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 .

Lesion-Aware Adaptive Fourier Neural Operator for CT-to-PSMA PET Synthesis in Prostate Cancer

Deep learning models that synthesize PET from CT or MRI can reduce patient dose and scanner demand, but are typically optimized with global losses such as L1 or mean squared error (MSE) that treat all voxels similarly. In whole-body PSMA-PET, tumor voxels occupy only a small fraction of the volume, yet carry the clinically relevant activity signal; as a result, models can achieve high structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) while still underestimating lesion activity or failing to preserve tumor-specific structure. Radiomics provides biologically meaningful descriptors of tumor intensity and texture, but direct radiomics conditioning is time-consuming because it requires feature extraction from delineated lesion regions. We propose LAFNO, a Lesion-Aware Adaptive Fourier Neural Operator for CT-to-PSMA-PET synthesis that replaces high-dimensional radiomics conditioning with two efficient CT-derived proxy channels. Motivated by radiomics analysis of PSMA-avid tumor core and peritumoral regions, LAFNO uses a contrast proxy for local density variation and a disorder proxy for local texture heterogeneity, both injected into the model bottleneck. LAFNO combines whole-volume reconstruction with lesion-level total lesion activity (TLA), tumor-core contrast, and peritumoral supervision. We evaluated LAFNO against four baseline architectures on the TCIA PSMA-PET-CT-Lesions dataset. LAFNO remained competitive on whole-volume image quality, achieving SSIM of 0.960 and 0.938 for 18F- and 68Ga-PSMA, respectively, while reducing per-patient TLA error to 48.3% and 64.0% for 18F- and 68Ga-PSMA, respectively, and achieving the highest tumor-core radiomics reproducibility across all feature classes for both tracers. Peritumoral reproducibility remained tracer-dependent, indicating that biological fidelity in synthetic PSMA-PET remains challenging.

Structured Proxy Features for Multimodal NSCLC Survival Prediction from Pretreatment CT

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.

Negative controls reveal volume-driven confounding in radiomics and imaging foundation model features

Radiomics and imaging foundation models promise non-invasive biomarkers of tumour biology, yet predictive signatures may reflect tumour volume or acquisition artifacts rather than meaningful image structure. We introduce READII-2-ROQC, an open-source framework that uses volume-preserving negative controls to assess whether radiomic and deep imaging features capture independent spatial signals. READII-2-ROQC generates voxel-perturbed images across tumour, background and whole-image regions using configurable randomization strategies, then compares feature behaviour and model performance between original and control images. Applied to three public cancer imaging cohorts, the framework processed 3,552 tumour volumes and extracted PyRadiomics and foundation-model features from original images and nine matched controls. Reproducing published survival and HPV-status signatures, we show that multiple models retain performance after spatial structure is destroyed, revealing volume-driven or contextual confounding, whereas others show perturbation-sensitive signal. READII-2-ROQC provides a scalable quality-control strategy for developing interpretable, biologically grounded imaging biomarkers and reproducible radiomics workflows.

Comparing the Performance of Foundation Model Derived Embeddings with Traditional Approaches for Distant Metastasis Prediction in Head and Neck Cancer

Background: Early prediction of distant metastasis (DM) risk in head and neck cancer (HNC) can enable timely interventions that may improve treatment outcomes. Many current machine learning methods rely on prior knowledge of the region of interest such as tumor segmentations, which require expert knowledge, is time-consuming and introduces user-dependent variability. Medical image-based foundation models have recently been developed for specific imaging modalities to streamline down-stream prediction tasks by extracting modality-relevant features. Purpose: In this study, we evaluate the effectiveness of using a foundation model as the feature extractor to predict DM risk in HNC patients and compare its performance with traditional approaches that require prior knowledge on the regions of interest. Methods: Preoperative CT images of 2327 patients from the RADCURE dataset were used. Three features-sets were created including radiomics, deep-learning based features, and CT Foundation derived features. The feature-sets were used individually in a multi-layer perceptron (MLP) to predict DM risk. Results: The model using CT Foundation embeddings outperformed the radiomics and deep learning-based models, achieving a Receiver Operating Characteristic Area Under the Curve (AUC) of 0.791, compared to AUC values of 0.772 and 0.753 for the radiomics and deep learning-based models, respectively. The CT Foundation based model had similar performance to a model that combined the use of radiomics and deep learning-based features that achieved an AUC of 0.794. Conclusions: Features based on foundation models offer a promising alternative to traditional radiomics while reducing the need for domain expertise and extensively annotated datasets. Their minimal preprocessing requirements also make them a more accessible and scalable option.

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.

SARFA: Segment Anything with Radiomic Feature Alignment

The Segment Anything Model (SAM) has demonstrated strong generalizability across a variety of segmentation tasks. However, SAM often struggles in situations where the target to be segmented is ambiguous. This poses a problem in medical imaging, where accurate delineation of targets such as tumors is vital, but even expert radiologists can disagree on the appropriate boundary for a target. Addressing this, we propose SARFA (Segment Anything with Radiomic Feature Alignment), a novel framework for improved medical image segmentation. Via probabilistic prompting, SARFA generates a diverse set of plausible masks for each input image and optimizes them with a radiomics-driven training objective based on Fréchet Radiomic Distance (FRD) and Direct Preference Optimization (DPO). By minimizing the FRD between masked predicted and ground truth regions within each image, SARFA encourages segmentation outputs whose anatomical and textural characteristics align with clinically meaningful ground truth representations, without relying solely on pixel-level overlap. Evaluated on computed tomography (CT) and magnetic resonance imaging (MRI) benchmarks, SARFA outperforms existing ambiguous segmentation methods, demonstrating the effectiveness of radiomic feature alignment and DPO-style candidate mask ranking as a training objective. Our code is available at https://github.com/tbwa233/SARFA.

Physically Aware Radiomics Without Interpolation: Disentangling Voxel Geometry and Signal Modification in CT and MRI

Objective: Radiomic texture features are usually computed in voxel-index neighborhoods, implicitly assuming isotropic spatial relationships. In anisotropic images, this can confound voxel geometry with interpolation-induced signal changes. We developed a voxel-spacing-aware radiomic framework that incorporates physical geometry into texture computation without resampling. Approach: We modified PyRadiomics to account for voxel spacing while preserving the native image signal. Four configurations were compared: native non-resampled extraction (NR), isotropic resampling (RS), voxel-spacing-aware extraction (VS), and fake-isotropic preprocessing (FK), in which spacing metadata were overwritten without altering the image array. Experiments included 685 LIDC-IDRI pulmonary nodules and 209 I-SPY2 breast MRI cases, with 196 radiomic descriptors. Robustness was assessed using ICC, within-subject variability, Friedman testing, feature selection, machine learning, a multilayer perceptron, and external validation. Main results: VS showed near-native agreement with NR: median ICC(A,1) was 0.9976 in CT and 0.9984 in MRI. RS produced lower agreement and larger deviations, while FK showed intermediate behavior, confirming that spacing metadata alone can affect radiomic features. Gradient-derived and neighborhood-sensitive descriptors were most affected by preprocessing. VS preserved predictive performance comparable to NR in external CT validation, whereas MRI showed greater variability across preprocessing strategies and classifiers. Significance: Voxel-spacing-aware extraction separates geometric modeling from interpolation-induced signal modification while preserving the native image signal, offering a coherent alternative to isotropic resampling for radiomic analysis of anisotropic CT and MRI.

ConRad: Efficient Conformal Prediction for Radiomics

Radiomic features derived from medical images and segmentation masks are used to support decision making in clinical imaging pipelines. In practice, these features are often computed from predicted masks, but segmentation models can be overconfident or poorly calibrated, making derived measurements appear more reliable than they are. Conformal prediction (CP) provides distribution-free prediction intervals with finite-sample marginal coverage guarantees, but black-box intervals for segmentation-derived radiomics can be inefficient because they ignore test-time information about image appearance, mask geometry, and segmentation uncertainty. We propose ConRad, a conformal framework for scalar radiomic targets that uses covariates derived from the predicted mask, input image, predicted radiomics, and boundary uncertainty to construct adaptive intervals while maintaining coverage. Across five 2D medical imaging datasets and 171 retained radiomic targets, we show that ConRad improves feature-level efficiency compared to baselines while maintaining near-nominal empirical coverage. Ablation results further indicate that segmentation boundary uncertainty features are the largest contributors to interval efficiency.

An Interpretable Deep Learning Framework for Discovery and Clinical Validation of Deep Radiomic Signatures in Tumor Classification

Imaging signatures are quantitative features extracted from medical images that provide clinically meaningful information for tumor diagnosis, characterization, prognosis, and treatment planning. Although deep learning has shown great potential for imaging signature discovery, its limited interpretability remains a major barrier to clinical adoption. Existing approaches often achieve high predictive performance but provide little biological insight into the identified signatures. We propose a unified framework for interpretable imaging signature discovery by integrating deep learning based segmentation, explainable classification, and radiomic analysis. A robust segmentation model is first used to accurately delineate tumors, followed by a Grad-CAM guided pipeline that identifies diagnostically important regions as candidate imaging signatures. A mutual information based adaptive thresholding strategy enables patient-specific signature extraction. The resulting signatures are validated using a downstream deep learning classification model, while radiomic features extracted from the signature regions are evaluated with traditional machine learning models and interpreted using SHAP to identify the most discriminative biomarkers. The proposed framework is evaluated on the public BUSI breast ultrasound, KiTS renal CT, and BraTS brain tumor datasets, as well as a private UF Health renal CT cohort. Compared with conventional whole-tumor radiomics, the proposed signature-based approach achieves improved discriminative performance while providing greater biological interpretability. By converting deep learning attention into reproducible quantitative imaging biomarkers, this framework offers an interpretable and reproducible solution for non-invasive tumor characterization and imaging biomarker discovery.

RadiomicNet: A Hybrid Radiomics-Guided Lightweight Architecture for Interpretable Medical Image Segmentation

Deep learning has achieved remarkable performance in medical image segmentation, yet it suffers from critical limitations: mathematical intractability, substantial parameter requirements, and lack of clinical interpretability. We propose RadiomicNet, a novel two-stream hybrid architecture that enhances standard deep learning by integrating handcrafted radiomics features directly into the segmentation learning process. The key contribution is the Radiomics Attention Gate (RAG), which leverages Gray-Level Co-occurrence Matrix (GLCM) and Local Binary Pattern (LBP) features to modulate skip-connection attention in a lightweight MobileNetV2-based encoder-decoder, providing ante-hoc interpretability without post-hoc approximations. A novel Radiomics Consistency Loss further enforces alignment between texture complexity and prediction uncertainty, reducing Expected Calibration Error (ECE) from 0.142 to 0.118. RadiomicNet achieves a Dice Similarity Coefficient (DSC) of 0.763 +/- 0.231 on the Breast Ultrasound Images (BUSI) dataset and 0.854 +/- 0.112 on Kvasir-SEG, outperforming U-KAN by 1.2% and 1.8%, respectively (p < 0.05, Wilcoxon signed-rank test), with only 3.27M parameters, 9.5x fewer than standard U-Net and 4.3x fewer than U-KAN. Gradient-based feature importance analysis reveals that GLCM dissimilarity (15.24%), GLCM energy (14.56%), and LBP entropy (11.49%) are the dominant radiomics cues, providing clinically meaningful explanations for segmentation decisions. The proposed approach demonstrates that compact, interpretable models grounded in domain knowledge can deliver state-of-the-art segmentation performance with substantially reduced computational overhead.

Foundation Models vs. Radiomics for Lung Computed Tomography: A Benchmark of Feature Extractors, Classification Heads, and Segmentation Choices

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.

Multimodal Brain Tumour Classification Using Feature Fusion

Clinicians diagnose brain tumors by synthesizing patient symptoms, medical history, and quantitative imaging data from modalities such as MRI and CT scans into a unified clinical judgement. However, most deep learning models rely on MRI/CT images alone, failing to replicate the clinicians multimodal reasoning. We explore a two-branch multimodal network combining raw MRI scans with 91 extracted radiomic features (intensity, texture, shape, and boundary descriptors) to classify brain tumors into glioma, meningioma, pituitary, and no-tumor. A pre-trained CNN backbone encodes the image stream, whereas a dedicated MLP encodes the radiomic stream. Both streams are fused via concatenation, gated, or bidirectional cross-modal attention strategies. Across nine experimental runs on a balanced 7,200 image dataset, all multimodal configurations outperform unimodal baselines with gated fusion achieving the best accuracy of 96.13%.

Radiomic Feature Selection Using Gradient Loss of Deep Neural Network for Lung Cancer Stage Detection

Radiomics enables extraction of quantitative imaging biomarkers from medical images and has become an important tool for computer-aided cancer diagnosis. However, radiomics datasets are typically high-dimensional with limited samples, making feature selection a critical step for building reliable predictive models. This study proposes a Gradient-Loss Recursive Feature Elimination (GL-RFE) framework that integrates gradient sensitivity analysis from a deep neural network to identify the most influential radiomic features for lung cancer stage detection. A total of 106 radiomic features were extracted from chest Computed Tomography (CT) scans using the PyRadiomics extension of the 3D Slicer platform. The proposed method evaluates feature importance by computing gradients of the network loss with respect to input features and recursively eliminates features with minimal contribution. The resulting top-15 radiomic features are used to train a deep neural network classifier for distinguishing early-stage and advanced-stage lung cancer. The proposed framework achieves strong classification performance, with accuracy of 90.22%, precision of 90.10%, recall of 90.24%, and F1-score of 90.16% on the test dataset. Visualization analyses, including correlation heat maps and distribution plots, further confirm reduced feature redundancy and improved class separability. Compared to conventional feature selection techniques, GL-RFE effectively captures nonlinear feature interactions and enhances model generalization. The presented protocol provides a reproducible and interpretable methodology for radiomics-based cancer stage detection and is particularly suitable for high-dimensional, small-sample biomedical datasets, with potential applications in other domains such as genomics and multimodal clinical analysis.

Radiomics- and Clinical Feature-Driven Prediction of Volumetric Response in Skull-Base Meningioma after CyberKnife Radiosurgery

Skull-base meningiomas are often characterized by favorable long-term prognosis, yet their anatomical complexity and proximity to critical neurovascular structures make treatment selection challenging. Stereotactic radiosurgery with CyberKnife represents an effective therapeutic option when surgical resection is not feasible; however, not all patients benefit equally from this treatment. Early identification of patients likely to respond to radiosurgery remains an open clinical problem. In this study, we propose a radiomics- and clinical feature-driven framework for predicting volumetric response in skull-base meningiomas treated with CyberKnife. Unlike most existing approaches that focus on progression-free survival or recurrence, our method targets volumetric response as an indicator of treatment efficacy. Pre-treatment MRI images from 104 patients were processed to extract radiomic features, which were combined with clinical variables and analyzed using six models. To ensure methodological rigor, the entire modeling process was implemented within a nested cross-validation scheme. Among the evaluated models, TabPFN achieved the best overall performance, with an AUC of 0.81 and consistently favorable classification metrics. These results suggest that advanced machine learning architectures, when combined with robust validation strategies, can effectively capture patterns associated with treatment response even in small-sample, high-dimensional settings.