bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-60. AUTOMATED QUANTIFICATION OF KI-67 PROLIFERATION INDEX BASED ON WHOLE SLIDE IMAGES IN PEDIATRIC BRAIN TUMORS
Authors: Familiar Ariana M , Kazerooni Anahita Fathi , Kim Meen Chul , Kraya Adam , Storm Phillip J , Oldridge Derek , Viaene Angela , Resnick Adam C , Nabavizadeh Ali 
Published: November 2024

Abstract
The use of AI methods with histopathological images (pathomics) has strong potential to aid pathologists in pediatric brain cancer diagnosis and prognosis given the morphological and molecular heterogeneity of these tumors. However, use of pathomics in this context has been relatively limited. One example is the IHC-based tumor proliferation index (percentage of Ki-67 positive cells amongst all malignant cells) which is often routinely reviewed by pathologists clinically but remains to be objectively quantified or reported in a standardized manner. As a result, analysis of this marker across patients at-scale and in data-driven methods remains largely hindered. Here, we explore the extension of an automated deep learning AI tool (DeepLIIF), originally trained and validated with adult breast/prostate/liver data, for quantification of Ki-67 index from digitized whole slide images of a cohort of pediatric brain tumors from the Children’s Brain Tumor Network (N=834). We find that derived Ki-67 scores largely agreed with neuropathologist-reported Ki-67 activity in original clinical notes and could be used to successfully stratify glioma/astrocytoma patients (N=200) into low- and high-grade groups (LGG: M=11.6; SEM=1.2; HGG: M=18.7; SEM=2; p=0.001). Ki-67 scores were also related to the survival status of the patients (Alive: M=11.8; SEM=1.1; Deceased: M=18.8; SEM=2.2; p=0.003). Summary statistics across tumor types (glioma, astrocytoma, medulloblastoma, ATRT, ependymoma, etc.) and molecularly defined subtypes are also compared, providing direct insights into distributional properties between these groups that has not previously been feasible. Our results show the ability of AI-powered methods to quantify routine histopathology metrics with little human input, allowing objective comparisons between patients and opening the door for precision medicine approaches with predictive analytics in clinical contexts.
PATH-63. M6A REGULATOR-BASED MOLECULAR CLASSIFICATION AND HUB GENES ASSOCIATED WITH IMMUNE INFILTRATION CHARACTERISTICS AND CLINICAL OUTCOMES IN DIFFUSE GLIOMAS
Authors: Lu Jie , Chen Siyu , Li Depei , Mou Yonggao 
Published: November 2024

Abstract

BACKGROUND
m6A methylation modification is a new regulatory mechanism involved in tumorigenesis and tumor-immunity interaction. However, its impact on glioma immune microenvironment and clinical outcome remains unclear.

METHODS
Comprehensive expression profiles of 18 m6A regulators were used to identify molecular subtypes exhibiting distinct m6A modification patterns in 1673 glioma samples sourced from public datasets. A multi-genes signature was constructed for predicting clinical outcome and response to immunotherapy in glioma patients. Immunohistochemistry and cellular experiments were performed for validation.

RESULTS
Two m6A subtypes of gliomas were identified. The m6A-low-risk subtype was characterized by paucity of immune infiltrates; Whereas the m6A-high-risk subtype had higher abundances of multiple immune cells including lymphocyte and macrophage as well as increased expression of PD-L1, corresponding to an immunosuppressive phenotype. The m6A-high-risk subtype had poorer survival than the m6A-low-risk subtype in both the glioblastoma and lower grade gliomas cohorts. Eight m6A-related hub genes of high prognostic significances were identified and selected for developing a scoring signature termed as m6Ascore. Elevated m6Ascore indicated worse survival for glioma patients under standard care, but showed enhanced response to immunotherapy. Moreover, we demonstrated that overexpression of FTO, a m6A demethylase, inhibited the expressions of m6A-related hub genes (PTX3, SPAG4), impaired glioma cell viability and reduced macrophage chemotaxis.

CONCLUSION
This work develops an immune- and clinical-relevant m6A subtyping and a scoring model, which enhances our understanding of the role of m6A modification in regulating immune infiltration microenvironment in gliomas and helps to identify patients who are more likely to benefit from immunotherapy.
PATH-64. UNDERSTANDING MECHANISTIC UNDERPINNINGS OF MOLECULAR SUBGROUPS OF MENINGIOMA
Authors: Nitturi Vijay , Lau Sean , Ledbetter Elizabeth , Nouri Shervin Hosseingholi , Klisch Tiemo , Patel Akash 
Published: November 2024

Abstract
Meningiomas are the most common intracranial tumors. In the past, they were thought to be indolent and could be treated by resection. The current standard of care utilizes WHO histopathological grading to identify malignant potential. Our lab identified three molecular groups (MenG A, B, and C) using CNVs, methylation, and/or expression profiling with different biological characteristics. These groups were independently validated and predicted recurrence more reliably than WHO grade. MenG A is genomically stable but harbors tumors with point mutations, mainly in TRAF7, KLF4, and AKT1. On the other hand, MenG B and C tumors have chromosome 22q arm deletion or loss of merlin, the protein product of the NF2 gene. Moreover, MenG B is characterized by DNA hypomethylation, while MenG C tumors show DNA hypermethylation and have additional chromosomal losses, most notably in chromosome 1p. Lastly, while MenG A/B are indolent, MenG C – comprising approximately 28% of meningiomas – recur frequently and are refractory to radiotherapy and/or surgery. How can two groups of tumors with the same driver mutation behave so differently? Hence, our lab is interested in (1) what molecular pathway/factor(s) are necessary for becoming any meningioma, and (2) what mechanisms are critical for the aggressiveness of MenG C. Here, we investigate the role of TRAF7 in meningioma biology. Toward this end, we study interactors, modulators, and individual mutations in cell culture. In addition, we use published exome sequencing and expression data to reveal possible connections between chromatin state and individual genes. In conclusion, a variety of underlying mechanisms drive meningioma tumorigenicity and aggressiveness. Elucidating these mechanisms could provide future therapeutic targets for currently untreatable meningiomas.
PATH-67. THE ROLE OF STATUS OF HER-2, ESTROGEN-RECEPTOR, BRCA 1, AND BRCA 2, IN THE INCIDENCE OF BRAIN METASTASIS IN BREAST CANCER
Authors: Altaf Ahmed , Gilani Ahmed , Azan Ali , Enam Ather 
Published: November 2024

Abstract
Breast cancer (BC) is the most diagnosed tumor in women and the second-leading cause of brain metastasis (BM), with a prevalence ranging from 10-36%. According to the Epidemiological Strategy and Medical Economics research program, advanced BC patients face an estimated 25% risk of developing BM within 2-3 years after the initial diagnosis. The frequency of BM is significantly increased by the primary tumor profile, including larger tumors, higher nuclear grade, HER-2 positivity, estrogen-receptor negativity, and triple-negative status. A gap remains in the classification of the BM site relative to primary tumor biomarkers, and the absence of multimodality treatment methodologies poses challenges to survival rates and quality of life in BC patients. This retrospective cross-sectional study at Aga Khan University Hospital identified 52 cases of brain metastasis secondary to breast cancer over a 10-year period. The median age of patients was 55 years, ranging from 32 to 78 years. Primary breast tumors were predominantly high-grade ductal carcinomas (65%), followed by lobular carcinomas (25%) and other rare histological types (10%). Secondary brain metastases were primarily located in the cerebrum (60%), cerebellum (25%), and brainstem (15%). Tumor profiles indicated a significant correlation between HER-2 positivity and the development of brain metastasis, with 70% of HER-2 positive patients presenting with extensive brain metastasis. Tumor progression varied, with a median time to brain metastasis of 2.5 years from the initial breast cancer diagnosis. Despite aggressive multimodality treatments, including surgery, radiation, and chemotherapy, the overall prognosis remained poor. The study found that early detection of HER-2 positive and triple-negative tumors could potentially delay the progression of brain metastasis through targeted therapies. Mortality rates in this cohort were high, with a median survival of 8 months following the diagnosis of brain metastasis. These findings underscore the need for improved diagnostic, preventive, and therapeutic strategies to manage brain metastasis in breast cancer patients.
NIMG-01. RADIOMIC DATA ANALYSIS WITH ENSEMBLE MACHINE LEARNING TECHNIQUES PREDICT GRADE, HISTOPATHOLOGIC SUBTYPE, AND 1P/19Q CO-DELETION STATUS IN PATIENTS WITH LOW-GRADE GLIOMAS
Authors: Panchawagh Suhrud 
Published: November 2024

Abstract
Low-grade gliomas (LGGs) are a diverse group of primary brain tumors characterized by their variable prognosis and treatment response. Traditionally, the management of LGGs has relied on histopathological analysis, which sometimes offers limited insight into tumor behavior and treatment outcomes. Recent advances in radiomics have enabled the extraction of detailed quantitative features from routine imaging, providing a non-invasive method to assess tumor characteristics. These radiomic features can capture underlying tumor heterogeneity more comprehensively than conventional methods. Integrating radiomic data with ensemble machine learning techniques offers a promising approach to enhance the prediction of tumor grade, histopathologic subtype, and genetic alterations such as 1p/19q co-deletion status in LGGs, potentially leading to more tailored therapeutic strategies. We combined radiomic-genomic data from 159 magnetic resonance imaging (MRI) scans from the updated LGG-1p19qDeletion dataset (Erickson 2020) and 114 MRI scans from the ReMIND dataset (Juvekar 2024). Expert radiologists performed segmentations. A total of 2446 extracted radiomic features were initially extracted. Feature selection was performed using wrapper- and filter-based techniques with cross-validation. Prediction models were built using machine learning techniques, including random forest and extreme gradient boosting. Using Random Forest, we achieved high accuracy in predicting histopathologic subtype (88.14%, AUC 96.68%) with precision of 87.86% and Dice score of 87.88%. For grade prediction (accuracy 76.19%, AUC 91.84%), precision was 73.91%, and the Dice score was 77.27%. For 1p/19q co-deletion status (accuracy 75.61%, AUC 82.74%), precision was 77.78%, and the Dice score was 73.68%. Our study establishes a robust radiomic workflow to predict tumor grade, histopathologic subtype, and 1p/19q co-deletion status in low-grade gliomas, enhancing diagnostic accuracy and treatment personalization. This methodology can be applied clinically to improve the stratification of treatment plans for low-grade gliomas, potentially leading to effective, personalized therapy options. Using multicentric data potentially improved external validity, something which past research lacked. Future research should focus on validating and deploying this model using observational multicentric study designs.
NIMG-03. USE OF ARTERIAL SPIN LABELING TO DIFFERENTIATE ICTAL PHENOMENON FROM TUMOR PROGRESSION IN HIGH GRADE ASTROCYTOMA
Authors: Zahid Anza , Thatikonda Nithisha , Dubey Prachi , Tremont-Lukats Ivo 
Published: November 2024

Abstract
A 39-year-old female with grade-3 left parietal IDH-mutant astrocytoma following resection presented with convulsive status. EEG showed electrographic seizures arising from the left parietal region. MRI-brain showed the left temporoparietal post-treatment bed without any contrast enhancement (Fig-1A). Arterial spin labeling (ASL) – MR perfusion showed markedly increased cerebral blood flow (CBF) in the left temporoparietal lobe (Fig-1 C, D) with corresponding diffusion restriction (Fig-1B). Repeat imaging two weeks after the seizure control showed complete resolution (Fig-2) suggesting the imaging abnormalities to be a peri-ictal phenomenon.1 ASL-MR perfusion is a highly sensitive marker of increased CBF with its emerging application in distinguishing tumor progression (increased CBF) from post-treatment changes such as radiation necrosis (reduced CBF).1,2 This case highlights the utility of ASL-MR perfusion in differentiating peri/post-ictal phenomenon (increased CBF without T1-contrast enhancement) from tumor progression (increased CBF with T1-contrast enhancement) when employed routinely in clinical oncology practice.
NIMG-10. THE ROLE OF FIBROBLAST ACTIVATION PROTEIN IN GLIOBLASTOMA AND GLIOSARCOMA – A COMPARISON OF TISSUE, 68GA-FAPI-46 POSITRON EMISSION TOMOGRAPHY AND SURVIVAL DATA
Authors: Oster Christoph , Kessler Lukas , Blau Tobias , Keyvani Kathy , Pabst Kim M , Fendler Wolfgang P , Costa Pedro Fragoso , Lazaridis Lazaros , Schmidt Teresa , Feldheim Jonas , Pierscianek Daniela , Schildhaus Hans-Ulrich , Sure Ulrich , Ahmadipour Yahya , Kleinschnitz Christoph , Guberina Nika , Stuschke Martin , Deuschl Cornelius , Scheffler Björn , Herrmann Ken , Kebir Sied , Glas Martin 
Published: November 2024

Abstract

BACKGROUND
Despite their unique histological features,gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast-activation-protein(FAP) is a component of a tumor-specific subpopulation of fibroblasts that play a critical role in tumor growth and invasion.However,the prognostic impact of FAP in glioblastoma and gliosarcoma is unclear.

METHODS
In a retrospective analysis,patients diagnosed with glioblastoma without sarcomatous differentiation and gliosarcoma were enrolled.Histological examination was performed using immunohistochemical FAP-staining and quantitative analysis with a standardized FAP-score.In a subset of patients,FAPI46-PET has been performed.The SUV-values are planned to be correlated with FAP-expression in the tumor tissue.Data obtained from immunohistochemical analysis and SUV-values are planned to be brought into perspective with clinically relevant prognostic factors,including survival estimates.

RESULTS
We enrolled 61 patients,including 13 diagnosed with gliosarcoma.Our analysis revealed that gliosarcomas exhibit significantly higher FAP-expression (median FAP-score: 3) compared to glioblastomas without sarcomatous differentiation (median FAP-score: 0.5, p&lt;0.0001),where FAP was predominantly observed in the perivascular space.In gliosarcomas,FAP was also expressed by neoplastic cells.Moreover,a significant relationship was established between the immunohistochemical FAP-scores and the SUVmean and SUVpeak values on PET,suggesting that the PET tracer uptake accurately reflects the tumor’s FAP-expression.However,the differential expression of FAP suggests its potential as both a diagnostic marker and a therapeutic target.This hypothesis is further supported by the application of 68Ga-FAPI-46-PET in a 66-year-old female patient with recurrent gliosarcoma,alongside immunohistochemical analysis of tumor tissue.Both methods identified elevated FAP-expression and uptake,underscoring the feasibility of FAP as a target for nuclear medicine therapies in brain tumors.

CONCLUSIONS
Our study establishes a significant correlation between SUVmean/SUVpeak in 68Ga-FAPI-46 PET scans and FAP-expression in glioblastoma.Gliosarcomas express significantly more FAP than other glioblastomas. These insights suggest FAP’s potential as a theranostic target.We plan to investigate the effectiveness of FAP-specific tracers in treating recurrent gliosarcoma,aiming to open new therapeutic avenues.
NIMG-17. PREDICTIVE VALUE OF THE BRAIN TUMOR REPORTING AND DATA SYSTEM SCORE (BT-RADS) ON FUNCTIONAL OUTCOMES AND PROGRESSION-FREE SURVIVAL IN GLIOBLASTOMA PATIENTS
Authors: Persico Michele , Assaye Tsion , Essien Michael , Weinberg Brent 
Published: November 2024

Abstract
The Brain Tumor Reporting and Data System Score (BT-RADS) is a novel eight-point classification system that standardizes magnetic resonance imaging (MRI) reporting in glioblastoma (GB) patients. While previous studies have demonstrated BT-RADS predictive value in the prognosis and overall survival of high-grade glioma patients, its association with functional outcomes and progression-free survival (PFS) in GB patients is unclear. We aim to evaluate the BT-RADS predictive value on functional outcomes assessed through the Karnofsky Performance Scale (KPS) at one year post-diagnosis and on PFS. BT-RADS from MRI ~3 months post-diagnosis after chemo-radiation therapy (BT-RADS_1), and ~6 months post-diagnosis after the 6-month maintenance temozolomide (TMZ) cycle (BT-RADS_2) were analyzed. BT-RADS was classified as low (BT-RADS score 0-3a) and high (BT-RADS score 3b-4). In a univariate logistic regression analysis, BT-RADS_1 was a significant predictor (p=0.04) in discriminating an unfavorable KPS from a favorable one. In a multivariate logistic regression, in which the best model fit was the model containing BT-RADS_1 and MGMT tumor status (model p value=0.03), the ROC analyses indicate that BT-RADS_1 is not better than chance in differentiating an unfavorable KPS from a favorable one (model AUC=0.65; 95% CI=0.55, 0.76). The discriminatory ability of BT-RADS scores alone in predicting KPS outcomes was modest, as indicated by the AUC. This underscores the need for larger sample sizes. In a final model of BTRADS_1 and BT-RADS_2, accounting for MGMT tumor status, the risk of tumor progression was 50% lower (p value=0.003) with a low BT-RADS (0-3a) in the BT-RADS _1 group and 38% lower (p value=0.03) with a low BT-RADS (0-3a) in the BT-RADS_2 group. Considering the above-discussed findings, BT-RADS may represent a new tool in the clinical management of glioblastoma patients by informing on disease progression, prognosis, and quality of life.
NIMG-19. DEUTERIUM METABOLIC IMAGING INTERROGATES THE HISTONE H3K27M MUTATION AND PROVIDES AN EARLY READOUT OF RESPONSE TO THERAPY IN DIFFUSE MIDLINE GLIOMAS
Authors: Taglang Celine , Batsios Georgios , Udutha Suresh , Gillespie Anne Marie , Lau Benison , Ji Sunjong , Mueller Sabine , Phoenix Timothy , Venneti Sriram , Koschmann Carl , Viswanath Pavithra 
Published: November 2024

Abstract
Diffuse midline gliomas (DMGs) are lethal primary brain tumors in children that are driven by recurrent lysine 27 to methionine mutations in histone H3 (H3K27M). Radiation is standard of care and the imipridones ONC201 and ONC206 have emerged as promising therapies for DMG patients. Although magnetic resonance imaging (MRI) is the mainstay for patient management, it does not reliably assess response to therapy. Therefore, the goal of this study was to identify metabolic alterations induced by H3K27M that can be leveraged for non-invasive metabolic imaging of DMGs. Using patient-derived (BT245, SF8628, SF7761, SU-DIPG-6, DIPG7, SU-DIPG-13) and syngeneic (26-B7, 26-C2) models, we show that the H3K27M mutation upregulates glucose metabolism via glycolysis to lactate. Silencing the H3K27M mutation reduces glycolytic capacity and depletes lactate, an effect that is associated with downregulation of rate-limiting glycolytic enzymes and transporters (SLC2A1, HK2, PFKFB3, PGK1, SLC16A3). Deuterium metabolic imaging (DMI) is a novel, clinical stage method of tracing glucose metabolism in vivo. Our studies show that lactate production from [6,6-2H]-glucose is spatially localized to tumor vs. normal brain in mice bearing intracranial BT245, SF8628 or 26-B7 xenografts at clinical magnetic field strength (3T). Lactate production from [6,6’-2H]-glucose is reduced in patient-derived (BT245, SF8628, SF7761) or syngeneic (26-B7) cells treated with radiation, ONC201 or ONC206. Importantly, lactate production is reduced at an early timepoint (5 days) following treatment with ONC206, when changes cannot be detected by MRI, in mice bearing intracranial BT245 or SF8628 xenografts. Collectively, our studies link the H3K27M mutation with elevated glycolysis and identify [6,6’-2H]-glucose as a safe, orally administered contrast agent for visualizing the metabolically active lesion and for imaging early response to therapy in DMGs in vivo. Clinical translation of our studies will provide physicians with a much-needed tool to determine whether DMG patients are responding to standard and experimental therapies under development.
NIMG-20. DWIBS FOR PRIMARY CANCER DETECTION IN INTRACRANIAL METASTASIS: TWO CASE REPORTS
Authors: Koyahara Yuki , Saito Norihiko , Hirai Nozomi , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Iwabuchi Satoshi 
Published: November 2024

Abstract

INTRODUCTION
Diffusion Weighted Whole Body Imaging with background body signal Suppression (DWIBS) is an imaging technique that encompasses comprehensive imaging of the entire body through diffusion-weighted imaging (DWI). In recent years, it has been increasingly utilized for investigating the etiology of fever or primary cancer. Here we present two cases of DWIBS for searching for primary cancer in patient with intracranial metastasis.

CASE PRESENTATION
Case1: A 60-year-old man presented with headache and diplopia and was admitted to our hospital. MRI revealed a tumor in the clivus exhibiting contrast enhancement. Endoscopic transsphenoidal surgery confirmed the diagnosis of squamous cell carcinoma. DWIBS demonstrated high intensity in a region similar to the esophagus seen on contrast-enhanced CT, leading to the diagnosis of brain metastasis from esophageal cancer. Case 2: A 50-year-old man presented with left facial paralysis and left hemiplegia and was admitted to our hospital. MRI revealed a tumor in the right middle frontal gyrus. Craniotomy confirmed the diagnosis of adenocarcinoma. Although the primary cancer remained unidentified upon initial examination, subsequent investigations revealed it originated from the lung. DWIBS showed high intensity in a region similar to the lung.

DISCUSSION
While FDG-PET is commonly utilized for cancer detection, its invasiveness and limitations prompt consideration of alternative modalities such as DWIBS. Recently there are some studies that have shown DWIBS to be superior to FDG PET in detecting esophageal and lung cancers. Thus, DWIBS may serve as a viable option for primary cancer screening in hospitals or communities where access to FDG PET is limited.

CONCLUSION
Its non-invasive nature makes DWIBS an appealing option for primary cancer detection, and further advancements are anticipated.