Radiomic model reliability is a central premise for its clinical translation. Presently, it is assessed using test-retest or external data, which, unfortunately, is often scarce in reality. Therefore, we aimed to develop a novel image perturbation-based method (IPBM) for the first of its kind toward building a reliable radiomic model. We first developed a radiomic prognostic model for head-and-neck cancer patients on a training (70%) and evaluated on a testing (30%) cohort using C-index. Subsequently, we applied the IPBM to CT images of both cohorts (Perturbed-Train and Perturbed-Test cohort) to generate 60 additional samples for both cohorts. Model reliability was assessed using intra-class correlation coefficient (ICC) to quantify consistency of the C-index among the 60 samples in the Perturbed-Train and Perturbed-Test cohorts. Besides, we re-trained the radiomic model using reliable RFs exclusively (ICC>0.75) to validate the IPBM. Results showed moderate model reliability in Perturbed-Train (ICC:0.565, 95%CI:0.518-0.615) and Perturbed-Test (ICC:0.596, 95%CI:0.527-0.670) cohorts. An enhanced reliability of the re-trained model was observed in Perturbed-Train (ICC:0.782, 95%CI:0.759-0.815) and Perturbed-Test (ICC:0.825, 95%CI:0.782-0.867) cohorts, indicating validity of the IPBM. To conclude, we demonstated capability of the IPBM toward building reliable radiomic models, providing community with a novel model reliability assessment strategy prior to prospective evaluation.

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