CFB-GBM v2.0: An Augmented Longitudinal Dataset for Multi-Modal Glioblastoma Segmentation, Radiomics, and RANO Progression Tracking

Longitudinal glioblastoma response assessment requires comparing subtle tumor changes across MRI time points using structured clinical criteria such as RANO. However, most deep learning methods predict response labels directly from imaging features, which limits clinical inspection, verification, and correction. We introduce TRACE, a RANO 2.0-aligned concept bottleneck model for interpretable 4-class glioblastoma response classification on longitudinal 3D MRI. TRACE processes paired baseline and follow-up multimodal MRI scans with a shared 3D vision encoder, predicts clinically meaningful tumor measurements as root concepts, computes downstream RANO-derived concepts through deterministic rules, and incorporates scan interval and new-lesion information as passthrough concepts. This design frames response assessment as structured concept reasoning rather than direct image-to-label prediction. Using 5-fold patient-wise cross-validation on the LUMIERE dataset, TRACE achieves a 4-class macro F1 of 0.4769 and a binary progression-versus-non-progression macro F1 of 0.7085. It improves over a concept bottleneck baseline and remains within the range of published non-interpretable deep learning approaches. Ablation studies show that the expert RANO graph and intervention-consistency training are important for performance, while intervention experiments demonstrate that correcting concepts can improve downstream predictions. These results suggest that structured concept bottlenecks offer a transparent and clinically aligned direction for longitudinal glioblastoma response assessment, while highlighting the need for larger protocol-aligned datasets and external validation.

Glioblastoma (GBM), an aggressive primary brain tumor, is routinely monitored with longitudinal MRI after treatment. Distinguishing stable disease (SD), pseudoprogression (PsP), and true progression (TP) remains challenging because these states can show overlapping MRI appearances despite different temporal trajectories. Existing longitudinal methods still face challenges in modeling scan-specific spatial variability, variable follow-up intervals, and complementary information from the observed follow-up state and its longitudinal change. We propose STRIDE, a framework for spatial-temporal representation of interval-conditioned disease evolution that takes paired post-treatment MRI scans and their inter-scan interval as input and predicts SD, PsP, or TP. The lesion-prior-guided spatial representation combines SoftGate and an Adaptive-window Hierarchical Transformer (AWHT) to emphasize lesion-related regions while preserving surrounding context. The time-conditioned latent transition uses pair-level context and the actual inter-scan interval to estimate interval-dependent representation changes between visits. The observed--transition fusion integrates the transition-estimated follow-up representation with the directly observed follow-up representation to jointly characterize the follow-up state and its longitudinal change. BraTS2024 is used to develop and evaluate the lesion-prior generator, while longitudinal pretraining on LUMIERE supports transfer before downstream adaptation to Burdenko. On the Burdenko three-class task, STRIDE achieves a macro ROC--AUC of 0.816 and a macro F1-score of 0.796. These results support its potential for more reliable longitudinal post-treatment GBM state assessment.

Background: Radiogenomics allows identification of radiological biomarkers for genomic phenotypes. In glioblastoma, these biomarkers could potentially complement patient stratification strategies. We aim to develop and analytically validate radiological biomarkers that capture immune cell signatures within IDH-wildtype glioblastoma microenvironment using radiogenomic analysis. Methods: This was a retrospective multicenter study using curated open-access anonymized imaging and genomic data from TCGA-GBM, CPTAC, IvyGAP, REMBRANDT and CGGA datasets. Imaging data consisted of MRI-based radiomic features extracted from necrotic core, enhancing and edema regions of deep learning-based auto-segmented tumors. Radiomic feature selections were performed using nested cross-validated LASSO. Support vector machine and ensemble models were trained using seventeen immune and cell-specific score labels extracted from deconvoluted transcriptomic data using pan-cancer and glioblastoma immune signature matrices as reference standards. Seventeen classifier models trained in three cross-cohort strategies were validated on three held-out datasets assessing stability and generalizability. Results: One-hundred-and-seventy-six patients were included in the study. The immune-related radiomic signatures obtained after feature selection were shape, first order and higher order radiomic features. Models predicting macrophage subtype immune signature showed stable mean performance on balanced accuracy (0.67) and precision (0.89) metrics for three independent holdout datasets with ensemble model outperforming support vector machine model. Conclusion: Radiogenomic models non-invasively predicted the macrophage subtype M0 immune signature in IDH-wildtype glioblastoma. These biomarkers have the potential to stratify patients for immunotherapy within prospective glioblastoma clinical trials.