Glioblastoma (GBM) remains the most aggressive tumor, urgently requiring novel therapeutic strategies. Here, we present a dry-to-wet framework combining generative modeling and experimental validation to optimize peptides targeting ATP5A, a potential peptide-binding protein for GBM. Our framework introduces the first lead-conditioned generative model, which focuses exploration on geometrically relevant regions around lead peptides and mitigates the combinatorial complexity of de novo methods. Specifically, we propose POTFlow, a \underline{P}rior and \underline{O}ptimal \underline{T}ransport-based \underline{Flow}-matching model for peptide optimization. POTFlow employs secondary structure information (e.g., helix, sheet, loop) as geometric constraints, which are further refined by optimal transport to produce shorter flow paths. With this design, our method achieves state-of-the-art performance compared with five popular approaches. When applied to GBM, our method generates peptides that selectively inhibit cell viability and significantly prolong survival in a patient-derived xenograft (PDX) model. As the first lead peptide-conditioned flow matching model, POTFlow holds strong potential as a generalizable framework for therapeutic peptide design.

Glioblastoma (GBM) is the most common aggressive, fast-growing brain tumor, with a grim prognosis. Despite clinical diagnostic advancements, there have not been any substantial improvements to patient prognosis. Histopathological assessment of excised tumors is the first line of clinical diagnostic routine. We hypothesize that automated, robust, and accurate identification of distinct histological sub-regions within GBM could contribute to morphologically understanding this disease at scale. In this study, we designed a four-step deep learning approach to classify six (6) histopathological regions and quantitatively evaluated it on the BraTS-Path 2024 challenge dataset, which includes digitized Hematoxylin \& Eosin (H\&E) stained GBM tissue sections annotated for six distinct regions. We used the challenge's publicly available training dataset to develop and evaluate the effectiveness of several variants of EfficientNet architectures (i.e., B0, B1, B2, B3, B4). EfficientNet-B1 and EfficientNet-B4 achieved the best performance, achieving an F1 score of 0.98 in a 5-fold cross-validation configuration using the BraTS-Path training set. The quantitative performance evaluation of our proposed approach with EfficientNet-B1 on the BraTS-Path hold-out validation data and the final hidden testing data yielded F1 scores of 0.546 and 0.517, respectively, for the associated 6-class classification task. The difference in the performance on training, validation, and testing data highlights the challenge of developing models that generalize well to new data, which is crucial for clinical applications. The source code of the proposed approach can be found at the GitHub repository of Indiana University Division of Computational Pathology: https://github.com/IUCompPath/brats-path-2024-enet.

Glioblastoma (GBM) is an aggressive primary brain tumor with a median survival of approximately 15 months. In clinical practice, the Stupp protocol serves as the standard first-line treatment. However, patients exhibit highly heterogeneous therapeutic responses which required at least two months before first visual impact can be observed, typically with MRI. Early prediction treatment response is crucial for advancing personalized medicine. Disease Progression Modeling (DPM) aims to capture the trajectory of disease evolution, while Treatment Response Prediction (TRP) focuses on assessing the impact of therapeutic interventions. Whereas most TRP approaches primarly rely on time-series data, we consider the problem of early visual TRP as a slice-to-slice translation model generating post-treatment MRI from a pre-treatment MRI, thus reflecting the tumor evolution. To address this problem we propose a Latent Diffusion Model with a concatenation-based conditioning from the pre-treatment MRI and the tumor localization, and a classifier-free guidance to enhance generation quality using survival information, in particular post-treatment tumor evolution. Our model were trained and tested on a local dataset consisting of 140 GBM patients collected at Centre François Baclesse. For each patient we collected pre and post T1-Gd MRI, tumor localization manually delineated in the pre-treatment MRI by medical experts, and survival information.

President Donald Trump signed an executive order Tuesday aimed at improving ways to identify and treat pediatric cancers using artificial intelligence.

The White House announced a $50 million investment in artificial intelligence research to predict cancer progression and minimize treatment side effects in children.

Glioblastoma is the most prevalent primary brain malignancy, distinguished by its highly invasive behavior and exceptionally high rates of recurrence. Conventional radiation therapy, which employs uniform treatment margins, fails to account for patient-specific anatomical and biological factors that critically influence tumor cell migration. To address this limitation, numerous computational models of glioblastoma growth have been developed, enabling generation of tumor cell distribution maps extending beyond radiographically visible regions and thus informing more precise treatment strategies. However, despite encouraging preliminary findings, the clinical adoption of these growth models remains limited. To bridge this translational gap and accelerate both model development and clinical validation, we introduce PREDICT-GBM, a comprehensive integrated pipeline and dataset for modeling and evaluation. This platform enables systematic benchmarking of state-of-the-art tumor growth models using an expert-curated clinical dataset comprising 255 subjects with complete tumor segmentations and tissue characterization maps. Our analysis demonstrates that personalized radiation treatment plans derived from tumor growth predictions achieved superior recurrence coverage compared to conventional uniform margin approaches for two of the evaluated models. This work establishes a robust platform for advancing and systematically evaluating cutting-edge tumor growth modeling approaches, with the ultimate goal of facilitating clinical translation and improving patient outcomes.

Glioblastoma is a highly invasive brain tumor with rapid progression rates. Recent studies have shown that glioblastoma molecular subtype classification serves as a significant biomarker for effective targeted therapy selection. However, this classification currently requires invasive tissue extraction for comprehensive histopathological analysis. Existing multimodal approaches combining MRI and histopathology images are limited and lack robust mechanisms for preserving shared structural information across modalities. In particular, graph-based models often fail to retain discriminative features within heterogeneous graphs, and structural reconstruction mechanisms for handling missing or incomplete modality data are largely underexplored. To address these limitations, we propose a novel sheaf-based framework for structure-aware and consistent fusion of MRI and histopathology data. Our model outperforms baseline methods and demonstrates robustness in incomplete or missing data scenarios, contributing to the development of virtual biopsy tools for rapid diagnostics. Our source code is available at https: //github.com/basiralab/MMSN/.

Charges against an American influencer and teen pilot who has been stranded on a remote island in the Antarctic since June have been dropped. Ethan Guo, 19, is alleged to have illegally landed his plane in Chilean territory after embarking on a solo trip to all seven continents to raise money for cancer research, according to local authorities. They accused him of providing false flight plan information to officials who detained him and opened an investigation. A judge has ordered him to leave the area, pay a $30,000 (£22,332) donation to a children's cancer foundation and is banned from re-entering Chilean territory for three years. Mr Guo made headlines last year when he began an attempt to become the youngest person to fly solo to all seven continents and collect donations for research into childhood cancer.

Glioblastoma, a highly aggressive brain tumor with diverse molecular and pathological features, poses a diagnostic challenge due to its heterogeneity. Accurate diagnosis and assessment of this heterogeneity are essential for choosing the right treatment and improving patient outcomes. Traditional methods rely on identifying specific features in tissue samples, but deep learning offers a promising approach for improved glioblastoma diagnosis. In this paper, we present our approach to the BraTS-Path Challenge 2024. We leverage a pre-trained model and fine-tune it on the BraTS-Path training dataset. Our model demonstrates poor performance on the challenging BraTS-Path validation set, as rigorously assessed by the Synapse online platform. The model achieves an accuracy of 0.392229, a recall of 0.392229, and a F1-score of 0.392229, indicating a consistent ability to correctly identify instances under the target condition. Notably, our model exhibits perfect specificity of 0.898704, showing an exceptional capacity to correctly classify negative cases. Moreover, a Matthews Correlation Coefficient (MCC) of 0.255267 is calculated, to signify a limited positive correlation between predicted and actual values and highlight our model's overall predictive power. Our solution also achieves the second place during the testing phase.

Background: Radiomics shows promise in characterizing glioblastoma, but its added value over clinical and molecular predictors has yet to be proven. This study assessed the added value of conventional radiomics (CR) and deep learning (DL) MRI radiomics for glioblastoma prognosis (<= 6 vs > 6 months survival) on a large multi-center dataset. Methods: After patient selection, our curated dataset gathers 1152 glioblastoma (WHO 2016) patients from five Swiss centers and one public source. It included clinical (age, gender), molecular (MGMT, IDH), and baseline MRI data (T1, T1 contrast, FLAIR, T2) with tumor regions. CR and DL models were developed using standard methods and evaluated on internal and external cohorts. Sub-analyses assessed models with different feature sets (imaging-only, clinical/molecular-only, combined-features) and patient subsets (S-1: all patients, S-2: with molecular data, S-3: IDH wildtype). Results: The best performance was observed in the full cohort (S-1). In external validation, the combined-feature CR model achieved an AUC of 0.75, slightly, but significantly outperforming clinical-only (0.74) and imaging-only (0.68) models. DL models showed similar trends, though without statistical significance. In S-2 and S-3, combined models did not outperform clinical-only models. Exploratory analysis of CR models for overall survival prediction suggested greater relevance of imaging data: across all subsets, combined-feature models significantly outperformed clinical-only models, though with a modest advantage of 2-4 C-index points. Conclusions: While confirming the predictive value of anatomical MRI sequences for glioblastoma prognosis, this multi-center study found standard CR and DL radiomics approaches offer minimal added value over demographic predictors such as age and gender.