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

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a median overall survival of 15 months. Longitudinal, multi-modal imaging datasets with comprehensive clinical and treatment data are essential to support the development of reproducible computational methods for treatment response prediction, disease progression modelling, and personalized medicine. We present CFB-GBM v2.0, an extension of our previously released CFB-GBM dataset comprising 264 GBM patients treated according to the standard Stupp protocol. The primary contribution of this release is the completion of Gross Tumour Volume (GTV) delineations across all available timepoints ($t_0$, $t_1$ and $t_2$), increasing the overall GTV completion rate from 35% to 97%. This was achieved using a nnU-Net model pre-trained on BraTS 2021 and fine-tuned on CFB-GBM ground-truth contours, with the generated segmentations validated by five radiation oncologists. From these longitudinal GTV annotations, volumetric RANO 2.0 response category labels were derived for all available temporality pairs ($t_0 \rightarrow t_1$, $t_0 \rightarrow t_2$ and $t_1 \rightarrow t_2$). To further ease dataset usability and reproducibility, brain masks computed with HD-BET and pre-computed radiomic features extracted with PyRadiomics are provided for each patient timepoint and MRI modality. Additionally, the WHO classification guideline (2016 vs. 2021) applicable to each patient's diagnosis is now explicitly documented. CFB-GBM v2.0 is publicly available on The Cancer Imaging Archive (TCIA) at https://www.cancerimagingarchive.net/collection/cfb-gbm .

Segmentation Robustness and Predictive Utility in Glioblastoma Radiomics: Evidence for a Trade-off in Survival Modelling

Radiomic biomarkers derived from magnetic resonance imaging (MRI) have been widely investigated as non-invasive tools for tumor characterization and prognostic modeling in glioblastoma (GBM). However, their clinical translation remains limited, in part due to sensitivity to tumor segmentation variability. In this study, we systematically investigate the relationship between feature robustness and predictive utility in GBM survival modeling using the University of Pennsylvania Glioblastoma Imaging, Genomics, and Radiomics (UPENN-GBM) cohort. A total of 4,752 radiomic features were obtained from multiparametric MRI across three tumor subregions: enhancing tumor (ET), peritumoral edema (ED), and necrotic core (NC). Feature robustness was quantified using the intraclass correlation coefficient (ICC) based on the automatic and expert-refined segmentation versions. Among features with valid ICC estimates, 48.1% were classified as robust. Survival prediction was evaluated using cross-validation with Coxnet, Random Survival Forest, and Gradient Boosting Survival Analysis models. In this cohort, radiomic feature inclusion showed no consistent improvement over the clinical baseline, and robustness filtering produced no detectable performance gain. Model-selected features were less robust than the overall feature pool, indicating a lack of enrichment for robustness. These findings suggest that robustness alone is not a reliable criterion for feature selection in radiomics-based survival modelling.

TRACE: A Concept Bottleneck Model for Longitudinal 3D Glioblastoma Response Assessment

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.

Do Foundation Models See Biology? Evaluating Attention Coherence with Spatial Transcriptomics in Glioblastoma

Whether attention maps from pathology foundation models capture genuine biology remains unknown, yet this question is critical for clinical trust and regulatory approval. We propose a spatial transcriptomics-based framework for orthogonal, hypothesis-free evaluation of attention and apply it to five pathology foundation models (CONCH v1.5, UNI v2, Virchow2, GigaPath, H-Optimus-1) and a ResNet50 baseline. Using attention-based multiple instance learning, we train single-task and multi-task models to predict five molecular alterations in glioblastoma on the CPTAC cohort, validate on an independent TCGA cohort, and evaluate biological coherence of attention maps against 87 transcriptional signatures using co-registered Visium spatial transcriptomics data from 18 samples. Internally, no single encoder dominates across all tasks, and external validation inverts internal performance rankings. Attention maps show a five-fold enrichment gradient from pathways (Cohen's d=0.329) to individual genes (d=0.055), indicating that attention captures emergent multi-gene transcriptional programs rather than individual molecular events. Spatially smooth attention maps do not imply biological coherence, and different encoders attend to distinct biological compartments. Our framework provides objective, quantitative assessment of what foundation models learn from histopathology, moving the field beyond qualitative saliency map review.