bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-16. ONCOPATH: OPTIMIZED TREATMENT GUIDELINE CONCORDANT PATHWAY PRESENTED ON A VISUAL-INTERACTIVE DASHBOARD FOR CLINICAL DECISION SUPPORT COMPUTED BY OVERLAYING PATIENT LONGITUDINAL DATA ON A KNOWLEDGE GRAPH
Authors: Snyder James , Alford Sharon Hensley , Kumar Tarun , Pindolia Kirit , Poisson Laila , Mahatma Shilpa , Mikkelsen Tom 
Published: November 2024

Abstract

BACKGROUND
OncoPath provides a visual analysis of a brain tumor patient’s longitudinal clinical data overlayed on disease specific pathways with the goal of reducing knowledge discordant care and insurance authorization burden. By ingesting, curating and visually presenting the patient experience on guidelines, OncoPath aims to streamline clinical decision making and related processes. Understanding the patient’s journey compared to treatment guidelines is of value in addressing health equity and guideline adoption in real world settings.

METHODS
Data from 44 glioma patients diagnosed and treated between 2016-2021 were uploaded to OncoPath using natural language processing and other tools to capture abstractable data elements. The data was overlayed on guidelines using recursive graph modeling. Using the knowledge graph of a patient’s history, the model also recommends treatment options in an interactive visual dashboard representing NCCN guidelines. The dashboard includes the guidelines in graphical format with associated references and notation.

RESULTS
28 males and 16 females age 21-38 years at diagnosis were abstracted. Cases represented 4 oligodendrogliomas, 13 astrocytomas, and 27 glioblastomas. Data was available through second line therapy, discharge to hospice or death. Cases were matched to the NCCN 2021 guidelines which was used for treatment decisions until November 2022. The patient data matched OncoPath except in 3 cases where KPS was not available resulting in premature pathway truncation. For these cases we inferred KPS based on subsequent treatment received to optimize the historic data.

CONCLUSION
To our knowledge, this is a first-of-a-kind technology in neuro-oncology that may improve time to treatment, reduce health utilization resources and can serve as a benchmarking tool for care delivery. The feasibility of clinically implementing such tools for decision support was demonstrated. This type of tool could be particularly useful in low-resource areas where disease specific expertise may not be available or to illuminate care discrepancies.
INNV-20. FLUORESCEIN GUIDED SURGERY FOR ATYPICAL BRAIN LESIONS: IS IT USEFULL? CASE SERIES USING A LOW-COST DEVICE
Authors: Campos Paiva Aline Lariessy , Araujo João Luiz Vitorino , Lovato Renan Maximillian , de Oliveira Jean Gonçalves , Veiga José Carlos Esteves 
Published: November 2024

Abstract

INTRODUCTION
Sodium Fluorescein (SF) enhances in areas in the brain with a disrupted Blood brain barrier (BBB). In neurosurgery, SF is extensive used for malignant brain tumors. Solitary brain abscesses (BA) are characterized by the pathognomonic finding of BBB disruption. Consequently, FL may have the potential to improve the intra-operative visualization of BA. Other infections also disrupt BBB and SF may guide these surgeries.

CASE SERIES
A 32-year old male patient, previously diagnosed with HIV presented with headache and during investigation MRI disclosure an extensive leptomeningeal commitment. Leptomeningeal biopsy guided by fluorescein and using Varioguide system was performed and the diagnosis was primary central nervous system lymphoma (Diffuse large B-cell). During surgery, it was observed increased fluorescence in arachnoid. A 72-year old woman presented with headache, impairment of mental status and epilepsy and a KPS of 60. Her initial hypothesis was metastasis but patient did not have a primary situs diagnosis. An open biopsy was performed through temporal posterior craniotomy. During surgery no visible well delimited tumor was found, even with ultrasound use. Fluorescein guided biopsy was performed. Histological evaluation showed an Epstein-Barr virus infection causing encephalitis. This is an extremely rare presentation of this type of infection and SF was extremely helpful to guide the procedure.

CONCLUSION
This paper reported atypical uses of SF for brain mass lesions surgeries. One of our cases is a unique presentation of a virus encephalitis which mimicked metastasis and other of increased fluorescence in Lymphoma. These atypical use of SF are relevant for further neurosurgical plannings Keywords: Fluorescein, Lymphoma, Biopsy
PATH-27. MOLECULAR, IMAGING, AND SURVIVAL MANIFESTATIONS IN MOLECULAR GLIOBLASTOMAS: INSIGHTS FROM A MULTI-NATIONAL STUDY
Authors: Park Yae Won , Youssef Gilbert , Freeman Nicolas , Teske Nico , Karschnia Philipp , Foltyn-Dumitru Martha , Banan Rouzbeh , Lee Matthew , Singh Kanwar , Park Ji Eun , Choi Kyu Sung , Wongsawaeng Doonyaporn , Chang Jong Hee , Kim Se Hoon , Lee Seung-Koo , Wen Patrick Y , Barajas Jr Ramon Francisco , Choi Seung Hong , Kim Ho Sung , Jain Rajan , Sahm Felix , Wick Wolfgang , Bendszus Martin , Vollmuth Philipp , Thon Niklas , Huang Raymond , Ahn Sung Soo 
Published: November 2024

Abstract
Apart from the traditional definition of IDH-wildtype GBM based on histological characteristics, IDH-wildtype diffuse gliomas previously assigned to histological grade 2 or 3 are now defined as IDH-wildtype GBM in the presence of qualifying molecular markers (TERTp mutation, EGFR amplification, or chromosome +7/-10) (“molecular GBM”) in the 2021 WHO classification. However, the clinical significance of molecular GBM is unrevealed. This collaboration aims to comprehensively evaluate the clinical, molecular, imaging characteristics, and prognosis of molecular GBMs in a multi-national dataset and stratify survival. Retrospective chart and imaging review was performed in 258 molecular GBM patients from eight centers across three continents. Clinical, molecular, imaging, and survival characteristics were analyzed. The median age of molecular GBM patients was 58 years (range: 23-83) with 139 males, with TERTp mutation (83 of 214 [38.8%]), EGFR amplification (160 of 204 [78.4%]), and chromosome +7/-10 (82 of 143 patients [57.3%]). The majority of tumors were located at the frontal and temporal lobes (48.4%) and exhibited non-contrast-enhancing (CE) tumors (73.7%). Gliomatosis cerebri pattern was shown with 27 patients (12.4%). The median OS was 28.1 months (95% confidence interval 22.1-34.1). There was significantly shorter survival in patients with high Ki-67 index (&gt; 20) compared to those with low Ki-67 index (median OS 19.3 vs. 31.5 months, log-rank test P = 0.002), while no survival differences were found according to histological grade or molecular diagnostics. Survival was significantly shorter in patients with infiltrative imaging appearance compared to those without (median OS 24.7 vs 41.0 months, log-rank test P = 0.014). In conclusion, survival within molecular GBM patients may be heterogeneous and associated with Ki-67 index and infiltrative imaging appearance.
PATH-28. KI-67 INDEX AS A PREDICTIVE MARKER OF MENINGIOMA RECURRENCE FOLLOWING SURGICAL RESECTION
Authors: Mizrachi Mark , Hartley Benjamin , Saleem Shahzaib , Hintz Eric , Ziemba Yonah , Li Jianyi , Goenka Anuj , Schulder Michael 
Published: November 2024

Abstract

BACKGROUND
Meningiomas are the most common primary intracranial tumors in adults. Although benign in a majority of cases, they have a variable clinical course and may recur even after a thorough surgical resection. Ki-67, a nuclear protein involved in cell cycle regulation, has been widely studied as a marker of cellular proliferation in various cancers. Here, we investigate the Ki-67 index, as a predictive marker of meningioma recurrence following resection.

METHODS
The medical records of 451 patients with previously untreated cranial meningiomas who underwent resections from January 2011 to January 2021 at North Shore University Hospital (NSUH) were reviewed. Collected data included WHO grade, Ki-67 proliferative index, degree of resection - gross (GTR) vs subtotal (STR) - as judged by the surgeon, tumor location, and meningioma recurrence. This study was approved by the NSUH Institutional Review Board IRB 21-1107.

RESULTS
There were 290 patients with grade I, 154 with grade II, and 7 with grade III meningiomas. Higher WHO grades were associated with higher rates of recurrence, with rates of 11.4 %, 27.9 %, and 71.4 % for grades 1, 2, and 3, respectively, and subtotal resection corresponded to a higher rate of recurrence than total resection (34.3 % and 13.4 %, respectively). Higher WHO grades also correlated with higher Ki-67 scores (2.59, 10.01, and 20.71) for grades 1, 2, and 3, respectively. A multivariate logistic regression model identified Ki-67 and degree of resection as independent predictive variables for meningioma recurrence, with Ki-67 specifically predicting recurrence in the WHO grade II subset when analyzed separately for WHO grades I and II.

CONCLUSION
Our 10-year retrospective study suggests that the Ki-67 index is an important predictive marker for recurrence of intracranial meningiomas following surgical resection, particularly among patients with WHO grade II tumors. Our findings add to a growing body of data that support inclusion of Ki-67 index in the WHO grading criteria for patients with meningiomas.
PATH-32. THE PROGNOSTIC IMPACT OF CDKN2A/B HETEROZYGOUS DELETIONS IN IDH-MUTANT GLIOMA
Authors: Ippen Franziska Maria , Hielscher Thomas , Friedel Dennis , Göbel Kirsten , Reuss David , Herold-Mende Christel , Krieg Sandro , von Deimling Andreas , Wick Wolfgang , Sahm Felix , Suwala Abigail 
Published: November 2024

Abstract

BACKGROUND
Homozygous deletions of CDKN2A/B have been shown to be a prognosticator for an unfavorable prognosis in gliomas, but the role of heterozygous CDKN2A/B deletions remains less well understood. The aim of this study was to assess the prognostic impact of CDKN2A/B heterozygous deletions in IDH-mutant low-grade astrocytoma and oligodendroglioma.

METHODS
Tissue samples diagnosed as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3 were collected from the archive of the Institute of Neuropathology in Heidelberg. DNA methylation analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples. Evaluation of the CDKN2A/B locus was performed by visual inspection of copy-number plots derived from methylation-array data for each case. Heterozygous and homozygous losses were assessed in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival probabilities were assessed using the Kaplan–Meier method.

RESULTS
A total of 334 low-grade glioma cases were identified. Those cases included 173 astrocytomas and 161 oligodendrogliomas. Heterozygous deletions in CDKN2A/B (37/173 in astrocytomas, 15/161 in oligodendrogliomas) did not confer worse survival outcomes compared to CDKN2A/B wildtype cases in neither low grade astrocytoma (p= 0.2556) nor oligodendroglioma (p= 0.2760), regardless of CNS WHO grade, which was further validated on a subgroup of astrocytoma, IDH mutant CNS WHO 4 cases (p= 0.1680).

CONCLUSION
In summary, our study suggests that heterozygous CDKN2A/B deletions do not confer worse survival rates with respect to OS and PFS in astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3.
PATH-33. THE IMPACT OF THE MOLECULAR CLASSIFICATION IN HISTOLOGICALLY DIAGNOSED GLIOBLASTOMAS
Authors: Arakawa Yoshiki , Kawauchi Takeshi , Makino Yasuhide , Katsuma Asako , Yoshioka Ema , Shofuda Tomoko , Kanematsu Daisuke , Yamamoto Etsuko , Takada Shigeki , Sano Noritaka , Tanji Masahiro , Mineharu Yohei , Kanemura Yonehiro 
Published: November 2024

Abstract

OBJECTIVE
Glioblastomas have been diagnosed based on traditional histological findings (necrosis, microvascular proliferation) and molecular genetic findings (IDH-wildtype, H3-wildtype, TERT promoter mutation, EGFR amplification, +7/−10 chromosome copy-number changes). Thus, IDH-wildtype and H3-wildtype glioblastomas can be classified into those with molecular genetic findings (defined as molecular glioblastoma) and those with only histological findings (defined as non-molecular glioblastoma). We re-evaluated the molecular genetics of patients diagnosed histologically with glioblastoma at our institution and examined their characteristics.

METHODS
A total of 275 cases diagnosed histologically as glioblastoma between December 2000 and March 2022 were included. Sanger sequencing (IDH1/2, Histone H3, TERTp) and MLPA for copy number analysis (PDGFRA, EGFR, CDKN2A, PTEN, MDM2, CDK4, TP53) were performed. The genetic analysis results and survival periods were analyzed.

RESULTS
Among the 275 cases, 151 initial glioblastomas met the criteria of IDH wild-type and H3 wild-type. Genetic analysis results that could be evaluated were obtained in 89 of these cases. TERT promoter mutation was present in 43 cases (48%), with 37% (16 cases) showing EGFR amplification and 19% (8 cases) showing EGFR gain/PTEN loss (+7/-10) simultaneously. On the other hand, TERT promoter wild-type was found in 45 cases (51%), with EGFR amplification in only 1 case (2%) and EGFR ain/PTEN loss in 4 cases (9%), and these 5 cases were judged to correspond to molecular glioblastoma. Adding one case with TERT promoter evaluation failure but EGFR amplification, the integrated molecular/non-molecular glioblastoma cases were 49 (55%)/40 (45%), revealing that both tumor types exist in nearly equal proportions. Survival curve analysis showed that median overall survivals of molecular and non-molecular glioblastoma were 17 and 29 months, respectively, showing a two-fold difference, and non-molecular glioblastoma had significantly better prognosis (P=0.0136).

CONCLUSION
It was revealed that tumors diagnosed as glioblastoma based on conventional histological findings can be broadly classified into molecular and non-molecular glioblastoma, with significant differences in prognosis.
PATH-36. DO GENE EXPRESSION PROFILES BETTER PREDICT OLIGODENDROGLIOMA SURVIVAL?
Authors: Roy Vijaylaxmi , Lath Devraj , Sreegiriraju Vijay , Sadasivam Subhashini , Ghanekar Yashoda , Goel Pallavi , Kumari Neha , Pawar Vikas , Madiraju Surya , Ray Amit 
Published: November 2024

Abstract
The WHO 2021 classification of oligodendroglioma grade 2 (G2) and grade 3 (G3), is separated by histopathology alone and does not universally reflect survival outcome. DNA methylation-based profiling also fails to separate oligodendroglioma grades. Our aim was to define transcriptome-based molecular subgroups that predict survival of oligodendroglioma (IDH-mutant and 1p/19q-codeleted) patients. Clinical and whole-transcriptome data for oligodendroglioma were obtained from TCGA (n=132), CGGA (n=53), and the Exsegen Genomics Research Biobank (n=16) (CTRI/2021/09/036861); while that of control brain samples (n=9) were obtained from CPTAC. Overall survival (OS) was significantly different in TCGA samples between WHO CNS G2 and G3 oligodendrogliomas (log-rank test, p=0.0001); but, not in CGGA (p=0.1833) or Exsegen (p&gt;0.06) samples. Genes with highly variable expression (Median Absolute Deviation, i.e. MAD&gt;1; 1645 genes) across TCGA oligodendroglioma and CPTAC control brain samples were used to exclude 9 oligodendroglioma samples with Pearson’s correlation&gt;0.75 with control brain samples. Consensus clustering (K-means and spectral) of remaining 124 TCGA oligodendroglioma samples identified three significantly different (SigClust, p&lt;0.05) transcriptomic classes using 1347 highly variable genes (MAD&gt;1) in these samples. Principal component analysis (PCA) on expression of 1347 genes in TCGA samples revealed partial overlap of G2 and G3 tumours; but transcriptomic classes with distinct OS could be identified at both extremes of survival. Gene expression signatures for each transcriptomic class were developed using core TCGA samples from each class. For further validation, gene signatures were used to predict the transcriptomic classes of CGGA and Exsegen samples based on highest cosine similarity between sample gene expression and gene signature of each transcriptomic class. OS was significantly different between the transcriptomic classes in TCGA samples and predicted ones in CGGA samples. Transcriptome profiling separated oligodendrogliomas into distinct classes which can predict survival and potentially augment grading and refine prognostication and treatment options.
PATH-38. INTRACRANIAL SARCOMA WITH DICER1 MUTATION IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1
Authors: Weisnicht Allison , Pytel Nicholas 
Published: November 2024

Abstract
A 16-year-old male with neurofibromatosis type 1 (NF1) and a history of low-grade gliomas presented for resection of a progressively enlarging, known low-grade glioma. On follow-up imaging for surgical planning of the low-grade glioma, a new area of concern was detected of a leptomeningeal-based lesion over the left frontal lobe. A biopsy of the frontal lobe lesion subsequently showed a primary intracranial sarcoma with DICER1 mutations, DICER1 p.Q1552 and p.D1709G. An important histology finding was that of prominent eosinophilic cytoplasmic globules, which are associated with intracranial sarcomas with DICER1 mutations. Additional molecular findings of this tumor included NF1 p.K1986fs and TP53 p.G279E mutations in the setting of this patient’s known history of NF1. A DICER mutation was not detected in the concurrent low-grade glioma at the time of his intracranial sarcoma diagnosis, thus thought not to be a germline-derived mutation. He went on to have a surgical resection with subsequent photon radiation therapy followed by consolidation chemotherapy. A Ewing sarcoma based regimen as per COG protocol AEWS1031 was selected for his therapy consisting of vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide (VDC-IE). This was chosen based on prior cases showing response to anthracycline-based regimens. This patient has overall shown improvement without signs of progression now 7 months out from his initial diagnosis. This case highlights the importance of recognizing the association of patients with NF1 being at an increased risk for the development of intracranial sarcomas with DICER1 mutations and correlation with histologic findings of eosinophilic cytoplasmic globules. It also points to the need for reporting these rare cases for optimization of therapy selection to provide a more standardized and evidence-based approach in the care for these patients.
PATH-45. TREATMENT OF FGFR1 – ALTERED WHO GRADE 1 GLIONEURONAL TUMORS WITH FGFR INHIBITOR ERDAFITINIB
Authors: Kushnirsky Marina , Gampel Bradley , Gultekin Sakir Humayun , Ivan Michael E , Komotar Ricardo J , Capo Hilda , Williams Basil , de la Fuente Macarena I 
Published: November 2024

Abstract

INTRODUCTION
Low-grade mitogen-activated protein kinase (MAPK) pathway-altered glioneuronal tumors carry distinct molecular alterations, which may represent therapeutic opportunities to avoid or delay toxic treatments like radiation. Erdafitinib is a pan-FGFR tyrosine kinase inhibitor, regulatorily approved in recurrent urothelial carcinoma, and is under clinical investigation for recurrent FGFR-altered gliomas (NCT05859334).

METHODS
We report two patients with FGFR1-altered rosette-forming glioneuronal tumors (RGNT) treated with erdafitinib.

RESULTS
Patient 1 is a 32-year-old woman who presented with obstructive hydrocephalus and a non-enhancing pineal tumor. She underwent a subtotal resection, with histopathology initially consistent with a low grade dysembryoplastic neuroepithelial tumor. She was under observant management for 7 years, and developed worsening symptoms with slow non-enhancing growth, although stable per RANO low grade criteria. The initial tissue was sent for next-generation sequencing (NGS) and DNA methylation profiling, revealing an FGFR1 pathogenic variant with DNA methylation profiling matching with RGNT. Patient began Erdafitinib 8 mg daily, and had stable disease per RANO at 6 months. She developed CTCAE grade 1 toxicities of subretinal fluid, fatigue, dry skin, and paronychia. Patient 2 is a 34-year-old man diagnosed 1 year prior with a tectal tumor, who underwent biopsy due to non-measurable/ non-enhancing progression. Histopathology was consistent with RGNT. NGS revealed FGFR1 mutation, PIK3CA mutation, and NF1 pathogenic variant, described in the literature as characteristic of RGNT. There was insufficient tissue for DNA methylation profiling. Patient started erdafitinib 8 mg daily and remains clinically stable for 1 month. He developed asymptomatic hyperphosphatemia (CTCAE grade 1). Both patients have tolerated treatment without interruptions or dose reductions.

CONCLUSION
Erdafitinib is a well-tolerated and potentially efficacious treatment of FGFR1- altered RGNT, and may avoid the need for radiation. Diagnosis of MAPK- altered low-grade glioneuronal tumors, specifically RGNT, is increasingly reliant on molecular data, and can significantly impact treatment options.
PATH-55. RAMAN-BASED MACHINE LEARNING PLATFORM REVEALS UNIQUE METABOLIC DIFFERENCES BETWEEN IDHMUT AND IDHWT GLIOMA
Authors: Lita Adrian , Sjöberg Joel , Păcioianu David , Celiku Orieta , Dowdy Tyrone , Păun Andrei , Gilbert Mark R , Noushmehr Houtan , Petre Ion , Larion Mioara 
Published: November 2024

Abstract

BACKGROUND
Formalin-fixed, paraffin-embedded (FFPE) tissue slides are routinely used in cancer diagnosis, clinical decision-making, and stored in biobanks, but their utilization in Raman spectroscopy-based studies has been limited due to the background coming from embedding media.

METHODS
Spontaneous Raman spectroscopy was used for molecular fingerprinting of FFPE tissue from 46 patient samples with known methylation subtypes. Spectra were used to construct tumor/non-tumor, IDH1WT/IDH1mut, and methylation-subtype classifiers. Support vector machine and random forest were used to identify the most discriminatory Raman frequencies. Stimulated Raman spectroscopy was used to validate the frequencies identified. Mass spectrometry of glioma cell lines and TCGA were used to validate the biological findings.

RESULTS
Here we develop APOLLO (rAman-based PathOLogy of maLignant glioma) – a computational workflow that predicts different subtypes of glioma from spontaneous Raman spectra of FFPE tissue slides. Our novel APOLLO platform distinguishes tumors from nontumor tissue and identifies novel Raman peaks corresponding to DNA and proteins that are more intense in the tumor. APOLLO differentiates isocitrate dehydrogenase 1 mutant (IDH1mut) from wildtype (IDH1WT) tumors and identifies cholesterol ester levels to be highly abundant in IDHmut glioma. Moreover, APOLLO achieves high discriminative power between finer, clinically relevant glioma methylation subtypes, distinguishing between the CpG island hypermethylated phenotype (G-CIMP)-high and G-CIMP-low molecular phenotypes within the IDH1mut types.

CONCLUSIONS
Our results demonstrate the potential of label-free Raman spectroscopy to classify glioma subtypes from FFPE slides and to extract meaningful biological information thus opening the door for future applications on these archived tissues in other cancers.