Baseline Radiomics as a Prognostic Tool for Clinical Benefit from Immune Checkpoint Inhibition in Inoperable NSCLC Without Activating Mutations.

Checkpoint inhibitors (ICIs) are key therapies for NSCLC, but current selection criteria, such as excluding mutation carriers and assessing PD-L1, lack sensitivity. As a result, many patients receive costly treatments with limited benefit. Therefore, this study aimed to predict which NSCLC patients would achieve durable survival (≥24 months) with immunotherapy. A comprehensive ensemble radiomics approach was applied to pretreatment CT scans to prognosticate overall survival (OS) and predict progression-free survival (PFS) in a cohort of 220 consecutive patients with inoperable NSCLC treated with first-line ICIs (pembrolizumab or atezolizumab, nivolumab or prolgolimab) as monotherapy or in combination. The radiomics pipeline evaluated four normalization methods (none, min-max, Z-score, mean), four feature selection techniques (ANOVA, RFE, Kruskal-Wallis, Relief), and ten classifiers (e.g., SVM, random forest). Using two to eight radiomics features, 1680 models were built in the Feature Explorer (FAE) Python package. Three feature sets were evaluated: clinicopathological (CP) only, radiomics only, and a combined set, using 6- and 12-month PFS and 24-month OS endpoints. The top 15 models were ensembled by averaging their probability scores. The best performance was achieved at 24-month OS with the combined CP and radiomics ensemble (AUC = 0.863, accuracy = 85%), followed by radiomics-only (AUC = 0.796, accuracy = 82%) and CP-only (AUC = 0.671, accuracy = 76%). Predictive performance was lower for 6-month (AUC = 0.719) and 12-month PFS (AUC = 0.739) endpoints. Our radiomics pipeline improved selection of NSCLC patients for immunotherapy and could spare non-responders unnecessary toxicity while enhancing cost-effectiveness.