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

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.

Radiomics is the established approach for CT-based lung cancer phenotyping, yet comparisons with foundation models rarely isolate contributions of feature extractor, classification head, and segmentation choice, or test cross-cohort robustness. We benchmark five feature extractors (Curia, Curia-2, DINOv3, Radiomics2D, Radiomics3D), seven classification heads (TabPFN, TabICL, XGBoost, CatBoost, Random Forest, logistic regression, Ridge), and three segmentation regimes on five tasks: tumor volume and stage classification, 2-year survival prediction, histology classification, and age prediction. Models are trained on LUNG1 (n=338) and evaluated on an internal test set (n=84) and the external LUNG2 cohort (n=211), with worst-case cross-cohort performance as the primary metric. The dominant design factor is task-dependent: segmentation drives volume and stage classification, while classifier choice drives survival, histology, and age prediction. Radiomics is competitive for tumor volume, tumor stage and survival (partly due to label-derivation effects for the former); Curia variants reach comparable peak scores for survival; DINOv3 falls slightly short across tasks. Patch and slice aggregation have negligible impact. We recommend Curia with tumor segmentation and a CatBoost head as a safe default, achieving the best mean rank across the three primary clinical tasks, though task-specific selection consistently outperforms any cross-task default. When tumor delineations are unavailable, Curia-2 with lung segmentation and logistic regression offers a competitive alternative. All pipelines use a two-stage design suited to small cohort sizes where end-to-end fine-tuning would risk overfitting.

Lung cancer results in roughly 1.8 million fatalities annually worldwide, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Despite advancements in treatment, survival stratification remains challenging due to intratumoral heterogeneity inadequately captured by conventional descriptors. Standard radiomic and deep learning techniques regard imaging features as independent quantities, overlooking structured interactions between tumor characteristics. We evaluate whether structured proxy features can enhance multimodal NSCLC survival prediction by augmenting pretreatment computed tomography (CT) representations, radiomics, and clinical variables with six simulation-derived features designed to capture interactions between heterogeneity and morphology. A radiomic-parameterized cellular automaton generates growth-rate and necrosis-ratio proxy features from baseline CT by using entropy and sphericity to compute low-dimensional proxy parameters. The imaging backbone is a Transformer-based Masked Autoencoder (TMAE), which was chosen after a systematic evaluation with alternative encoders within the same pipeline and provides attention-based visualizations that highlight tumor regions receiving higher model attention. On the public Lung1 cohort (n = 390), the primary four-modality fusion attained a C-index of 0.641 (iAUC 0.731, log-rank p < 0.001). The primary result compares favorably with prior multimodal results on Lung1 (C-index 0.631; iAUC 0.592 [15]) under a comparable evaluation protocol, while a separate exploratory coefficient-optimization analysis achieved a best observed C-index of 0.662 (iAUC 0.748). These results indicate that, in addition to conventional radiomic, deep, and clinical representations within the Lung1 benchmark, simulation-derived proxy features may provide complementary predictive information within this fixed Lung1 benchmark.