bluuebunny/crossref_metadata_2025_split huggingface dataset:
INNV-01. METASTATIC GLIOBLASTOMA TO THE LUNG TREATED WITH LENVATINIB
Authors: Yuen Carlen , Pekmezci Melike , Bao Silin , Kong Xiao-Tang 
Published: November 2024

Abstract
Glioblastoma is the most common malignant brain tumor. Despite its invasive nature, extra-cranial glioblastoma metastases are rare. We present a case of a 63 year-old woman with metastatic glioblastoma to the lung. Sarcomatous histology, a reported risk factor for disseminated disease, was found. Genomic alterations of TP53 mutation, TERT mutation, PTEN mutation, and +7/-10 were also uncovered. Early evidence suggests these molecular aberrations are common in metastatic glioblastoma. Treatment with third-line lenvatinib resulted in a mixed response. This case contributes to the growing body of evidence for the role of genomic alterations for predictive risk in metastatic glioblastoma. There remains an unmet need for treatment of metastatic glioblastoma.
INNV-02. BRAINMETS: A CLINICIAN-FRIENDLY SOFTWARE TO MANUALLY SEGMENT BRAIN METASTASES AND DETECT PRIMARY TUMOR ORIGIN USING DEEP LEARNING
Authors: Panchawagh Suhrud 
Published: November 2024

Abstract
Estimates suggest that around 20%-40% of cancer patients are affected by brain metastases. A subset of these patients first present with central nervous system manifestations with an unknown primary. The issue then arises regarding which region of the body should be imaged, if not the entire body, exposing the patient to more radiation. To address this issue, streamline workflows, and save precious time, we developed a software clinicians can use to identify primary tumor locus. “BrainMets” is a user-friendly software that handles a DICOM input, allows the user to segment the region(s) of interest manually, and uses a deep learning model to predict the most likely tumor origin. The model is a mixed-effects neural network pre-trained on radiomic features from open-source data by Ocaña-Tienda et al. (2023) using 637 high-resolution imaging studies from 10 different medical centers with an accuracy of 90.5%, precision of 92.7%, recall of 87.8%, and F1 score of 90.2%. The software leverages the open-source software 3D-Slicer to help segment regions of interest, extract radiomic features, and make predictions. It is built using Flask, a Python package for backend development. The frontend user interface is created using HTML/CSS and Bootstrap. The “BrainMets” software thus strives to enhance diagnostic workflow significantly, reduce appointment times for scans, and improve patient experience. Future enhancements include integrating more AI models, improving healthcare IT system compatibility, and updating datasets to boost predictive accuracy and generalizability. This tool sets a new standard in personalized medicine, optimizing treatment strategies for cancer patients with brain metastases. As adoption increases, it could substantially improve patient outcomes and reduce healthcare costs associated with misdiagnosis and overtreatment. Further research and development will focus on expanding its applicability across various types of cancers.
INNV-03. BEYOND ANALGESICS: PHOTOBIOMODULATION THERAPY AS A PARADIGM SHIFT IN PAIN MANAGEMENT
Authors: UWISHEMA Olivier 
Published: November 2024

Abstract

BACKGROUND
Pain constitutes a primary cause of medical care demand and disability among patients. The predominant method employed for pain management entails analgesic administration. Nonetheless, prolonged use of analgesics may lead to adverse effects, including cardiovascular and gastrointestinal complications. Photobiomodulation therapy (PBMT) emerges as a novel approach to pain treatment, demonstrating effective pain reduction and anti-inflammatory properties. This systematic review aims to elucidate the impacts of PBMT on pain modulation and assess its potential for widespread application.

METHODS
A systematic review was conducted utilizing Boolean operators combining terms such as “Photobiomodulation” AND “Pain Management”; “Photobiomodulation therapy” AND “pain”; “PBMT” AND “Pain”. Electronic databases including Cochrane Library, PubMed, and Scopus were searched. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement.

RESULTS
The systematic review revealed that PBMT is a non-invasive, safe, and cost-effective technique for pain management. It has demonstrated efficacy across various conditions, encompassing neurological and musculoskeletal disorders. PBMT can complement existing interventions such as exercise programs, transcutaneous electrical nerve stimulation (TENS), or surgical procedures. However, further research with long-term follow-up is warranted to validate these findings.

CONCLUSIONS
PBMT emerges as a promising modality for pain management, offering a non-invasive alternative with favorable safety profiles. Its efficacy in diverse conditions underscores its potential utility as an adjunctive or standalone treatment option. Nonetheless, additional studies with extended follow-up periods are necessary to confirm and further elucidate its therapeutic benefits.
INNV-07. IVOSIDENIB AND BEVACIZUMAB IN HEAVILY PRETREATED PATIENTS WITH IDH1 MUTANT GLIOMAS
Authors: Patel Mallika P , Ziv Michal Nisnboym , Minor Maria , Johnson Margaret O , Batich Kristen , Low Justin , Shoaf Madison L , Khasraw Mustafa , Friedman Henry S , Ashley David M , Desjardins Annick , Peters Katherine B 
Published: November 2024

Abstract
Isocitrate dehydrogenase 1 (IDH1) inhibitors are transforming the treatment of patients with non-enhancing IDH1 mutant gliomas that have only undergone surgical resection. Questions remain on the utility of IDH1 inhibitors in patients that have received prior therapies such as radiation therapy (RT) and chemotherapy (e.g. temozolomide (TMZ)) and have progressive disease. We evaluated the safety and efficacy of ivosidenib, an oral IDH1 inhibitor, in combination with bevacizumab (BEV), a monoclonal antibody targeting VEGF-A, in IDH1 mutant glioma patients that were heavily pretreated. Fourteen patients received combination ivosidenib and bevacizumab starting between February 2021 to July 2023. In our small cohort, patient age range was 26 to 73 years with seven female patients and seven male patients. Diagnoses represented were astrocytoma, IDH1 mutant (n=10) and oligodendroglioma, IDH1 mutant (n=4). At the time of IDH1 therapy initiation, the majority of patients (n=10) had a grade 3 tumor. All patients (n=14) had canonical IDH1 mutation (p.Arg132His) and had enhancing disease. Therapies initiated prior to ivosidenib therapy included: prior RT (n=12), prior TMZ (n=14) and prior BEV (n=10). The median number of progressions prior to initiation of ivosidenib combination therapy was 3 (range 2 to 6). All patients received ivosidenib dosed at 500 mg daily with bevacizumab doses varying from 5 to 15 mg/kg IV dosed every 2 to 3 weeks. Combination therapy was well tolerated with minimal patients experiencing toxicities requiring dose interruptions; diarrhea (n=2), creatine phosphokinase elevations (n=1), QTc prolongation (n=1), and thrombocytopenia (n=1). The median treatment duration on ivosidenib combination therapy was 4.42 months (range 0.69 to 11.4 months). In this cohort, the combination of ivosidenib and bevacizumab was well tolerated. More information is needed on the benefit of ivosidenib in combination with other therapies and in heavily pretreated patients with IDH1 mutant gliomas.
INNV-15. A PIVOTAL, MULTICENTER TRIAL OF FOCUSED ULTRASOUND FOR BLOOD-BRAIN BARRIER DISRUPTION FOR PLASMA-BASED LIQUID BIOPSY IN PATIENTS WITH GLIOBLASTOMA (LIBERATE)
Authors: Ahluwalia Manmeet , Ozair Ahmad , Burns Terence , McDermott Michael , Sahgal Arjun , DeGroot John , Mogilner Alon , Hibert Matthew , Zhu Julia , Shah Bhavya , Patel Toral , Rincon-Torroella Jordina , Mishra Mark , Everson Richard , Sporrer Justin , Hilliard Justin , Bezchlibnyk Yarema , Weinberg Jeffrey , Cifarelli Christopher , Rezai Ali , Lipsman Nir , Woodworth Graeme 
Published: November 2024

Abstract

BACKGROUND
Liquid biopsy in glioblastoma (GBM) is hindered by insufficient requisite circulating-tumor (ct) and cell-free (cf) DNA in blood due to blood-brain barrier (BBB). This limits the identification of blood-based tumor biomarkers along with biomarker-driven systemic therapies. Real-time image-guided low-intensity focused ultrasound (LIFU) plus IV microbubble oscillators, leads to non-invasive BBB disruption.

METHODS
LIBERATE is an ongoing, prospective, multi-center, self-controlled, pivotal trial investigating safety and technical efficacy of LIFU-based BBB disruption for increasing blood ctDNA and cfDNA levels in adult GBM patients (aged 18-80 years). Patients with suspected GBM planned for biopsy/resection at ten US centers are being enrolled. Patients with multifocal tumors or tumors arising from deep midline, thalamus, cerebellum, or brainstem are excluded. Patients are administered IV microbubbles for enhanced sonication effects, after which MR-guided BBB disruption using 220kHz LIFU device is performed with real-time acoustic-feedback-control for effective microbubble activation. Pre- and post-LIFU, phlebotomy and MRI brain are performed. Primary study endpoint is defined, per subject, as ratio between their blood cfDNA level 1-hour post-LIFU procedure compared to blood cfDNA pre-procedure. Primary study hypothesis is that BBB disruption leads to ≥2-fold rise in blood cfDNA. Secondary hypothesis is that there exists ≥75% agreement between biomarker pattern in blood cfDNA sample obtained 1-hour post-LIFU and biomarker pattern in tumor tissue obtained later. Trial is powered to evaluate both primary and secondary hypotheses. Based on assumed true agreement rate of 91% and one-sided alpha=0.025, an exact test for binomial proportions provides N=50 with 84% power for secondary hypothesis. Exploratory endpoints include (1) sensitivity of detection of specific somatic mutations in ctDNA from blood collected pre- and post-LIFU, (2) ctDNA estimation in samples collected at 30-minutes, 1-hour, 2-hour, and 3-hour post-LIFU to determine time of greatest yield, (3) correlation of MRI parameters related to grading of BBB disruption and ctDNA-based biomarkers from post-LIFU blood samples. Patient enrollment commenced in 2022 and remains ongoing (NCT05383872).
INNV-18. FOCUS ON CURRENT AND EMERGING TREATMENT OPTIONS FOR GLIOMA: A COMPREHENSIVE REVIEW
Authors: Lucke-Wold Brandon , Shafique Muhammad Ashir , Mustafa Muhammad Saqlain , Haseeb Abdul 
Published: November 2024

Abstract
This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient’s quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.
INNV-23. UNDERSTANDING THE BURDEN OF MIDH1/2 DIFFUSE GLIOMA AND THE COMPLEXITY OF NAVIGATING THE PATIENT PATHWAY: INSIGHTS FROM PATIENTS AND CAREGIVERS
Authors: Oliver Kathy , Burton Mary , Cardinal Craig , LaHay Shannon , Leon Bernard , Mallett Rebecca , Rogers Sarah , Tse Chris 
Published: November 2024

Abstract
Diffuse gliomas with mutations in isocitrate dehydrogenase 1 or 2 (mIDH1/2) are characterized by a slow-progressing yet life-limiting disease predominantly in young people. We report interim findings from a qualitative study to describe the mIDH1/2 diffuse glioma patient pathway, experience of the disease, and treatment approaches. Patients, caregivers, and patient-association group (PAG) representatives undertook individual interviews, with patients also completing standardized exercises as pre-work. Materials were developed in collaboration with the International Brain Tumour Alliance. Patients were aged ≥12 years with mIDH1/2 glioma and last resection ≥6 months before enrollment, either undergoing active observation or receiving chemotherapy/radiotherapy. Caregivers were living with the patient. PAG representatives were active members of a brain tumor PAG. From November 2023 to March 2024, 30 patients (Australia: n=10; China: n=6; France, UK: n=5 each; Canada, Japan: n=2 each), two caregivers (China, Australia: n=1 each) and one PAG (UK) participated. Median age of patients was 41.5 years, with 17 astrocytoma and 13 oligodendroglioma diagnoses. Presentation symptoms, circumstances of diagnosis and treatment, access to care, and navigation in the healthcare system differed per patient and within countries. Surgical resection was perceived as a crucial stage, both feared and desired. A second opinion was more often sought for surgery than for subsequent treatment approaches. Patients undergoing chemotherapy/radiotherapy (n=17) or active observation (n=13) expressed substantial physical, socioeconomic, financial, and psychological burden. Patients receiving active observation experienced strong and ongoing anxiety, as the uncertainty of tumor recurrence took a toll on their emotional wellbeing in the long term. The experience of people living with mIDH1/2 diffuse glioma is heterogeneous regarding their pathway and complexity navigating the healthcare system, with a substantial psychological and socioeconomic impact. Improved education, as well as facilitating early navigation and prioritizing shared decision-making along the disease pathway, will better support people living with mIDH1/2 diffuse glioma.
PATH-01. SELLAR SOLITARY FIBROUS TUMORS WHO GRADE II AND III: MIMICS OF NON-FUNCTIONING PITUITARY ADENOMAS
Authors: Persico Michele , Weinberg Brent , Shu Hui-Kuo , Zhong Jim 
Published: November 2024

Abstract
Solitary fibrous tumors WHO grade II and III (SFTs II/III) are rare mesenchymal neoplasia accounting for 0.4% of primary central nervous system tumors. SFTs II/III located in the sella turcica region are even rarer and, since the first case described in 1983, only 21 case reports of sellar/suprasellar SFTs II/III (ssSFTs II/III) have been described to this day. We aim to analyze ssSFTs II/III and to demonstrate that can be differentiated from non-functioning pituitary adenomas through pathological examination alone. We analyzed 20 case reports of ssSFTs II/III identified through PubMed and Google searches and a new unpublished case presented at Emory University. ssSFTs II/III are equally represented in both sexes, with 11 cases over 21 occurring in females and the mean age of onset at 46 years old. Clinically, ssSFTs II/III present with compression symptoms related to the tumor location. Headache, visual field defects, and anterior hypopituitarism-related symptoms are frequent chief complaints. As such, almost all cases of ssSFTs II/III had a pre-biopsy working diagnosis of non-functioning pituitary adenomas. The differentiation between SFTs II/III and pituitary adenomas based on imaging findings remains challenging, and surgical biopsies are necessary for a definitive diagnosis. ssSFTs II/III surgical reports describe a unifying trait of a highly vascular tumor adherent to the dura that bleeds profusely after resection. These characteristics are less consistent with a pituitary adenoma. The genetic hallmark of SFTs at all anatomical sites is paracentric inversions at 12q13, fusing the NAB2 and STAT6 genes, with consequent overexpression of STAT6. Pituitary adenomas lack this genetic signature. ssSFTs II/III have an overlapping presentation and similar imaging findings of pituitary adenomas, but different management and prognosis. Hence, it is crucial to include ssSFTs II/III among the pre-biopsy differential of sellar/suprasellar masses identified on imaging. Pathology confirmation is required to guide therapy.
PATH-06. TRANSLATION INTO CLINICAL PRACTICE OF THE G1-G7 MOLECULAR SUBGROUP CLASSIFICATION OF GLIOBLASTOMA
Authors: Georgescu Maria-Magdalena 
Published: November 2024

Abstract
Glioblastoma is the most frequent and malignant primary brain neoplasm. Glioblastoma growth is promoted by alterations in mediators from five major pathways: MAPK and PI3K canonical growth pathways, telomere elongation/TERT, cell cycle G1-phase and the p53 pathway. In a recent breakthrough study on a prospective Discovery cohort, I proposed the first all-inclusive molecular classification of glioblastoma into seven subgroups, G1-G7, based on MAPK pathway activation. New data from a subsequent, prospective Validation cohort validated the G1-G7 molecular subgroup classification, showing significant demographic and molecular differences between subgroups. Beside the initial histologic diagnosis, the G1-G7 classification requires next generation sequencing (NGS) of formalin-fixed paraffin-embeded (FFPE) samples and genomic-transcriptomic correlations between DNA mutations, copy number variations (CNVs) and RNA expression. Thus, in the Combined cohort containing tumors from over 220 glioblastoma patients, aproximately 75% of cases fell into three major subgroups, G1/EGFR, G3/NF1 and G7/Other, whereas the rest of 25% cases made up the four minor subgroups, G2/FGFR3, G4/RAF, G5/PDGFRA and G6/Multi-RTK. The name of the mutated most upstream, non-redundant, MAPK pathway effector corresponds to each subgroup, except for the G7/Other subgroup in which MAPK activation is minimal and PI3K pathway activation is dominant. The effectors of the other four pathways may be redundant; however, genomic-transcriptomic correlations showed subgroup specificity, with opposing trends for the G1/EGFR and G7/Other molecular subgroups. This first, all-inclusive, molecular subgroup classification of glioblastoma in a large prospective patient cohort allowed integrated pathway analysis, risk stratification and demographic comparison between Caucasian/White and African-American/Black patients. Most importantly, its implementation into clinical practice opened the avenue to controlled therapeutic approaches.
PATH-07. CLINICAL AND RADIOGRAPHIC FEATURES OF DIFFUSE GLIOMA MOLECULAR SUBTYPES IN ACCORDANCE WITH THE 2021 CNS5 WHO CLASSIFICATION
Authors: Jo Jasmin , Mondia Mark , Arewa Josephine , How Andrew , Patrie James , Dueck Nicholas , Gilbow Reed , Goschka Andrew , Joyner David , Patel Sohil H , Lopes M Beatriz , Schiff David 
Published: November 2024

Abstract

BACKGROUND
The incorporation of molecular parameters into WHO CNS5 has led to reclassification of many gliomas. We undertook to describe presenting clinical and radiographic features of diffuse adult gliomas according to CNS5 category.

METHODS
We reviewed pathology reports, clinical and MRI data at presentation of 972 adult patients with glioma diagnosed between 1/2010-2/2022. Continuous variables were presented as median; categorical variables as numbers and percentages, and comparison were performed using chi-square test.

RESULTS
736 patients had sufficient data for CNS5 re-classification and were included in the analysis: Grade 2 IDH-mutant (IDHmut) astrocytoma (A2) n=69, grade 3 IDHmut astrocytoma (A3) n=37, grade 4 IDHmut astrocytoma (A4), n=32, grade 2 oligodendroglioma (O2) n=60, grade 3 oligodendroglioma (O3) n=23, and grade 4 IDH-wildtype glioblastoma (GBM) n=515. Age at presentation significantly differed between grade 2&3 gliomas and grade 4 (mean age:39 versus 61.7; p&lt;0.001); A4 were also younger than GBM (39.8 versus 63.1). A majority in all categories except grade 2 gliomas were male. Seizure was more common in IDHmut gliomas than GBM (58.4% versus 31.8%;p&lt;0.001), while cognitive impairment was more common in GBM than in IDHmut gliomas (64.4% versus 34.4%;p&lt;0.001) and in A4 (64% versus 40.6%;p=0.013). Focal deficits at presentation were more frequent in GBM than in IDHmut gliomas (74.2% versus 30.5%;p&lt;0.001), but not significantly different compared to A4 (74.2% versus 58.1%;p=0.06). Contrast enhancement on MRI was more frequent in GBM compared to IDHmut gliomas (93% versus 48%;p&lt;0.001), but similar frequency with A4 (93% versus 96%;p=1.00). The minimum ADC was significantly higher in IDHmut glioma including A4 than GBM(p&lt;0.001). Calcification was more common in oligodendroglioma than astrocytoma and GBM (p&lt;0.001), and more frequent in A4 than GBM(p=0.016).

CONCLUSION
Significant differences in the clinical presentation and radiologic features exist among CNS5 glioma subtypes, informing potential diagnosis, management and prognosis at initial presentation.