julilili42/papers huggingface dataset:
OS02.6.A MICCAI BRAIN TUMOR SEGMENTATION - METASTASES (BRATS-METS) 2025 LIGHTHOUSE CHALLENGE: COMPETITIVE ENVIRONMENT FOR THE DEVELOPMENT OF ROBUST AUTOMATIC SEGMENTATION ALGORITHMS FOR PRE- AND POST-TREATMENT BRAIN METASTASES
2025-10-01

Abstract BACKGROUND Volumetric analysis of brain metastatic lesions is of great relevance in neuro-oncology. Since manual annotation of a lesion is a laborious and time-consuming task, utilizing artificial intelligence (AI) tools for automated segmentation of brain metastases has shown promising potential, but published algorithms are not incorporated into clinical practice because of poor generalizability across institutions. Large publicly available and well-annotated datasets from across the world are critical for further clinical translation. MATERIAL AND METHODS The Brain Tumor Segmentation - Metastases (BraTS-METS) 2025 Lighthouse Challenge provides a competitive environment where scientists from various disciplines can benchmark their AI-based algorithms for automatic segmentation of pre- and post-treatment brain metastases on a well-curated publicly available brain metastasis dataset comprising 1,778 multiparametric brain MRI cases. Each case consists of T1-weighed, T1 post-contrast and FLAIR sequences. The cases were retrospectively obtained from 8 institutions in the USA and overseas, and underwent 3D nnU-Net pre-segmentation, followed by manual refinements performed by medical students and neuroradiologists, and a final approval by two independent board-certified neuroradiologists. A testing dataset was prepared through four rounds of annotation: two completed ‘from scratch’ and two following 3D nnU-Net pre-segmentation, all conducted by two independent neuroradiologists, with the segmentation process screen recorded for future analysis. This allowed us to establish inter- and intra-rater variability in brain metastases segmentation and create a reference standard dataset that will be publicly available after the conclusion of the challenge. The model performance of the participating teams in the challenge will be assessed via the following metrics: Dice Similarity Coefficient (DSC), Normalized Surface Distance (NSD), sensitivity, and precision of the model. RESULTS A multi-annotator testing dataset of 75 MRI cases of brain metastases and 300 segmentations (150 created ‘from scratch’ and 150 from 3D nnU-Net pre-segmentations of the cases) was developed as a new reference standard. The mean intra- and inter-rater DSC for the segmentations ‘from scratch’ were 0.68 and 0.59, respectively. The mean intra- and inter-rater DSC for the segmentations built upon 3D nnU-Net pre-segmentations were 0.88 and 0.77, respectively. CONCLUSION The BraTS-METS 2025 Lighthouse Challenge is a key initiative designed to advance the use of AI to improve characterization of brain metastases by providing algorithms for automatic segmentation of all lesions and peritumoral edema that are measured against a novel reference standard based on rigorous multi-annotator brain MRI segmentations.
P07.10.B INTER-RATER AGREEMENT FROM A MULTI-NATIONAL EXPERT PANEL ON RESECTABILITY OF RECURRENT GLIOBLASTOMA: A COMPLEMENTARY POST-HOC ANALYSIS OF THE PROSPECTIVE, RANDOMIZED DIRECTOR TRIAL
2025-10-01

Abstract BACKGROUND The role of re-resection in recurrent glioblastoma remains controversial. Associations between higher extents of re-resection and prolonged survival might be explained by the assumption that tumors in less functional (surgically more accessible) brain areas identify with an inherently better prognosis. We used the DIRECTOR cohort on recurrent glioblastoma to (I) assess heterogeneity in the expected ‘resectability’ among surgical experts and (II) explore whether ‘resectability’ or residual tumor is associated with survival. MATERIAL AND METHODS DIRECTOR was a randomized, prospective multicenter trial assessing two temozolomide regimens for first glioblastoma relapse. Patients could have a re-resection per centers’ preference. As no outcome differences between the two study arms were encountered, we pooled the arms to achieve a homogenously treated cohort. For each IDH-wildtype glioblastoma with baseline MRI available, eleven surgical neuro-oncologists rated tumor resectability. Cohen’s kappa estimated inter-rater agreement. Ratings on resectability and actual postoperative tumor were correlated with survival. RESULTS We studied 69 patients with first glioblastoma recurrence, including 40 individuals who underwent re-resection prior to temozolomide re-challenge. In patients who received a re-resection, a ‘meaningful resection’ was deemed feasible by 0-50% of the raters in 4/40 cases (10.0%), by 51-80% in 6/40 cases (15.0%), and by 81-100% in 30/40 cases (75.0%). Among patients without post-operative contrast-enhancing tumor, pre-operative agreement that tumors were resectable was high (agreement by &amp;gt;81-100% of raters: 23/24 cases, 95.8%). In patients who were managed without re-resection, in only 3/29 patients (10.4%) all raters agreed that tumors were not resectable; while 1-50% of the raters judged tumors as resectable in 14/29 patients (48.3%), 51-80% in 7/29 patients (24.1%), and 81-100% in 5/29 patients (17.2%). Knowledge of clinical factors virtually never changed the initial judgment based on MRI alone. Surgical decision-making varied between raters, ranging from 29 to 59/69 cases being classified as ‘resectable’ (kappa: 0.405). In the overall cohort, consensus on resectability by &amp;gt;80% of the raters was not associated with favourable post-recurrence survival (10.4 ± 1.8 vs 10.0 ± 3.0 months, p = 0.924) or progression-free survival (2.0 ± 0.5 vs 1.9 ± 0.2 months, p = 0.757). Compared to submaximal resection or no re-resection, patients with complete resection of the enhancement had longer survival, particularly in MGMT unmethylated tumors. CONCLUSION Assessment of feasibility for re-resections in recurrent glioblastoma substantially varies between surgical experts. An objective consensus on resectability remains undefined, with major implications for practice and trial stratification. ACKNOWLEDGMENT DIRECTOR investigators.
JS04.7.A IDENTIFICATION OF BCL FAMILY MEMBERS AS MODULATORS OF REGORAFENIB EFFICACY IN EXPERIMENTAL GLIOMA
2025-10-01

Abstract BACKGROUND Glioblastoma are aggressive primary tumors of the central nervous system with limited systemic treatment options. Regorafenib, a multi-tyrosine kinase inhibitor, demonstrated improved median overall survival in the phase 2 REGOMA trial for progressive glioblastoma, compared to the control arm with Lomustin. However, these results were not confirmed in the GBM AGILE adaptive clinical trial platform. To discover potential modifiers of the therapeutic efficacy of regorafenib, we investigated functionally guided combination therapy strategies in experimental glioma models. MATERIAL AND METHODS We employed a genome-wide CRISPR-Cas9 functional genomics approach, including both activation and knockout screens, followed by genetic, pharmacological, and functional validation. Regorafenib-induced molecular changes were analyzed at the RNA and protein levels. Selected functionally guided combination therapies were evaluated in vivo using several well-established orthotopic glioma mouse models, including the syngeneic, immunocompetent SMA560/VM/Dk model. Post-treatment brain tumor tissue was further analysed via immunohistochemistry. RESULTS We discovered potential regulators of regorafenib efficacy, including ARAF, BCL2, BCL2L1, FOXC1, ITGB3, PLCE1 and SERAC1. Combining regorafenib with the Bcl-2/Bcl-xL inhibitor navitoclax significantly improved therapeutic efficacy compared to monotherapy in vitro, ex vivo, and in vivo. RNA sequencing revealed regorafenib-dependent modulation of the Bcl-2 downstream target chemokine receptor 1 (CCR1). We further characterized the role of CCR1 as a functional mediator of the observed synergy with Bcl-2 family inhibition. Additionally, we detected regorafenib-induced changes in the myeloid compartment of the glioma-associated microenvironment in post-treatment murine tissue. CONCLUSION We utilized a functional genomics-based target discovery approach with subsequent multi-level validation to identify modulators of regorafenib efficacy. Our findings reveal actionable targets and support the rationale for combinatorial treatment strategies, particularly co-inhibition of Bcl-2 family proteins. These results provide a strong biological rationale for clinical evaluation of regorafenib in combination with navitoclax.
P15.09.A EVALUATION OF AN ART-BASED INTERVENTION IN NEURO-ONCOLOGICAL PATIENTS - A PILOT STUDY
2025-10-01

Abstract BACKGROUND Brain tumor diagnoses often cause significant psychological distress in patients and their caregivers, frequently accompanied by neurocognitive deficits and personality changes. Art observation has been shown to positively affect neurocognition and activate brain regions involved in reflective processing, such as the Default Mode Network. This study aimed to evaluate the feasibility and psychosocial impact of a structured art-based intervention. METHODS In this single-center study, brain tumor patients and their relatives participated in guided art tours at a local museum. Each session centered around three themes grounded in the principles of neuroaesthetics. During the 60-minute tours, selected artworks were discussed from both a neuroscientific perspective by a neurosurgeon and an artistic perspective by an art historian. The experience was complemented by carefully chosen music that matched the themes. Vital signs were recorded before and after each session. Participants also completed a study-specific questionnaire assessing the perceived emotional and cognitive effects of the intervention, using a 4-point Likert scale (1 = strongly disagree to 4 = strongly agree). Additionally, validated instruments were used to measure psychological distress and health-related quality of life. The primary outcomes included feasibility, emotional responses based on questionnaire data, and changes in vital signs. RESULTS A total of 16 patients (7 male, 9 female patients) and 11 caregivers attended eight sessions between August 2023 and July 2024; additional sessions followed from March to May 2025. Overall, 25 of 27 participants (14 patients, 11 caregivers) completed the evaluation. Most reported positive experiences: 21 participants (12 patients, 9 caregivers) felt emotionally relieved; 17 (11 patients, 6 caregivers) experienced cognitive stimulation; 20 (11 patients, 9 caregivers) reported increased curiosity; and 20 (12 patients, 8 caregivers) described a positive impact on daily life. Negative responses were rare, with only 4 participants disagreeing or strongly disagreeing with feeling emotionally relieved. No adverse events occurred, and vital signs remained stable, in patients and caregivers. CONCLUSION This pilot study demonstrates that the art-based intervention is feasible and well accepted by both neuro-oncology patients and their caregivers. Preliminary results support further investigation of art observation as a complementary therapeutic approach.
OS05.8.A DISSECTING RESISTANCE TO CDK4/6 INHIBITION IN EXPERIMENTAL GLIOMA VIA GENOME-WIDE CRISPR-CAS9 SCREENING
2025-10-01

Abstract BACKGROUND CDK4/6 inhibitors exhibit therapeutic potential in several tumor entities. Their clinical efficacy in glioblastoma might be limited by intrinsic and acquired resistance mechanisms. Understanding underlying genetic and molecular factors of this resistance might inform the design of effective therapeutic strategies. Genome-wide CRISPR-Cas9 screens offer a powerful approach to systematically identify resistance drivers and synthetic lethal interactions, paving the way for rational combination therapies. MATERIAL AND METHODS We conducted genome-wide CRISPR-Cas9 knockout and activation screens in human glioma cell lines LN229 and GS9 under CDK4/6 inhibition using Brunello and Calabrese libraries. Top hits were validated using functional assays. Furthermore, we conducted bulk RNA sequencing of treated and untreated cells for transcriptomic insights into drug response modifiers and molecular pathways involved. RESULTS Functional genomics identified Ambra1 and CCNE1 as key drivers of resistance. Both Ambra1 knockout and CCNE1 overexpression, conferred resistance across both long-term and stem-like glioma models. Additionally, knockout of CHEK1 and FAM122A uncovered synthetic lethal interactions with CDK4/6 inhibition. Functional validation confirmed that glioma cells rely on CHEK1 or FAM122A for cell cycle progression, with cell line specific sensitivity. Transcriptomic analyses consistently highlighted alterations in pathways associated with cell cycle regulation, DNA replication, and the Fanconi anemia pathway. Of note, several differentially expressed genes overlapped with screen hits, supporting the robustness of our findings. Notably, pharmacological inhibition of CHEK1, both in vitro and ex vivo, enhanced sensitivity to CDK4/6 inhibition in a sequence-dependent manner, indicating a critical role of the sequence of drug administration. CONCLUSION Our functional genomics approach uncovers mediators of acquired resistance and synthetic lethality in the context to CDK4/6 inhibitors in glioma. Co-targeting of CHEK1 or FAM122A with CDK4/6 inhibitors represents a promising therapeutic strategy to overcome resistance and improve the therapeutic efficacy. Ongoing in vivo studies using xenograft and syngeneic glioma models aim to validate the survival benefit of these combinations and to elucidate their impact on the tumor microenvironment.
P08.11.A MANAGEMENT OF IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME FOLLOWING CAR-T CELL THERAPY IN CLINICAL PRACTICE: A MULTICENTRIC, RETROSPECTIVE, REAL-WORLD ANALYSIS OF TREATMENT APPROACHES AND OUTCOMES
2025-10-01

Abstract BACKGROUND Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and potentially severe adverse event following chimeric antigen receptor (CAR) T-cell therapy. Although early intervention is essential, real-world data on ICANS management are still scarce. This study investigated treatment approaches and outcomes in patients with ICANS across six CAR T-certified centers in Germany. METHODS This retrospective, multicenter study evaluated treatment initiation and sequencing strategies in 165 patients with confirmed ICANS following CD19- or BCMA-directed CAR T-cell therapy. Among them, 155 (93.9%) had relapsed/refractory B-cell lymphoma, 8 (4.8%) had multiple myeloma, and 2 (1.2%) had acute lymphoblastic leukemia. The CAR T-cell products used were Axi-cel in 105 patients (63.6%), Brexu-cel in 25 (15.15%), Tisa-cel in 19 (11.5%), Liso-cel in 8 (4.8%), Ide-cel in 7 (4.2%), and Cilta-cel in 1 (0.6%). Data were collected via standardized questionnaires and medical chart reviews, focusing on the timing and therapeutic sequence of corticosteroids, IL-1 receptor antagonists, and anti-seizure therapies. RESULTS Median patient age was 64 years (19-85), and median ECOG performance status before CAR T-cell transfusion was 1 (0-3). The median duration of ICANS was 4 days (1-155), with a median ASTCT grade of 2 (1-5). Preceding or concomitant cytokine release syndrome (CRS) occurred in 163/165 patients (98.7%) with a median ASTCT grade of 2 (1-4). CNS involvement was present in 26/165 patients (15.7%). Seizure prophylaxis varied across centers: one center administered it to all 11 of its patients (11/11, 100%), two centers decided treatment in a fraction of their patients (6/17, 35.2% and 2/50, 4%), while the remaining two centers did not provide prophylaxis to any of their patients (0/87). Corticosteroids were administered in 135/165 patients (81.8%), with a median time interval of 0 days (0-4) from ICANS onset. Anakinra was used in 25/165 patients (15.2%) across five centers, with initiation at a median of 1 day (0-41) after ICANS onset. Of these, 17/25 patients (68%) received high-dose anakinra (&amp;gt;200mg/d). ICANS duration was significantly extended with treatment delay of anakinra (p&amp;lt;0.0035). Prolonged ICANS duration (&amp;gt;7d) was associated with inferior progression-free survival (PFS) and overall survival (p&amp;lt;0.068, p&amp;lt;0.015). In multivariate analysis, CNS involvement was an independent predictor of inferior PFS (p&amp;lt;0.043, HR 1.07-5.48). CONCLUSION Our study reveals discrepancies in ICANS management across treatment centers in Germany. Delayed anakinra administration was linked to prolonged ICANS duration, indicating that timely treatment may help limit the extent of neurotoxicity. Prolonged neurotoxicity was associated with inferior PFS. Future prospective studies are needed to determine the optimal timing and combination of treatment in ICANS.
P15.17.A END-OF-LIFE CHALLENGES IN NEURO-ONCOLOGICAL PATIENT CARE: A YOUNGNOA SURVEY
2025-10-01

Abstract BACKGROUND Malignant brain tumors inevitably recur, leading to progressive neurological decline. Palliative care is essential for optimizing patient outcomes, yet its integration into neuro-oncology remains inconsistent. We conducted a nationwide survey to evaluate palliative care practices among German neuro-oncologists and assessed the impact of physicians’ comfort on end-of-life discussions in patient care. MATERIAL AND METHODS A nationwide, anonymous survey was distributed to 481 neuro-oncologists who are members of the Neuro-oncology Working Group of the German Cancer Society. The questionnaire, developed in collaboration with board-certified palliative care specialists, evaluated physicians’ demographic characteristics, palliative care knowledge, and access to palliative care resources. RESULTS Of 92 respondents, 81 (88%) reported comfort in discussing end-of-life issues, while 11 (12%) expressed discomfort. Physicians comfortable with these discussions more frequently addressed withholding of life-sustaining interventions (88% versus 55%, p=0.011), arranged home care (81% versus 64%, p=0.019), and facilitated hospice placement (68% versus 36%, p=0.021). They also initiated these conversations earlier and observed greater patient receptivity to palliative care (p=0.049). These associations remained significant in multivariable logistic regression. CONCLUSION While most neuro-oncologists report comfort with end-of-life discussions, this comfort strongly influences timing and extent of palliative care integration. Our findings highlight the need for structured palliative care training to ensure timely and effective discussions, ultimately improving care for neuro-oncological patients.
P03.22.A USE OF POSITRON EMISSION TOMOGRAPHY (PET) IN PATIENTS WITH BRAIN TUMOURS AMONG EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER - BRAIN TUMOUR GROUP (EORTC-BTG) SITES
2025-10-01

Abstract BACKGROUND Data on the use of positron emission tomography (PET) among neuro-oncology centers in Europe are scarce. MATERIAL AND METHODS From 06/2024 to 08/2024, a cross-sectional survey among European Organization for Research and Treatment in Cancer - Brain Tumor Group (EORTC-BTG) sites was performed to gain insights into the availability and use of PET across brain tumor centers in Europe. RESULTS In total, 312 sites were invited, and 103 replies from 20 countries were recorded. PET was available at 96/103 (93.2%) sites, and 74 of these reported PET use in patients with central nervous system neoplasms. Most frequently, PET was performed in glioma (69/74, 93.2%), followed by brain metastasis (58/74, 78.4%), meningioma (52/74, 70.3%), and CNS lymphoma (46/74, 62.2%). Amino acid PET was performed at 62/71 sites (87.3%, 3 not reported [n.r.]), and most frequently in glioma (58/59, 98.3%) and for differentiation of treatment-related changes from tumour progression (58/59, 98.3%). The prevailing amino acid tracer was [18F]FET (45/59, 76.3%), followed by [18F]FDOPA (22/59, 37.3%) and [11C]methionine (15/59, 25.4%). Dynamic acquisition protocols for amino acid PET were used by 35/59 (59.3%) sites. Somatostatin receptor (SSTR) PET was applied at 50/68 sites (73.5%, 6 n.r.) and mainly in meningioma (48/49, 98.0%) and for patient selection before radioligand therapy (41/49, 83.7%) as well as for target volume definition in radiotherapy (33/49, 67.3%). PET was reportedly covered by statutory health insurance at 46/59 (78.0%) centres for amino acid PET and 33/49 (67.3%) for SSTR PET. Reasons for not using PET in clinical routine included limited availability of tracers (14/29, 48.3%), high cost (11/29, 37.9%), and PET not perceived necessary (8/29, 27.6%). CONCLUSION PET is widely used within the EORTC BTG network, underscoring the feasibility of PET-based clinical trial endpoints which support the generation of evidence for further implementation in clinical routine. As our survey may be prone to selection and non-response bias, a comprehensive analysis of PET application patterns would be desirable.
Revolutionizing Pediatric Gene and Cell Therapy: The Hope for Lipid-Based Nanoparticles in Blood Disorders
2025-10-01

The rapidly advancing field of lipid-based nanoparticles (LNPs) as delivery systems for nucleic acids has the potential to revolutionize treatment strategies. LNPs have demonstrated exceptional versatility in delivering genetic material and therapeutic agents to target cells. In gene and cell therapy, LNPs could serve as efficient carriers for introducing genetic materials into the cells, addressing inherited genetic disorders at their root. Their minimal toxicity and immune response make them particularly suitable for pediatric applications. Additionally, the scalability and cost-effectiveness of LNP production offer practical advantages over methods such as viral vectors and electroporation (EP), improving accessibility to advanced therapies for children worldwide. In 2018, the first FDA-approved LNP-based siRNA therapy (Patisiran/ Onpattro®) for treating hereditary amyloidosis brought attention to the feasibility of LNPs for gene therapy. Eventually, authorization and approval of the mRNA-LNP vaccines against COVID-19 (Comirnaty® of BioNTech/Pfizer and SpikeVax® of Moderna) was another milestone for the development of LNP-based nucleic acid therapies. Later, LNPs were applied successfully for the delivery of pDNA, mRNA and siRNA in many types of genetic disorders and cancers. This innovative approach offers a brighter future for pediatric healthcare, where children can look forward to healthier and more fulfilling lives. This review paper provides an overview of the applications of LNPs in gene and cell therapies with a special focus on their pre-clinical application in primary cells, including natural killer cells, T cells, and hematopoietic stem cells, highlighting LNPs' efficacy, safety profile, and potential for transforming the landscape of pediatric healthcare in the future.
On multi-propagator angular integrals
2025-10-01

A bstract We study multi-propagator angular integrals, a class of phase-space integrals relevant to processes with multiple observed final states and a test-bed for transferring loop-integral technology to phase-space integrals without reversed unitarity. We present an Euler integral representation similar to the Lee-Pomeransky representation and explicitly describe a recursive IBP reduction and dimensional shift relations for the general case of n denominators. On the level of master integrals, applying a differential equation approach, we explicitly calculate the previously unknown angular integrals with four denominators for any number of masses to finite order in ε . Extending the idea of dimensional recurrence, we explore the decomposition of angular integrals into branch integrals reducing the number of scales in the master integrals from ( n + 1) n /2 to n + 1. To showcase the potential of this method, we calculate the massless three denominator integral and establish all-order results in ε , including a resummation of soft logarithms.