from Center B. The median overall survival was 134 months and did not differ between the cohorts (p=0.29). Overall, the median T1/T2 ratio was 0.79 (range 0.15-1.0). Tumors displaying a T1/T2 ratio of 0.33 or lower showed significantly larger residual tumor volumes postoperatively (median 17.9 cm3 versus 4.6 cm3, p=0.03). The median extent of resection in these patients was 65% versus 90% (p=0.03). The ratio itself did not correlate with overall survival. In multivariable analyses, larger postoperative tumor volumes were associated with shorter survival times (HR 1.02, 95% CI 1.01-1.03, p&lt;0.01).

CONCLUSION
The T1/T2 ratio might be a good indicator for diffuse tumor growth on MRI and is associated with resectability in patients with IDH-mutant astrocytoma. This ratio might aid to identify patients in which an oncologically relevant tumor volume reduction cannot be safely achieved.
SURG-47. SUPRAMAXIMAL RESECTION IMPROVES OVERALL SURVIVAL IN PATIENTS WITH MGMT-UNMETHYLATED GLIOBLASTOMA
Authors: Mendoza Mireles Eduardo Erasmo , Blakstad Hanne , Mughal Awais Ahmad , Server Andres , Brandal Petter , Leske Henning , Aarhus Mads , Helseth Eirik , Rønning Pål Andre , Vik-Mo Einar O 
Published: November 2024

Abstract

INTRODUCTION
Glioblastoma is highly resistant to radio- and chemotherapy and its heterogeneity is a therapeutic challenge. O6-methylguanine–DNA methyltransferase (MGMT) promotor methylation is an established biomarker for favorable effect of chemotherapy. Supramaximal resection has proven predict the best overall survival (OS), but whether this benefit applies equally to patients with different MGMT-promotor methylation status is still to be debated.

MATERIAL AND METHODS
Population based retrospective study that examined all adult patients in South-Eastern Norway that underwent resection for IDH wildtype glioblastoma between January 2019 and December 2021. Extent of resection (EOR) was classified according to RANO resect classification and MGMT-promotor methylation status by pyrosequencing-qPCR.

RESULTS
The study included 281 patients. MGMT-promotor methylated patients (MGMT+) had a median OS of 18.4 months compared to 13.1 months in MGMT-unmethylated (MGMT-) patients (p&lt;0.0001). Patients with supramaximal resection had a median OS of 20.4 months compared to 14.9 months (p&lt;0.01) with maximal resection. For patients with supramaximal resection we found no significant difference in median OS (25.5 vs. 18.3 months (p=0.24)) dependent on MGMT-status. Separated analysis between MGMT-status and EOR showed a median survival of 18.3, 13.4 (p&lt;0.001), and 8.5 (p&lt;0.001) months for MGMT-, and 25.5, 18.4 (p=.99), and 9.0 (p&lt;0.001) months for MGMT+ in patients where supramaximal-, maximal-, and submaximal resection was achieved, respectively.

CONCLUSIONS
Patients with supramaximal resection and MGMT+ have a 50% 2-years survival probability. In patients where supramaximal resection was achieved, survival benefit was not dependent on MGMT-status. There was a significant improved survival in MGMT- patients between supramaximal and maximal resection, that was not present for MGMT+ patients. Intraoperative molecular diagnosis has the potential to guide the surgical strategy dependent on MGMT-promotor methylation status, especially in tumors where supramaximal resection has a higher risk of new neurological deficits.
SURG-48. LASER INTERSTITIAL THERMAL THERAPY REMODELS THE TUMOR IMMUNE LANDSCAPE IN A MOUSE GLIOMA MODEL
Authors: Giles David , Woodiwiss Timothy , Han Rowland , McCornack Colin , Beck Loren , Fu Yiwei , Leidig Will , Anzaldua-Campos Markus , Mok David , Cleary Ryan , Kim Albert 
Published: November 2024

Abstract

BACKGROUND
Laser interstitial thermal therapy (LITT), a minimally invasive surgical technique for tumor ablation, is increasingly being used to treat primary and recurrent glioma. While the primary goal of using LITT has been to destroy tumor tissue, little is known about the impact of LITT on the overall immune response. To investigate changes in the tumor immune landscape, we utilized a mouse model of LITT and applied it to a poorly immunogenic mouse model of glioma.

METHODS
SB28 glioma cells were implanted in the right frontal lobe of C57BL/6 mice, and on day 7, an optical fiber is inserted into the tumor, paired with a thermocouple for real-time temperature monitoring. A 30W laser was activated in pulses to maintain a peri-lesional temperature of 44C for 150-180 seconds. The tumor and LITT-associated immune response was analyzed by multiparameter flow cytometry, single cell RNA-seq, and multiplex immunofluorescence.

RESULTS
LITT (versus sham control) triggered an increase in neutrophils in the tumor during the acute phase at day 3 following treatment. Total immune cell numbers increased over time in both sham- and LITT-treated mice, but there was a significant increase at post-LITT day 7 in select adaptive immune cell populations including type 1 conventional dendritic cells, NK cells, and gamma delta T cells. Monocytes/macrophages comprised the majority of the immune infiltrate, and multiplex immunofluorescence revealed these populations localized to the perimeter of the LITT lesion. scRNA-seq also revealed enrichment of a Fabp5- and Gpnmb-expressing macrophage subset following LITT.

CONCLUSIONS
LITT modifies the tumor immune infiltrate with increases in neutrophils as well as select adaptive cell and macrophage subsets. Future studies will explore adjunct therapies to further augment the immune response in the setting of LITT.
SURG-52. LEPTOMENINGEAL DISSEMINATION AFTER GAMMATILE AND LITT IN HIGH GRADE ASTROCYTOMA PATIENTS
Authors: Magalhaes Pereira Rosalina , Mian Tabarak , Patel Toral , Dan Tu , Youssef Michael 
Published: November 2024

Abstract

PURPOSE
To present a case series of leptomeningeal dissemination after localized treatment with GammaTile or laser interstitial thermal therapy (LITT) in patients with high grade astrocytoma.

BACKGROUND
Leptomeningeal dissemination occurs primarily in glioblastoma patients with prolonged survival and those who undergo aggressive treatment courses. Targeted therapies such as GammaTile (which contains cesium-131 radiation-emitting seeds) or LITT may provide localized disease control following recurrence and serve as an immediate treatment modality for patients with recurrent disease in the weeks leading up to radiotherapy or systemic treatment.

METHODS
We retrospectively reviewed all consecutive patients with high grade astrocytoma treated with GammaTile or LITT who were found to have leptomeningeal dissemination of disease. Histological diagnosis, NGS and immunohistochemistry of tumor tissue were performed at both original diagnosis and at time of GammaTile placement or LITT procedure. Leptomeningeal dissemination was diagnosed through MRI findings on brain and spine. Cases were analyzed for time to development of leptomeningeal dissemination, median overall survival, survival from time of leptomeningeal dissemination diagnosis, time of dissemination to second radiation therapy. Tumor location, MGMT status and other molecular markers were also reviewed.

RESULTS
Out of 90 high grade astrocytoma patients treated with gamma tile radiation, 4 progressed to exhibit disseminated disease. There were 2 female patients, mean age was 50 years. Location of tumor was in the left temporal lobe in 3 patients and right temporal in 1. They were all IDH wild type. Two were MGMT methylated, two were non methylated. The median time from initial glioma diagnosis to LMD was 221 months (range 11-152) and overall survival after disseminated disease diagnosis was 7.5 weeks (range 3–13).

CONCLUSION
Leptomeningeal dissemination is a devastating complication of aggressive gliomas. Currently, there is no standard treatment for disseminated disease in high grade astrocytoma patients. Systemic therapy is needed following localized therapies to control disease. Further research into new therapies is needed to allow for better outcomes.
TMET-02. CELL-INTRINSIC METABOLIC PHENOTYPES IDENTIFIED IN GLIOBLASTOMA PATIENTS USING MASS SPECTROMETRY IMAGING OF 13C-LABELED GLUCOSE METABOLISM
Authors: Tsyben Anastasia , Dannhorn Andreas , Hamm Gregory , Couturier Dominique-Laurent , Briggs Mayen , Mair Richard , Brindle Kevin 
Published: November 2024

Abstract
Glioblastoma (GB) is an inherently heterogeneous and invasive primary brain cancer. Genomic and transcriptomic studies have attempted to classify GB into subtypes that predict survival and that have different therapeutic vulnerabilities. An outstanding question and technical challenge is to visualize the metabolism of a tumour within its native microenvironment and understand to what extent its metabolism is driven by the microenvironment. Patients with GB tumours were infused with [U-13C]glucose and intra-operative multi-regional tumour samples were rapidly snap frozen for analysis using mass spectrometry imaging (MSI). Tissue microenvironment was assessed using multiplexed antibodies in immunocytochemistry (IMC) of contiguous sections. Isotope tracking in human-derived neurospheres and patient-derived xenografts were used to confirm the presence of metabolic phenotypes detected in the human samples and to test the susceptibility of each phenotype to a panel of drugs targeting cellular metabolism. Three metabolic signatures were identified in patient tumours: glycolytic, oxidative and a mixed glycolytic/oxidative phenotype. The phenotypes did not correlate with microenvironmental features, including proliferation rate, immune cell infiltration, and vascularisation. The phenotypes were retained when patient-derived cells were grown in vitro, or as orthotopically implanted xenografts, and were robust to changes in oxygen concentration, demonstrating their cell intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes are large enough to be detected using clinically applicable metabolic imaging techniques. The phenotypes also demonstrate differential drug sensitivities, suggesting imaging of these phenotypes may be used to stratify patients for personalised therapy trials. This is the first report to demonstrate high resolution imaging of metabolic fluxes in a human tumour in vivo and the presence of different metabolic phenotypes within GB that are tumour cell intrinsic and largely independent of the tumour microenvironment.