A Simulation-Based Stress-Testing Framework for Evaluating the Transportability of Imaging-Derived Logistic Risk...

Background: Imaging-based logistic models are widely used for non-invasive risk stratification; however, their structural robustness and transportability across heterogeneous biological contexts remain insufficiently examined. Purpose: This study aimed to develop a simulation-based stress-testing framework to evaluate the structural robustness and transportability of a radiology-adapted logistic risk model across distinct cutaneous lesion phenotypes under both aligned and structurally perturbed conditions. Methods: A simulation-based methodological framework was implemented using three synthetic cohorts representing nodular, subcutaneous, and vascular lesion phenotypes (n = 2000 per cohort). Model performance was evaluated under naïve transfer, recalibration, and revision conditions. To address potential structural alignment bias, additional simulation scenarios incorporating coefficient perturbations, nonlinear transformations, and interaction effects were used to generate outcome processes partially independent from the original model structure. Model performance was assessed using discrimination (ROC-AUC, PR-AUC), calibration metrics, decision curve analysis, and Monte Carlo-based stability assessments. Results: Under naïve transfer, discrimination remained stable across phenotypes (ROC-AUC ≈ 0.78-0.84). Calibration shifts were observed but were effectively corrected through recalibration. Under structurally perturbed outcome generation, discrimination showed only modest reduction, while overall performance patterns remained consistent. Structural variables demonstrated high transferability, whereas vascular features exhibited phenotype-dependent variability. Decision curve analysis indicated consistent clinical utility across relevant thresholds. Conclusions: The radiology-adapted logistic model demonstrated structural robustness across heterogeneous phenotype conditions, with performance variations driven primarily by calibration differences rather than structural failure. Importantly, robustness was preserved under conditions of structural perturbation, supporting the model's stability beyond idealized alignment assumptions. These findings suggest that simulation-based stress-testing frameworks provide a rigorous methodological approach for evaluating model transportability prior to large-scale clinical validation.