Radiomics-based machine learning to evaluate immunotherapy efficacy in non-small cell lung cancer patients with bone...

Assessing treatment response in bone metastases from non-small cell lung cancer (NSCLC) remains a major clinical challenge, particularly for patients receiving immune checkpoint inhibitors (ICIs). The existing response criteria are not optimized for osseous disease, leading to inconsistent evaluation. We aimed to develop and validate a radiomics-based machine learning (ML) framework to non-invasively distinguish immunotherapy response categories-progression, stable disease, and partial response-in NSCLC patients with bone metastases.

Chest computed tomography (CT) scans from 99 NSCLC patients were analyzed before and during ICI therapy. Bone structures were automatically segmented using TotalSegmentator, and 1051 radiomic features were extracted per time point. Clinical variables were incorporated as optional features. Three ML classifiers-random forest, XGBoost, and support vector machine-were trained using fivefold cross-validation. A multistep feature selection pipeline (correlation filtering, mutual information, recursive feature elimination, and ReliefF ranking) was applied. Model performance was evaluated using area under the curve (AUC), $F1$ -score, accuracy, sensitivity, and specificity, with additional statistical testing using Kruskal-Wallis, Mann-Whitney $U$ , bootstrapping, and permutation analysis.

Inter-rater agreement for radiological response categories was high (Cohen's kappa = 0.91). Post-treatment radiomic features yielded the best performance. The random forest model achieved an AUC of 0.94, an $F1$ -score of 0.79, an accuracy of 0.79, a sensitivity of 0.80, and a specificity of 0.83. Clinical features did not meaningfully improve performance. Models based on the largest lesion showed lower accuracy than those using the overall response.

Post-treatment CT radiomics captured therapy-induced skeletal changes and enabled differentiation of immunotherapy response categories in NSCLC bone metastases. These findings highlight radiomics as a non-invasive tool for response assessment and guiding personalized treatment strategies.