The aim of this work was to investigate radiomic analysis of contrast and non-contrast enhanced planning CT images of oesophageal cancer (OC) patients in terms of stability, dimensionality and contrast agent dependency. The prognostic significance of CT-based radiomic features was also evaluated. Different 2D and 3D radiomic features were extracted from contrast and non-contrast enhanced CT images of 213 patients from the multi-centre SCOPE1 randomised controlled trial (RCT) in OC. Feature stability was evaluated by randomly dividing patients into three groups and identifying textures with similar distributions among groups with a Kruskal-Wallis analysis. A paired two-sided Wilcoxon signed rank test was used to assess for significant differences in the remaining corresponding 2D and 3D stable features. A prognostic model was constructed using clinical characteristics and remaining filtered features. The discriminative ability of significant variables was tested using Kaplan-Meier analysis. A total of 238 2D and 3D radiomic features were computed from oesophageal CT images. More than 75 features were stable if extracted from homogeneous cohort (contrast or non-contrast enhanced CT images) and inhomogeneous cohort (contrast and non-contrast enhanced CT images). Among the remaining corresponding stable features computed from both cohorts, only 4 features did not show a statistically significant difference if obtained in 2D or in 3D (p-value < 0.05). A Cox regression model constructed using 5 clinical variables (age, sex, tumour, node and metastasis (TNM) stage, WHO performance status and contrast administration) and 4 radiomic variables (inverse variance_GLCM, large distance emphasis_GLDZM, zone distance non uniformity norm_GLDZM, zone distance variance_GLDZM), identified one radiomic feature (zone distance variance_GLDZM) that was significantly associated with overall survival (p-value = 0.032, HR = 1.25, 95% CI = 1.02–1.52). A significant difference in overall survival between groups was found when considering a threshold of zone distance variance_GLDZM equals to 1.70 (X² = 7.692, df = 1, p-value = 0.006). Zone distance variance_GLDZM was identified as the only stable CT radiomic feature statistically correlated with overall survival, independent of dimensionality and contrast administration. This feature was able to identify high-risk patients and if validated, could be the subject of a future clinical trial aiming to improve clinical decision making and personalise OC treatment.

Blood cell morphology assessment via light microscopy constitutes a cornerstone of haematological diagnostics, providing crucial insights into diverse pathological conditions. This complex task demands expert interpretation owing to subtle morphological variations, biological heterogeneity and technical imaging factors that obstruct automated approaches. Conventional machine learning methods using discriminative models struggle with domain shifts, intraclass variability and rare morphological variants, constraining their clinical utility. We introduce CytoDiffusion, a diffusion-based generative classifier that faithfully models the distribution of blood cell morphology, combining accurate classification with robust anomaly detection, resistance to distributional shifts, interpretability, data efficiency and uncertainty quantification that surpasses clinical experts. Our approach outperforms state-of-the-art discriminative models in anomaly detection (area under the curve, 0.990 versus 0.916), resistance to domain shifts (0.854 versus 0.738 accuracy) and performance in low-data regimes (0.962 versus 0.924 balanced accuracy). In particular, CytoDiffusion generates synthetic blood cell images that expert haematologists cannot distinguish from real ones (accuracy, 0.523; 95% confidence interval: [0.505, 0.542]), demonstrating good command of the underlying distribution. Furthermore, we enhance model explainability through directly interpretable counterfactual heat maps. Our comprehensive evaluation framework establishes a multidimensional benchmark for medical image analysis in haematology, ultimately enabling improved diagnostic accuracy in clinical settings.